R0 resection following chemo (radio)therapy improves survival of primary inoperable pancreatic cancer patients. Interim results of the German randomized CONKO-007± trial - Fietkau, Rainer; Grützmann, Robert; Wittel, U. A.; Croner, R. S.; Jacobasch, L.; Neumann, U. P.; Reinacher-Schick, A.; Imhoff, D.; Boeck, S.; Keilholz, L.; Oettle, H.; Hohenberger, Werner; et al. (Strahlentherapie und Onkologie, 2020)
Purpose: Chemotherapy with or without radiotherapy is the standard in patients with initially nonmetastatic unresectable pancreatic cancer. Additional surgery is in discussion. The CONKO-007 multicenter randomized trial examines the value of radiotherapy. Our interim analysis showed a significant effect of surgery, which may be relevant to clinical practice. Methods: One hundred eighty patients received induction chemotherapy (gemcitabine or FOLFIRINOX). Patients without tumor progression were randomized to either chemotherapy alone or to concurrent chemoradiotherapy. At the end of therapy, a panel of five independent pancreatic surgeons judged the resectability of the tumor. Results: Following induction chemotherapy, 126/180 patients (70.0%) were randomized to further treatment. Following study treatment, 36/126 patients (28.5%) underwent surgery; (R0: 25/126 [19.8%]; R1/R2/Rx [n = 11/126; 6.1%]). Disease-free survival (DFS) and overall survival (OS) were significantly better for patients with R0 resected tumors (median DFS and OS: 16.6 months and 26.5 months, respectively) than for nonoperated patients (median DFS and OS: 11.9 months and 16.5 months, respectively; p = 0.003). In the 25 patients with R0 resected tumors before treatment, only 6/113 (5.3%) of the recommendations of the panel surgeons recommended R0 resectability, compared with 17/48 (35.4%) after treatment (p < 0.001). Conclusion: Tumor resectability of pancreatic cancer staged as unresectable at primary diagnosis should be reassessed after neoadjuvant treatment. The patient should undergo surgery if a resectability is reached, as this significantly improves their prognosis.
CRIS-Team Scopus Importer:2020-09-25
Keywords: Neoadjuvant chemoradiotherapy; Pancreatic adenocarcinoma; Prospective randomized multicenter trial; Surgery; Tumor resectability

R1 resection for pancreatic carcinoma - Kersting, S.; Haller, F.; Grützmann, Robert; Weber, Georg (Chirurg, 2017)
Surgery is the only potentially curative therapeutic approach in patients with pancreatic ductal adenocarcinoma (PDAC); however, achieving a negative (R0) resection margin is not always possible.The impact of R1 resection margins on survival rates and treatment options (surgical and multimodal) for intraoperatively and postoperatively identified R1 resection margins.For intraoperatively diagnosed R1 resection margins, a re-resection (e.g. pancreas, main bile duct, stomach, superior mesenteric and portal vein) can be performed to achieve R0 resection margins. Arterial resections and the resection of additional organs are occasionally technically feasible and can be performed in an individual approach. New neoadjuvant and adjuvant treatment strategies have increased the rate of resectable PDAC and have improved the outcome of patients with R0/R1 resected PDACs.An R0 resection is the primary goal of surgery in patients with PDAC as R1 resections are correlated with a poor outcome.
EVALuna2:6902

Radical Resection in Entero-Pancreatic Neuroendocrine Tumors: Recurrence-Free Survival Rate and Definition of a Risk Score for Recurrence - Merola, Elettra; Pascher, A.; Rinke, A.; Bartsch, D. K.; Zerbi, A.; Nappo, G.; Carnaghi, C.; Ciola, M.; Mcnamara, M. G.; Zandee, W.; Bertani, E.; Marcucci, S.; et al. (Annals of Surgical Oncology, 2022)
Background Surgery with radical intent is the only potentially curative option for entero-pancreatic neuroendocrine tumors (EP-NETs) but many patients develop recurrence even after many years. The subset of patients at high risk of disease recurrence has not been clearly defined to date. Objective The aim of this retrospective study was to define, in a series of completely resected EP-NETs, the recurrence-free survival (RFS) rate and a risk score for disease recurrence. Patients and Methods This was a multicenter retrospective analysis of sporadic pancreatic NETs (PanNETs) or small intestine NETs (SiNETs) [G1/G2] that underwent R0/R1 surgery (years 2000-2016) with at least a 24-month follow-up. Survival analysis was performed using the Kaplan-Meier method and risk factor analysis was performed using the Cox regression model. Results Overall, 441 patients (224 PanNETs and 217 SiNETs) were included, with a median Ki67 of 2% in tumor tissue and 8.2% stage IV disease. Median RFS was 101 months (5-year rate 67.9%). The derived prognostic score defined by multivariable analysis included prognostic parameters, such as TNM stage, lymph node ratio, margin status, and grading. The score distinguished three risk categories with a significantly different RFS (p < 0.01). Conclusions Approximately 30% of patients with EP-NETs recurred within 5 years after radical surgery. Risk factors for recurrence were disease stage, lymph node ratio, margin status, and grading. The definition of risk categories may help in selecting patients who might benefit from adjuvant treatments and more intensive follow-up programs.
CRIS-Team WoS Importer:2022-06-03

Radio(chemo)therapy in anaplastic thyroid cancer—high locoregional but low distant control rates—a monocentric analysis of a tertiary referral center - Schmied, Matthias; Lettmaier, Sebastian; Semrau, Sabine; Traxdorf, Maximilian; Mantsopoulos, Konstantinos; Müller-Hübner, Sarina; Iro, Heinrich; Denz, Axel; Grützmann, Robert; Fietkau, Rainer; Haderlein, Marlen (Strahlentherapie und Onkologie, 2022)
Background: Anaplastic thyroid cancer (ATC) is a lethal disease with highly aggressive disease progression. This study analyses the influence of radio(chemo)therapy, R(C)T, on disease control, survival rates and predictors for survival. Patients and methods: A total of 33 patients with ATC, treated at a tertiary referral center between May 2001 and April 2020 were included. Univariate and multivariate analysis were used to investigate correlates of R(C)T and predictors on disease control and survival rates. Results: Median follow-up was 4 months. In UICC stage IVA and IVB median overall survival (OS) was 8 months, median progression-free survival (PFS) was 6 months. Patients with UICC stage IVA and IVB and patients being irradiated with a radiation dose of more than 60 Gy showed increased OS. Of these patients, 3 were alive and free from disease. All of them receiving cisplatin-based radiochemotherapy and a minimum radiation dose of 66 Gy. UICC stage IVC showed a median OS of 2.5 months and a median PFS of 1 month. Only 2 of 16 patients had local failure. Conclusion: Depending on UICC stage, RT with high radiation dose can lead to improved OS or at least higher locoregional control. A limiting factor is the high incidence of distant metastases; therefore modern systemic treatment options should be integrated into multimodal therapy concepts.
CRIS-Team Scopus Importer:2022-05-20
Keywords: Anaplastic thyroid cancer; Chemotherapy; Multimodal treatment; Radiation dose; Radiotherapy

Randomised controlled monocentric trial to compare the impact of using professional actors or peers for communication training in a competency-based inverted biochemistry classroom in preclinical medical education - Schneider, Achim; Messerer, David Alexander Christian; Kühn, Veronika; Horneffer, Astrid; Bugaj, Till Johannes; Nikendei, Christoph; Kühl, Michael; Kühl, Susanne Julia (BMJ Open, 2022)
Objective In medical education, biochemistry topics are usually knowledge based, and students often are unaware of their clinical relevance. To improve students' awareness of the relevance, we integrated communication skills training into biochemistry education. No studies before have examined the difference between peer and standardised patient (SP) role plays where students explain the biochemical background of a disease in patient-centred language. Therefore, we evaluated whether students' self-perceived competency in Canadian Medical Education Directives for Specialists (CanMEDS) roles and their opinion of the quality of role play differ if the layperson is played by peers or SPs. Methods We randomly assigned medical students in a preclinical semester to one of the two groups. The groups used predefined scripts to role play a physician-parent consultation with either a peer (peer group) or an SP (SP group) in the parent role. Students then assessed the activity's effects on their competency in CanMEDS roles and motivation and the relevance of the role play. To determine whether students achieved biochemistry learning goals, we evaluated results of a biochemistry exam. Results Students' self-perceived competency improved in both groups. The SP group rated their competency in the roles Scholar' and Professional' significantly higher than the peer group did. The peer group rated their competency in the role of Medical Expert' significantly higher if they played the role of the parent rather than physician or observer. The SP group agreed more that they were motivated by the role play and wanted to receive more role play-based teaching. The SP group perceived the role play as being realistic and rated the feedback discussion as more beneficial. The examination results were the same in both groups. Conclusion We showed that role plays in a biochemistry seminar improve students' self-perceived competency. The use of SPs has some advantages, such as being more realistic.
CRIS-Team Scopus Importer:2022-06-10
Keywords: Biochemistry; EDUCATION & TRAINING (see Medical Education & Training); MOLECULAR BIOLOGY

Randomisierte kontrollierte Studien und Real-World-Evidence in der Marktzulassung und Überwachung von Hochrisikoprodukten – Das Beispiel Paclitaxel - Behrendt, C. A.; Rother, Ulrich; Rümenapf, G.; Uhl, C.; Görtz, H.; Böckler, D. (Gefässchirurgie, 2020)
In 2018 and 2020, two meta-analyses using summary-level data from randomized controlled trials reported worse mortality following the application of paclitaxel-coated stents and balloons in femoropopliteal and crural arteries. These results initiated a heated global discussion concerning the validity of this association, while various observational studies using clinical and administrative registries proved the safety of coated devices. This article aimed to summarize the development and adoption of paclitaxel-coated balloons and stents for the treatment of peripheral arterial occlusive disease in clinical practice, research, and practice guidelines. It especially focusses on the European Unionʼs medical device regulation, which has far-reaching implications for the market approval and monitoring of high-risk medical devices.
CRIS-Team Scopus Importer:2020-11-13
Keywords: Administrative data; Health-care research; Quality indicators; Routine data; Validity

Randomized controlled trials and real-world evidence for market access and surveillance of high-risk products—The example of paclitaxel - Behrendt, C. ‑.A.; Rother, Ulrich; Rümenapf, G.; Uhl, C.; Görtz, H.; Böckler, D. (Gefässchirurgie, 2020)
In 2018 and 2020, two meta-analyses using summary-level data from randomized controlled trials reported worse mortality following the application of paclitaxel-coated stents and balloons in femoropopliteal and crural arteries. These results initiated a heated global discussion concerning the validity of this association, while various observational studies using clinical and administrative registries proved the safety of coated devices. This article aimed to summarize the development and adoption of paclitaxel-coated balloons and stents for the treatment of peripheral arterial occlusive disease in clinical practice, research, and practice guidelines. It especially focusses on the European Unionʼs medical device regulation, which has far-reaching implications for the market approval and monitoring of high-risk medical devices.
CRIS-Team Scopus Importer:2020-12-11
Keywords: Administrative data; Health-care research; Quality indicators; Routine data; Validity

Randomized phase 2 trial of chemoradiotherapy plus induction or consolidation chemotherapy as total neoadjuvant therapy for locally advanced rectal cancer: CAO/ARO/AIO-12 - Hofheinz, R.; Fokas, E.; Allgaeuer, M.; Polat, B.; Klautke, G.; Grabenbauer, G.; Fietkau, Rainer; Kuhnt, T.; Staib, L.; Brunner, T.; Grosu, A.; Schmiegel, W.; et al. (ANNALS OF ONCOLOGY, 2019)
CRIS-Team WoS Importer:2019-08-09

Randomized Phase II Trial of Chemoradiotherapy Plus Induction or Consolidation Chemotherapy as Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer: CAO/ARO/AIO-12 - Fokas, Emmanouil; Allgäuer, Michael; Polat, Bülent; Klautke, Gunther; Grabenbauer, Gerhard G.; Fietkau, Rainer; Kuhnt, Thomas; Staib, Ludger; Brunner, Thomas; Grosu, Anca-Ligia; Schmiegel, Wolff; Jacobasch, Lutz; et al. (Journal of Clinical Oncology, 2019)
PURPOSE: Total neoadjuvant therapy is a new paradigm for rectal cancer treatment. Optimal scheduling of preoperative chemoradiotherapy (CRT) and chemotherapy remains to be established. PATIENTS AND METHODS: We conducted a multicenter, randomized, phase II trial using a pick-the-winner design on the basis of the hypothesis of an increased pathologic complete response (pCR) of 25% after total neoadjuvant therapy compared with standard 15% after preoperative CRT. Patients with stage II or III rectal cancer were assigned to group A for induction chemotherapy using three cycles of fluorouracil, leucovorin, and oxaliplatin before fluorouracil/oxaliplatin CRT (50.4 Gy) or to group B for consolidation chemotherapy after CRT. Secondary end points included toxicity, compliance, and surgical morbidity. RESULTS: Of the 311 patients enrolled, 306 patients were evaluable (156 in group A and 150 in group B). CRT-related grade 3 or 4 toxicity was lower (37% v 27%) and compliance with CRT higher in group B (91%, 78%, and 76% v 97%, 87%, and 93% received full-dose radiotherapy, concomitant fluorouracil, and concomitant oxaliplatin in groups A and B, respectively); 92% versus 85% completed all induction/consolidation chemotherapy cycles, respectively. The longer interval between completion of CRT and surgery in group B (median 90 v 45 days in group A) did not increase surgical morbidity. A pCR in the intention-to-treat population was achieved in 17% in group A and in 25% in group B. Thus, only group B (P < .001), but not group A (P = .210), fulfilled the predefined statistical hypothesis. CONCLUSION: Up-front CRT followed by chemotherapy resulted in better compliance with CRT but worse compliance with chemotherapy compared with group A. Long-term follow-up will assess whether improved pCR in group B translates to better oncologic outcome.
CRIS-Team Scopus Importer:2019-12-10

Rapid generation of monocyte-derived antigen-presenting cells with dendritic cell-like properties - Cunningham, Sarah; Hackstein, Holger (Transfusion, 2021)
Background: One of the major challenges in cellular therapy is the establishment and validation of simple and fast production protocols meeting good manufacturing practice (GMP) requirements. Dendritic cells (DCs) are of particular therapeutic interest, due to their critical role in T cell response initiation and regulation. Conventional wisdom states that DC generation from monocytes is a time-consuming protocol, taking up to 7–9 days. Study Design and Methods: This study systematically screened and validated numerous culture components and conditions to identify the minimal requirements, which can give rise to functional monocyte-derived antigen-presenting cells (MoAPCs) in less than 48 h (36 h MoAPC). A total of 36 h MoAPCs were evaluated in terms of surface marker expression, endocytic capability, and induction of antigen-specific T cell expansion via flow cytometry. Results: Screening of media compositions, glucose concentrations, and surface marker kinetics, particularly DC-SIGN as a DC-specific marker, allowed the generation of DC-like APCs in 36 h (36 h MoAPCs). A total of 36 h MoAPCs displayed a similar phenotype to 48 h MoAPC and standard 7 d MoDCs in terms of HLA-DP,DQ,DR, CD83, and DC-SIGN expression, while CD1a was preferentially expressed in standard MoDCs. Functional evaluation revealed that 36 h MoAPCs displayed reduced endocytosis capabilities and IL-12p70 production. However, 36 h MoAPCs were able to induce T cell expansion both in an allogenic and antigen-specific setting. Conclusion: Our results indicate that mature 36 h MoAPCs possess DC-like capabilities by inducing antigen-specific T cell responses. This study has important implications for the generation of DC-based cellular therapies, allowing a more cost and time-efficient generation of APCs.
CRIS-Team Scopus Importer:2021-04-09
Keywords: 36 h MoAPCs; 48 h MoAPC; antigen-presenting cells; monocytes

Rapidly fatal SMARCA4-deficient undifferentiated sarcoma originating from hybrid hemosiderotic fibrolipomatous tumor/pleomorphic hyalinizing angiectatic tumor of the foot - Agaimy, Abbas; Meidenbauer, Norbert; Sukov, William R.; Stöhr, Robert; Vieth, Michael; Roemer, Frank; Grützmann, Robert; Folpe, Andrew L. (Virchows Archiv, 2021)
Pleomorphic hyalinizing angiectatic tumor (PHAT) of soft parts and hemosiderotic fibrolipomatous tumor (HFLT) are two rare low-grade locally recurring neoplasms with predilection for the foot/ankle. Recent studies support a close link between the two entities, and origin of PHAT from HFLT and occurrence of hybrid HFLT/PHAT have been documented. Both lesions often harbor TGFBR3 or MGEA5 rearrangements. Rare sarcomas originating from HFLT/PHAT have been reported, typically resembling myxofibrosarcoma or myxoinflammatory fibroblastic sarcoma. We describe a novel SMARCA4-deficient undifferentiated sarcoma with rhabdoid features originating from hybrid HFLT/PHAT in the foot of a 54-year-old male. The tumor pursued a highly aggressive course with rapid regrowth after resection and multiple metastases resulting in patient's death within 5 months, despite systemic chemotherapy. Immunohistochemistry revealed SMARCA4 loss in the undifferentiated sarcoma, but not in the HFLT/PHAT. Molecular testing confirmed TGFBR3/MGEA5 rearrangements. This report expands the phenotypes of sarcomas developing from pre-existing PHAT/HFLT.
CRIS-Team WoS Importer:2021-08-27

Rapid qPCR-based quantitative immune cell phenotyping in mouse tissues - Huang, Jinghao; Demmler, Richard; Mohamed Abdou, Mariam; Thoma, Oana-Maria; Weigmann, Benno; Waldner, Maximilian; Stürzl, Michael; Naschberger, Elisabeth (Journal of Investigative Medicine, 2024)
The immune microenvironment plays an important role in the regulation of diseases. The characterization of the cellular composition of immune cell infiltrates in diseases and respective models is a major task in pathogenesis research and diagnostics. For the assessment of immune cell populations in tissues, fluorescence-activated cell sorting (FACS) or immunohistochemistry (IHC) are the two most common techniques presently applied, but they are cost intensive, laborious, and sometimes limited by the availability of suitable antibodies. Complementary rapid qPCR-based approaches exist for the human situation but are lacking for experimental mouse models. Accordingly, we developed a robust, rapid RT-qPCR-based approach to determine and quantify the abundance of prominent immune cell populations such as T cells, helper T (Th) cells, cytotoxic T cells, Th1 cells, B cells, and macrophages in mouse tissues. The results were independently validated by the gold standards IHC and FACS in corresponding tissues and showed high concordance.
CRIS-Team Scopus Importer:2023-12-22
Keywords: FACS; IHC; immune cell phenotyping; mouse tissue; RT-qPCR

Reactivation and persistence of human herpesvirus-8 infection in B cells and monocytes by Th-1 cytokines increased in Kaposi's sarcoma. - Monini, Paolo; Colombini, Sandra; Stürzl, Michael; Goletti, Delia; Cafaro, Aurelio; Sgadari, Cecilia; Buttò, Stefano; Franco, Marina; Leone, Patrizia; Fais, Stefano; Leone, Pasqualina; Melucci-Vigo, Gianna; et al. (Blood, 1999)
Patients with Kaposi's sarcoma (KS) have a human herpesvirus-8 (HHV-8) load higher than patients without KS and present a CD8(+) T-cell activation with production of Th1-type cytokines both in tissues and peripheral blood mononuclear cells (PBMC). Because in tissues of KS patients detection of inflammatory cytokines (IC) can precede detection of HHV-8 DNA and because signs of immunoactivation and/or dysregulation can precede KS development, we investigated the effect of IC on HHV-8 infection. To achieve this goal, PBMC and purified cell populations from 45 patients with KS and 45 patients at risk of KS were analyzed for HHV-8 DNA and/or gene expression and for cell survival, growth, and phenotype before or after culture with or without the IC increased in KS. The results indicate that PBMC that are polymerase chain reaction (PCR)-positive at day 0 generally loose the virus upon culture. However, the presence of IC maintains HHV-8 DNA load in cultured cells. In addition, IC increase viral load to detectable levels in PBMC from serologically positive patients that were PCR-negative before culture. gamma Interferon is sufficient for these effects, whereas tumor necrosis factor and interleukin-6 have little or no activity. The increase of HHV-8 DNA by IC is observed after short-term (7 days) or long-term (28 days) culture of the cells and occurs in one or both of the two circulating cell types that are infected in vivo: B cells and monocytes. In both cases it is associated with lytic gene expression, suggesting that virus reactivation is one of the most likely mechanisms for the effect of IC on virus load. However, IC have also effects on the cells target of HHV-8 infection, because they increase B-cell survival and induce the growth and differentiation of monocytes into KS-like spindle cells with markers of endothelial macrophages. Because cells with markers of endothelial macrophages are present in blood and lesions from KS patients and are infected by HHV-8, these data may explain the high HHV-8 load associated with KS development and suggest that infected monocytes may carry the virus to tissues, transmit the infection, or differentiate in loco in spindle cells with endothelial macrophage markers.

Reactivation and role of HHV-8 in Kaposi's sarcoma initiation. - Ensoli, Barbara; Stürzl, Michael; Monini, Paolo (Advances in Cancer Research, 2001)
Kaposi's sarcoma (KS) is an angioproliferative disease occurring in several clinical-epidemio-logic forms but all associated with infection by the human herpesvirus-8 (HHV-8). At least in early stages, KS is a reactive disease associated with a state of immune dysregulation characterized by CD8+ T-cell activation and production of Th1-type inflammatory cytokines (IC) that precedes lesion development. In fact, evidence indicates that IC can trigger lesion formation by inducing the activation of endothelial cells that leads to adhesion and tissue extravasation of lymphomonocytes, spindle cell formation, and angiogenesis, and HHV-8 reactivation that, in turn, leads to virus spread to all circulating cell types and virus dissemination into tissues. Due to virus escape mechanisms and deficient immune responses toward HHV-8, virus reactivation and spread are not controlled by the immune system but induce immune responses that may paradoxically exacerbate the reactive process. The virus is recruited into "activated" tissue sites where it finds an optimal environment for growth. In fact, viral load is very low in early lesions, whereas almost all spindle cells are infected in late-stage lesions. Although early KS is a reactive process of polyclonal nature that can regress, in time and in the presence of immunodeficiency, it can progress to a true sarcoma. This is likely due to the long-lasting expression of HHV-8 latency genes in spindle cells associated with the deregulated expression of oncogenes and oncosuppressor genes and, for AIDS-KS, with the effects of the HIV-1 Tat protein.

Real-time ECG monitoring and arrhythmia detection using Android-based mobile devices - Gradl, Stefan; Kugler, Patrick; Lohmüller, Clemens; Eskofier, Björn (Engineering in Medicine and Biology Society, EMBC, 2012, 2012)
We developed an application for Android™-based mobile devices that allows real-time electrocardiogram (ECG) monitoring and automated arrhythmia detection by analyzing ECG parameters. ECG data provided by pre-recorded files or acquired live by accessing a Shimmer™ sensor node via Bluetooth™ can be processed and evaluated. The application is based on the Pan-Tompkins algorithm for QRS-detection and contains further algorithm blocks to detect abnormal heartbeats. The algorithm was validated using the MIT-BIH Arrhythmia and MIT-BIH Supraventricular Arrhythmia databases. More than 99% of all QRS complexes were detected correctly by the algorithm. Overall sensitivity for abnormal beat detection was 89.5% with a specificity of 80.6%. The application is available for download and may be used for real-time ECG-monitoring on mobile devices. © 2012 IEE

Recapitulating Drug Treatment in a Dish - Investigating the Impact of 2D Versus 3D In Vitro Cancer Models and Different Treatment Schemes on Drug Response - Sankarasubramanian, Sushmitha; Kroger, Anne-Claire; Pfohl, Ulrike; Loskutov, Jurgen; Linnebacher, Michael; Regenbrecht, Christian; Regenbrecht, Christian; Wedeken, Lena (ONCOLOGY RESEARCH AND TREATMENT, 2022)
CRIS-Team WoS Importer:2022-12-16

Recent Advances in Good Manufacturing Practice-Grade Generation of Dendritic Cells - Cunningham, Sarah; Hackstein, Holger (Transfusion Medicine and Hemotherapy, 2020)
Dendritic cells (DCs) are pivotal regulators of immune responses, specialized in antigen presentation and bridging the gap between the innate and adaptive immune system. Due to these key features, DCs have become a pillar of the continuously growing field of cellular therapies. Here we review recent advances in good manufacturing practice strategies and their individual specificities in relation to DC production for clinical applications. These take into account both small-scale experimental approaches as well as automated systems for patient care.
CRIS-Team Scopus Importer:2020-12-11
Keywords: Dendritic cells; Good manufacturing practice; Monocytes

Recommendations on conservative therapy and secondary prevention of peripheral arterial disease (PAD): an evidence-based information brochure for sufferers - Rosenberg, Yvonne; Goertz, Hartmut; Rother, Ulrich; Uhl, Christian; Stavroulakis, Konstantinos; Pfeiffer, Manfred; Pfeiffer-Krahl, Mechtild; Behrendt, Christian-Alexander (Gefässchirurgie, 2021)
Peripheral arterial disease (PAD) is considered a common disease affecting more than 230 million people worldwide and has a bad prognosis. Owing to the systemic, progressive nature of atherosclerosis and the involvement of several vascular beds, not only is there a risk of vascular amputations but also a reduction in the general life expectancy. The thorough exhaustion of conservative therapy is considered an important pillar of complementary care, but this is not always successfully implemented. Besides structured exercise training, smoking cessation, optimisation of nutrition and body weight, antihypertensive therapy, as well as antidiabetic therapy and lipid-lowering therapy, the optimal pharmacological treatment is considered a central topic. This article is aimed at providing evidence-based recommendations for the best medical treatment for PAD in layman's terms.
CRIS-Team WoS Importer:2022-01-07

Recurrent shock and pulmonary edema due to acetazolamide medication after cataract surgery - Zimmermann, S.; Achenbach, Susanne; Wolf, M.; Janka, Rolf Matthias; Marwan, M.; Mahler, V. (Heart & Lung, 2014)
We report a patient with recurrent shock and transient non-cardiogenic pulmonary edema within a period of two months - every time occurring after cataract surgery and a single oral dose of standard post-operative medication with acetazolamide.Records of the intensive care unit, review of the literature.This case demonstrates a rare but severe side effect of acetazolamide. We also present a review of the literature to raise the awareness of health care providers for this special form of non-cardiogenic pulmonary edema.
EVALuna2:11868

Reduced circulating B cells and plasma IgM levels are associated with decreased survival in sepsis - A meta-analysis - Krautz, Christian; Maier, Sarah L.; Brunner, Maximilian; Langheinrich, Melanie; Giamarellos-Bourboulis, Evangelos J.; Gogos, Charalambos; Armaganidis, Apostolos; Kunath, Frank; Grützmann, Robert; Weber, Georg (Journal of Critical Care, 2018)
BACKGROUND: B cell function and antibody production are crucial factors in host protection during inflammation. We aimed to synthesize the available evidence on the association between the reduction of circulating B cells and plasma immunoglobulin (IgM) levels and decreased survival during sepsis. METHODS: We performed a systematic search in PubMed, Embase, ISI Web of Knowledge, Cochrane Central Register of Controlled Trials, BioMed Central, and Science Direct. We selected studies with data on circulating B cells and plasma IgM levels within the initial 24 h after sepsis onset. RESULTS: In total nine studies (n = 992 patients) were identified. Circulating B cells were reduced in septic patients as compared to non-septic patients (mean difference [MD] -88.2 cells/μl; 95% confidence interval [CI] -148.6–27.9). Sepsis non-survivors showed a significant reduction of circulating B cells and IgM levels compared to sepsis survivors (MD -77.1 cells/μl; 95% CI -111.4–42.7 and MD -20.9 mg/dl; 95% CI -33.8–8.0, respectively). CONCLUSIONS: Our results suggest that a reduction of circulating B cells and IgM levels at sepsis onset are associated with decreased sepsis survival. However, due to methodological limitations and the risk of bias, we need further prospective studies to confirm this association. REGISTRATION: The protocol was registered (PROSPERO 2016:CRD42016053184).
EVALuna2:32856

Reduced cytotoxicity by mutation of lysine 590 of Pseudomonas exotoxin can be restored in an optimized, lysine-free immunotoxin. - Ammon, Anna-Maria; Mellenthin, Lisa; Emmerich, C.; Naschberger, Elisabeth; Stürzl, Michael; Mackensen, Andreas; Müller, Fabian (Immunotherapy Advances, 2022)
Immunotoxins, which are fusion proteins of an antibody fragment and a fragment of a bacterial or a plant toxin, induce apoptosis in target cells by inhibition of protein synthesis. ADP-ribosylating toxins often have few lysine residues in their catalytic domain. As they are the target for ubiquitination, the low number of lysines possibly prevents ubiquitin-dependent degradation of the toxin in the cytosol. To reduce this potential degradation, we aimed to generate a lysine-free (noK), Pseudomonas exotoxin (PE)-based immunotoxin. The new generation 24 kDa PE, which lacks all but the furin-cleavage site of domain II, was mutated at lysine 590 (K590) and at K606 in a CD22-targeting immunotoxin and activity was determined against various B cell malignancies in vitro and in vivo. On average, K590 mutated to arginine (R) reduced cytotoxicity by 1.3-fold and K606R enhanced cytotoxicity by 1.3-fold compared to wild type (wt). Mutating K590 to histidine or deleting K590 did not prevent this loss in cytotoxicity. Neither stability nor internalization rate of K590R could explain reduced cytotoxicity. These results highlight the relevance of lysine 590 for PE intoxication. In line with in vitro results, the K606R mutant was more than 1.8-fold more active than the other variants in vivo suggesting that this single mutation may be beneficial when targeting CD22-positive malignancies. Finally, reduced cytotoxicity by K590R was compensated for by K606R and the resulting lysine-free variant achieved wt-like activity in vitro and in vivo. Thus, PE24-noK may represent a promising candidate for down-stream applications that would interfere with lysines.
EVALuna2:505954

Reducing Patient Burden and Improving Data Quality With the New Cleveland Clinic Colorectal Cancer Quality of Life Questionnaire - Zutshi, Massarat; Aiello, Alexandra; Fuerst, Alois; Golcher, Henriette; Parc, Yann; Galandiuk, Susan; Hull, Tracy L.; Ruppert, Reinhard (Diseases of the colon & rectum, 2020)
BACKGROUND: The Cleveland Clinic Colorectal Cancer Quality of Life Questionnaire was developed in response to the need for a new, fast, and comprehensive tool for evaluating quality of life in patients who have colorectal cancer. Available surveys such as the SF-12, SF-36, Functional Assessment of Cancer Therapy-Colorectal, and European Organization for Research and Treatment of Cancer are either too general to be informative or too lengthy to complete. OBJECTIVE: The aim was to validate the Cleveland Clinic Foundation Colorectal Quality of Life Questionnaire. DESIGN: Data were obtained as part of a prospective randomized controlled trial. SETTINGS: This was a worldwide multicenter study with 2 domestic and 5 international locations. PATIENTS: This study randomly assigned 190 patients between the ages of 18 and 80 undergoing surgery for low rectal cancer. Of those randomly assigned, 142 with partially complete surveys were analyzed for selection bias and acceptability, and 95 with complete surveys were analyzed for survey validity. INTERVENTIONS: Patients received either a J-pouch, side-to-end anastomosis, or straight anastomosis. MAIN OUTCOME MEASURE: The study evaluated survey validity measures such as standardized Cronbach α for internal consistency and Spearman correlation coefficients for construct validity, convergent validity, and responsiveness. Univariate analyses were used to assess discriminative validity. RESULTS: Sufficient acceptability, construct, and convergent validity and responsiveness were achieved. All scores showed great internal consistency (Cronbach α >0.8). Superior discriminative ability was demonstrated by significant differences (p < 0.05) in 2 of 7 scores between neoadjuvant treatment groups, and in 6 of 7 scores between complication groups, none of which were detected by the SF-12 or Functional Assessment of Cancer Therapy-Colorectal surveys. LIMITATIONS: Limitations included a small sample size, cultural differences, and failure to assess test-retest ability of the questionnaire. CONCLUSIONS: The Cleveland Clinic Colorectal Cancer Quality of Life Questionnaire is an efficient and reliable quality-of-life measure that better incorporates factors specific to colorectal cancer surgery. See Video Abstract at http://links.lww.com/DCR/B155. REDUCIENDO LA CARGA AL PACIENTE Y MEJORANDO LA CALIDAD DE DATOS CON EL NUEVO CUESTIONARIO DE CALIDAD DE VIDA EN CÁNCER COLORRECTAL DE CLEVELAND CLINIC (CCF-CAQL): El cuestionario de calidad de vida en cáncer colorrectal de Cleveland Clinic se desarrolló en respuesta a la necesidad de una herramienta nueva, rápida e integral para evaluar la calidad de vida en pacientes con cáncer colorrectal. Los cuestionarios disponibles como SF-12, SF-36, FACT-C y EORTC son demasiado generales para ser informativas o demasiado largas para completar.El objetivo fue validar el cuestionario de calidad de vida colorrectal de la Cleveland Clinic Foundation.Los datos se obtuvieron como parte de un ensayo prospectivo aleatorizado y controlado.Este fue un estudio multicéntrico mundial con dos sedes nacionales y cinco internacionales.Este estudio aleatorizó a 190 pacientes entre las edades de 18 y 80 sometidos a cirugía por cáncer rectal bajo. De aquellos aleatorizados, 142 con encuestas parcialmente completas se analizaron para determinar el sesgo de selección y la aceptabilidad, y 95 con encuestas completas se analizaron para determinar la validez de la encuesta.Los pacientes recibieron un reservorio en J, anastomosis latero-terminal o anastomosis termino-terminal.El estudio evaluó medidas de validez de la encuesta, como el Alfa de Cronbach estandarizado para la consistencia interna y los coeficientes de correlación de Spearman para la validez de construcción, la validez de convergencia y la capacidad de respuesta. Se utilizaron análisis univariados para evaluar la validez discriminativa.Se obtuvo suficiente aceptabilidad, construcción, validez de convergencia, y capacidad de respuesta. Todos los puntajes mostraron una gran consistencia interna (alfa de Cronbach > 0.8). Una capacidad discriminativa superior fue demostrada por diferencias significativas (p < 0.05) en dos de siete puntajes entre grupos de tratamiento neoadyuvante, y en seis de siete puntajes entre grupos de complicaciones, ninguno de los cuales fue detectado por SF-12 o FACT-C.Las limitaciones incluyeron un tamaño de muestra pequeño, diferencias culturales y la falta de evaluación de la confiabilidad test-retest del cuestionario.El Cuestionario de Calidad de Vida en Cáncer Colorrectal de Cleveland Clinic es una medida de calidad de vida eficiente y confiable que incorpora mejor factores específicos asociados a la cirugía de cáncer colorrectal. Consulte Video Resumen en http://links.lww.com/DCR/B155.
CRIS-Team Scopus Importer:2020-03-17

Reduktion der Tinnituslautstärke: Pilotstudie zur Abschwächung von tonalem Tinnitus mit schwellennahem, individuell spektral optimiertem Rauschen - Schilling, Anne; Krauß, Patrick; Hannemann, R.; Schulze, Holger; Tziridis, Konstantin (HNO, 2020)
Background: Around 15% of the general population is affected by tinnitus, but no real cure exists despite intensive research. Based on our recent causal model for tinnitus development, we here test a new treatment aimed at counteracting the perception. This treatment is based on the stochastic resonance phenomenon at specific auditory system synapses that is induced by externally presented near-threshold noise. Objective: This pilot study will investigate whether individually spectrally adapted noise can successfully reduce chronic tonal/narrow-band tinnitus during stimulation. Materials and methods: Hearing loss (HL) as well as tinnitus pitch (TP) and loudness (TL) were audiometrically measured in 22 adults (46.6±16.3 years; 4 women) with tinnitus. Based on these measurements, up to eight different noise stimuli with five intensities (−20 to +20 dB SL) were generated. These were presented for 40 s each via audiologic headphones in a soundproof chamber. After each presentation, the change in TL was rated on a five-level scale (−2 to +2). Results: We found patients (n = 6) without any improvement in their TL perception as well as patients with improvement (n = 16), where stimulation around the TP was most effective. The groups differed in post-hoc analysis of their audiograms: the effectiveness of our new therapeutic strategy obviously depends on the individual HL, and was most effective in normal-hearing tinnitus patients and those with mild HL. Conclusion: Subjective TL could be reduced in 16 out of 22 patients during stimulation. For a possible success of a future therapy, the HL seems to be of relevance.
CRIS-Team Scopus Importer:2020-11-20
Keywords: Hearing loss; Individualized therapy; Pure tone audiometry; Stochastic resonance; Tinnitus questionnaires

Regression of apoptosis-resistant colorectal tumors by induction of necroptosis in mice - He, Gui-Wei; Günther, Claudia; Thonn, Veronika; Yu, Yu-Qiang; Martini, Eva; Buchen, Barbara; Neurath, Markus; Stürzl, Michael; Becker, Christoph (Journal of Experimental Medicine, 2017)
Cancer cells often acquire capabilities to evade cell death induced by current chemotherapeutic treatment approaches. Caspase-8, a central initiator of death receptor-mediated apoptosis, for example, is frequently inactivated in human cancers via multiple mechanisms such as mutation. Here, we show an approach to overcome cell death resistance in caspase-8-deficient colorectal cancer (CRC) by induction of necroptosis. In both a hereditary and a xenograft mouse model of caspase-8-deficient CRC, second mitochondria-derived activator of caspase (SMAC) mimetic treatment induced massive cell death and led to regression of tumors. We further demonstrate that receptor-interacting protein kinase 3 (RIP3), which is highly expressed in mouse models of CRC and in a subset of human CRC cell lines, is the deciding factor of cancer cell susceptibility to SMAC mimetic-induced necroptosis. Thus, our data implicate that it may be worthwhile to selectively evaluate the efficacy of SMAC mimetic treatment in CRC patients with caspase-8 deficiency in clinical trials for the development of more effective personalized therapy.
EVALuna2:15307

Reliability of determining the resectability of locally progressed pancreatic ductal adenocarcinomas - results from the CONKO-007 multicenter randomized controlled trial (EudraCT:2009-014476-21) - Wittel, U. A.; Golcher, H.; Gruetzmann, R.; Bechstein, W. O.; Belyaev, O.; Uhl, W.; Ghadimi, M.; Hopt, U.; Pirkl, A.; Lubgan, Dorota; Hohenberger, Werner; Oettle, H.; et al. (2018)
EVALuna2:36518

Repeated cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with recurrent peritoneal carcinomatosis - Vassos, Nikolaos; Förtsch, Thomas; Aladashvili, Archil; Hohenberger, Werner; Croner, Roland S. (World Journal of Surgical Oncology, 2016)
Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has become the treatment of choice for resectable peritoneal carcinomatosis (PC) and improved the survival of these patients. The situation changes if PC recurs and repeated CRS with HIPEC is considered. The patient selection and outcome of the repeated approach has not been well described. We analyzed our cohort and share the experiences.Ninety-three CRS/HIPEC procedures, performed in 85 patients during the period 2001-2013, were examined in a retrospective analysis. Type of primary, ECOG status, peritoneal cancer index (PCI), completeness of cytoreduction (CC), duration of hospitalization, postoperative morbidity, mortality, and disease-free/overall survival were reviewed.Six patients (7%) underwent a second CRS/HIPEC (median interval between the two procedures: 26 months, range 8-61) including two patients with mesotheliomas, one patient with ovarian adenocarcinoma, one patient with leiomyosarcoma of uterus, one patient with colon adenocarcinoma, and one patient with appendiceal adenocarcinoma. The last two patients underwent a third CRS/HIPEC, 25 and 36 months, after the second procedure. The median PCI was 14 (range, 4-26) during the first and 20 (range, 7-39) during the second CRS/HIPEC of these patients. Completeness of cytoreduction score of 0 (CC-0) was achieved in all first procedures and in 67% of second procedures (CC-0; n=4 and CC-1; n=2). A CC-0 score was possible in both of the third procedures. The mean operating time was 444 min (range, 198-642) and 427 min (range, 239-617) during the first and the second procedure. Median intensive care unit (ICU) was 2 days, and hospital stay after second CRS/HIPEC was 17 days (range, 7-50). The 30-day morbidity after repeated CRS/HIPEC was 33% (16% for grade III-IV complications), and there was no 30-day mortality neither after the second nor after the third CRS/HIPEC. Median disease-free interval between first CRS/HIPEC and peritoneal recurrence was 17 months (range, 8-30). Median disease-free survival of 18 months (range, 4-33) was achieved after the second CRS/HIPEC. After a median follow-up of 74 months (range, 39-151), all patients are alive with disease (n=5) or disease free (n=1) under chemotherapy.In experienced centers, repeated CRS/HIPEC can be performed with safety. Patient selection and correct timing is of particular importance in achieving control of the disease. Repeated CRS/HIPEC should be considered as treatment option for selected patients with recurrent PC.
EVALuna2:15226

Repeating of local therapy of distant metastases increases overall survival in patients with synchronous metastasized rectal cancer-a monocentric analysis - Haderlein, Marlen; Lettmaier, Sebastian; Langheinrich, Melanie; Schmid, Axel; Semrau, Sabine; Hecht, Markus; Beck, Michael; Schmidt, Daniela; Grützmann, Robert; Fietkau, Rainer; Denz, Axel (International Journal of Colorectal Disease, 2018)
PURPOSE: The aim was to evaluate the outcome of treatment-naive patients with synchronous metastatic rectal cancer after chemotherapy with FOLFOXIRI followed by local therapeutic procedures of all tumor lesions as complete as possible. METHODS: We reviewed data of 30 patients with synchronous distant metastatic rectal cancer who underwent chemotherapy with FOLFOXIRI and subsequent local therapy in our institution. RESULTS: Median follow-up was 28 months (range: 8; 74). Cumulative overall survival (OS) and progression-free survival (PFS) was 93.3, 76.9, 55.6% and 46.2, 29.7, 29.7% after 1, 2, 4 years. Non-response to chemotherapy with FOLFOXIRI was associated with a highly significant decreased OS (p < 0.0001). The consistent use of local ablative procedures led to a statistically significant increase in OS (p < 0.0001), but not in PFS (p = 0.635). Patients with ≤ 4 distant metastases showed a better OS (p = 0.033). CONCLUSIONS: Response to intensified first-line chemotherapy with FOLFOXIRI, treatment of the primary rectal tumor, and repeated thorough local ablative procedures in patients with synchronous metastasized rectal cancer may lead to long-term survival, even in a subset of patients with unresectable disease at initial diagnosis.
EVALuna2:36458

Reply - A brief comment on pneumothorax during the extubation period of esophageal atresia repair - Diez, Sonja; Müller, Hanna (Pediatrics and Neonatology, 2021)
CRIS-Team Scopus Importer:2021-01-29

Reply by the Authors of the Original Article - Dudek, Wojciech; Schreiner, Waldemar; Haj Khalaf, Mohamed; Sirbu, Horia (Thoracic and Cardiovascular Surgeon, 2021)
CRIS-Team WoS Importer:2022-01-14

Reply to D. Sargent et al - Glimelius, Bengt; Hohenberger, Werner; Matzel, Klaus; Sugihara, Kenichi; Quirke, Philip (Journal of Clinical Oncology, 2016)
EVALuna2:15248

Reprogramming Sacral Neuromodulation for Sub-Optimal Outcomes: Evidence and Recommendations for Clinical Practice - Dudding, Thomas C.; Lehur, Paul A.; Sorensen, Michael; Engelberg, Stefan; Bertapelle, Maria Paola; Chartier-Kastler, Emmanuel; Everaert, Karel; Van Kerrebroeck, Philip; Knowles, Charles H.; Lundby, Lilli; Matzel, Klaus; Munoz-Duyos, Arantxa; et al. (Neuromodulation, 2021)
Objectives: In some patients treated for urinary or fecal incontinence with sacral neuromodulation (SNM) persistence of symptoms, a reduction in efficacy or adverse effects of stimulation can occur. In such situations, further programming of the SNM device can help resolve problems. Infrequently hardware failure is detected. This article aims to provide practical guidance to solve sub-optimal outcomes (troubleshooting) occurring in the course of SNM therapy. Materials and Methods: A systematic literature review was performed. Collective clinical experience from an expert multidisciplinary group was used to form opinion where evidence was lacking. Results: Circumstances in which reprogramming is required are described. Actions to undertake include changes of electrode configuration, stimulation amplitude, pulse frequency, and pulse width. Guidance in case of loss of efficacy and adverse effects of stimulation, developed by a group of European experts, is presented. In addition, various hardware failure scenarios and their management are described. Conclusions: Reprogramming aims to further improve patient symptoms or ensure a comfortable delivery of the therapy. Initial changes of electrode configuration and adjustment of stimulation parameters can be performed at home to avoid unnecessary hospital visits. A logical and stepwise approach to reprogramming can improve the outcome of therapy and restore patient satisfaction.
CRIS-Team Scopus Importer:2021-07-30
Keywords: Fecal incontinence; reprogramming; sacral neuromodulation; troubleshooting; urinary incontinence

Resection of pancreatic cancer in Europe and USA: an international large-scale study highlighting large variations - Huang, Lei; Jansen, Lina; Balavarca, Yesilda; Molina-Montes, Esther; Babaei, Masoud; Van Der Geest, Lydia; Lemmens, Valery; Van Eycken, Liesbet; De Schutter, Harlinde; Johannesen, Tom B.; Fristrup, Claus W.; Mortensen, Michael B.; et al. (Gut, 2017)
Resection can potentially cure resectable pancreatic cancer (PaC) and significantly prolong survival in some patients. This large-scale international study aimed to investigate variations in resection for PaC in Europe and USA and determinants for its utilisation.Data from six European population-based cancer registries and the US Surveillance, Epidemiology, and End Results Program database during 2003-2016 were analysed. Age-standardised resection rates for overall and stage I-II PaCs were computed. Associations between resection and demographic and clinical parameters were assessed using multivariable logistic regression models.A total of 153 698 records were analysed. In population-based registries in 2012-2014, resection rates ranged from 13.2% (Estonia) to 21.2% (Slovenia) overall and from 34.8% (Norway) to 68.7% (Denmark) for stage I-II tumours, with great international variations. During 2003-2014, resection rates only increased in USA, the Netherlands and Denmark. Resection was significantly less frequently performed with more advanced tumour stage (ORs for stage III and IV versus stage I-II tumours: 0.05-0.18 and 0.01-0.06 across countries) and increasing age (ORs for patients 70-79 and >=80 versus those <60 years: 0.37-0.63 and 0.03-0.16 across countries). Patients with advanced-stage tumours (stage III-IV: 63.8%-81.2%) and at older ages (>=70 years: 52.6%-59.5%) receiving less frequently resection comprised the majority of diagnosed cases. Patient performance status, tumour location and size were also associated with resection application.Rates of PaC resection remain low in Europe and USA with great international variations. Further studies are warranted to explore reasons for these variations.
EVALuna2:15298

Resection of pancreatic cancer in Europe and USA: An international large-scale study highlighting large variations - Huang, Lei; Jansen, Lina; Balavarca, Yesilda; Molina-Montes, Esther; Babaei, Masoud; Van Der Geest, Lydia; Lemmens, Valery; Van Eycken, Liesbet; De Schutter, Harlinde; Johannesen, Tom B.; Fristrup, Claus W.; Mortensen, Michael B.; et al. (Gut, 2019)
Objective: Resection can potentially cure resectable pancreatic cancer (PaC) and significantly prolong survival in some patients. This large-scale international study aimed to investigate variations in resection for PaC in Europe and USA and determinants for its utilisation. Design: Data from six European population-based cancer registries and the US Surveillance, Epidemiology, and End Results Program database during 2003-2016 were analysed. Age-standardised resection rates for overall and stage I-II PaCs were computed. Associations between resection and demographic and clinical parameters were assessed using multivariable logistic regression models. Results: A total of 153 698 records were analysed. In population-based registries in 2012-2014, resection rates ranged from 13.2% (Estonia) to 21.2% (Slovenia) overall and from 34.8% (Norway) to 68.7% (Denmark) for stage I-II tumours, with great international variations. During 2003-2014, resection rates only increased in USA, the Netherlands and Denmark. Resection was significantly less frequently performed with more advanced tumour stage (ORs for stage III and IV versus stage I-II tumours: 0.05-0.18 and 0.01-0.06 across countries) and increasing age (ORs for patients 70-79 and ≥80 versus those <60 years: 0.37-0.63 and 0.03-0.16 across countries). Patients with advanced-stage tumours (stage III-IV: 63.8%-81.2%) and at older ages (≥70 years: 52.6%-59.5%) receiving less frequently resection comprised the majority of diagnosed cases. Patient performance status, tumour location and size were also associated with resection application. Conclusion: Rates of PaC resection remain low in Europe and USA with great international variations. Further studies are warranted to explore reasons for these variations.
CRIS-Team Scopus Importer:2019-05-03
Keywords: age; pancreatic cancer; population-based; surgical resection; TNM stage; variation

Residual aggregates in platelet products: what do we know? - Ringwald, J.; Antoon, M.; Eckstein, Reinhold; Cardoso, M. (Vox Sanguinis, 2014)
Platelet (PLT) aggregates can occur during or after PLT component processing. However, very few reports investigating the phenomenon and its clinical significance have been published. In this review, currently available information about aggregates in PLT products is summarized and possible causal factors as well as preventive strategies are discussed.A review of the MEDLINE® database for relevant publications from 1960 to May 2013 was conducted.It is well known that PLT aggregates may occur during or after the PLT product preparation process. These aggregates normally dissipate with rest and agitation. However, in some rare cases, the aggregates do not dissipate within 24 h and can persist up to the end of storage. Exposure to low temperature, low pH, short resting period after collection, different collection systems, presence of bubbles or foam inside the PLT bag, PLT-container interactions, proper product mixing and donor-dependent variables may have an impact on the formation of PLT aggregates. Although publications are rare, the presence of small numbers of PLT aggregates appears to have only limited impact on PLT in vitro quality. Furthermore, data on the clinical impact of PLT aggregates are lacking.Despite the fact that PLT aggregates occur in PLT products, published data on this topic remain scant. Considering the concern of clinicians about this phenomenon, more studies are needed which should focus on the possible clinical impact of such aggregates and precautions to avoid PLT aggregate formation in PLT products.
EVALuna2:15971

Response to 6 cycles of chemotherapy with FOLFIRINOX is predictive of overall survival in patients with locally advanced unresectable pancreatic cancer - Haderlein, Marlen; Lubgan, Dorota; Lettmaier, S.; Semrau, S.; Wolf, W.; Golcher, H.; Hohenberger, Werner; Fietkau, Rainer (2016)
EVALuna2:15236

Results of combined vascular reconstruction and free flap transfer for limb salvage in patients with critical limb ischemia - Meyer, Alexander; Goller, Katja; Horch, Raymund E.; Beier, Justus; Taeger, Christian; Arkudas, Andreas; Lang, Werner (Journal of Vascular Surgery, 2015)
Combined vascular reconstruction and free flap transfer has been established in centers as a feasible therapeutic option in cases with critical limb ischemia (CLI) and large tissue defects otherwise destined for major amputation. However, the number of patients treated with this combined approach is limited, and data regarding long-term follow-up and functional outcome are scarce. We therefore report our 10-year experience in free flap transplantation after vascular reconstruction as a last attempt for limb salvage, with special emphasis of complication rate, limb salvage, and postoperative mobility.CLI patients undergoing combined vascular reconstruction and consequent free flap transfer from 2003 to 2013 were retrospectively observed. Of 80 cases in total, patients with traumatic and oncologic indications were excluded; 33 (mean age, 66 years; range, 51-82 years) of these cases were performed for limb salvage and were included in this study. Long-term follow-up was possible in 32 of 33 patients (mean, 58 months; range, 2-126 months).Thirty-three patients were analyzed. We performed arterial revascularization with 9 arteriovenous loops, 23 bypass grafts (10 popliteal-pedal, 9 femoral-crural, and 4 femoral-popliteal), and 1 venous interposition graft. For defect coverage, tissue transfer was comprised of six different flap entities (10 latissimus dorsi, 2 gracilis, 1 anterior lateral thigh, 7 rectus abdominis, 11 radialis, and 2 greater omentum flaps). Complications occurred in 16 of 33 patients (49%). Early complications included eight acute occlusions of arterial reconstructions; major bleedings were seen in eight patients as well. There were two flap losses and one major amputation in the early postoperative period. No in-hospital deaths were observed. Late results revealed a limb salvage rate of 87% after 1 year and 83% after 5 years. Amputation-free survival was 87% after 1 year and 75% after 5 years. Overall survival was 100% and 87% after 1 year and 5 years, respectively. Follow-up showed 42% of patients with no limitations in ambulation, 54% with maintained preoperative ambulatory status, and one bedridden patient.The combined approach for limb salvage in CLI patients is associated with excellent results in limb salvage and functional outcome in patients who would otherwise be candidates for major amputation, despite an initially elevated complication rate. The option of combined revascularization with free tissue transfer should be evaluated in all mobile patients with CLI, large tissue defects, and exposed tendon or bone structures before major amputation. However, further studies are required to support these results.
EVALuna2:15203

Results of combined vascular reconstruction by means of AV loops and free flap transfer in patients with soft tissue defects - Meyer, Alexander; Horch, Raymund E.; Schöngart, Elisabeth; Beier, Justus; Taeger, Christian; Arkudas, Andreas; Lang, Werner (Journal of Plastic Reconstructive and Aesthetic Surgery, 2016)
Free flap transplantation to vascular reconstructions as arteriovenous (AV) loops has been established in centers as a feasible therapeutic option for defect reconstruction in the absence of proper recipient vessels, caused by oncologic resections, radiation, or trauma. We report our 10-year experience in free flap transplantation after vascular reconstruction with special emphasis on complication rate and postoperative mobility.Forty-seven patients (mean age: 60 years, range: 19-86) were included. Defect etiology was posttraumatic in 19 patients; 14 defects were due to oncological resections and seven sternal osteomyelitis; three patients presented with radiation ulcers, two with aseptic femoral head necrosis, and one with defects caused by acne inversa and hip joint prosthesis infection. Long-term follow-up was 45 months (range: 0-126). We performed arterial revascularization with 36 AV loops, eight bypass grafts, and three venous interposition grafts. Subsequent tissue transfer comprised 24 latissimus dorsi, two vastus lateralis, one gracilis, one anterior lateral thigh (ALT), 16 rectus abdominis, one radialis forearm, and two osteocutaneous vascularized fibula flaps.Complications occurred in 25/47 patients (53%). Early complications included five acute occlusions of arterial reconstructions and six major bleedings. There were six flap losses and three major amputations. Two in-hospital deaths were observed (4%). Overall survival accounted for 89.0 and 74.7% after 1 and 5 years, respectively.The 5-year survival rate in long-term follow-up is favorable, despite an initially elevated complication rate. Successful defect coverage can be achieved by this method in a high percentage of patients.
EVALuna2:15223

Results of isolated limb perfusion for metastasized malignant melanoma - Schellerer, Vera; Frenger, Johannes; Merkel, Susanne; Göhl, Jonas; Kersting, Stephan; Grützmann, Robert; Erdmann, Michael; Förtsch, Thomas (Surgical Oncology-Oxford, 2021)
Background and objectives: Locoregional metastases are typical biological manifestations of advanced malignant melanomas. Treatment with hyperthermic isolated limb perfusion (HILP) should be considered in affected patients. In the present study, we have analyzed the results of HILPs performed in our department. Patients and methods: Eighty patients with locoregional metastases of the extremities received HILP at the Department of Surgery between January 2007 and December 2016. The mean follow-up was 38 months. Results: The study included 50 men and 30 women (mean age: 63 years). The median time between melanoma diagnosis and HILP was 25 months (range: 1–219 months). HILP was performed in curative (n = 45) and palliative (n = 35) intention. Seventy-five patients received a drug combination of melphalan/dactinomycin and five patients received a drug combination of melphalan/tumor necrosis factor-alpha. Remission rates were determined in 72 of 80 patients (90%) as follows: partial response n = 28, complete response n = 25, no response n = 19. Of the 25 patients with complete response, 13 patients developed a new tumor manifestation during follow-up (locoregional recurrences n = 4; distant metastases n = 3; both n = 6). The median overall survival rate was 33 months. Tumor stage influenced the survival rate significantly (p = 0.001). Patients with complete response showed a significantly better overall survival than patients with partial or no response (p = 0.016). Conclusion: HILP is an effective therapeutic option in patients with locoregional metastases. This procedure carries a certain risk of side effects and adverse events but overall results in good response rates. Therefore, HILP should be offered to selected patients based on an individual discussion, considering their health status and oncological prognosis.
CRIS-Team Scopus Importer:2021-05-21
Keywords: Hyperthermic isolated limb perfusion; In-transit metastases; Malignant melanoma; Recurrence; Survival

Results of Renal Transplantation on Alloplastic Arterial Grafts - Sagban, Tolga Atilla; Regus, Susanne; Heller, Katharina; Jacobi, Johannes; Apel, Hendrik; Keck, Bastian; Richterstetter, Mario; Eckardt, Kai-Uwe; Wullich, Bernd; Lang, Werner (Urologia Internationalis, 2016)
The aim of this retrospective study was to report results of a consecutive series of kidney transplant patients in whom the renal artery was implanted on a prosthetic vascular graft (PVG).Between January 2011 and December 2014, 208 deceased donor renal transplantations (68 female, 140 male, mean age 52, SD 16 years) were performed. Medical charts and outpatient clinical records of patients who had undergone renal artery implantation on a PVG were reviewed. Extensive literature research added to our 4 patients further 170 published cases during 1989 and 2015 and was compared with regular transplanted patients. Data on patient characteristics, prior vascular procedures, postoperative and long-term outcome were collected.Patients with transplant renal artery anastomosis on a PVG were 4 years older than the control group. Function of the graft was similar in these patients compared to regular renal transplant patients. Resistance indices assessed in our clinic over the entire follow-up period showed also no significant difference between the 2 groups. Thirty-day mortality was 6% (none in our group), which occurred mostly in combination when renal transplantation and PVG replacement was performed simultaneously.Grafting of the renal artery to a PVG is feasible and yields good results, despite the technical difficulties involved.
EVALuna2:3839

Results of Surgical and Conservative Treatment for Enterocutaneous Fistulas. Is there an Indication for Conservative Treatment? - Schildberg, C. W.; Raptis, Dimitrios; Langheinrich, M.; Hohenberger, Werner; Horbach, T. (Zentralblatt für Chirurgie, 2016)
The manifestation of enterocutaneous fistulas is varied. They can range from controlled secretion via the abdominal wall to septic disease. The disease is categorised into low-, moderate- and high-output fistulas. Often the only option is surgical treatment. Occasionally, there is spontaneous healing under conservative treatment. The aim of this study was to work out a possible subgroup of patients who benefit from conservative treatment. Material und Methods: Ninety-nine patients were treated for enterocutaneous fistulas from 1 January 1995 to 31 December 2005. Seventy patients underwent surgery, 29 patients were treated conservatively. All data was collected prospectively using an admission form and was analysed retrospectively. Conservative treatment consisted of fasting with parenteral nutrition, while fistulas in the surgical group were treated by suture repair or resection. Additive treatments such as vacuum dressings or TNF-? medication for patients with Crohn's disease were not performed.In our study we achieved a total cure rate of 69%, with an average hospital stay of 38 days. Surgical treatment led to significantly better results compared with conservative treatment (83 vs. 34%). Mortality in the surgical group was distinctly, but not significantly reduced at 7%, compared with 14% in the conservative group. The fistulas that healed after conservative treatment were low-output fistulas only.Enterocutaneous fistulas are diseases associated with long hospital stays and, therefore, expensive treatment. Low-output fistulas may heal spontaneously. The best results are achieved by surgical treatment. More recent treatments such as vacuum therapy and TNF-? medication for patients with Crohn's disease are promising approaches. In the future, many of these will have to be combined with surgical treatment.
EVALuna2:15208

Results of Surgical Treatment of Hiatal Hernia. - Schildberg, C. W.; Perrakis, Aristotelis; Croner, R.; Schellerer, Vera; Haupt, Werner; Weidinger, T.; Hohenberger, Werner; Horbach, T. (Zentralblatt für Chirurgie, 2014)
Background: Hiatus hernias are considered as the most prominent form of diaphragmatic hernias. The passage is defined through the oesophageal hiatus, resulting in a superdiaphragmatic displacement of parts of the stomach or the complete stomach, respectively. In our work we investigated the treatment of partial thoracic stomach with both open and minimally invasive surgical procedures emphasising the view on operating data, the success of the surgery and recurrence rates. Patients with mesh insertion for hernia defect closures were considered separately.Material and Method: 94 Patients were treated in the period from 01.01.2003 to 01.06.2010. The ratio male/female was 2 : 1. The median age was 66 years. All data were prospectively collected by means of surgical protocols and data from the central patient records and analysed retrospectively. The statistical analyses were performed with SPSS 18.0 (SPSS Inc., Chicago, IL, USA). Any existing significances were determined using the T-test.Results: Of the 94 patients, 65 were operated laparoscopically. In the case of nine patients an initial laparoscopic surgery had to be changed to an open procedure. The reasons for switching surgical procedures were splenic bleeding in the case of 2 patients, intestinal injury due to perforation by the trocar in one case and unclear surgical situs in 6 cases. The postoperative complication rate was 24 %. The main reasons were a delayed achievement of passage. The mortality rate was 0 %. The comparison between laparoscopic and open groups showed, by comparable complication and recurrence rates, a shorter recovery time in favour of patients operated on laparoscopically. Additionally it can be stated that a bridge closure with mesh (ePTFE) had no significant influence on the postoperative outcome. Therefore we cannot confirm the postulated poor postoperative results of other groups. Conclusion: In summary, the clear trend in the surgical treatment of hiatus hernias is to minimally invasive surgery. Only for patients with multiple previous operations, who are expected to have strong adhesions, the operation with comparable morbidity and mortality rates can also be planned primarily as open. In this case, however, longer postoperative recovery times must be expected. Large defects can be treated with comparable complication and recurrence rates by mesh insertion (ePTFE).
EVALuna2:15112

Retrospective analysis of survival after resection of pancreatic renal cell carcinoma metastases - Ruekert, Felix; Distler, Marius; Ollmann, David; Lietzmann, Anja; Birgin, Emrullah; Teoule, Patrick; Grützmann, Robert; Wilhelm, Torsten J. (International Journal of Surgery, 2016)
Previous reports showed an excellent survival for patients after resection of pancreatic metastases from renal cell cancer (pRCC) and reported several predictive factors. This study aims to give more evidence to reported risk factors by analyzing a large cohort of patients with pancreatic resection due to pRCC.We retrospectively analyzed all pancreatic resections due to pRCC between January 1993 and October 2014 in two German pancreatic surgery centers. Predictive factors were analyzed using the chi square test.Surgery was performed in 40 patients. Mean survival after resection was 147.9 months (SD 25.6 months). No predictive factors for survival were identified. Pathological examination showed that five out of 21 patients with examined peripancreatic lymph nodes had lymph node metastases.Although our analysis comprised the biggest cohort of patients with pRCC it rendered no significant predictor for survival. This might be due to the overall excellent prognosis of study patients and the relatively rare condition with a limited number of patients. Several patients had lymph node metastases. Therefore lymphadenectomy should be considered in pRCC resection if the health condition of the patient permits this. By this more aggressive approach to pRCC, a better prognosis after resection might be achieved.
EVALuna2:15253

Retrospective cohort study of combined approach for trunk reconstruction using arteriovenous loops and free flaps - Arkudas, Andreas; Horch, Raymund E.; Regus, Susanne; Meyer, Alexander; Lang, Werner; Schmitz, Marweh; Boos, Anja; Ludolph, Ingo; Beier, Justus (Journal of Plastic Reconstructive and Aesthetic Surgery, 2017)
Defect reconstruction of the trunk can be performed using microsurgical free flap transplantation. In cases of missing or inappropriate recipient vessels, microsurgical defect reconstruction of the trunk can be achieved by combining free flaps with arteriovenous loops. Here we present our 5-year experience of trunk reconstruction using AV loops and free flaps in a retrospective evaluation. We analyzed 32 cases of trunk reconstruction using a combined approach of free flap transplantation and arteriovenous loops between 2011 and 2016 regarding postoperative complications and perioperative course. Twenty-one patients suffered from sternal defects, 4 from presacral defects, 3 patients presented with lateral chest wall defects, 2 patients suffered from lumbosacral defects, 1 patient had a gluteal defect and 1 patient a defect at the clavicle. In all cases, free flap transplantation and arteriovenous loop creation were performed in a two-stage procedure. There were 8 thromboses of the arteriovenous loops with 4 flap failures. Only 1 flap loss was located in the sternal region, whereas one presacral flap and both lumbosacral flaps were lost. Reconstruction of large soft tissue defects of the trunk by a combined approach with an arteriovenous loop creation and consecutive free flap transplantation represents a reliable procedure in ventral and posterior cranial localization, whereas in the caudal posterior region, AV loop thrombosis can occur. Therefore, to minimize flap loss, a two-stage procedure should be performed.
EVALuna2:15321

Revaskularisation beim diabetischen Fußsyndrom? Wann und wie? - Rother, Ulrich; Görtz, Hartmut; Uhl, Christian; Stavroulakis, Konstantinos; Marchiori, Elena; Classen, Simon; Neufang, Achim; Larena-Avellaneda, Axel; Dovzhanskiy, Dmitriy; Behrendt, Christian Alexander (Gefässchirurgie, 2024)
Diabetes mellitus is one of the cardiovascular risk factors for which the prevalence and incidence have increased worldwide in recent years. There are currently some 537 million people worldwide who suffer from diabetes mellitus. This disease with the diabetic foot syndrome also represents a challenge for the treating vascular surgeon. The diagnostics of a possible simultaneously present peripheral arterial occlusive disease (PAOD) represent a particularly difficult challenge in the routine practice. The question of the treatment of this PAOD is also not trivial. The question is on the timing of the treatment and the selection of the treatment procedure. This article first gives an overview of the diagnostic options for PAOD in cases of diabetes mellitus. Finally, the results of the various treatment options are presented and classified in the clinical context.
CRIS-Team Scopus Importer:2024-03-15
Keywords: Angiosome concept; Diabetes mellitus; Peripheral arterial occlusive disease; Revascularization methods; Treatment procedures

Revaskularisation vor Defektdeckung – essenzielle Schnittstelle zwischen plastischer Chirurgie und Gefäßchirurgie - Meyer, Alexander; Rother, Ulrich; Thamm, Oliver C. (Zentralblatt für Chirurgie, 2023)
Treatment of complex ischemic lower leg defects with exposure of deep anatomic structures represents a considerable challenge to involved specialties. In selected patients, limb salvage can be achieved as an alternative to major amputation by means of a combined approach including arterial reconstruction and subsequent free flap transfer. Arterial reconstruction can be performed either by endovascular or open surgical treatment (bypass reconstruction or implantation of an arteriovenous loop) preliminary to defect reconstruction using microsurgical free flap transplantation. Whereas the aim of the arterial reconstruction comprises the establishment of sufficient perfusion and creation of adequate target vessels for the free flap transfer, the selection of the appropriate flap entity depends on the extent of the wound as wells as on the presence of osteomyelitis. Arterial reconstruction and defect reconstruction can be performed as one-stage or two-stage procedure and has become an established and feasible treatment approach in centers. Evaluation of microperfusion by means of indocyanine green can further increase safety and feasibility of this method. Against this background, combined arterial reconstruction and subsequent free flap transfer provides excellent results in terms of amputation free survival and postoperative mobility. Essential is however an individualized decision making in consideration of patient selection and possible contraindications. This approach may be evaluated in mobile patients with complex wounds prior to major amputation.
CRIS-Team Scopus Importer:2023-12-01
Keywords: bypass surgery; combined operation/surgical intervention; distal bypass surgery; endovascular; free microsurgical tissue transfer; vascular surgery

Reverse transfected cell microarrays in infectious disease research - Konrad, Andreas; Jochmann, Ramona; Kühn, Elisabeth; Naschberger, Elisabeth; Chudasama, Priya; Stürzl, Michael (Methods in Molecular Biology, 2011)
Several human pathogenic viruses encode large genomes with often more than 100 genes. Viral pathogenicity is determined by carefully orchestrated co-operative activities of several different viral genes which trigger the phenotypic functions of the infected cells. Systematic analyses of these complex interactions require high-throughput transfection technology. Here we have provided a laboratory manual for the reverse transfected cell microarray (RTCM; alternative name: cell chip) as a high-throughput transfection procedure, which has been successfully applied for the systematic analyses of single and combination effects of genes encoded by the human herpesvirus-8 on the NF-kappaB signal transduction pathway. In order to quantitatively determine the effects of viral genes in transfected cells, protocols for the use of GFP as an indicator gene and for indirect immunofluorescence staining of cellular target proteins have been included. RTCM provides a useful methodological approach to investigate systematically combination effects of viral genes on cellular functions.
Created from Fastlane, Scopus look-up
Keywords: Cell chip; High-throughput; Human herpesvirus-8; KSHV; Microarray; Transfection

Risk-Adapted Neoadjuvant Chemoradiotherapy in Rectal Cancer: Final Report of the OCUM Study - Ruppert, Reinhard; Junginger, Theodor; Kube, Rainer; Strassburg, Joachim; Lewin, Andreas; Baral, Joerg; Maurer, Christoph A.; Sauer, Joerg; Lauscher, Johannes; Winde, Guenther; Thomasmeyer, Rena; Stelzner, Sigmar; et al. (Journal of Clinical Oncology, 2023)
PURPOSEWe investigated whether neoadjuvant chemoradiotherapy (nCRT) in patients with rectal cancer can be restricted to those at high risk of locoregional recurrence (LR) without compromising oncological outcomes.PATIENTS AND METHODSIn a prospective multicenter interventional study, patients with rectal cancer (cT2-4, any cN, cM0) were classified according to the minimal distance between the tumor, suspicious lymph nodes or tumor deposits, and mesorectal fascia (mrMRF). Patients with a distance >1 mm underwent up-front total mesorectal excision (TME; low-risk group), whereas those with a distance a‰ 1 mm and/or cT4 and cT3 tumors in the lower rectal third received nCRT followed by TME surgery (high-risk group). The primary end point was 5-year LR rate.RESULTSOf the 1,099 patients included, 884 (80.4%) were treated according to the protocol. A total of 530 patients (60%) underwent up-front surgery, and 354 (40%) had nCRT followed by surgery. Kaplan-Meier analyses revealed 5-year LR rates of 4.1% (95% CI, 2.7 to 5.5) for patients treated per protocol, 2.9% (95% CI, 1.3 to 4.5) after up-front surgery, and 5.7% (95% CI, 3.2 to 8.2) after nCRT followed by surgery. The 5-year rate of distant metastases was 15.9% (95% CI, 12.6 to 19.2) and 30.5% (95% CI, 25.4 to 35.6), respectively. In a subgroup analysis of 570 patients with lower and middle rectal third cII and cIII tumors, 257 (45.1%) were at low-risk. The 5-year LR rate in this group was 3.8% (95% CI, 1.4 to 6.2) after up-front surgery. In 271 high-risk patients (involved mrMRF and/or cT4), the 5-year rate of LR was 5.9% (95% CI, 3.0 to 8.8) and of metastases 34.5% (95% CI, 28.6 to 40.4); disease-free survival and overall survival were the worst.CONCLUSIONThe findings support the avoidance of nCRT in low-risk patients and suggest that in high-risk patients, neoadjuvant therapy should be intensified to improve prognosis. ;copy; American Society of Clinical Oncology.
CRIS-Team Scopus Importer:2023-09-15

Risk factors for appendiceal neoplasm and malignancy among patients with acute appendicitis - Brunner, Maximilian; Lapins, Philipp; Langheinrich, Melanie; Baecker, Justus; Krautz, Christian; Kersting, Stephan; Grützmann, Robert; Maak, Matthias; Weber, Georg (International Journal of Colorectal Disease, 2019)
Purpose: Non-operative management of acute uncomplicated appendicitis has shown promising results but might carry the risk of delayed diagnosis of premalignant or malignant appendiceal tumors found by chance in 0.7–2.5% of appendiceal specimen after appendectomy. Purpose of this study was to analyze whether appendiceal tumors are associated with a complicated appendicitis and to determine risk factors for appendiceal neoplasm and malignancy in patients with acute appendicitis. Methods: We performed a retrospective analysis of 1033 adult patients, who underwent appendectomy for acute appendicitis from 2010 to 2016 at the University hospital Erlangen. Data included patients’ demographics; comorbidities; pre-, intra- and postoperative findings; and histopathological results. Complicated appendicitis was defined in the presence of perforation or abscess. Results: Appendiceal neoplasm respectively malignancy rate was 2.8% respectively 1.5%. Using univariate analysis, we identified seven risk factors at least for appendiceal neoplasm or malignancy: age, ASA, C-reactive protein, appendiceal diameter, perforation, intraoperative perithyphilitic abscess, and complicated appendicitis. Risk for appendiceal neoplasm or malignancy was 4.4% respectively 2.7% in complicated acute appendicitis compared to 2.0% respectively 1.0% in uncomplicated appendicitis (p = 0.043 respectively p = 0.060). In multivariate analysis, age ≥ 50 years and a diameter of the appendix in the sonography ≥ 13 mm were independent risk factors predicting the presence of appendiceal neoplasm and malignancy. Conclusion: Among patients with appendicitis, there are relevant risk factors predicting appendiceal tumors, especially age and appendiceal diameter in sonography. But the identified risk factors have a low sensitivity and specificity, so obtaining a confident preoperative diagnosis is challenging.
CRIS-Team Scopus Importer:2019-12-20
Keywords: Appendectomy; Appendiceal neoplasm; Complicated appendicitis; Malignancy; Risk factors

Risk Factors for Conversion from Laparoscopic to Open Appendectomy - Bancke Laverde, Bruno Leonardo; Maak, Matthias; Langheinrich, Melanie; Kersting, Stephan; Denz, Axel; Krautz, Christian; Weber, Georg; Grützmann, Robert; Brunner, Maximilian (Journal of Clinical Medicine, 2023)
(1) Background: Since its introduction in the 1990s, laparoscopic appendectomy has become established over the years and is today considered the standard therapy for acute appendicitis. In some cases, however, a conversion to the open approach is still necessary. The primary aim of this study was to identify risk factors for the need to convert from the laparoscopic to an open approach during appendectomy for acute appendicitis. (2) Methods: A retrospective analysis of 1220 adult patients who underwent laparoscopic appendectomy for acute appendicitis from 2010 to 2020 at the University Hospital Erlangen was performed. Data, including patient demographics and pre-, intra-, and postoperative findings, were collected and compared between patients with and without conversion. (3) Results: The conversion rate in our cohort was 5.5%. A higher preoperative WBC count and CRP (OR 1.9, p = 0.042, and OR 2.3, p = 0.019, respectively), as well as the presence of intraoperative perforation, necrosis or gangrene, perityphlitic abscess and peritonitis (OR 3.2, p = 0.001; OR 2.3, p = 0.023; OR 2.6, p = 0.006 and OR 2.0, p = 0.025, respectively) were identified as independent risk factors for conversion from the laparoscopic to the open approach. Conversion was again independently associated with higher morbidity (OR 2.2, p = 0.043). (4) Conclusion: The laparoscopic approach is feasible and safe in the majority of patients with acute appendicitis. Only increased inflammatory blood markers could be detected as the preoperative risk factors potentially influencing the choice of surgical approach but only with low specificity and sensitivity. For the decision to convert, intraoperative findings are additionally crucial. However, patients with conversion should receive special attention in the postoperative course, as these have an increased risk of developing complications.
CRIS-Team Scopus Importer:2023-07-28
Keywords: acute appendicitis; conversion; laparoscopic approach; morbidity

Risk factors for postoperative morbidity, prolonged length of stay and hospital readmission after appendectomy for acute appendicitis - Laverde, Bruno Leonardo Bancke; Maak, Matthias; Langheinrich, Melanie; Kersting, Stephan; Denz, Axel; Krautz, Christian; Weber, Georg; Grützmann, Robert; Brunner, Maximilian (European Journal of Trauma and Emergency Surgery, 2023)
PurposeThe aim of the present study was to identify risk factors associated with postoperative morbidity and major morbidity, with a prolonged length of hospital stay and with the need of readmission in patients undergoing appendectomy due to acute appendicitis.MethodsWe performed a retrospective analysis of 1638 adult patients who underwent emergency appendectomy for preoperatively suspected acute appendicitis from 2010 to 2020 at the University Hospital Erlangen. Data including patient demographics, pre-, intra-, and postoperative findings were collected and compared between different outcome groups (morbidity, major morbidity, prolonged length of postoperative hospital stay (LOS) and readmission) from those patients with verified acute appendicitis (n = 1570).ResultsRate of negative appendectomies was 4%. In patients with verified acute appendicitis, morbidity, major morbidity and readmission occurred in 6%, 3% and 2%, respectively. Mean LOS was 3.9 days. Independent risk factors for morbidity were higher age, higher preoperative WBC-count and CRP, lower preoperative hemoglobin, longer time to surgery and longer duration of surgery. As independent risk factors for major morbidity could be identified higher age, higher preoperative CRP, lower preoperative hemoglobin and longer time to surgery. Eight parameters were independent risk factors for a prolonged LOS: higher age, higher preoperative WBC-count and CRP, lower preoperative hemoglobin, need for conversion, longer surgery duration, presence of intraoperative complicated appendicitis and of postoperative morbidity. Presence of malignancy and higher preoperative WBC-count were independent risk factors for readmission.ConclusionAmong patients undergoing appendectomy for acute appendicitis, there are relevant risk factors predicting postoperative complications, prolonged hospital stays and readmission. Patients with the presence of the identified risk factors should receive special attention in the postoperative course and may benefit from a more individualized therapy.
CRIS-Team WoS Importer:2023-03-03

Risk Factors for Postoperative Morbidity, Suture Insufficiency, Re-Surgery and Mortality in Patients with Gastroduodenal Perforation - Treuheit, Julia; Krautz, Christian; Weber, Georg; Grützmann, Robert; Brunner, Maximilian (Journal of Clinical Medicine, 2023)
(1) Background: The aim of the present study was to identify risk factors associated with postoperative morbidity, suture/anastomotic insufficiency, re-surgery, and mortality in patients undergoing surgery for gastroduodenal perforation. (2) Methods: A retrospective analysis of 273 adult patients who received surgical treatment for gastroduodenal perforation from January 2006 to June 2021 at the University Hospital Erlangen was performed. The patient demographics and preoperative, intraoperative, and postoperative parameters were collected and compared among the different outcome groups (in-hospital morbidity, suture/anastomotic insufficiency, re-surgery, and 90-day mortality). (3) Results: In-hospital morbidity, suture/anastomotic insufficiency, need for re-surgery, and 90-day mortality occurred in 71%, 10%, 26%, and 25% of patients, respectively. The independent risk factors for morbidity were a significantly reduced general condition, a lower preoperative hemoglobin level, and a higher preoperative creatinine level. The independent risk factors for suture/anastomotic insufficiency could be identified as an intake of preoperative steroids and a perforation localization in the proximal stomach or duodenum. The four parameters were independent risk factors for the need for re-surgery: a significantly reduced general condition, a perforation localization in the proximal stomach, a higher preoperative creatinine level, and a higher preoperative CRP level. An age over 66 years and a higher preoperative CRP level were independent risk factors for 90-day mortality. (4) Conclusions: Our study could identify relevant risk factors for the postoperative outcome of patients undergoing surgical treatment for gastroduodenal perforation. Patients exhibiting the identified risk factors should receive heightened attention in the postoperative period and may potentially benefit from personalized and tailored therapy.
CRIS-Team Scopus Importer:2023-10-20
Keywords: gastroduodenal perforation; morbidity; mortality; re-surgery; risk factors; surgery; suture insufficiency

Risk Factors for Regional and Systemic Metastases in Patients with Sentinel Lymph Node-negative Melanoma - Erdmann, Michael; Sigler, Dominic; Uslu, Ugur; Göhl, Jonas; Grützmann, Robert; Schuler, Gerold; Schellerer, Vera (Anticancer Research, 2018)
BACKGROUND: Sentinel lymph node status is a strong prognostic factor in melanoma. However, up to 21% of sentinel lymph node-negative patients develop locoregional and distant metastases during follow-up. AIM: To analyze risk factors for locoregional and distant metastasis in patients with sentinel lymph node-negative melanoma. PATIENTS AND METHODS: A total of 545 patients underwent sentinel lymph node biopsy (SNB) between 2005 and 2013 at our hospital. Data for 449 patients with a negative SNB were analyzed regarding risk factors and development of metastases. Follow-up was performed until 2016. RESULTS: A total of 72 SNB-negative patients developed metastases, including 25 (34.7%) distant and 47 (63.3%) locoregional metastases. Locoregional metastases occurred earlier compared to distant metastases (with a mean of 24.2 and 23.5 months for regional lymph node and cutaneous metastases, respectively, vs. 31.4 months for distant metastases). Patients with metastases despite negative SNB had a greater tumor thickness (p=0.001), a higher rate of nodular melanoma (p=0.001), ulceration (p<0.001), and were older (p=0.05) compared to SNB-negative patients without subsequent metastases. Out of SNB-negative patients, 16% developed metastases. CONCLUSION: Close clinical follow-up including sonography of the draining lymph node region is mandatory for melanoma patients regardless of SNB status.
EVALuna2:203619

Robot-assisted liver resection - Aselmann, H.; Moeller, T.; Kersebaum, J. -N.; Egberts, J. H.; Croner, R.; Brunner, Michaela; Grützmann, Robert; Becker, T. (Chirurg, 2017)
Robotic liver resection can overcome some of the limitations of laparoscopic liver surgery; therefore, it is a promising tool to increase the proportion of minimally invasive liver resections. The present article gives an overview of the current literature. Furthermore, the results of a nationwide survey on robotic liver surgery among hospitals in Germany with a DaVinci system used in general visceral surgery and the perioperative results of two German robotic centers are presented.
EVALuna2:15283

Roboterassistierte viszeralchirurgische Eingriffe in Deutschland: Eine Analyse zum aktuellen Stand sowie zu Trends der letzten 5 Jahre anhand von StuDoQ|Robotik-Registerdaten - Brunner, Maximilian; Elgendy, Amr; Denz, Axel; Weber, Georg; Grützmann, Robert; Krautz, Christian (Die Chirurgie, 2023)
Robot-assisted systems have been increasingly used in general surgery for several years. Accordingly, the number of systems installed in Germany has also rapidly increased. While around 100 robot-assisted systems were used in German hospitals in 2018, this figure had already risen to more than 200 by 2022. The aim of this article is to present the current state of development and trends in robotic surgery in Germany. For this purpose, data from the StuDoQ|Robotics register were analyzed. Furthermore, a descriptive analysis of concomitant diagnosis-related groups (DRG) data was carried out via the Federal Statistical Office (Destatis), for a better assessment of the representativeness of the StuDoQ|Robotics register data. In both data sets, the annual number of robot-assisted visceral surgery procedures in Germany steadily increased. Compared to the DRG data, only 3.7% up to a maximum of 36.7% of all robot-assisted procedures performed were documented in the StuDoQ|Robotics register, depending on the type of procedure. Colorectal resections were the most frequent robot-assisted procedures (StuDoQ: 32.5% and 36.7% vs. DRG data: 24.2% and 29.7%) and had, for example, low mortality rates (StuDoQ: 1% and 1% vs. DRG data: 2.3% and 1.3%). Due to the low coverage rates of robot-assisted esophageal, gastric, pancreatic and liver interventions, no valid statements could be derived from the StuDoQ data for these areas. With the current coverage rates, the informative value of the StuDoQ|Robotics register is considerably limited for some types of intervention. In the future, measures should therefore be explored that lead to a significant increase in the coverage rates.
CRIS-Team Scopus Importer:2023-08-11
Keywords: Hospital billing data; Robotic colorectal surgery; Robotic hepato-pancreato-biliary surgery; Robotic surgery of the upper gastrointestinal tract; StuDoQ register

Robotic and laparoscopic liver surgery for colorectal liver metastases: an experience from a German Academic Center - Rahimli, Mirhasan; Perrakis, Aristotelis; Schellerer, Vera; Gumbs, Andrew; Lorenz, Eric; Franz, Mareike; Arend, Joerg; Negrini, Victor-Radu; Croner, Roland Siegfried (World Journal of Surgical Oncology, 2020)
Background Minimally invasive liver surgery (MILS) in the treatment of colorectal liver metastases (CRLM) is increasing in incidence. The aim of this work was to present our experience by reporting short-term and long-term outcomes after MILS for CRLM with comparative analysis of laparoscopic (LLS) and robotic liver surgery (RLS). Methods Twenty-five patients with CRLM, who underwent MILS between May 2012 and March 2020, were selected from our retrospective registry of minimally invasive liver surgery (MD-MILS). Thirteen of these patients underwent LLS and 12 RLS. Short-term and long-term outcomes of both groups were analyzed. Results Operating time was significantly longer in the RLS vs. the LLS group (342.0 vs. 200.0 min; p = 0.004). There was no significant difference between the laparoscopic vs. the robotic group regarding length of postoperative stay (8.8 days), measured blood loss (430.4 ml), intraoperative blood transfusion, overall morbidity (20.0%), and liver surgery related morbidity (4%). The mean BMI was 27.3 (range from 19.2 to 44.8) kg/m(2). The 30-day mortality was 0%. R0 resection was achieved in all patients (100.0%) in RLS vs. 10 patients (76.9%) in LLS. Major resections were carried out in 32.0% of the cases, and 84.0% of the patients showed intra-abdominal adhesions due to previous abdominal surgery. In 24.0% of cases, the tumor was bilobar, the maximum number of tumors removed was 9, and the largest tumor was 8.5 cm in diameter. The 1-, 3- and 5-year overall survival rates were 84, 56.9, and 48.7%, respectively. The 1- and 3-year overall recurrence-free survival rates were 49.6 and 36.2%, respectively, without significant differences between RLS vs. LLS. Conclusion Minimally invasive liver surgery for CRLM is safe and feasible. Minimally invasive resection of multiple lesions and large tumors is also possible. RLS may help to achieve higher rates of R0 resections. High BMI, previous abdominal surgery, and bilobar tumors are not a barrier for MILS. Laparoscopic and robotic liver resections for CRLM provide similar long-term results which are comparable to open techniques.
CRIS-Team WoS Importer:2021-01-08

Robotic-Assisted Liver Surgery - Croner, R.; Perrakis, Aristotelis; Grützmann, Robert; Hohenberger, Werner; Brunner, Michaela (Zentralblatt für Chirurgie, 2016)
The advantages of minimally invasive liver resections for selected patients are evident. Robots provide new innovations that will influence minimally invasive liver surgery in the future. This article presents our initial experience with this technology in our patient population. Material und Methods: In 14 patients with benign or malignant liver tumours, robotic-assisted liver surgery was performed. Selection criteria were compensated liver function and resection of <= 3 liver segments. Chronic liver disease or previous abdominal surgery were no exclusion criteria.Malignant liver tumours were removed in 10 patients (71 %) and benign symptomatic liver tumors in 3 patients (21 %), respectively, with histopathologically negative margins (R0). One patient suffering from HCC underwent intraoperative ablation. In one case (7 %) conversion was necessary. Mean operation time was 296 min (120-458 min); mean estimated blood loss was 319 ± 298 ml. The mean hospital stay of the patients was 8 days (3-17 days). Three patients (21 %) suffered from postoperative complications, which were manageable by conservative treatment (Clavien-Dindo I) in 2 cases (14 %). One patient (7 %) needed endoscopic treatment for postoperative bile leak (Clavien-Dindo III a). No patient died intra- or perioperatively.Robotic-assisted liver surgery is a safe procedure, which provides patients with all benefits of minimally invasive surgery. This highly advanced technology requires surgeons to strive for an increasing level of specialisation, in addition to being well-trained in liver surgery. Hence, a clear definition of the procedures and standardised teaching programs are necessary.
EVALuna2:15228

Robotic complete mesocolic excision for right colon cancer: Learning curve, training, techniques, approach, platforms, and future perspectives - Piozzi, Guglielmo Niccolò; Subramaniam, Sentilnathan; Duhoky, Rauand; Hohenberger, Werner; Khan, Jim S. (Laparoscopic, Endoscopic and Robotic Surgery, 2024)
Colon cancer has the fifth highest incidence worldwide and has the sixth highest mortality. Compared with rectal cancer, colon cancer currently has the worst 5-year overall survival for patients with stage II and III disease. Complete mesocolic excision has been developed as a standardized and optimized surgical technique for the excision of colon cancers. This technique has traditionally been performed through an open approach since laparoscopy is generally considered technically challenging. The robotic approach has been slowly implemented for colon cancer, but the newest robotic platforms allow for a safer and optimized approach for right colon cancer. Several robotic approaches have been developed and explored. The expansion of the current robotic platform ecosystem is gradually providing new outputs in the application of the robotic approach to complete mesocolic excision. This review gains an oversight of existing literature on robotic complete mesocolic excision for right colon cancer (learning curve, training, techniques, approach, platforms, and future perspectives).
CRIS-Team Scopus Importer:2024-04-19
Keywords: Colon cancer; Colorectal surgery; Complete mesocolic excision; Robotic platform; Robotic surgery

Robotic liver surgery for minor hepatic resections: a comparison with laparoscopic and open standard procedures - Croner, Roland S.; Perrakis, Aristotelis; Hohenberger, Werner; Brunner, Michaela (Langenbecks Archives of Surgery, 2016)
Minimally invasive liver surgery is increasing worldwide. The benefit of the robot in this scenario is currently controversially discussed. We compared our robotic cases vs. laparoscopic and open minor hepatic resections and share the experience.From 2011 to 2015, ten patients underwent robotic and 19 patients underwent laparoscopic minor liver resections in the Department of Surgery, University Hospital Erlangen. These patients were compared to a case-matched control group of 53 patients. The perioperative prospectively collected data were analyzed retrospectively.Blood loss was significantly decreased in the robotic (306 ml) and laparoscopic (356 ml) vs. the open (903 ml) surgery group (p = 0.001). Mean tumor size was 4.1-4.8 cm in all groups (p = 0.571). Negative surgical margins were present in 94 % of the open and 100 % of the laparoscopic and robotic group (p = 0.882). Time for surgery was enlarged for robotic (321 min) vs. laparoscopic (242 min) and open (186 min) surgery (p = 0.001). Postoperative hospitalization was decreased after robotic (7 days) and laparoscopic (8 days) vs. open (10 days) surgery (p = 0.004). Total morbidity was 17 % for open, 16 % for laparoscopic, and 1 % for robotic cases (p = 0.345). Postoperative pain medication and elevation of liver enzymes were remarkably lower after minimally invasive vs. open procedures.Minimally invasive liver surgery can be performed safely for minor hepatic resections and should be considered whenever possible. Minor liver resections can be performed by standard laparoscopy equivalent to robotic procedures. Nevertheless, the robot adds a technical upgrade which may have benefits for challenging cases and major liver surgery.
EVALuna2:15231

Robotic Pancreatic Resections: Feasibility and Advantages - Croner, Roland S. (Indian Journal of Surgery, 2015)
The robot is an innovative tool to perform complex pancreatic resections. It upgrades conventional laparoscopy by adding specific ergonomic technical details (e.g., EndoWrist). Robotic complex pancreatic operations such as pancreaticoduodenectomy can be carried out safe with equal oncological results, morbidity, and mortality compared to open procedures. The patients benefit from less blood loss, decreased hospitalization, and all other benefits of minimally invasive surgery. Nevertheless, the robot has some limitations like missing haptic feedback and the high costs. It has to find its indications beneath conventional laparoscopic procedures, which is currently extensively discussed. But the available technology is certainly convincing, and a further improvement can be expected which will increase its widespread in the future.
EVALuna2:15218

Roflumilast inhibits tumor growth and migration in STK11/LKB1 deficient pancreatic cancer - Zhang, Shuman; Yun, Duo; Yang, Hao; Eckstein, Markus; Elbait, Gihan Daw; Zhou, Yaxing; Lu, Yanxi; Yang, Hai; Zhang, Jinping; Dörflein, Isabella; Britzen-Laurent, Nathalie; Pfeffer, Susanne; et al. (Cell Death Discovery, 2024)
Pancreatic cancer is a malignant tumor of the digestive system. It is highly aggressive, easily metastasizes, and extremely difficult to treat. This study aimed to analyze the genes that might regulate pancreatic cancer migration to provide an essential basis for the prognostic assessment of pancreatic cancer and individualized treatment. A CRISPR knockout library directed against 915 murine genes was transfected into TB 32047 cell line to screen which gene loss promoted cell migration. Next-generation sequencing and PinAPL.py- analysis was performed to identify candidate genes. We then assessed the effect of serine/threonine kinase 11 (STK11) knockout on pancreatic cancer by wound-healing assay, chick agnosia (CAM) assay, and orthotopic mouse pancreatic cancer model. We performed RNA sequence and Western blotting for mechanistic studies to identify and verify the pathways. After accelerated Transwell migration screening, STK11 was identified as one of the top candidate genes. Further experiments showed that targeted knockout of STK11 promoted the cell migration and increased liver metastasis in mice. Mechanistic analyses revealed that STK11 knockout influences blood vessel morphogenesis and is closely associated with the enhanced expression of phosphodiesterases (PDEs), especially PDE4D, PDE4B, and PDE10A. PDE4 inhibitor Roflumilast inhibited STK11-KO cell migration and tumor size, further demonstrating that PDEs are essential for STK11-deficient cell migration. Our findings support the adoption of therapeutic strategies, including Roflumilast, for patients with STK11-mutated pancreatic cancer in order to improve treatment efficacy and ultimately prolong survival.
CRIS-Team Scopus Importer:2024-04-12

Role of guanylate binding protein-1 in vascular defects associated with chronic inflammatory diseases - Hammon, Matthias; Herrmann, Martin; Bleiziffer, Oliver; Pryymachuk, Galyna; Andreoli, Laura; Munoz, Luis Enrique; Amann, Kerstin Ute; Mondini, Michele; Gariglio, Marisa; Airo, Paolo; Schellerer, Vera; Hatzopoulos, Antonis K.; et al. (Journal of Cellular and Molecular Medicine, 2011)
Rheumatic autoimmune disorders are characterized by a sustained pro-inflammatory microenvironment associated with impaired function of endothelial progenitor cells (EPC) and concomitant vascular defects. Guanylate binding protein-1 (GBP-1) is a marker and intracellular regulator of the inhibition of proliferation, migration and invasion of endothelial cells induced by several pro-inflammatory cytokines. In addition, GBP-1 is actively secreted by endothelial cells. In this study, significantly increased levels of GBP-1 were detected in the sera of patients with chronic inflammatory disorders. Accordingly we investigated the function of GBP-1 in EPC. Interestingly, stable expression of GBP-1 in T17b EPC induced premature differentiation of these cells, as indicated by a robust up-regulation of both Flk-1 and von Willebrand factor expression. In addition, GBP-1 inhibited the proliferation and migration of EPC in vitro. We confirmed that GBP-1 inhibited vessel-directed migration of EPC at the tissue level using the rat arterio-venous loop model as a novel quantitative in vivo migration assay. Overall, our findings indicate that GBP-1 contributes to vascular dysfunction in chronic inflammatory diseases by inhibiting EPC angiogenic activity via the induction of premature EPC differentiation. © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.
Created from Fastlane, Scopus look-up
Keywords: Endothelial progenitor cells; Guanylate binding protein-1; Inflammation; Rheumatic autoimmune disorders; Rheumatoid arthritis; Systemic lupus erythematosus; Systemic sclerosis

Role of IFN-gamma-activation of distinct tumor and stromal cell populations in colorectal carcinoma pathogenesis - Britzen-Laurent, Nathalie; Guo, Wei; Langer, Victoria; Khoziainova, Svetlana; Weisenburger, Thomas; Winkler, Thomas; Straube, Julia; Waldner, Maximilian; Becker, Christoph; Naschberger, Elisabeth; Skottke, Lisa; Tripal, Philipp; et al. (CANCER RESEARCH, 2019)
CRIS-Team WoS Importer:2019-10-22

RREB1::MRTFB fusion-positive extra-glossal mesenchymal neoplasms: A series of five cases expanding their anatomic distribution and highlighting significant morphological and phenotypic diversity - Agaimy, Abbas; Din, Nasir Ud; Dermawan, Josephine K.; Haller, Florian; Melzer, Katja; Denz, Axel; Baumhoer, Daniel; Stöhr, Robert; Grützmann, Robert; Antonescu, Cristina R. (Genes Chromosomes & Cancer, 2022)
The RREB1::MRTFB (former RREB1::MKL2) fusion characterizes ectomesenchymal chondromyxoid tumors (EMCMT) of the tongue. Only five molecularly confirmed extra-glossal EMCMT cases have been reported recently; all occurring at head and neck or mediastinal sites. We herein describe five new cases including the first two extracranial/extrathoracic cases. The tumors occurred in three male and two female patients with an age ranging from 18 to 61 years (median, 28). Three tumors were located in the head and neck (jaw, parapharyngeal space, and nasopharyngeal wall) and two in the soft tissue (inguinal and presacral). The tumor size ranged from 3.3 to 20 cm (median, 7). Treatment was surgical without adjuvant treatment in all cases. Two cases were disease-free at 5 and 17 months; other cases were lost to follow-up. Histologically, the soft tissue cases shared a predominant fibromyxoid appearance, but with variable cytoarchitectural pattern (cellular perineurioma-like whorls and storiform pattern in one case and large polygonal granular cells embedded within a chondromyxoid stroma in the other). Two tumors (inguinal and parapharyngeal) showed spindled to ovoid and round cells with a moderately to highly cellular nondescript pattern. One sinonasal tumor closely mimicked nasal chondromesenchymal hamartoma (NCMH). Mitotic activity was low (0-5 mitoses/10 hpfs). Immunohistochemical findings were heterogeneous with variable expression of S100 (2/5), EMA (2/3), CD34 (1/4), desmin (1/4), and GFAP (1/3). Targeted RNA sequencing revealed the same RREB1::MRTFB fusion in all cases, with exon 8 of RREB1 being fused to exon 11 of MRTFB. This study expands the topographic spectrum of RREB1::MRTFB fusion-positive mesenchymal neoplasms, highlighting a significant morphological and phenotypic diversity. Overall, RREB1::MRTFB-rearranged neoplasms seem to fall into two subcategories: tumors with lobulated, chondroid, or myxochondroid epithelioid morphology (Cases 2 and 3) and those with more undifferentiated hypercellular spindle cell phenotype (Cases 1, 4, and 5). Involvement of extracranial/extrathoracic sites and the NCMH-like pattern are novel. The biology of these likely indolent or benign tumors remains to be verified in the future.
CRIS-Team WoS Importer:2022-07-29

"Run-off" synthesis and application of defined single-stranded DNA hybridization probes. - Stürzl, Michael; Roth, Willy Kurt (Analytical Biochemistry, 1990)
A simple and efficient method for synthesizing radioactively labeled single-stranded DNA hybridization probes with Thermus aquaticus (Taq) DNA polymerase is described. This is done in a "run-off" polymerization with repeated cycles of denaturation, annealing, and extension. It leads to high yields of a single-stranded DNA of defined length (up to 5000 nt), which is labeled to a high specific activity (1.3 x 10(8) cpm/micrograms DNA). These hybridization probes are equally sensitive as nick-translated DNA probes, but strand specific. This was tested by slot blot hybridization with in vitro-transcribed target RNAs and by Northern blotting. The use of single-stranded DNA hybridization probes combines the benefits of DNA stability and single-strand RNA probes.

Rupture Risk and Etiology of Visceral Artery Aneurysms and Pseudoaneurysms: A Single-Center Experience - Regus, Susanne; Lang, Werner (Vascular and Endovascular Surgery, 2016)
The aim of this study was to analyze differences in rupture risk and etiology of visceral artery aneurysms (VAAs) and visceral artery pseudoaneurysms (VAPAs) in a single-center experience.We retrospectively reviewed all patients with a VAA or VAPA after treatment by open surgical or endovascular repair (ER) in our institution. Patient history, treatment details, and outcome were recorded and analyzed.From January 1996 to April 2014, 29 (12 women) patients with 33 aneurysms (26 VAAs and 7 VAPAs) were treated in elective and urgent settings by open repair or ER. Etiology was quite different, most common was atherosclerosis (61.5%) in VAA and chronic pancreatitis (85.7%) in VAPA. Rupture rate was 19.2% in VAA and 42.9% in VAPA, whereas mean size of ruptured VAA was 4.4 cm and of ruptured VAPA was 2 cm. Open repair (suture, ligation, and aneurysmectomy with or without arterial reconstruction) and ER (coil embolization in the packing technique) were performed in half of all cases. After follow-up (72-month VAA and 82-month VAPA), aneurysm-free survival was reported to be 95% in VAA and 100% in VAPA.Chronic pancreatitis seems to be a prominent risk factor for the development of VAPA in this single-center experience. Modern endovascular techniques with promising short- and long-term results could broaden indications to treat asymptomatic VAA and VAPA.
EVALuna2:15271

Sacral malformations: use of imaging to optimise sacral nerve stimulation - Povo, A.; Arantes, Mavilde; Matzel, Klaus; Barbosa, Joselina; Ferreira, M. A. (International Journal of Colorectal Disease, 2016)
The success of sacral nerve stimulation, a common treatment for pelvic floor disorders, depends on correct placement of the electrodes through the sacral foramina. When the bony anatomy and topography of the sacrum and sacral spinal nerves are intact, this is easily achieved; where sacral anomalies exist, it can be challenging. A better understanding of common sacral malformations can improve the success of sacral nerve stimulation (SNS) electrode placement.We reviewed 998 consecutive MRI scans performed to investigate low back pain in patients who had undergone CT and/or X-ray.Congenital sacral malformations were found in 24.1%, the most common being sacral meningeal cysts (16%) and spina bifida occulta (9.9%). Others were lumbosacral transitional vertebrae (2.5%), anterior occult meningocele (0.5%), partial sacral agenesis (0.2%) and vertebral dysplasia of S1 (0.2%).This radiologic review uncovered a high incidence of sacral malformations, and most were asymptomatic. All surgeons who perform SNS should have a basic understanding of sacral malformations, their incidence and effect on foraminal anatomy. Imaging will aid procedural planning.
EVALuna2:15263

Sacral nerve stimulation for faecal incontinence and constipation: a European consensus statement - Maeda, Yasuko; O'Connell, P. R.; Lehur, P. -A.; Matzel, Klaus; Laurberg, S. (Colorectal Disease, 2015)
In Europe during the last decade sacral nerve stimulation (SNS) or sacral neuromodulation (SNM) has been used to treat faecal incontinence (FI) and constipation. Despite this, there is little consensus on baseline investigations, patient selection and operative technique. A modified Delphi process was conducted to seek consensus on the current practice of SNS/SNM for FI and constipation.A systematic literature search of SNS for FI and constipation was conducted using PubMed. A set of questions derived from the search and expert opinion were answered on-line on two occasions by an international panel of specialists from Europe. A 1-day face-to-face meeting of the experts finalized the discussion.Three hundred and ninety-three articles were identified from the literature search, of which 147 fulfilled the inclusion criteria. Twenty-two specialists in FI and constipation from Europe participated. Agreement was achieved on 43 (86%) of 50 domains including the set-up of service, patient selection, baseline investigations, operative technique and programming of the device. The median of agreement was 95% (35-100%).Consensus was achieved on the majority of domains of SNS/SNM for FI and constipation. This should serve as a benchmark for safe and quality practice of SNS/SNM in Europe.
EVALuna2:15199

Sacral nerve stimulation for faecal incontinence in patients with sacral malformation - Brunner, Michaela; Cui, Z.; Matzel, Klaus (International Journal of Colorectal Disease, 2017)
Sacral nerve stimulation (SNS) is a common and effective treatment for faecal incontinence (FI), but accessibility of the sacral nerves is mandatory. In some cases, electrode placement fails for unknown reasons. A frequent cause could be sacral malformations, which have a high incidence (up to 24.1%) and can be unsuspected.We report two patients with FI consequent to congenital anorectal malformation and associated sacral malformation. Despite partial sacral agenesis, SNS was feasible in both. They benefitted greatly from SNS, with an improved ability to postpone the urge up to at least 15 min, reduced incontinence episodes (at least 50%), and significantly better quality of life.SNS may be feasible in patients with FI, even in the presence of sacral malformation. However, clinicians should be aware of the attendant technical difficulties. Preoperative imaging, preferably with MRI of the sacrum, is advisable. If the sacral spinal nerves are inaccessible technically, pudendal nerve stimulation could be considered, if anatomy permits.
EVALuna2:15239

Sacral neuromodulation for constipation and fecal incontinence in children and adolescents – study protocol of a prospective, randomized trial on the application of invasive vs. non-invasive technique - Besendörfer, Manuel; Kirchgatter, Annemarie; Carbon, Roman; Weiss, Christel; Müller, Hanna; Matzel, Klaus; Diez, Sonja (Trials, 2024)
Background: A therapeutic effect of sacral neuromodulation (SNM) on fecal incontinence (FI) and quality of life has been proven in adults. SNM is, however, rarely used in pediatric cases. The aim of the study is to investigate effects of SNM in pediatric constipation in a prospective parallel-group trial. Methods: A monocentric, randomized, unblinded, parallel-group trial is conducted. SNM is conducted in the invasive variant and in an innovative, external approach with adhesive electrodes (enteral neuromodulation, ENM). We include patients with constipation according to the ROME IV criteria and refractory to conventional options. Patients with functional constipation and Hirschsprung’s disease are able to participate. Participants are allocated in a 1:1 ratio to either SNM or ENM group. Clinical data and quality of life is evaluated in regular check-ups. Neuromodulation is applied continuously for 3 months (end point of the study) with follow-up-points at 6 and 12 months. Findings are analyzed statistically considering a 5% significance level (p ≤ 0.05). Outcome variables are defined as change in (1) episodes of abdominal pain, (2) episodes of FI, (3) defecation frequency, (4) stool consistency. Improvement of proprioception, influence on urinary incontinence, quality of life and safety of treatment are assessed as secondary outcome variables. We expect a relevant improvement in both study groups. Discussion: This is the first trial, evaluating effects of neuromodulation for constipation in children and adolescents and comparing effects of the invasive and non-invasive application (SNM vs. ENM). Trial registration: The study is registered with clinicaltrials.gov, Identifier NCT04713085 (date of registration 01/14/2021).
CRIS-Team Scopus Importer:2024-04-05
Keywords: Chronic refractory constipation; Enteral neuromodulation; Fecal incontinence; Functional constipation; Hirschsprung’s disease; Sacral nerve stimulation; Sacral neuromodulation

Sacral Neuromodulation for Fecal Incontinence and Constipation: Evidence, Programming and Long-term Management Sakralnervmodulation in der Therapie der Stuhlinkontinenz und Obstipation: Evidenz, Programmierung und Langzeitmanagement - Bittorf, Birgit; Matzel, Klaus (Zentralblatt für Chirurgie, 2023)
Background Over the last two decades, sacral neuromodulation (SNM) has established its role in the treatment of functional pelvic organ-/pelvic floor disorders. Even though the mode of action is not fully understood, SNM has become the preferred surgical treatment of fecal incontinence. Methods and Results A literature search was carried out on programming sacral neuromodulation and long-term outcomes in treating fecal incontinence and constipation. Sacral neuromodulation was found to be successful in the long term. Over the years, the spectrum of indications has expanded, and now includes patients presenting with anal sphincter lesions. The use of SNM for low anterior resection syndrome (LARS) is currently under clinical investigation. Findings of SNM for constipation are less convincing. In several randomised crossover studies, no success was demonstrated, even though it is possible that subgroups may benefit from the treatment. Currently the application cannot be recommended in general. The pulse generator programming sets the electrode configuration, amplitude, pulse frequency and pulse width. Usually pulse frequency and pulse width follow a default setting (14 Hz, 210 s), while electrode configuration and stimulation amplitude are adjusted individually to the patient need and perception of stimulation. Despite low infection rates and few electrode-/pulse generator dysfunctions, up to 65% of patients require surgical reintervention during long term follow-up - in 50% of cases because of battery depletion, which is an expected event. At least one reprogramming is necessary in about 75% of the patients during the course of the treatment, mostly because of changes in effectiveness, but rarely because of pain. Regular follow-up visits appear to be advisable. Conclusion Sacral neuromodulation can be considered to be a safe and effective long-term therapy of fecal incontinence. To optimise the therapeutic effect, a structured follow-up regime is advisable.
CRIS-Team Scopus Importer:2023-06-30
Keywords: fecal incontinence; long-term management; programming; sacral neuromodulation

Sacral neuromodulation for persistent faecal incontinence after laparoscopic ventral rectopexy for high-grade internal rectal prolapse - Mishra, A.; Prapasrivorakul, S.; Gosselink, M. P.; Gorissen, K. J.; Hompes, R.; Jones, O.; Cunningham, C.; Matzel, K. E.; Lindsey, I. (Colorectal Disease, 2016)
Internal rectal prolapse is recognized as an aetiological factor in faecal incontinence. Patients found to have a high-grade internal rectal prolapse on routine proctography are offered a laparoscopic ventral rectopexy after failed maximum medical therapy. Despite adequate anatomical repair, faecal incontinence persists in a number of patients. The aim of this study was to evaluate the outcome of sacral neuromodulation in this group of patients.Between August 2009 and January 2012, 52 patients who underwent a laparoscopic ventral rectopexy for faecal incontinence associated with high-grade internal rectal prolapse had persistent symptoms of faecal incontinence and were offered sacral neuromodulation. Symptoms were evaluated before and after the procedure using the Fecal Incontinence Severity Index (FISI) and the Gastrointestinal Quality of Life Index (GIQLI).Temporary test stimulation was successful in 47 (94%) of the patients who then underwent implantation of a permanent pulse generator. The median FISI score 1 year after sacral neuromodulation was lower than the median score before [34 (28-59) vs 19 (0-49); P < 0.01], indicating a significant improvement in faecal continence. Quality of life (GIQLI) was significantly better after starting sacral neuromodulation [78 (31-107) vs 96 (55-129); P < 0.01].Patients may benefit from sacral neuromodulation for persisting faecal incontinence after laparoscopic ventral rectopexy.
EVALuna2:15207

Sacral Neuromodulation: Standardized Electrode Placement Technique - Matzel, Klaus E.; Chartier-Kastler, Emmanuel; Knowles, Charles H.; Lehur, Paul A.; Munoz-Duyos, Arantxa; Ratto, Carlo; Rydningen, Mona B.; Sorensen, Michael; Van Kerrebroeck, Philip; De Wachter, Stefan (Neuromodulation, 2017)
Sacral neuromodulation (SNM) (sacral nerve stimulation SNS) has become an established therapy for functional disorders of the pelvic organs. Despite its overall success, the therapy fails in a proportion of patients. This may be partially due to inadequate electrode placement with suboptimal coupling of the electrode and nerve. Based on these assumptions the technique of sacral spinal neuromodulation has been redefined. All descriptions relate to the only currently available system licensed for all pelvic indications (Medtronic Interstim® ).An international multidisciplinary working party of ten individuals highly experienced in performing SNM convened two meetings (including live operating) to standardize the implant procedure. This report addresses the main steps to optimal electrode lead placement in temporal sequence.Key elements of the electrode placement are radiological marking, the use of a curved stylet, the entry of the electrode into the sacral foramen and its progression through the foramen, its placement guided by a combination of a typical appearance in fluoroscopy and achieving specific motor/sensory responses with stimulation. The report describes quadripolar electrode placement and then either insertion of a connecting percutaneous extension lead or permanent implantation of the programmable device.Standardization of electrode placement may ensure close electrode proximity to the target nerve providing a higher likelihood for optimal effect with less energy consumption (better battery longevity), more programming options with more electrode contacts close to the nerve and reduced likelihood of side-effects. The potentially better clinical outcome needs to be demonstrated.
EVALuna2:15315

Safety of medical compression stockings in patients with diabetes mellitus or peripheral arterial disease - Rother, Ulrich; Grussler, Anna; Griesbach, Colin; Almási-Sperling, Veronika; Lang, Werner; Meyer, Alexander (BMJ Open Diabetes Research and Care, 2020)
Introduction Compression therapy is highly effective in the treatment of many venous diseases, including leg edema. However, its relevance in patients with peripheral arterial disease (PAD) or diabetes mellitus is critically discussed. The aim of the present study was to assess the influence of compression therapy on microperfusion and its safety in patients with PAD or diabetes mellitus. Research design and methods A prospective analysis of 94 consecutive patients (44 patients with diabetes, 45 patients with PAD and 5 healthy controls) undergoing medical compression therapy was performed. Microperfusion was assessed by a combined method of white light tissue spectrometry and laser Doppler flowmetry under medical compression therapy (classes I and II), in different body positions (supine, sitting, standing and elevated position of the leg) and at different locations (great toe, lateral ankle and calf). Results During the entire study, no compression-related adverse events occurred. Evaluation of microcirculation parameters (oxygen saturation of hemoglobin and flow) at the different locations and in sitting and standing positions (patients with diabetes and PAD) under compression therapy classes I and II revealed no tendency for reduced microperfusion in both groups. In contrast, in the elevated leg position, all mean perfusion values decreased in the PAD and diabetes groups. However, the same effect was seen in the healthy subgroup. Conclusions In consideration of the present inclusion criteria, use of medical compression stockings is safe and feasible in patients with diabetes or PAD. This study did not find relevant impairment of microperfusion parameters under compression therapy in these patient subgroups in physiologic body positions. Trial registration number NCT03384758.
CRIS-Team Scopus Importer:2020-06-16
Keywords: chronic diabetic complications; microcirculation; peripheral arterial occlusive disease

Sakrale Neuromodulation - Matzel, Klaus E.; Bittorf, B. (Coloproctology, 2020)
Over the last few years sacral neuromodulation has evolved to become the mainstay of surgical treatment of fecal incontinence. The electrode positioning is the crucial element of the operative intervention. With suboptimal electrode placement the probability of treatment success is reduced, the risk of negative side effects is increased and the energy consumption of the stimulation is increased resulting in reduced longevity of the battery and higher treatment costs. Preliminary findings indicate that the modified technique of electrode placement using intraoperative imaging and a curved stylet leads to better electrode positioning. The modified technique of electrode placement in sacral neuromodulation enables a more precise and effective treatment.
CRIS-Team Scopus Importer:2020-03-06
Keywords: Curved stylets; Electrode placement; Fecal incontinence; Sacral spinal nerve stimulation; Tined lead electrode

Salivary Markers for Quantitative Dehydration Estimation During Physical Exercise - Ring, Matthias; Lohmueller, Clemens; Rauh, Manfred; Mester, Joachim; Eskofier, Björn (IEEE Journal of Biomedical and Health Informatics, 2017)

Scavenging of bacteria or bacterial products by magnetic particles functionalized with a broad-spectrum pathogen recognition receptor motif offers diagnostic and therapeutic applications - Friedrich, Bernhard; Lyer, Stefan; Janko, Christina; Unterweger, Harald; Brox, Regine; Cunningham, Sarah; Dutz, Silvio; Taccardi, Nicola; Bikker, Floris J.; Hurle, Katrin; Sebald, Heidi; Lenz, Malte; et al. (Acta Biomaterialia, 2022)
Sepsis is a dysregulated host response of severe bloodstream infections, and given its frequency of occurrence and high mortality rate, therapeutic improvements are imperative. A reliable biomimetic strategy for the targeting and separation of bacterial pathogens in bloodstream infections involves the use of the broad-spectrum binding motif of human GP-340, a pattern-recognition receptor of the scavenger receptor cysteine rich (SRCR) superfamily that is expressed on epithelial surfaces but not found in blood. Here we show that these peptides, when conjugated to superparamagnetic iron oxide nanoparticles (SPIONs), can separate various bacterial endotoxins and intact microbes (E. coli, S. aureus, P. aeruginosa and S. marcescens) with high efficiency, especially at low and thus clinically relevant concentrations. This is accompanied by a subsequent strong depletion in cytokine release (TNF, IL-6, IL-1β, Il-10 and IFN-γ), which could have a direct therapeutic impact since escalating immune responses complicates severe bloodstream infections and sepsis courses. SPIONs are coated with aminoalkylsilane and capture peptides are orthogonally ligated to this surface. The particles behave fully cyto- and hemocompatible and do not interfere with host structures. Thus, this approach additionally aims to dramatically reduce diagnostic times for patients with suspected bloodstream infections and accelerate targeted antibiotic therapy. Statement of significance: Sepsis is often associated with excessive release of cytokines. This aspect and slow diagnostic procedures are the major therapeutic obstacles. The use of magnetic particles conjugated with small peptides derived from the binding motif of a broad-spectrum mucosal pathogen recognition protein GP-340 provides a highly efficient scavenging platform. These peptides are not found in blood and therefore are not subject to inhibitory mechanisms like in other concepts (mannose binding lectine, aptamers, antibodies). In this work, data are shown on the broad bacterial binding spectrum, highly efficient toxin depletion, which directly reduces the release of cytokines. Host cells are not affected and antibiotics not adsorbed. The particle bound microbes can be recultured without restriction and thus be used directly for diagnostics.
CRIS-Team Scopus Importer:2022-03-11
Keywords: GP-340; Magnetic nanoparticles; Pathogen binding; Sepsis; SRCR domain

Schwann Cells Do Not Promote Myogenic Differentiation in the EPI Loop Model - Xu, Zhou; Arkudas, Andreas; Munawar, Muhammad; Schubert, Dirk W.; Fey, Tobias; Weisbach, Volker; Mengen, Lilly; Horch, Raymund E.; Cai, Aijia (Tissue Engineering - Part A, 2024)
In skeletal muscle tissue engineering, innervation and vascularization play an essential role in the establishment of functional skeletal muscle. For adequate three-dimensional assembly, biocompatible aligned nanofibers are beneficial as matrices for cell seeding. The aim of this study was to analyze the impact of Schwann cells (SC) on myoblast (Mb) and adipogenic mesenchymal stromal cell (ADSC) cocultures on poly-e-caprolactone (PCL)collagen I-nanofibers in vivo. Human Mb/ADSC cocultures, as well as Mb/ADSC/SC cocultures, were seeded onto PCL-collagen I-nanofiber scaffolds and implanted into the innervated arteriovenous loop model (EPI loop model) of immunodeficient rats for 4 weeks. Histological staining and gene expression were used to compare their capacity for vascularization, immunological response, myogenic differentiation, and innervation. After 4 weeks, both Mb/ADSC and Mb/ADSC/SC coculture systems showed similar amounts and distribution of vascularization, as well as immunological activity. Myogenic differentiation could be observed in both groups through histological staining (desmin, myosin heavy chain) and gene expression (MYOD, MYH3, ACTA1) without significant difference between groups. Expression of CHRNB and LAMB2 also implied neuromuscular junction formation. Our study suggests that the addition of SC did not significantly impact myogenesis and innervation in this model. The implanted motor nerve branch may have played a more significant role than the presence of SC.
CRIS-Team Scopus Importer:2024-02-16
Keywords: electrospun nanofibers; EPI-loop; mesenchymal stromal cells; myoblasts; myogenic differentiation; schwann cells

Screening for pancreatic cancer in individuals with genetic susceptibility - Grützmann, Robert; Brunner, Maximilian (Hepatobiliary Surgery and Nutrition, 2023)
CRIS-Team WoS Importer:2023-06-02
Keywords: Pancreatic cancer; screening; genetic susceptibility; guideline; BRCA

Selection of patients with rectal cancer for neoadjuvant therapy using pre-therapeutic MRI-Results from OCUM trial - Stelzner, Sigmar; Ruppert, Reinhard; Kube, Rainer; Strassburg, Joachim; Lewin, Andreas; Baral, Joerg; Maurer, Christoph A.; Sauer, Joerg; Lauscher, Johannes; Winde, Guenther; Thomasmeyer, Rena; Bambauer, Cornelius; et al. (European Journal of Radiology, 2022)
Purpose: No consensus is available on the appropriate criteria for neoadjuvant chemoradiotherapy selection of patients with rectal cancer. The purpose was to evaluate the accuracy of MRI staging and determine the risk of over-and undertreatment by comparing MRI findings and histopathology. Method: In 609 patients of a multicenter study clinical T-and N categories, clinical stage and minimal distance between the tumor and mesorectal fascia (mrMRF) were determined using MRI and compared with the histopathological categories in resected specimen. Accuracy, sensitivity, specificity, positive predictive, and negative predictive value (NPV) were calculated. Overstaging was defined as the MRI category being higher than the histopathological category. mrMRF and circumferential resection margin (CRM) were judged as tumor free at a minimal distance > 1 mm. The chi-squared test or Fisher's exact test were used. P < 0.05 was considered significant. Results: The T category was correct in 63.5% (386/608) of patients; cT was overstaged in 22.9% (139/608) and understaged in 13.5% (82/608). MRI accuracy for lymph node involvement was 56.5% (344/609); 22.2% (28/ 126) of patients with clinical stage II and 28.1% (89/317) with clinical stage III disease were diagnosed by histopathology as stage I. The accuracy for tumor free CRM was 86.5% (527/609) and the NPV was 98.1% (514/ 524). In 1.7% (9/524) mrMRF was false negative. Conclusion: MRI prediction of the tumor-free margin is more reliable than the prediction of tumor stage. MRF status as determined MRI should therefore be prioritized for decision making.
CRIS-Team WoS Importer:2022-02-04

Sensitive and specific detection of EML4-ALK rearrangements in non-small cell lung cancer (NSCLC) specimens by multiplex amplicon RNA massive parallel sequencing - Moskalev, Evgeny; Frohnauer, Judith; Merkelbach-Bruse, Sabine; Schildhaus, Hans-Ulrich; Dimmler, Arno; Schubert, Thomas; Boltze, Carsten; Koenig, Helmut; Fuchs, Florian; Sirbu, Horia; Rieker, Ralf J.; Agaimy, Abbas; et al. (Lung Cancer, 2014)
Recurrent gene fusions of anaplastic lymphoma receptor tyrosine kinase (ALK) and echinoderm microtubule-associated protein-like 4 (EML4) have been recently identified in 5% of non-small cell lung cancers (NSCLCs) and are targets for selective tyrosine kinase inhibitors. While fluorescent in situ hybridization (FISH) is the current gold standard for detection of EML4-ALK rearrangements, several limitations exist including high costs, time-consuming evaluation and somewhat equivocal interpretation of results. In contrast, targeted massive parallel sequencing has been introduced as a powerful method for simultaneous and sensitive detection of multiple somatic mutations even in limited biopsies, and is currently evolving as the method of choice for molecular diagnostic work-up of NSCLCs.We developed a novel approach for indirect detection of EML4-ALK rearrangements based on 454 massive parallel sequencing after reverse transcription and subsequent multiplex amplification (multiplex ALK RNA-seq) which takes advantage of unbalanced expression of the 5' and 3' ALK mRNA regions. Two lung cancer cell lines and a selected series of 32 NSCLC samples including 11 cases with EML4-ALK rearrangement were analyzed with this novel approach in comparison to ALK FISH, ALK qRT-PCR and EML4-ALK RT-PCR.The H2228 cell line with known EML4-ALK rearrangement showed 171 and 729 reads for 5' and 3' ALK regions, respectively, demonstrating a clearly unbalanced expression pattern. In contrast, the H1299 cell line with ALK wildtype status displayed no reads for both ALK regions. Considering a threshold of 100 reads for 3' ALK region as indirect indicator of EML4-ALK rearrangement, there was 100% concordance between the novel multiplex ALK RNA-seq approach and ALK FISH among all 32 NSCLC samples.Multiplex ALK RNA-seq is a sensitive and specific method for indirect detection of EML4-ALK rearrangements, and can be easily implemented in panel based molecular diagnostic work-up of NSCLCs by massive parallel sequencing.
EVALuna2:1847

SERPINC1 c.1247dupC: a novel SERPINC1 gene mutation associated with familial thrombosis results in a secretion defect and quantitative antithrombin deficiency - Ruf, Maximilian; Cunningham, Sarah; Wandersee, Alexandra; Brox, Regine; Achenbach, Susanne; Strobel, Julian; Hackstein, Holger; Schneider, Sabine (Thrombosis Journal, 2024)
BACKGROUND: Antithrombin (AT) is an important anticoagulant in hemostasis. We describe here the characterization of a novel AT mutation associated with clinically relevant thrombosis. A pair of sisters with confirmed type I AT protein deficiency was genetically analyzed on suspicion of an inherited SERPINC1 mutation. A frameshift mutation, c.1247dupC, was identified and the effect of this mutation was examined on the cellular and molecular level. METHODS: Plasmids for the expression of wild-type (WT) and mutated SERPINC1 coding sequence (CDS) fused to green fluorescent protein (GFP) or hemagglutinin (HA) tag were transfected into HEK293T cells. Subcellular localization and secretion of the respective fusion proteins were analyzed by confocal laser scanning microscopy and Western blot. RESULTS: The c.1247dupC mutation results in a frameshift in the CDS of the SERPINC1 gene and a subsequently altered amino acid sequence (p.Ser417LysfsTer48). This alteration affects the C-terminus of the AT antigen and results in impaired secretion as confirmed by GFP- and HA-tagged mutant AT analyzed in HEK293T cells. CONCLUSION: The p.Ser417LysfsTer48 mutation leads to impaired secretion, thus resulting in a quantitative AT deficiency. This is in line with the type I AT deficiency observed in the patients.
EVALuna2:553194
Keywords: Hereditary antithrombin deficiency; Secretion defect; Frameshift mutation; Thrombosis

Serum concentrations of fibroblast growth factor 2 are increased in HIV type 1-infected patients and inversely related to survival probability. - Ascherl, Gudrun; Sgadari, Cecilia; Bugarini, Roberto; Bogner, Johannes; Schatz, Octavian; Ensoli, Barbara; Stürzl, Michael (Aids Research and Human Retroviruses, 2001)
HIV-1-infected patients develop a generalized vasculopathy that is clinically most evident as Kaposi's sarcoma (KS), a multifocally appearing endothelial cell-derived tumor. Fibroblast growth factor 2 (FGF-2) is a potent autocrine and paracrine mitogen of endothelial cells and has been implicated in the cell proliferation and angiogenesis observed in KS. Here we determined by ELISA the FGF-2 serum concentrations in different clinical groups of HIV-1-infected patients. AIDS-KS patients (n = 53) and HIV-1-infected patients without KS (n = 39) revealed significantly increased FGF-2 serum concentrations (median, 4.5 and 4.6 pg/ml, respectively), as compared with the healthy control group (n = 22; median, 2.2 pg/ml; p < 0.01). FGF-2 concentrations were highest in untreated HIV-1-infected patients (median, 8.6 pg/ml) and were significantly decreased in patients undergoing antiretroviral therapy (AZT-median, 4.5 pg/ml; HAART-median, 2.5 pg/ml; p < 0.01). In addition, FGF-2 serum concentrations above 5.2 pg/ml were associated with a statistically significant higher risk of death in HIV-1-infected patients. Multivariate analysis showed that this effect is independent of CD4 levels, localization of KS (cutaneous or visceral), AIDS-defining opportunistic diseases, and therapy. Circulating FGF-2 may contribute to AIDS-associated vasculopathy and may be a sensitive and easily accessible surrogate marker to determine the survival time of HIV-1-infected patients and the efficacy of antiretroviral therapy.

SERUM IL-6 CONCENTRATION CORRELATES WITH PLAQUE VULNERABILITY AND RUPTURE IN PATIENTS WITH SEVERE CAROTID STENOSIS - Dietel, B.; Urschel, K.; Tauchi, Miyuki; Achenbach, Susanne (ATHEROSCLEROSIS, 2022)
CRIS-Team WoS Importer:2022-10-14

Setting a benchmark in surgical training robotic training under the European School of Coloproctology, ESCP - Gomez Ruiz, M.; Tou, S.; Matzel, Klaus (Colorectal Disease, 2019)
CRIS-Team WoS Importer:2019-04-16

SGLT2 inhibitors in patients with peripheral arterial disease: a missed opportunity or a risk of amputation? - Behrendt, Christian-Alexander; Rother, Ulrich (Gefässchirurgie, 2022)
CRIS-Team WoS Importer:2022-06-03

Short- and long term effects of epidural analgesia on morbidity and mortality of esophageal cancer surgery - Heinrich, Stefan; Janitz, Katrin; Merkel, Susanne; Klein, Peter; Schmidt, Joachim (Langenbecks Archives of Surgery, 2015)
Perioperative regional anesthesia with consecutive reduction of intra- and postoperative systemic opioid requirements in order to improve oncological result after cancer surgery has only been addressed by a few reports. This hypothesis has never been proved in esophageal cancer with a long-term follow-up of more than 5 years. Therefore, we addressed the impact on short- and long-term outcomes of epidural analgesia for esophagus cancer surgery.All available records from patients who underwent esophageal cancer surgery from 1995 to 2005 were retrospectively analyzed. Short- and long-term outcome variables including opioid requirements, duration of ICU-stay, survival, and cancer recurrence were compared between patients with and patients without epidural analgesia for abdomino-right-thoracic esophagectomy.Overall, the analysis included 153 patients, 118 received epidural analgesia; in 35 patients, epidural analgesia was avoided. We found significantly increased postoperative median opioid consumption (10-day intravenous morphine equivalent 187 versus 104 mg) and duration of ICU hospitalization (10.1 vs. 5.9 days, p < 0.05) in the non-epidural group compared with the epidural group. However, there were no significant differences in cancer recurrence (23 % non-epidural group, 27 % epidural group), 1-year mortality (14 vs. 11 %), or 5-year survival (29 vs. 28 %) between the two patient groups.The results of our study underline the well-known clinical benefits of epidural analgesia for esophagus surgery. However, we found no evidence that the further oncological outcome is determined or significantly influenced by the presence or absence of epidural analgesia.
EVALuna2:15179

Short and Long Term Outcome for Patients with Surgical Removal of Sacrococcygeal Teratoma in Newborns and Infancy - Ai, Maria; Schellerer, Vera; Besendörfer, Manuel (ONCOLOGY RESEARCH AND TREATMENT, 2020)
CRIS-Team WoS Importer:2020-03-20

Short-chain fatty acids induced lung tumor cell death and increased peripheral blood CD4+ T cells in NSCLC and control patients ex vivo - Thome, Carolin; Tausche, Patrick; Hohenberger, Katja; Yang, Zuqin; Krammer, Susanne; Trufa, Denis; Sirbu, Horia; Schmidt, Joachim; Neurath-Finotto, Susetta (Frontiers in Immunology, 2024)
Background: Despite therapy advances, one of the leading causes of cancer deaths still remains lung cancer. To improve current treatments or prevent non-small cell lung cancer (NSCLC), the role of the nutrition in cancer onset and progression needs to be understood in more detail. While in colorectal cancer, the influence of local microbiota derived SCFAs have been well investigated, the influence of SCFA on lung cancer cells via peripheral blood immune system should be investigated more deeply. In this respect, nutrients absorbed via the gut might affect the tumor microenvironment (TME) and thus play an important role in tumor cell growth. Objective: This study focuses on the impact of the short-chain fatty acid (SCFA) Sodium Butyrate (SB), on lung cancer cell survival. We previously described a pro-tumoral role of glucose on A549 lung adenocarcinoma cell line. In this study, we wanted to know if SB would counteract the effect of glucose and thus cultured A549 and H520 in vitro with and without SB in the presence or absence of glucose and investigated how the treatment with SB affects the survival of lung cancer cells and its influence on immune cells fighting against lung cancer. Methods: In this study, we performed cell culture experiments with A549, H520 and NSCLC-patient-derived epithelial cells under different SB levels. To investigate the influence on the immune system, we performed in vitro culture of peripheral mononuclear blood cells (PBMC) from control, smoker and lung cancer patients with increasing SB concentrations. Results: To investigate the effect of SB on lung tumor cells, we first analyzed the effect of 6 different concentrations of SB on A549 cells at 48 and 72 hours cell culture. Here we found that, SB treatment reduced lung cancer cell survival in a concentration dependent manner. We next focused our deeper analysis on the two concentrations, which caused the maximal reduction in cell survival. Here, we observed that SB led to cell cycle arrest and induced early apoptosis in A549 lung cancer cells. The expression of cell cycle regulatory proteins and A549 lung cancer stem cell markers (CD90) was induced. Additionally, this study explored the role of interferon-gamma (IFN-γ) and its receptor (IFN-γ-R1) in combination with SB treatment, revealing that, although IFN-γ-R1 expression was increased, IFN-γ did not affect the efficacy of SB in reducing tumor cell viability. Furthermore, we examined the effects of SB on immune cells, specifically CD8+ T cells and natural killer (NK) cells from healthy individuals, smokers, and NSCLC patients. SB treatment resulted in a decreased production of IFN-γ and granzyme B in CD8+ T cells and NK cells. Moreover, SB induced IFN-γ-R1 in NK cells and CD4+ T cells in the absence of glucose both in PBMCs from controls and NSCLC subjects. Conclusion: Overall, this study highlights the potential of SB in inhibiting lung cancer cell growth, triggering apoptosis, inducing cell cycle arrest, and modulating immune responses by activating peripheral blood CD4+ T cells while selectively inducing IFN-γ-R1 in NK cells in peripheral blood and inhibiting peripheral blood CD8+ T cells and NK cells. Thus, understanding the mechanisms of action of SB in the TME and its influence on the immune system provide valuable insights of potentially considering SB as a candidate for adjunctive therapies in NSCLC.
CRIS-Team Scopus Importer:2024-05-03
Keywords: A549; glucose; IFN-γ-receptor; lung cancer; NSCLC; short chain fatty acids (SCFA); sodium butyrate; T cells

Short-term outcomes of laparoscopic ventral rectopexy for obstructed defecation in patients with overt pelvic structural abnormalities-a Chinese pilot study - Ye, G. Y.; Wang, Z.; Matzel, K. E.; Cui, Z. (International Journal of Colorectal Disease, 2017)
As laparoscopic ventral rectopexy (LVR) gained increasing popularity in the past decade, studies from non-western area remain rare. The aim of this pilot study is to evaluate the efficacy and safety of LVR for obstructed defecation (OD) in Chinese patients with overt pelvic structural abnormalities.A series of 19 consecutive patients is presented undergoing LVR for OD. All patients showed various forms of pelvic structural abnormalities which were verified by dynamic defecography exam. Data was prospectively recorded and the functional outcomes were evaluated using the Cleveland Clinic Constipation Score (CCCS) and Patients Assessment of Constipation Quality of Life Score (PAC-QoL).Pelvic structural abnormalities of the 19 patients included external rectal prolapse (ER) in 10.5% (2/19), high grade internal rectal prolapse (IR) in 57.8% (11/19), rectocele in 52.6% (10/19), enterocele in 15.7% (3/19), cystocele/vaginal prolapse in 15.7 (3/19), descending perineum (DP) in 63.5% (12/19). 89.4% patients (17/19) showed at least two co-existed abnormalities and 15.7% (3/19) showed multicompartmental abnormalities. The mean follow-up was 9 months (range 1-18). No mesh-related complication was observed. At last available follow-up (LAFU), improvement of OD symptom was observed in 15 (78.9%) patients, the mean scores of CCCS decreased from 17 to 10 (p < 0.05), all four subsets of PAC-QoL scores improved, and three of them (physical discomfort, worries and concerns, satisfaction) showed statistical significance (p < 0.05).Laparoscopic ventral rectopexy appears to be a safe and effective procedure for obstructed defecation in Chinese patients with overt pelvic structural abnormalities in short-term follow-up.
EVALuna2:15314

Should salvage surgery be considered for local recurrence after definitive chemoradiation in locally advanced non-small cell lung cancer? - Schreiner, Waldemar; Dudek, Wojciech; Lettmaier, Sebastian; Fietkau, Rainer; Sirbu, Horia (Journal of Cardiothoracic Surgery, 2016)
Incidence of local relapse after definitive chemoradiation (>59 Gy) for locally advanced non-small-cell lung cancer (NSCLC) is high, irrespective of high dose radiation applied. Experience with salvage lung resections in patients with locally relapsed NSCLC after definitive chemoradiation is limited. We present our series of salvage lung resections for local NSCLC relapse after curative-intent chemoradiation for locally advanced tumor.Nine consecutive patients with local tumor recurrence or persistence following definitive chemoradiation were reviewed. Kaplan-Meier analysis was used to assess patient survival.All patients received definitive radiation (median dose 66.2 Gy) with concurrent chemotherapy. Tumor stage prior to chemoradiation was IIIA in 8 patients and IV in 1. In 4 patients tumor invaded the chest wall, in 2 the spine and in 1 the aorta. Median interval between chemoradiation and salvage resection was 30.2 weeks. Nine patients underwent 9 resections (6 lobectomies, 1 bilobectomy, 1 pneumonectomy and 1 bi-segmentectomy). One death occurred on the 12th postoperative day. Median overall survival was 23 months; postoperative 3-year survival was 47 %. Median progression-free survival was 21 months.Salvage lung resection for locally recurrent or persisted NSCLC in selected patients with locally advanced NSCLC following definitive chemoradiation is a worthwhile treatment option.
EVALuna2:18249

Should the Benefit of Adjuvant Chemotherapy in Colon Cancer Be Re-Evaluated? - Pahlman, Lars A.; Hohenberger, Werner; Matzel, Klaus; Sugihara, Kenichi; Quirke, Philip; Glimelius, Bengt (Journal of Clinical Oncology, 2016)
EVALuna2:15225

Sicherheitsabstand von 2 cm ist bei Exzision von Hautmelanomen dicker als 2 mm ausreichend - Hohenberger, Werner (Strahlentherapie und Onkologie, 2019)
CRIS-Team Scopus Importer:2019-11-05

Side effects and major adverse cardiac events caused by fractional flow reserve measurement: a systematic review and meta-analysis of 12,215 patients - Altstidl, Johannes Michael; Gaede, Luise; Tröbs, Monique; Marwan, Mohamed; Achenbach, Susanne (EUROPEAN HEART JOURNAL, 2022)
CRIS-Team WoS Importer:2023-03-03

Significance of Examined Lymph Node Number in Accurate Staging and Long-term Survival in Resected Stage I-II Pancreatic Cancer - More is Better? A Large International Population-based Cohort Study - Huang, Lei; Jansen, Lina; Balavarca, Yesilda; Van Der Geest, Lydia; Lemmens, Valery; Groot Koerkamp, Bas; Van Santvoort, Hjalmar C.; Grützmann, Robert; Besselink, Marc G.; Schrotz-King, Petra; Brenner, Hermann (Annals of Surgery, 2019)
Objective: This large international cohort study aimed to investigate the associations of examined lymph node (ELN) number with accurate staging and long-term survival in pancreatic adenocarcinoma (PaC) and to robustly determine the minimal and optimal ELN thresholds. Summary Background Data: ELN number is an important quality metric in cancer care. The recommended minimal ELN number in PaC to accurately stage cancer varies greatly across guidelines, and the optimal number especially to adequately stratify patient survival has not yet been established. Methods: Population-based data on patients with stage I to II PaC resected in 2003 to 2015 from the US Surveillance, Epidemiology, and End Results (SEER)-18 Program and Netherlands National Cancer Registry (NCR) were analyzed. Associations of ELN number with stage migration and survival were evaluated using multivariable-adjusted logistic and Cox regression models, respectively. The series of odds ratios (ORs) for negative-to-positive node stage migration and hazard ratios (HRs) for survival with more ELNs were fitted using a LOWESS smoother, and structural breakpoints were determined by Chow test. Results: Overall 16,241 patients were analyzed. With increasing ELN number, both cohorts exhibited significant proportional increases from nodenegative to node-positive disease [ORSEER-18=1.05, 95% confidence interval (CI) = 1.04-1.05; ORNCR = 1.10, 95% CI = 1.08-1.12] and serial improvements in survival (HRSEER-18 = 0.98, 95% CI = 0.98-0.99; HRNCR = 0.98, 95% CI = 0.97-0.99) per additional ELN after controlling for confounders. Associations for stage migration and survival remained significant in most stratifications by patient, tumor, and treatment factors. Cut-point analyses suggested a minimal threshold ELN number of 11 and an optimal number of 19, which were validated both internally in the derivative US cohort and externally in the Dutch cohort with the ability to well discriminate different probabilities of both survival and stage migration. Conclusions: In stage I to II PaC, more ELNs are associated with more precise nodal staging, which might largely explain the survival association. Our observational study does not suggest causality, and does not encourage more extended lymphadenectomy before further randomized evidence is obtained. Our results robustly conclude 11 ELNs as the minimal and suggest 19 ELNs as the optimal cut-points, for evaluating quality of lymph node examination and possibly for stratifying postoperative prognosis.
CRIS-Team Scopus Importer:2019-08-27
Keywords: accurate staging; examined lymph node count; large international population-based cohort study; long-term survival; pancreatic cancer; threshold

Silenced ZNF154 is associated with longer survival in resectable pancreatic cancer - Wiesmüller, Felix; Kopke, Josephin; Aust, Daniela; Roy, Janine; Dahl, Andreas; Pilarsky, Christian; Grützmann, Robert (International Journal of Molecular Sciences, 2019)
Pancreatic cancer has become the third leading cause of cancer-related death in the Western world despite advances in therapy of other cancerous lesions. Late diagnosis due to a lack of symptoms during early disease allows metastatic spread of the tumor. Most patients are considered incurable because of metastasized disease. On a cellular level, pancreatic cancer proves to be rather resistant to chemotherapy. Hence, early detection and new therapeutic targets might improve outcomes. The detection of DNA promoter hypermethylation has been described as a method to identify putative genes of interest in cancer entities. These genes might serve as either biomarkers or might lead to a better understanding of the molecular mechanisms involved. We checked tumor specimens from 80 patients who had undergone pancreatic resection for promoter hypermethylation of the zinc finger protein ZNF154. Then, we further characterized the effects of ZNF154 on cell viability and gene expression by in vitro experiments. We found a significant association between ZNF154 hypermethylation and better survival in patients with resectable pancreatic cancer. Moreover, we suspect that the cell growth suppressor SLFN5 might be linked to a silenced ZNF154 in pancreatic cancer.
CRIS-Team Scopus Importer:2019-11-12
Keywords: Biomarker; DNA methylation; Methylation-specific PCR; Pancreatic cancer; PDAC; SLFN5; ZNF154

Simultaneous and sensitive determination of the main metabolites of the plasticizer DEHP and its substitutes DEHTP, DINCH and TEHTM in human urine by coupling of on-line SPE, UHPLC and tandem mass spectrometry - Kuhlmann, Laura; Muench, Frank; Göen, Thomas; Eckert, Elisabeth (Analytical Methods, 2022)
With the prominent but toxicologically critical plasticizer di-(2-ethylhexyl) phthalate (DEHP) declining, alternative plasticizers are increasingly used leading to a continuously more diverse exposure situation of humans with multiple plasticizers. Therefore, an on-line SPE-LC-MS/MS method for the simultaneous determination of the most relevant urinary biomarkers of exposure to DEHP and the alternative plasticizers 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH), di-(2-ethylhexyl) terephthalate (DEHTP) and tri-(2-ethylhexyl) trimellitate (TEHTM) was developed. The method is characterized by a high sensitivity with limits of detection ranging from 0.006 to 0.047 mu g L-1 combined with an easy and straightforward sample preparation procedure. The wide linear working range of the method enables a reliable determination of analyte background levels in the general population as well as its potential use for monitoring studies investigating elevated plasticizer exposure settings. The method was successfully applied to urine samples from ten volunteers without occupational exposure to plasticizers revealing ubiquitous background exposure levels of the common plasticizers DEHP, DEHTP and DINCH.
CRIS-Team WoS Importer:2022-10-14

Simultaneous gene silencing of KRAS and anti-apoptotic genes as a multitarget therapy - Werner, Kristin; Lademann, Franziska; Thepkaysone, May-Linn; Jahnke, Beatrix; Aust, Daniela; Kahlert, Christoph; Weitz, Juergen; Grützmann, Robert; Pilarsky, Christian; Pilarsky, Christian; Weber, Georg (Oncotarget, 2016)
Pancreatic cancer is one of the most lethal tumor types worldwide and an effective therapy is still elusive. Targeted therapy focused against a specific alteration is by definition unable to attack broad pathway signaling modification. Tumor heterogeneity will render targeted therapies ineffective based on the regrowth of cancer cell sub-clones. Therefore multimodal therapy strategies, targeting signaling pathways simultaneously should improve treatment.SiRNAs against KRAS and the apoptosis associated genes BCLXL, FLIP, MCL1L, SURVIVIN and XIAP were transfected into human and murine pancreatic cancer cell lines. Induction of apoptosis was measured by Caspase 3/7 activation, subG1 FACS analysis and PARP cleavage. The therapeutic approach was tested in a subcutaneous allograft model with a murine cancer cell line.By using siRNAs as a systematic approach to remodel signal transduction in pancreatic cancer the results showed increasing inhibition of proliferation and apoptosis induction in vitro and in vivo. Thus, siRNAs are suitable to model multimodal therapy against signaling pathways in pancreatic cancer. Improvements in in vivo delivery of siRNAs against a multitude of targets might therefore be a potential therapeutic approach.
EVALuna2:15258

SMARCA4-deficient pulmonary adenocarcinoma: clinicopathological, immunohistochemical, and molecular characteristics of a novel aggressive neoplasm with a consistent TTF1neg/CK7pos/HepPar-1pos immunophenotype - Agaimy, Abbas; Fuchs, Florian; Moskalev, Evgeny; Sirbu, Horia; Hartmann, Arndt; Haller, Florian (Virchows Archiv, 2017)
Alterations in SMARCA4, a member of the chromatin remodeling Switch Sucrose Non-Fermentable (SWI/SNF) complex, characterize a subset of non-small cell lung cancer (NSCLC), but detailed morphological and immunophenotypic description of this tumor type is lacking. We describe 20 NSCLC cases found on routine screening not to express SMARCA4 by immunohistochemistry (IHC). These tumors were stained for CK7, TTF1, SMARCA2, SMARCA4, SMARCB1, and HepPar-1 and analyzed for molecular alterations, using a 160 cancer-related gene panel including the full coding sequence of SMARCA4. Patients were eight females and 12 males aged 41 to 76 (median, 60). Of 18 tumors with detailed data, 14 presented with synchronous distant metastases (M1). Histological examination showed predominantly solid adenocarcinoma (n = 15), frankly rhabdoid (n = 3) and mucinous (n = 2) patterns. Except for the rhabdoid cases, all tumors showed at least focal unequivocal glands and lacked squamous differentiation, justifying a diagnosis of adenocarcinoma. IHC showed a distinctive uniform immunophenotype (CK7+/HepPar-1+/TTF1-) in 18/20 cases. Only 2/16 cases showed limited weak expression of neuroendocrine markers. EGFR mutations and EML4-ALK and ROS1 gene rearrangements were not found in any of the examined cases. Next-generation sequencing, using a 160 cancer-related gene panel, revealed concurrent SMARCA4 and TP53 mutations in nine of the 12 (75%) successfully tested cases. Our study highlights (1) the morphological diversity of SMARCA4-deficient lung adenocarcinoma, (2) the consistent absence of expression of TTF1 in the presence of expression of HepPar-1, (3) absence of EGFR driver mutations, and (4) frequent inactivating SMARCA4 mutations as underlying mechanism of the observed SMARCA4 protein loss. SMARCA4-deficient pulmonary adenocarcinoma is emerging as a distinctive, albeit phenotypically heterogeneous molecular subgroup of TTF1-negative NSCLC. Uniform HepPar-1 expression in this subset of NSCLC may represent a diagnostic pitfall and merits further studies to explore the mechanisms involved.
EVALuna2:34083

SMARCB1(INI1)-deficient sinonasal basaloid carcinoma: a novel member of the expanding family of SMARCB1-deficient neoplasms - Agaimy, Abbas; Koch, Michael; Lell, Michael; Semrau, Sabine; Dudek, Wojciech; Wachter, David; Knöll, Antje; Iro, Heinrich; Haller, Florian; Hartmann, Arndt (American Journal of Surgical Pathology, 2014)
Poorly differentiated sinonasal carcinomas are a heterogenous group of aggressive neoplasms that encompasses squamous cell carcinoma including basaloid variant, lymphoepithelial carcinoma, sinonasal undifferentiated carcinoma, and neuroendocrine-type small cell carcinoma. We herein describe 3 cases of a hitherto unreported variant combining features of basaloid carcinoma with variable intermingled rhabdoid cells. Patients were 2 women (aged 28 and 35) and a man (52 y) who presented with sinonasal masses. All had advanced local disease with bone involvement (pT4). None had a history of irradiation or a family history of rhabdoid tumors. Treatment was surgery and adjuvant chemoradiation. One patient developed liver, lung, pleural, and pericardial metastases (63 mo) and is currently (70 mo) alive under palliative treatment. Another developed recurrent cervical lymph node metastases and died of disease 8.5 years later. The youngest patient was disease-free at last follow-up 7 years later. Histologic features were very similar in all 3 cases and showed intimate admixture of compact basaloid cell nests with peripheral palisading, perivascular pseudorosettes, and a few scattered rhabdoid cells. Rhabdoid cells were more extensive in the metastasis in 1 case but formed a minor inconspicuous component in the primary tumors in all cases. Striking features common to all cases were (1) basaloid "blue" appearance at low power, (2) papilloma-like exophytic component, (3) extensive pagetoid surface growth with prominent denuding features, and (4) replacement of underlying mucous glands mimicking an inverted papilloma. Clear-cut origin from benign papilloma and overt squamous differentiation were lacking. Diffuse (2) or partial (1) p16 expression was noted, but all cases lacked human papillomavirus DNA by molecular tests. In situ hybridization was negative for Epstein-Barr virus. Immunohistochemistry showed diffuse expression of pancytokeratin. CK5 and vimentin showed intermingling of CK5/vimentin basaloid and CK5/vimentin rhabdoid cells. Complete loss of nuclear SMARCB1 expression was seen in all cases including also the denuding carcinoma in situ-like surface lesions. To our knowledge, this variant of sinonasal carcinoma has not been reported before. The identical features in all 3 cases suggest a specific disease rather than a nonspecific dedifferentiated phenotype. Awareness of this rare variant and thus reporting of additional cases is necessary for defining its full morphologic and biological spectrum.
EVALuna2:6600

SMYD2 targets RIPK1 and restricts TNF-induced apoptosis and necroptosis to support colon tumor growth - Yu, Yidong; Thonn, Veronika; Patankar, Jay; Thoma, Oana-Maria; Waldner, Maximilian; Zielinska, Marta; Bao, Lili; Gonzalez Acera, Miguel; Wallmueller, Stefan; Engel, Felix; Stürzl, Michael; Neurath, Markus; et al. (Cell Death & Disease, 2022)
SMYD2 is a histone methyltransferase, which methylates both histone H3K4 as well as a number of non-histone proteins. Dysregulation of SMYD2 has been associated with several diseases including cancer. In the present study, we investigated whether and how SMYD2 might contribute to colorectal cancer. Increased expression levels of SMYD2 were detected in human and murine colon tumor tissues compared to tumor-free tissues. SMYD2 deficiency in colonic tumor cells strongly decreased tumor growth in two independent experimental cancer models. On a molecular level, SMYD2 deficiency sensitized colonic tumor cells to TNF-induced apoptosis and necroptosis without affecting cell proliferation. Moreover, we found that SMYD2 targeted RIPK1 and inhibited the phosphorylation of RIPK1. Finally, in a translational approach, pharmacological inhibition of SMYD2 attenuated colonic tumor growth. Collectively, our data show that SMYD2 is crucial for colon tumor growth and inhibits TNF-induced apoptosis and necroptosis.
CRIS-Team WoS Importer:2022-01-21

Social media use in German visceral surgeons : a cross-sectional study of a national cohort - Bosselmann, C. M.; Griffiths, B.; Gallagher, H. J.; Matzel, K. E.; Brady, R. R. W. (Colorectal Disease, 2017)
Engagement in social media is increasing. Medical professionals have been adapting LinkedIn, a professional networking site, and Twitter, a micro-blogging service, for a number of uses. This development has been described for a number of medical specialties, but there remains a paucity of European data. A study was undertaken to measure engagement and activity of German visceral surgeons on social media platforms.Visceral surgeons were identified from 15 regional Associations of Statutory Health Insurance Physicians (Kassenärztliche Vereinigungen) opt-in registers. A manual search was subsequently performed across key professional social media platforms. Presence of a profile and key markers of use were recorded.575 visceral surgeons were identified. 523 (93%) were male. 183 (31%) surgeons engaged in professional social media. 22 (3.8%) used Twitter, producing a mean of 16.43 tweets with a mean of 7.57 followers. 137 (24%) surgeons had a profile on LinkedIn with a mean of 46.36 connections. Female surgeons were less connected on LinkedIn (p<0.005). 60 (10%) used Xing, with a mean of 27.95 connections. There were no significant differences in use of social media between surgeons from Eastern and Western Germany (p=0.262) or male and female surgeons (p=0.399).German visceral surgeons are less engaged and less active on social media than previously examined cohorts. Loco-regional, cultural, demographic and regulatory matters may have a significant influence on uptake. If this surgical cohort wishes to have a wider international presence then education on the potential benefits of these tools may be needed. This article is protected by copyright. All rights reserved.
EVALuna2:15313

Solitary fibrous tumors/hemangiopericytomas with different variants of the NAB2-STAT6 gene fusion are characterized by specific histomorphology and distinct clinicopathological features - Barthelmeß, Sarah; Geddert, Helene; Boltze, Carsten; Moskalev, Evgeny; Bieg, Matthias; Sirbu, Horia; Brors, Benedikt; Wiemann, Stefan; Hartmann, Arndt; Agaimy, Abbas; Haller, Florian (American Journal of Pathology, 2014)
Recurrent somatic fusions of the two genes, NGFI-A-binding protein 2 (NAB2) and STAT6, located at chromosomal region 12q13, have been recently identified to be presumable tumor-initiating events in solitary fibrous tumors (SFT). Herein, we evaluated a cohort of 52 SFTs/hemangiopericytomas (HPCs) by whole-exome sequencing (one case) and multiplex RT-PCR (all 52 cases), and identified 12 different NAB2-STAT6 fusion variants in 48 cases (92%). All 52 cases showed strong and diffuse nuclear positivity for STAT6 by IHC. We categorized the fusion variants according to their potential functional effects within the predicted fusion protein and found strong correlations with relevant clinicopathological features. Tumors with the most common fusion variant, NAB2ex4-STAT6ex2/3, corresponded to classic pleuropulmonary SFTs with diffuse fibrosis and mostly benign behavior and occurred in older patients (median age, 69 years). In contrast, tumors with the second most common fusion variant, NAB2ex6-STAT6ex16/17, were found in much younger patients (median age, 47 years) and represented typical HPCs from deep soft tissue with a more aggressive phenotype and clinical behavior. In summary, these molecular genetic findings support the concept that classic pleuropulmonary SFT and deep-seated HPC are separate entities that share common features but correlate to different clinical outcome.
EVALuna2:6577

Soluble intercellular adhesion molecule-1 is a prognostic marker in colorectal carcinoma - Schellerer, Vera; Langheinrich, Melanie C.; Zver, Veronika; Grützmann, Robert; Stürzl, Michael; Gefeller, Olaf; Naschberger, Elisabeth; Merkel, Susanne (International Journal of Colorectal Disease, 2019)
PurposeSerological tumor markers are routinely used to monitor tumor onset and progression. In colorectal carcinoma (CRC), the carcinoembryonic antigen (CEA) is roughly elevated in 50% of patients at initial diagnosis. Soluble ICAM-1 (sICAM-1) is elevated in different cancers. The aim of this study was to evaluate the prognostic relevance of sICAM-1 combined with CEA in patients with CRC.MethodsIn blood samples of 297 CRC patients, sICAM-1 was determined by ELISA and CEA by microparticle enzyme immunoassay the day before oncologic resection. Separation in patients with sICAM-1(high) and sICAM-1(low) was performed by minimum p value approach; separation in CEA normal and elevated was performed according to the established diagnostic cutoff. Clinical data were obtained from the prospective collected data from the Erlangen Registry for Colorectal Carcinomas.ResultsCancer-related 5-year survival rate of patients with sICAM-1(low) (<290ng/ml, n=208) was significantly increased (83.4%) as compared to that of patients with sICAM-1(high) (290ng/ml, n=89) (66.2%; p<0.001). Patients with normal CEA concentrations (n=199; 90.8%) showed a significantly (p<0.001) improved cancer-related 5-year survival rate compared to patients with elevated CEA concentrations (n=98; 52.1%). Moreover, high sICAM-1 was an independent risk factor (hazard ratio 1.6) in multivariate analysis. Of note, increased sICAM-1 levels, either within normal or within elevated CEA, allowed to identify high-risk subgroups, both for overall (p<0.001) and cancer-related survival (p<0.001).ConclusionApplication of a novel risk score combining CEA/sICAM-1 serum concentrations allows the identification of high-risk groups for poor survival in CRC patients.
CRIS-Team WoS Importer:2019-02-21

SPARCL1 is an angiocrine inhibitor of tumorigenesis in colorectal carcinoma - Tenkerian, Clara; Regensburger, Daniela; Langer, Victoria; Klingler, Anika; Borau, Anne; Sticht, Heinrich; Ramming, Andreas; Wohlfahrt, Thomas; Schmid, Benjamin; Meniel, Valerie; Grützmann, Robert; Britzen-Laurent, Nathalie; et al. (CANCER RESEARCH, 2019)
CRIS-Team WoS Importer:2019-10-15

Species-, organ- and cell-type-dependent expression of SPARCL1 in human and mouse tissues. - Klingler, Anika; Regensburger, Daniela; Tenkerian, Clara; Britzen-Laurent, Nathalie; Hartmann, Arndt; Stürzl, Michael; Naschberger, Elisabeth (PLoS ONE, 2020)
SPARCL1 is a matricellular protein with anti-adhesive, anti-proliferative and anti-tumorigenic functions and is frequently downregulated in tumors such as colorectal carcinoma or non-small cell lung cancer. Studies have identified SPARCL1 as an angiocrine tumor suppressor secreted by tumor vessel endothelial cells, thereby exerting inhibitory activity on angiogenesis and tumor growth, in colorectal carcinoma. It is unknown whether SPARCL1 may exert these homeostatic functions in all organs and in other species. Therefore, SPARCL1 expression was comparatively analysed between humans and mice in a systematic manner. Murine Sparcl1 (mSparcl1) is most strongly expressed in the lung; expressed at an intermediate level in most organs, including the large intestine; and absent in the liver. In human tissues, SPARCL1 (hSPARCL1) was detected in all organs, with the strongest expression in the stomach, large intestine and lung, mostly consistent with the murine expression pattern. A striking difference between human and murine tissues was the absence of mSparcl1 expression in murine livers, while human livers showed moderate expression. Furthermore, mSparcl1 was predominantly associated with mural cells, whereas hSPARCL1 was detected in both mural and endothelial cells. Human SPARCL1 expression was downregulated in different carcinomas, including lung and colon cancers. In conclusion, this study revealed species-, organ- and cell-type-dependent expression of SPARCL1, suggesting that its function may not be similar between humans and mice.

Spectrum of peristomal Dermatoses - Dietmaier, Louisa; Summa, S.; Erfurt-Berge, Cornelia (JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, 2021)
CRIS-Team WoS Importer:2021-04-16

Spincter preservation after selective chemoradiotherapy of rectal cancer : Interim results of the OCUM study - Baral, J.; Schon, M. R.; Ruppert, R.; Ptok, H.; Strassburg, J.; Brosi, P.; Kreis, M. E.; Lewin, A.; Sauer, J.; Sawicki, S.; Schiffmann, L.; Winde, G.; et al. (Chirurg, 2015)
In a prospective multicenter observational study (OCUM) neoadjuvant chemoradiotherapy (nRCT) was selectively administered depending on the risk of local recurrence and based on the distance between tumor and mesorectal fascia in pretherapeutic high-resolution magnetic resonance imaging (MRI).Frequency and quality of abdominoperineal excision (APE) and sphincter preserving operations.Of 642 patients treated in 13 hospitals 389 received surgery alone and 253 nRCT followed by surgery. By univariate and multivariate analysis risk factors for APE were determined. Quality parameters were the quality grade of mesorectal excision, the pathohistological involvement of the circumferential resection margin and intraoperative local dissemination of tumor cells.In 12.8 % of the patients APE was performed. Independent risk factors for APE were tumor location in the lower third of the rectum and the individual hospitals, where APE varied between 0 and 32 %. This variation was chiefly caused by the different case mix. Hospitals with a high APE rate (> 30 %) treated significantly more patients with very low lying carcinomas (< 3 cm above the anal verge) and more advanced tumors. The median height of the tumor in cases of APE was nearly equal in all participating hospitals. Independent on the number of cases the quality of rectal surgery was high. Within the patient groups of primary surgery and nRCT the oncological quality parameter did not significantly differ between sphincter preservation and APE. As far as sphincter preservation is concerned the results justify a selective application of nRCT in patients with rectal carcinoma. The long-term results still have to be awaited.
EVALuna2:15215

Spontaneous Pneumothorax due to Ectopic Deciduosis: A Case Report - Dudek, Wojciech; Schreiner, Waldemar; Strehl, Johanna; Sirbu, Horia (Thoracic and Cardiovascular Surgeon Reports, 2014)
This report presents a 20-week pregnant 38-year-old woman with right-sided pneumothorax due to pulmonary deciduosis. Initial pleural drainage was ineffective. Video-assisted thoracoscopy revealed areas of consolidation within the lung parenchyma. A wedge resection with partial pleurectomy was performed. Histopathological examination showed subpleural decidual implants. The patient made a full recovery and was discharged on day 5. Videoscopic inspection of the lung parenchyma and pleura with resection of decidual foci is the recommended treatment for pneumothorax in pregnant women with pleuropulmonary deciduosis in whom classical pleural drainage is ineffective.
EVALuna2:25169

Spread through Air Spaces (STAS) in Solitary Pulmonary Metastases from Colorectal Cancer (CRC) - Haj Khalaf, Mohamed; Sirbu, Horia; Hartmann, Arndt; Agaimy, Abbas; Dudek, Wojciech; Higaze, Mostafa; Rieker, Ralf (Thoracic and Cardiovascular Surgeon, 2022)
Background Spread through air spaces (STAS) is a recently described route of tumor invasion associated with poor prognosis in primary lung cancer. Aim of this study was to investigate the presence of STAS and to assess its prognostic significance in patients undergoing pulmonary metastasectomy (PM) for solitary metastases from colorectal cancer (CRC). Materials and Methods All 49 CRC patients (30 male and 19 female, median age 66 years) who underwent PM between January 2008 and December 2015 were retrospectively analyzed. Results STAS was identified in 26.5% ( n = 13) of resected specimens. Location of pulmonary lesions (central vs. peripheral) was assessed based on the available computed tomography imaging ( n = 47, 96%). STAS was detected in all five patients with central metastases (100%) versus 7 of 42 (17%) with peripheral metastases ( p = 0.0001). Locoregional recurrence occurred in STAS-positive patients ( n = 4 of 13 vs. n = 0 of 36), all STAS-negative patients remained recurrence-free ( p = 0.003). Median number of alveoli with STAS involvement was four (range from 2 to 9). There was statistically positive relationship between the number of alveoli invaded with STAS and locoregional recurrence of metastases ( p = 0.0001). The presence of STAS is not a factor affecting the 5-year overall survival rate ( p = 0.6651). Conclusion We identified STAS as a frequent finding in resected CRC lung metastases and found insignificant association with outcome.
CRIS-Team WoS Importer:2022-10-28

Standardization of the Definition and Surgical Management of Splenic Flexure Carcinoma by an International Expert Consensus Using the Delphi Technique: Room for Improvement? - Benlice, Cigdem; Parvaiz, Amjad; Baca, Bilgi; Hohenberger, Werner; Miskovic, Danilo; Stocchi, Luca; Steele, Scott; Kim, Seon Hahn; Holm, Torbjörn; Spinelli, Antonino; Gogenur, Ismail; Panis, Yves; et al. (Diseases of the colon & rectum, 2023)
BACKGROUND: Surgical management of splenic flexure carcinoma remains controversial. OBJECTIVE: This study aimed to establish an expert international consensus on splenic flexure carcinoma management. DESIGN: A 3-round online-based Delphi study was conducted between September 2020 and April 2021. SETTING: The first round included 18 experts from 12 different countries. For the second and third rounds, each expert in the first round was asked to invite 2 more colorectal surgeons (n = 47). Out of 47 invited experts, 89% (n = 42) participated in the second and third rounds of the consensus. INTERVENTIONS: A total of 35 questions were created and sent via the online questionnaire tool. MAIN OUTCOME MEASURES: Levels of recommendation based on voting concordance were graded as follows: more than 75% agreement was defined as strong, between 50% and 75% as moderate, and below 50% as weak. RESULTS: There was moderate consensus on the definition of splenic flexure (55%) as 10 cm from either side where the distal transverse colon turns into the proximal descending colon. Also, experts recommended an abdominopelvic CT scan plus intraoperative exploration (moderate consensus, 72%) for tumor localization and cancer registry. Segmental colectomy was the preferred technique for the management of splenic flexure carcinoma in the elective setting (72%). Moderate consensus was achieved on the technique of complete mesocolic excision and central vascular ligation principles for splenic flexure carcinoma (74%). Only strong consensus was achieved on the surgical approach for minimally invasive surgery (88%). LIMITATIONS: Subjective decisions are based on individual expert clinical experience and not evidence based. CONCLUSIONS: This is the first internationally conducted Delphi consensus study regarding splenic flexure carcinoma. The definition of splenic flexure remains ambiguous. To more effectively compare oncologic outcomes among different cancer registries, guidelines need to be developed to standardize each domain and avoid arbitrary definitions. See Video Abstract at http://links.lww.com/DCR/C143 . ESTANDARIZACIN DE LA DEFINICIN Y MANEJO QUIRRGICO DEL CARCINOMA DE NGULO ESPLNICO ESTABLECIDO POR UN CONSENSO INTERNACIONAL DE EXPERTOS UTILIZANDO LA TCNICA DELPHI ESPACIO PARA MEJORAR: ANTECEDENTES:El tratamiento quirúrgico del cáncer de ángulo esplénico sigue siendo controvertido.OBJETIVO:Establecer un consenso internacional de expertos sobre el manejo del cáncer del ángulo esplénico.DISEÑO:Se condujo un estudio Delphi en línea de 3 rondas entre septiembre de 2020 y febrero de 2021.ESCENARIO:La primera ronda incluyó a 18 expertos de 12 países distintos. Para la segunda y tercera rondas, a cada experto de la primera ronda se le pidió que invitara a 2 cirujanos colorrectales más de su región (n = 47). De los 47 expertos invitados, el 89% (n = 42) participó en la segunda y tercera ronda del consenso.INTERVENCIONES:Se crearon y enviaron un total de 35 preguntas a través de la herramienta de cuestionario en línea.PRINCIPALES MEDIDAS DE RESULTADO:Los niveles de recomendación basados en la concordancia de votos fueron jerarquizados de la siguiente manera: más del 75% de acuerdo se definió como fuerte, entre 50 y 75% como moderado y por debajo del 50% como débil.RESULTADOS:Hubo un consenso moderado sobre la definición de ángulo esplénico (55%) como 10 cm desde cualquier lado donde el colon transverso distal se convierte en el colon descendente proximal. Así también, los expertos recomendaron la tomografía computarizada abdominopélvica más la exploración intraoperatoria (consenso moderado, 72%) para la localización del tumor y el registro del ángulo esplénico. La colectomía segmentaria fue la técnica preferida para el tratamiento del cáncer de ángulo esplénico en el caso de ser electivo (72%). Se logró un consenso moderado sobre la técnica de escisión completa del mesocolon y los principios de ligadura vascular a nivel central para el cáncer de ángulo esplénico (74%). Solo se logró un fuerte consenso sobre el abordaje quirúrgico para la cirugía mínimamente invasiva (88%).LIMITACIONES:Decisiones subjetivas basadas en la experiencia clínica de expertos individuales y no basadas en evidencia.CONCLUSIONES:Este es el primer estudio internacional de consenso Delphi realizado sobre el cáncer de ángulo esplénico. Si bien encontramos un consenso moderado sobre las modalidades de diagnóstico preoperatorio y el manejo quirúrgico, la definición de ángulo esplénico sigue siendo ambigua. Para comparar de manera más efectiva los resultados oncológicos entre diferentes registros de cáncer, se deben desarrollar pautas para estandarizar cada dominio y evitar definiciones arbitrarias. Consulte Video Resumen en http://links.lww.com/DCR/C143 . (Traducción-Dr. Osvaldo Gauto ).
CRIS-Team Scopus Importer:2023-06-02

STAT1 deficiency supports PD-1/PD-L1 signaling resulting in dysfunctional TNFα mediated immune responses in a model of NSCLC - Friedrich, Juliane; Heim, Lisanne; Trufa, Denis; Sirbu, Horia; Rieker, Ralf; Neurath-Finotto, Susetta; Chiriac, Mircea-Teodor (Oncotarget, 2018)
In this study we described that Signal Transducer and Activator of Transcription 1 (STAT1) is a key point regulator of PD-1 in tumour infiltrating lymphocytes and PD-L1 in Tumour associated macrophages (TAM) in NSCLC. In our murine model of adenocarcinoma targeted deletion of Stat1 was found associated with enhanced tumour growth, impaired differentiation into M1-like macrophages from the bone marrow, the accumulation of tumor associated macrophages overexpressing PD-L1 and impaired T cell responses in the tumor microenvironment by affecting TNFα responses. In our human NSCLC patient cohort we found that loss of isoforms STAT1 α and STAT1β mRNA in the tumoural region of the lung correlates with increased tumor size in NSCLC patients. Therefore, STAT1 isoform regulation could be considered for future therapeutical strategies associated to current immune-checkpoint blockade therapy in NSCLC.
EVALuna2:207415

STAT3 activation through IL-6/IL-11 in cancer-associated fibroblasts promotes colorectal tumour development and correlates with poor prognosis - Heichler, Christina; Scheibe, Kristina; Schmied, Anabel; Geppert, Carol-Immanuel; Schmid, Benjamin; Wirtz, Stefan; Thoma, Oana Maria; Kramer, Viktoria; Waldner, Maximilian; Büttner, Christian; Farin, Henner; Pešić, Marina; et al. (Gut, 2019)
Objective: Cancer-associated fibroblasts (CAFs) influence the tumour microenvironment and tumour growth. However, the role of CAFs in colorectal cancer (CRC) development is incompletely understood. Design: We quantified phosphorylation of STAT3 (pSTAT3) expression in CAFs of human colon cancer tissue using a tissue microarray (TMA) of 375 patients, immunofluorescence staining and digital pathology. To investigate the functional role of CAFs in CRC, we took advantage of two murine models of colorectal neoplasia and advanced imaging technologies. In loss-of-function and gain-of-function experiments, using genetically modified mice with collagen type VI (COLVI)-specific signal transducer and activator of transcription 3 (STAT3) targeting, we evaluated STAT3 signalling in fibroblasts during colorectal tumour development. We performed a comparative gene expression profiling by whole genome RNA-sequencing of fibroblast subpopulations (COLVI+ vs COLVI-) on STAT3 activation (IL-6 vs IL-11). Results: The analysis of pSTAT3 expression in CAFs of human TMAs revealed a negative correlation of increased stromal pSTAT3 expression with the survival of colon cancer patients. In the loss-of-function and gain-of-function approach, we found a critical role of STAT3 activation in fibroblasts in driving colorectal tumourigenesis in vivo. With different imaging technologies, we detected an expansion of activated fibroblasts in colorectal neoplasias. Comparative gene expression profiling of fibroblast subpopulations on STAT3 activation revealed the regulation of transcriptional patterns associated with angiogenesis. Finally, the blockade of proangiogenic signalling significantly reduced colorectal tumour growth in mice with constitutive STAT3 activation in COLVI+ fibroblasts. Conclusion: Altogether our work demonstrates a critical role of STAT3 activation in CAFs in CRC development.
CRIS-Team Scopus Importer:2019-11-19
Keywords: colorectal cancer

Sternal osteomyelitis - Surgical treatment concepts - Beier, Justus; Arkudas, Andreas; Lang, Werner; Weyand, Michael; Horch, Raymund E. (Chirurg, 2016)
Sternal osteomyelitis is a potentially fatal condition following cardiac surgery. Sternal osteomyelitis should be diagnosed as early as possible followed by an interdisciplinary radical debridement. Subsequently plastic reconstructive surgery is necessary for defect reconstruction. This can be achieved by a number of established pedicled and free flap plastic surgery procedures. The choice of flap procedures is based on defect geometry and the individual patient situation, including potential flap donor sites. Smaller defects can generally be reconstructed by pedicled flap transfer. For extensive sternal defects, free flap transplantation is now a well-established therapeutic option. In some patients lacking sufficient recipient vessels, the creation of an arteriovenous (AV) loop as recipient vessel is necessary. In summary, successful therapy of sternal osteomyelitis is based on early interdisciplinary treatment by the various surgical subspecialties.
EVALuna2:15235

Sternal resection and reconstruction for secondary malignancies - Dudek, Wojciech; Schreiner, Waldemar; Horch, Raymund E.; Sirbu, Horia (Journal of Thoracic Disease, 2018)
Background: Limited data on sternal and/or anterior chest wall resections for secondary malignancies exist. The purpose of this study was to examine the perioperative outcomes and postoperative overall survival (OS) in patients who underwent sternal and/or anterior chest wall resections for secondary sternal tumors (SSTs). Methods: A retrospective analysis of all patients who underwent resection of SSTs at single institution between 2000 and 2016 has been performed. OS was estimated using the Kaplan-Meier method. Results: Ten patients underwent sternal and/or anterior chest wall resection for SSTs with curative (70%) or palliative (30%) intent. Two (20%) patients underwent complete and 8 (80%) partial sternal and/or anterior chest wall resection. There were no perioperative deaths, major complications occurred in 3 (30%) patients. Tumor resection was complete (R0) in 5 (50%) patients. The 5-year OS rate was 40%. No OS difference in R0 vs. R1 resections was observed. Conclusions: Sternal and/or anterior chest wall resections for SSTs can be performed with low morbidity and mortality. Complete SST resection does not assure favorable OS. Sternal resections can be considered palliative treatment option in patients with stable stage IV disease with isolated sternal involvement.
EVALuna2:35731

Sternocostal dislocation following open correction of pectus excavatum-"stairway phenomenon": complication management by means of sternocostal locking titanium plate osteosynthesis - Schulz-Drost, Stefan; Syed, Julia; Besendörfer, Manuel; Carbon, Roman T. (Thoracic and Cardiovascular Surgeon, 2014)
Some open surgical methods describe complete sternocostal dissection with subsequent resynthesis. Lack of consolidation with painful sternocostal instability and retrosternal dislocation of sternal rib tips are possible complications.Seven patients with symptomatic unilateral sternocostal dislocation were included in this study. After diagnosis, confirmed by three-dimensional computed tomography (CT), patients underwent open surgery. All affected ribs were reset and fixed to the sternum with the aid of titanium implants.The patients had, on average, unilateral dislocation of 3.4 rib joints with 15.4 mm retrosternal dislocation, which was fixed with 2.3 plates. A titanium splint was also employed. The recurrent nature of the problem made procedures very time-consuming (average operation time: 3 hours 25 minutes). One patient suffered strong intraoperative bleeding requiring transfusion of blood products and access enlargement. Follow-up examinations showed high patient satisfaction (grade of 1.7; rating scale 1-6). Remaining rib instabilities were observed just as infrequently as were material failures. The sternocostal rib splint in the costal cartilage became loose and was removed. One patient exhibited a pectoral muscle asymmetry. No other complications were observed.The term "stairway phenomenon" describes the dislocation of sternocostal joints. Observed after open pectus excavatum correction it can trigger substantial physical complaints. Thus, preserving those joints during pectus repair is strongly recommended. Locking titanium plates are a safe alternative to sternocostal suture fixation and is characterized by high patient satisfaction.
EVALuna2:15685

Stimulation of the soluble guanylate cyclase (sGC) inhibits fibrosis by blocking non-canonical TGF? signalling - Beyer, Christian; Zenzmaier, Christoph; Palumbo-Zerr, Katrin; Mancuso, Rossella; Distler, Alfiya; Dees, Clara; Zerr, Pawel; Huang, Jingang; Maier, Christiane; Pachowsky, Milena; Friebe, Andreas; Sandner, Peter; et al. (Annals of the Rheumatic Diseases, 2015)
We have previously described the antifibrotic role of the soluble guanylate cyclase (sGC). The mode of action, however, remained elusive. In the present study, we describe a novel link between sGC signalling and transforming growth factor ? (TGF?) signalling that mediates the antifibrotic effects of the sGC.Human fibroblasts and murine sGC knockout fibroblasts were treated with the sGC stimulator BAY 41-2272 or the stable cyclic guanosine monophosphate (cGMP) analogue 8-Bromo-cGMP and stimulated with TGF?. sGC knockout fibroblasts were isolated from sGCI(fl/fl) mice, and recombination was induced by Cre-adenovirus. In vivo, we studied the antifibrotic effects of BAY 41-2272 in mice overexpressing a constitutively active TGF-?1 receptor.sGC stimulation inhibited TGF?-dependent fibroblast activation and collagen release. sGC knockout fibroblasts confirmed that the sGC is essential for the antifibrotic effects of BAY 41-2272. Furthermore, 8-Bromo-cGMP reduced TGF?-dependent collagen release. While nuclear p-SMAD2 and 3 levels, SMAD reporter activity and transcription of classical TGF? target genes remained unchanged, sGC stimulation blocked the phosphorylation of ERK. In vivo, sGC stimulation inhibited TGF?-driven dermal fibrosis but did not change p-SMAD2 and 3 levels and TGF? target gene expression, confirming that non-canonical TGF? pathways mediate the antifibrotic sGC activity.We elucidated the antifibrotic mode of action of the sGC that increases cGMP levels, blocks non-canonical TGF? signalling and inhibits experimental fibrosis. Since sGC stimulators have shown excellent efficacy and tolerability in phase 3 clinical trials for pulmonary arterial hypertension, they may be further developed for the simultaneous treatment of fibrosis and vascular disease in systemic sclerosis.
EVALuna2:12978

Stoma care in pyoderma gangrenosum - Summa, Scarlett; Hofmann, Gabriele; Erfurt-Berge, Cornelia (Coloproctology, 2021)
Pyoderma gangrenosum is a rare inflammatory skin disorder presenting with ulcerations. Peristomal pyoderma gangrenosum confronts the treating physician with diagnostic and therapeutic challenges. Pyoderma gangrenosum is often not recognized early enough but an interdisciplinary treatment approach should be initiated as soon as possible as wound care alone will not lead to healing of these skin alterations. Wound care in combination with stoma care is often difficult in these cases and with unreliable obturation of stoma and infiltration of the skin protection materials it is associated with impairments in the quality of life of the person affected. The aim of wound care is to protect the wound from stoma leakage and to ensure sufficient stoma care by changing the materials for stoma care at regular intervals.
CRIS-Team WoS Importer:2021-12-31

Strangulation and necrosis of right hemicolon as an extremely rare complication of Spigelian hernia - Velimezis, Georgios; Vassos, Nikolaos; Kapogiannatos, Georgios; Koronakis, Dimitrios; Salpiggidis, Christos; Perrakis, Evangelos; Perrakis, Aristotelis (Archives of Medical Science, 2016)
EVALuna2:15264

Structural proteins of Kaposi's sarcoma-associated herpesvirus antagonize p53-mediated apoptosis - Chudasama, Priya; Konrad, A.; Jochmann, R.; Lausen, Berthold; Holz, Patrick; Naschberger, Elisabeth; Neipel, Frank; Britzen-Laurent, Nathalie; Stürzl, Michael (Oncogene, 2015)
The tumor suppressor p53 is a central regulatory molecule of apoptosis and is commonly mutated in tumors. Kaposi's sarcoma-associated herpesvirus (KSHV)-related malignancies express wild-type p53. Accordingly, KSHV encodes proteins that counteract the cell death-inducing effects of p53. Here, the effects of all KSHV genes on the p53 signaling pathway were systematically analyzed using the reversely transfected cell microarray technology. With this approach we detected eight KSHV-encoded genes with potent p53 inhibiting activity in addition to the previously described inhibitory effects of KSHV genes ORF50, K10 and K10.5. Interestingly, the three most potent newly identified inhibitors were KSHV structural proteins, namely ORF22 (glycoprotein H), ORF25 (major capsid protein) and ORF64 (tegument protein). Validation of these results with a classical transfection approach showed that these proteins inhibited p53 signaling in a dose-dependent manner and that this effect could be reversed by small interfering RNA-mediated knockdown of the respective viral gene. All three genes inhibited p53-mediated apoptosis in response to Nutlin-3 treatment in non-infected and KSHV-infected cells. Addressing putative mechanisms, we could show that these proteins could also inhibit the transactivation of the promoters of apoptotic mediators of p53 such as BAX and PIG3. Altogether, we demonstrate for the first time that structural proteins of KSHV can counteract p53-induced apoptosis. These proteins are expressed in the late lytic phase of the viral life cycle and are incorporated into the KSHV virion. Accordingly, these genes may inhibit cell death in the productive and in the early entrance phase of KSHV infection.
EVALuna2:8221

Study protocol for an International Prospective Observational Cohort Study for Optimal Bowel Resection Extent and Central Radicality for Colon Cancer (T-REX study) - Shiozawa, Manabu; Ueno, Hideki; Shiomi, Akio; Kim, Nan Kyu; Kim, Jin Cheon; Tsarkov, Petr; Grützmann, Robert; Dulskas, Audrius; Liang, Jin Tung; Samalavičius, Narimantas; West, Nick; Sugihara, Kenichi (Japanese Journal of Clinical Oncology, 2021)
This is a prospective observational cohort study aiming to include 4000 patients with stages I to III colon cancer treated at 35 specialist institutions in Japan, South Korea, Germany, Russia, Lithuania and Taiwan. The anatomical distribution of lymph nodes and feeding arteries are investigated using surgical specimens according to pre-specified categorizing methods using intraoperative anatomical markings. Primary analyses are performed to identify the general principles of metastatic lymph node distribution in terms of its relation to the location of the primary tumor and feeding arteries. Secondary analyses will be used to estimate prognostic outcomes according to bowel resection length and central radicality and will be used to evaluate the quality of resected surgical specimens. Through in-depth lymph node mapping, standardized criteria for the definite area of 'regional' lymph node resection in routine surgical procedures can be identified, which is expected to contribute to international standardization in colon cancer surgery (ClinicalTrials.gov NCT02938481).
CRIS-Team Scopus Importer:2021-01-15
Keywords: bowel resection margin; complete mesocolic excision; D3 dissection; lymph node mapping; lymphadenectomy

Successful Generation of CD19 Chimeric Antigen Receptor T Cells from Patients with Advanced Systemic Lupus Erythematosus - Kretschmann, S.; Völkl, Simon; Reimann, Hannah; Krönke, Gerhard; Schett, Georg; Achenbach, Susanne; Lutzny-Geier, Gloria; Müller, Fabian; Mougiakakos, Dimitrios; Dingfelder, Janin; Flamann, Cindy; Hanssens, L.; et al. (Transplantation and Cellular Therapy, 2022)
Although it has been shown that the production of functional chimeric antigen receptor T cells is feasible in patients with B-cell malignancies, it is currently unclear whether sufficient amounts of functional autologous CAR T cells can be generated from patients with autoimmune diseases. Intrinsic T-cell abnormalities and T-cell–targeted immune suppression in patients with autoimmunity may hamper the retrieval of sufficient T cells and their transduction and expansion into CAR T cells. Patients with active systemic lupus erythematosus (SLE) underwent leukapheresis after tapering glucocorticoids and stopping T-cell–suppressive drugs. This material was used as source for manufacturing anti-CD19 CAR T-cell products (CAR) in clinical scale. Cells were transduced with a lentiviral anti-CD19 CAR vector and expanded under good manufacturing practice (GMP) conditions using a closed, semi-automatic system. Functionality of these CAR T cells derived from autoimmune patient cells was tested in vitro. Six SLE patients were analyzed. Leukapheresis could be successfully performed in all patients yielding sufficient T-cell numbers for clinical scale CAR T-cell production. In addition, CAR T cells showed high expansion rates and viability, leading to CAR T cells in sufficient doses and quality for clinical use. CAR T cells from all patients showed specific cytotoxicity against CD19+ cell lines in vitro. GMP grade generation of CD19 CAR T-cell products suitable for clinical use is feasible in patients with autoimmune disease.
CRIS-Team Scopus Importer:2022-12-23
Keywords: Chimeric antigen receptor; Systemic lupus erythematosus; T cells

Successful Long-term Treatment of Diversion Colitis with Topical Coconut Oil Application - Zundler, Sebastian; Dietz, Lisa; Matzel, Klaus E.; Geppert, Carol-Immanuel; Becker, Emily; Rath, Timo; Neurath, Markus; Atreya, Raja (American Journal of Gastroenterology, 2018)
CRIS-Team WoS Importer:2019-02-22

Successful Multidisciplinary Treatment with Secondary Metastatic Liver Resection after Downsizing by Palliative Second-Line Treatment of Colorectal Cancer: A Curative Option - Wein, Axel; Görtz, Rüdiger; Wolff, Kerstin; Ostermeier, Nicola; Busse, Daniel; Kremer, Andreas; Koch, Franz; Hagel, Alexander; Farnbacher, Michael; Kammerer, Ferdinand J.; Neurath, Markus; Grützmann, Robert; et al. (Case Reports in Oncology, 2016)
The prognostic outcome following progression after palliative first-line treatment for patients suffering from metastatic colorectal adenocarcinoma is generally poor. Long-term relapse-free survival with palliative second-line treatment may be achieved in only a limited number of individual cases.A 37-year-old patient presented with bilobar liver metastases of colon cancer confirmed by histology with wild-type K-RAS (exon 2). Due to progressive disease after eight cycles of first-line therapy with FOLFIRI plus cetuximab, second-line chemotherapy with modified FOLFOX4 (mFOLFOX4) plus bevacizumab was initiated. During four cycles of mFOLFOX4 plus bevacizumab (2 months), no higher-grade toxicity occurred. Liver MRI with contrast medium revealed downsizing of the segment II/III metastases, as well as regressive, small, faint, hardly definable lesions in segments VI and IVb. The interdisciplinary tumor board of the University of Erlangen thus decided to perform resection of the liver metastases. Segments II and III were resected, and the liver metastases in segments IVa and VI were excised (R0). Histopathology confirmed three of the R0-resected metastases to be completely necrotic, with residual scarring. As perioperative therapy, four additional cycles of mFOLFOX4 plus bevacizumab were administered postoperatively. No higher-grade toxicity was observed. Three years after the initial diagnosis, the patient is relapse free, professionally fully reintegrated, and has an excellent performance status.Patients suffering from metastatic colorectal cancer may benefit from multidisciplinary treatment with secondary metastatic liver resection after downsizing by palliative second-line treatment. In individual cases, patients may even have a curative treatment option, provided that close interdisciplinary collaboration exists.
EVALuna2:2220

Successful treatment of a patient with middle aortic syndrome and renovisceral involvement using aorto-aortic bypass: case report and review of recent literature - Meyer, Alexander; Kuefner, Michael A.; Schmid, Andrea; Heinz, Marco; Lang, Werner (Annals of Vascular Surgery, 2014)
Middle aortic syndrome (MAS), defined as localized abdominal or thoracic aortic hypoplasia, represents an extraordinary rare condition, often diagnosed in younger patients with severe renal hypertension. Etiology is divided into congenital and acquired causes (e.g., Takayasu disease). Because of its extremely unfavorable course, treatment of symptomatic patients is mandatory, whereas open surgery with aorto-aortic bypass or patch aortoplasty is considered the standard therapy. This report describes a case of a 19-year-old Macedonian woman presenting with MAS and renal hypertension who was successfully treated with aorto-aortic bypass, including reconstruction of both renal and the hepatic and superior mesenteric arteries, and reviews the current literature.
EVALuna2:14342

Successful treatment of COVID-19 infection with convalescent plasma in B-cell-depleted patients may promote cellular immunity - Kremer, Andreas E.; Kremer, Anita; Willam, Carsten; Völkl, Simon; Verhagen, Johan; Achenbach, Susanne; van der Meijden, Edith; Lang, Vanessa; Aigner, Michael; Maier, Clara; Tenbusch, Matthias; Korn, Klaus; et al. (European Journal of Immunology, 2021)
Treatment with convalescent plasma has been shown to be safe in coronavirus disease in 2019 (COVID-19) infection, although efficacy reported in immunocompetent patients varies. Nevertheless, neutralizing antibodies are a key requisite in the fight against viral infections. Patients depleted of antibody-producing B cells, such as those treated with rituximab (anti-CD20) for hematological malignancies, lack a fundamental part of their adaptive immunity. Treatment with convalescent plasma appears to be of general benefit in this particularly vulnerable cohort. We analyzed clinical course and inflammation markers of three B-cell-depleted patients suffering from COVID-19 who were treated with convalescent plasma. In addition, we measured serum antibody levels as well as peripheral blood CD38/HLA-DR-positive T-cells ex vivo and CD137-positive T-cells after in vitro stimulation with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-derived peptides in these patients. We observed that therapy with convalescent plasma was effective in all three patients and analysis of CD137-positive T-cells after stimulation with SARS-CoV-2 peptides showed an increase in peptide-specific T-cells after application of convalescent plasma. In conclusion, we here demonstrate efficacy of convalescent plasma therapy in three B-cell-depleted patients and present data that suggest that while application of convalescent plasma elevates systemic antibody levels only transiently, it may also boost specific T-cell responses.
CRIS-Team Scopus Importer:2021-09-17
Keywords: B-cell deficiency; convalescent plasma; COVID-19; SARS-CoV-2; T-cell immunity

Successful treatment of COVID-19 with convalescent plasma in B-cell depleted patients may promote cellular immunity - Kremer, Andreas; Kremer, Anita; Willam, Carsten; Verhagen, Johan; Achenbach, Susanne; Van Der Meiden, E.; Lang, Vanessa; Aigner, M.; Maier, Clara; Tenbusch, Matthias; Korn, Klaus; Lutzny-Geier, Gloria; et al. (ONCOLOGY RESEARCH AND TREATMENT, 2021)
CRIS-Team WoS Importer:2022-03-25

Surface anatomical landmarks for the location of posterior sacral foramina in sacral nerve stimulation - Povo, A.; Arantes, M.; Matzel, K. E.; Barbosa, Joselina; Ferreira, M. A.; Pais, D.; Rodriguez-Baeza, A. (Techniques in Coloproctology, 2016)
Sacral nerve stimulation is a common treatment for various pelvic floor disorders. It consists of the percutaneous introduction of electrodes through the posterior sacral foramina for therapeutic stimulation of the target sacral spinal nerve. The aim of our study was to determine the surface anatomical landmarks of the sacrum to facilitate identification of the posterior sacral foramina.This study was conducted on 20 human cadavers. The cadavers were placed in a prone position, and all the soft tissues of the sacral region were removed to allow exposure of the osseous structures. Different measurements were taken in relation to the posterior sacral foramina, the posterior superior iliac spine (PSIS) and the median sacral crest (MSC). A median coefficient of variation (CV) was determined.The diameter of the second sacral foramen showed the greatest variability. The distances between each individual foramen and the MSC had an acceptable variability (CV < 20%). In contrast, the distance between foramina had a high variability. The distance between PSIS and the second posterior sacral foramen was also found to have an acceptable variability (CV < 20%). However, the angle formed by an horizontal line between PSIS and a line between PSIS and S2 foramina had high variability.We found that the distance between sacral foramina and MSC is relatively constant while the distance between foramina and the relations between foramina and PSIS is highly variable. Detailed knowledge of the anatomy may facilitate electrode placement and is complementary to the regular use of fluoroscopy.
EVALuna2:15262

Surgeon experience affects outcome of forearm arteriovenous fistulae more than outcomes of upper-arm fistulae - Regus, Susanne; Almási-Sperling, Veronika; Rother, Ulrich; Meyer, Alexander; Lang, Werner (Journal of Vascular Access, 2017)
There is still an ongoing discussion about the influence of vascular surgeon experience on the immediate and long-term outcome of newly created arteriovenous fistula (AVF) for patients on hemodialysis (HD). The aim of this study was to compare failure and patency rates of AVF between experienced consultants and resident trainees with special focus on location of the anastomosis on the forearm or upper arm.Between November 2012 and September 2016, 159 patients (83 on HD and 76 preemptive) received an AVF (90 radiocephalic [RCAVF] on the forearm; 69 brachiocephalic [BCAVF] in the elbow) by two experienced vascular surgeons (group A; n = 74) or five residents in training with one-to-four years of experience (group B; n = 85). We compared the two groups for demographic and treatment data, immediate failures (IF), bleeding complications and patency rates.There were no significant differences in demographic data between the two groups. Vessel diameters were significantly lower for forearm compared to upper arm arteries (p = 0.026) and veins (p = 0.05). There was a significantly increased risk for IF in group B for RCAVF (p = 0.003), but not for BCAVF (p = 1.000). Furthermore, the cumulative primary patency was reduced in group B for RCAVF (p<0.001), but not for BCAVF (p = 0.899).Surgeon experience seems to have more influence on the immediate and long-term outcome of newly created forearm AVF compared to those located on the upper arm.
EVALuna2:15320

Surgery along the embryological planes for colon cancer: a systematic review of complete mesocolic excision - Gouvas, Nikolaos; Agalianos, Christos; Papaparaskeva, Kleio; Perrakis, Aristotelis; Hohenberger, Werner; Xynos, Evaghelos (International Journal of Colorectal Disease, 2016)
Complete mesocolic excision (CME) for colonic cancer offers a surgical specimen of higher quality, with higher number of lymph nodes compared to conventional colectomy. However, evidence on oncological outcomes is limited. The aim of the present study is to review recent literature and provide more information regarding the effect of CME colectomy on short- and long-term outcomes.PubMed and MEDLINE databases were searched, and articles in English reporting data on CME were reviewed. Intraoperative events; postoperative morbidity and mortality; histopathological characteristics, including macroscopic assessment, number, and status of retrieved lymph nodes; and oncological outcomes were the end-points.Thirty-two studies were analyzed. As regards the macroscopic assessment, a larger specimen (p = 0.02) that contains a higher number of lymph nodes (p < 0.00001) is acquired after CME. Two studies report a higher disease-free survival, in stage I and II and particularly in stage III disease after CME. CME by laparoscopy offers comparable outcomes, as regards intraoperative blood loss and immediate postoperative morbidity and mortality rates. Specimen quality is similar after either approach, for cancers located at the right and left colon, but not at the transverse colon.There is strong evidence that CME offers a longer central pedicle that contains more lymph nodes than conventional surgery for colon cancer. CME represents the surgical background for the maximum lymph node harvest, an important quality marker for the surgical outcome. However, and according to present data, there is limited evidence that colectomy in terms of CME leads to improved long-term oncological outcomes.
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Surgery for metastases, anatomical and ethical limits : Special aspect: oligometastases - Perrakis, Aristotelis; Juratli, T. A.; Hohenberger, Werner; Croner, R. S.; Schackert, G. (Chirurg, 2016)
The surgical resection of metastases is nowadays feasible in selected patients with multifocal metastatic disease due to the implementation of interdisciplinary multimodal therapeutic options. Anatomical limitations do not seem to represent obstacles which cannot be overcome because of the development of new surgical techniques. The cornerstone of the selection of patients is the correct staging diagnosis achieved through modern diagnostic tools; however, surgery alone does not always offer acceptable survival and recurrence-free rates. Furthermore, in every complex surgical procedure there is the risk of morbidity and mortality; therefore, parameters such as alternative therapeutic modalities, the individual situation of the patient and tumor biology have to be considered in order to make the correct selection of patients. This is one of the major future challenges and should never be driven by unfounded hopes and expectations of the patients. The same principle also applies for brain metastases, which represent the most common brain tumors. Approximately 70 % of patients with brain metastases have 1-3 lesions (oligometastases). Treatment is now individualized and the goal of therapy has shifted towards long-term survival (>= 24 months) and improved quality of life. Under this aspect surgery is one of the important treatment options, particularly in patients with a single metastasis or oligometastases. Furthermore, approximately 20 % of patients who have recurrent brain metastases, successfully undergo a complete resection of tumors and with a Karnofsky performance status (KPS) score > 70 show a long-term survival of >= 24 months.
EVALuna2:15224

Surgery for Pulmonary Metastases: Long-Term Survival in 281 Patients - Dudek, Wojciech; Schreiner, Waldemar; Haj Khalaf, Mohamed; Sirbu, Horia (Thoracic and Cardiovascular Surgeon, 2021)
Background Despite weak evidence, pulmonary metastasectomy (PM) is widely performed with intent to improve patient survival. Our single-institution analysis aims to evaluate outcomes and to identify factors influencing survival of patients undergoing PM for metastases from wide range of primary tumors.
CRIS-Team WoS Importer:2021-05-21

Surgery of colorectal lung metastases : Results of a survey in Germany - Dudek, Wojciech; Schreiner, Waldemar; Stapel, Philipp; Vassos, N.; Grützmann, Robert; Sirbu, Horia (Chirurg, 2017)
There is no evidence from randomized trials on the prognostic significance of pulmonary metastasectomy of colorectal cancer. The objective of this study was to assess the current criteria for indications, preoperative diagnostics and preferred operative techniques of pulmonary metastasectomy in Germany.An anonymous survey was carried out in 239 German centers performing thoracic surgery in October 2015.Chest computed tomography (CT, 98%), liver CT (62%), pelvis CT (39%) and fluorodeoxyglucose positron emission tomography (FDG-PET, 37%) were used by the respondents (65% of participants) for preoperative staging. Pulmonary metastasectomy was most commonly performed for solitary lung metastasis without extrathoracic disease (96%), >1 ipsilateral lung metastases without extrathoracic disease (94.8%), solitary lung metastasis with resectable hepatic metastases (92%) and resectable bilateral lung metastases without extrathoracic disease (91%). Of the respondents 95% performed open lung metastasectomy, 82% video-assisted thoracic surgery, 18% radiofrequency ablation, 53% used laser-assisted open resection and 46% indicated that there was no scientific consensus on pulmonary metastasectomy.The majority of respondents performed pulmonary metastasectomy for solitary and multiple, unilateral and bilateral lung metastases without extrathoracic disease and/or local recurrence of primary tumors. The coexistence of resectable liver metastases was not an absolute contraindication for surgery. Of the respondents 46% expressed the need for prospective randomized studies to improve the evidence on pulmonary metastasectomy for colorectal cancer.
EVALuna2:15251

Surgical anatomy of the rectum: a series of video tutorials – a video vignette - Wedel, Thilo; Gómez Ruiz, Marcos; Tou, Samson; Stelzner, Sigmar; Matzel, Klaus (Colorectal Disease, 2022)
CRIS-Team Scopus Importer:2022-12-23

Surgical and oncological outcome after extended lymph node dissection for carcinoma of the stomach and the esophagogastric junction: a retrospective analysis from an experienced single center - Raptis, Dimitrios; Maak, Matthias; Krautz, Christian; Merkel, Susanne; Brunner, Maximilian; Agaimy, Abbas; Hartmann, Arndt; Semrau, Sabine; Ott, Oliver; Fietkau, Rainer; Siebler, Jürgen; Grützmann, Robert; et al. (Archives of Medical Science, 2024)
Introduction: Gastric cancer remains the fourth leading cause of cancer-related death in Europe, while the proportion of adenocarcinomas of the esophagogastric junction has risen by more than one third over recent years. In 2018, 14,700 new cases of gastric cancer were estimated in Germany, while the 5-year relative survival rate is reported to be 33% for women and 30% for men; in the USA almost the same rate was reported, with 31% 5-year survival. Material and methods: Between 2001 and 2014, 590 patients with a diagnosis of gastric cancer underwent surgery in our institution, including 120 Siewert type II/III carcinomas of the esophagogastric junction. All patients underwent distal resection of the stomach, gastrectomy or total gastrectomy combined with transhiatal distal esophageal resection. All operations included D2-D3 lymph node dissection (LND). Data were recorded by the cancer registry of the department of surgery and analyzed retrospectively. Results: The patients were classified according to the TNM (UICC 2010) and Lauren classification. 29% of the patients underwent primary surgery and 31% received neoadjuvant therapy. The median number of harvested lymph nodes was 33 for patients diagnosed with gastric cancer, and 29 for esophagogastric adenocarcinomas, respectively. The anastomotic leak rate was 3%. In this study, the 5-year overall survival rate was 51% concerning gastric carcinomas, 44% for Siewert type II and 47% for Siewert III cancers of the esophagogastric junction. Conclusions: Increased survival with low complication rates were achieved after individualized and multimodal treatment concepts combined with consistently applied extended lymphadenectomy.
CRIS-Team Scopus Importer:2024-04-19
Keywords: D3 dissection; gastric cancer; Siewert II/III

Surgical approaches and oncological outcomes in the management of duodenal gastrointestinal stromal tumors (Gist) - Vassos, Nikolaos; Perrakis, Aristotelis; Hohenberger, Werner; Croner, Roland S. (Journal of Clinical Medicine, 2021)
Background: Duodenal gastrointestinal stromal tumors (GIST) are a rare subset of GIST. Their surgical management in this anatomically complex region consists of varied approaches, and the administration of imatinib mesylate (IM) has not been clarified. Methods: We retrospectively reviewed patients with duodenal GIST treated during a 10-year-period. We analysed the clinicopatho-logical characteristics and survival factors and evaluated the perioperative and long-term outcomes based on the extent of resection ((ocal-resection (LR) versus pancreaticoduodenectomy (PD)) and the IM-administration. The median follow-up period was 60 months (range, 12–140). Results: A total of thirteen patients (M:F = 7:6) with median age of 64 years (range, 42–77) underwent resection of duodenal GIST. Median tumor size was 5.2 cm (range, 1.5–13.3). Eight patients (61.5%) underwent LR and five patients (38.5%) PD. R0-resection was achieved in 92.5%. Neoadjuvant IM-therapy was administered in five patients leading to tumor downsizing and in 40% to less-extended resection. The PD group consisted of larger tumors with higher mitotic count, mostly located in D2 (p = 0.031). The PD group had longer operative time (p = 0.026), longer hospital stay (p = 0.016), and higher rate of postoperative complications (p = 0.128). The actuarial 1-, 3-, and 5-year overall survival were 92.5%, 84%, and 73.5%, respectively, whereas the disease-free survival rates at 1, 3, and 5 years were 91.5%, 83%, and 72%, respectively. A tendency towards increased risk of disease recurrence was demonstrated for patients with tumor >5 cm and high-risk potential. There was not statistic survival benefit for one or the other surgical approach. Conclusion: The type of resection depends on duodenal site of origin and tumor size. LR can be the treatment of choice for duodenal GIST whenever technically feasible. Recurrence of duodenal GIST is dependent on tumor biology rather than surgical approach. Administration of IM in neaodjuvant setting should be considered in cases with high-risk GIST scheduled for PD since it might facilitate less-extended resection.
CRIS-Team Scopus Importer:2021-10-22
Keywords: Duodenum; gastrointestinal stromal tumors; GIST; Imatinib; Surgery

Surgical fixation of sternal fractures: preoperative planning and a safe surgical technique using locked titanium plates and depth limited drilling - Schulz-Drost, Stefan; Oppel, Pascal; Grupp, Sina; Schmitt, Sonja; Carbon, Roman Th.; Mauerer, Andreas; Hennig, Friedrich; Buder, Thomas (Journal of Visualized Experiments, 2015)
Different ways to stabilize a sternal fracture are described in literature. Respecting different mechanisms of trauma such as the direct impact to the anterior chest wall or the flexion-compression injury of the trunk, there is a need to retain each sternal fragment in the correct position while neutralizing shearing forces to the sternum. Anterior sternal plating provides the best stability and is therefore increasingly used in most cases. However, many surgeons are reluctant to perform sternal osteosynthesis due to possible complications such as difficulties in preoperative planning, severe injuries to mediastinal organs, or failure of the performed method. This manuscript describes one possible safe way to stabilize different types of sternal fractures in a step by step guidance for anterior sternal plating using low profile locking titanium plates. Before surgical treatment, a detailed survey of the patient and a three dimensional reconstructed computed tomography is taken out to get detailed information of the fracture's morphology. The surgical approach is usually a midline incision. Its position can be described by measuring the distance from upper sternal edge to the fracture and its length can be approximated by the summation of 60 mm for the basis incision, the thickness of presternal soft tissue and the greatest distance between the fragments in case of multiple fractures. Performing subperiosteal dissection along the sternum while reducing the fracture, using depth limited drilling, and fixing the plates prevents injuries to mediastinal organs and vessels. Transverse fractures and oblique fractures at the corpus sterni are plated longitudinally, whereas oblique fractures of manubrium, sternocostal separation and any longitudinally fracture needs to be stabilized by a transverse plate from rib to sternum to rib. Usually the high convenience of a patient is seen during follow up as well as a precise reconstruction of the sternal morphology.
EVALuna2:15820

Surgical Indications for Diverticulitis in Germany: Are All Operations Justified? - Schildberg, C. W.; Schellerer, Vera; Croner, R.; Oberländer, H.; Hohenberger, Werner (Zentralblatt für Chirurgie, 2015)
Pathological changes of preexisting sigma diverticulosis into a state of sigma diverticulitis are possible. Treatment of sigma diverticulitis accounts for a significant proportion of emergency treatments in clinics. The number of patients treated for sigma diverticulitis has risen steadily in recent years. Although it can be observed that operated cases making 7 % compared with 14 % to all stationary admissions, there is a less marked increase. Nevertheless, the question should be clarified as to how high the proportion of complicated surgical cases is in relation to non-complicated cases. It is important to clarify, in this context, if each operation is justified or whether in some cases there is over-treatment.All data relating to Germany, were prospectively collected by the treating hospitals using the DRG and evaluated by the Federal Statistical Office. The treatment numbers from Erlangen were prospectively collected from the encrypted DRG and analysed retrospectively by the coding officer. The investigated period lasted from 2005 to 2010. To demonstrate some treatment options, the following possible forms of therapy were examined with reference to the Hansen/Stock classification.In Germany, about 40 % of stationary patients with sigma diverticulitis are treated surgically. It is striking that in about two thirds of all operated patients uncomplicated forms of diverticulitis were present. The remainder consisted of covered or free perforations. For these complicated forms, various treatment approaches have been established. Ultimately, in dependence of timing these are always surgically treated. In the milder forms the general indication for surgery has come into discussion as the recommendation for a surgical approach after the second relapse in the symptom-free interval is being questioned by several groups based on the age of the studies on which the recommendations are based.A significant increase in hospital admissions and surgically treated patients is demonstrated. Striking was that a closer analysis of data revealed that mainly non-complicated cases were surgically treated. This should be seen as a clear indication for an over-treatment. Therefore, possibly not all surgeries performed are justified. In the case of complicated forms, in consideration of various treatment paths, surgery is inevitable in most cases.
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Survival after radical completion dissection or observation for sentinel node metastasis in melanoma - Hohenberger, Werner (Strahlentherapie und Onkologie, 2017)
EVALuna2:15295

Survival analysis in rectal carcinoma after neoadjuvant chemoradiation: various methods with different results - Merkel, Susanne; Weber, Klaus; Göhl, Jonas; Agaimy, Abbas; Fietkau, Rainer; Hohenberger, Werner; Grützmann, Robert; Hermanek, Peter (International Journal of Colorectal Disease, 2017)
Survival is an important indicator of outcome quality in rectal carcinoma. The 5-year survival rate is the typical outcome measurement. In patients with neoadjuvant chemoradiation followed by curative surgery, 7 years of follow-up is recommended. Different methods of survival analysis lead to different results. Here, we compared four different methods.The data of 439 patients with rectal carcinoma treated with neoadjuvant chemoradiation followed by curative total mesorectal excision (TME) surgery between 1995 and 2010 were analysed. After stratifying by stage, relative survival (RS), cancer-related survival (CRS), overall survival (OS) and disease-free survival (DFS) were compared. In particular, the 3-year disease-free survival rate was compared to the 5- and 7-year overall survival rates.In the total cohort, the 5-year survival rates ranged from 90% (RS), over 84% (CRS) and 83% (OS) to 72% (DFS). Depending on the stage of disease, the differences between the 5-year survival rates varied between 10 and 32 percentage points. The differences were lowest in UICC stage y0 and highest in UICC stage yIV. The 3-year DFS-rate was always lower (worse) than the 5-year OS rate and higher (better) than the 7-year OS rate, with the exception of stage yIV.Comparisons of survival are only meaningful if the same methods are applied. The 3-year rate of DFS was always worse than the rate of 5-year OS. Therefore, the 3-year rate of DFS appears to be a useful surrogate indicator in rectal carcinoma treatment studies.
EVALuna2:6896

Survival and Prognostic Analysis after Pulmonary Metastasectomy for Head and Neck Cancer - Dudek, Wojciech; AlMoussa, Emad; Schreiner, Waldemar; Mantsopoulos, Konstantinos; Sirbu, Horia (Thoracic and Cardiovascular Surgeon, 2020)
BACKGROUND: There is no consensus on the value of pulmonary metastasectomy (PM) for head and neck cancer (HNC). The aim of our single-institution study was to evaluate outcomes and to examine factors influencing 5-year survival of patients undergoing resections for HNC lung metastases. METHODS: All HNC patients undergoing curative-intent PM between January 2008 and December 2018 were retrospectively analyzed. The impact of factors related to primary tumor, metastases, and associated therapy on patient survival was evaluated using the univariable Cox proportional hazard model. Cutoff values of continuous variables were determined by a receiver operating characteristic analysis. RESULTS: In total, 44 patients (32 males and 12 females, with a median age of 65 years) underwent PM for metastatic HNC. There was one perioperative death, and major complications occurred in 2 (4.5%) patients. The median interval between the treatment of primary tumor and PM was 19.4 months (range: 0-151 months). Median size of the largest resected pulmonary lesion was 1.3 cm (range: 0.3-6.9 cm). Mean follow-up was 21 months (range: 0-123 months), and 5-year overall survival (OS) rate after the first PM was 41%. Resection was complete (R0) in all patients. Larger size of pulmonary metastasis (≥1.4 cm; hazard ratio: 4.49; 95% confidence interval: 1.79-11.27) was a significantly negative prognostic factor. CONCLUSION: Despite the lack of randomized controlled trials, PM for HNC is a reasonable therapeutic option with favorable survival in a selected population. In patients with larger pulmonary lesions, shorter OS after PM is to be expected.
CRIS-Team Scopus Importer:2020-06-30

Survival-associated factors and a prognostic nomogram in resected pancreatic cancer: A large international population-based cohort study - Huang, L.; Balavarca, Y.; Van Der Geest, L.; Lemmens, V.; Van Eycken, L.; De Schutter, H.; Johannesen, T. B.; Zadnik, V.; Primic-Zakelj, M.; Magi, M.; Grützmann, Robert; Besselink, M. G.; et al. (ANNALS OF ONCOLOGY, 2018)
CRIS-Team WoS Importer:2019-03-08

Survival outcome and prognostic factors after pancreatoduodenectomy for distal bile duct carcinoma: a retrospective multicenter study - Petrova, Ekaterina; Rueckert, Felix; Zach, Sebastian; Shen, Yinfeng; Weitz, Juergen; Grützmann, Robert; Wittel, Uwe A.; Makowiec, Frank; Hopt, Ulrich T.; Bronsert, Peter; Kuehn, Florian; Rau, Bettina M.; et al. (Langenbecks Archives of Surgery, 2017)
Pancreatoduodenectomy is the most common operative procedure performed for distal bile duct carcinoma. Data on outcome after surgery for this rare malignancy is scarce, especially from western countries. The purpose of this study is to explore the prognostic factors and outcome after pancreatoduodenectomy for distal bile duct carcinoma.Patients receiving pancreatoduodenectomy for distal bile duct carcinoma were identified from institutional databases of five German and one Russian academic centers for pancreatic surgery. Univariable and multivariable general linear model, Kaplan-Meier method, and Cox regression were used to identify prognostic factors for postoperative mortality and overall survival.N = 228 patients operated from 1994 to 2015 were included. Reoperation (OR 5.38, 95%CI 1.51-19.22, p = 0.010), grade B/C postpancreatectomy hemorrhage (OR 3.73, 95%CI 1.13-12.35, p = 0.031), grade B/C postoperative pancreatic fistula (OR 4.29, 95%CI 1.25-14.72, p = 0.038), and advanced age (OR 4.00, 95%CI 1.12-14.03, p = 0.033) were independent risk factors for in-hospital mortality in multivariable analysis. Median survival was 29 months, 5-year survival 27%. Positive resection margin (HR 2.07, 95%CI 1.29-3.33, p = 0.003), high tumor grade (HR 1.71, 95%CI 1.13-2.58, p = 0.010), lymph node (HR 1.68, 95%CI 1.13-2.51, p = 0.011), and distant metastases (HR 2.70, 95%CI 1.21-5.58, p = 0.014), as well as severe non-fatal postoperative complications (HR 1.64, 95%CI 1.04-2.58, p = 0.033) were independent negative prognostic factors for survival in multivariable analysis.Distant metastases and positive resection margin are the strongest negative prognostic factors for survival after pancreatoduodenectomy for distal bile duct carcinoma; thus, surgery with curative intent is only warranted in patients with local disease, where R0 resection is feasible.
EVALuna2:15301

Survival outcome following surgical versus non-surgical treatment of colorectal lung metastasis—a retrospective cohort study - Denz, Axel; Hahn, Veronika; Weber, Klaus; Weber, Georg; Grützmann, Robert; Krautz, Christian; Brunner, Maximilian (Langenbecks Archives of Surgery, 2024)
Purpose: The optimal management of colorectal lung metastases (CRLM) is still controversial. The aim of this study was to compare surgical and non-surgical treatment for CRLM regarding the prognostic outcome. Methods: This retrospective single-center cohort study included 418 patients, who were treated from January 2000 to December 2018 at a German University Hospital due to their colorectal carcinoma and had synchronous or metachronous lung metastases. Patients were stratified according the treatment of the CRLM into two groups: surgical resection of CRLM versus no surgical resection of CRLM. The survival from the time of diagnosis of lung metastasis was compared between the groups. Results: Two- and 5-year overall survival (OS) from the time of diagnosis of lung metastasis was 78.2% and 54.6%, respectively, in our cohort. Patients undergoing pulmonary metastasectomy showed a significantly better 2- and 5-year survival compared to patients with non-surgical treatment (2-year OS: 98.1% vs. 67.9%; 5-year OS: 81.2% vs. 28.8%; p < 0.001). Multivariate Cox regression revealed the surgical treatment (HR 4.51 (95% CI = 2.33–8.75, p < 0.001) and the absence of other metastases (HR 1.79 (95% CI = 1.05–3.04), p = 0.032) as independent prognostic factors in patients with CRLM. Conclusion: Our data suggest that patients with CRLM, who qualify for surgery, benefit from surgical treatment. Randomized controlled trials are needed to confirm our findings. Clinical trial registry number: The work has been retrospectively registrated at the German Clinical Trial Registry (DRKS00032938).
CRIS-Team Scopus Importer:2024-04-26
Keywords: Colorectal carcinoma; Lung metastases; Non-surgical treatment; Outcome; Overall survival; Surgical resection

Symptoms in Pectus Deformities: A Scoring System for Subjective Physical Complaints - Ewert, Franziska; Syed, Julia; Kern, Sonja; Besendörfer, Manuel; Carbon, Roman T.; Schulz-Drost, Stefan (Thoracic and Cardiovascular Surgeon, 2017)
Background The literature is silent on the relationship between symptoms and the Haller index. Nor is there a classification of the severity of the physical complaints. Materials and Methods Retrospectively, data from 128 patients (102 funnel, 25 pigeon chest patients, and 1 mixed type) were evaluated. To objectify the symptoms, we developed a score to describe the level of physical ailments. This score includes 10 different symptoms as well as the situation or frequency in which they occur and an impact factor. This depends on how much they affect everyday life. Results Pectus excavatum patients express physical complaints more frequently than pectus carinatum patients who actually suffer more from psychological stress. We could not find a correlation between the Haller index and symptoms or levels of ailment. Conclusion Pectus deformities are likely to cause physical and psychological complaints. Since the subjective symptoms did not show any correlation to the chest severity index, they are supposed to be independent from the deformity's extent.
EVALuna2:35787

Systems biology of the IMIDIA biobank from organ donors and pancreatectomised patients defines a novel transcriptomic signature of islets from individuals with type 2 diabetes - Solimena, Michele; Schulte, Anke M.; Marselli, Lorella; Ehehalt, Florian; Richter, Daniela; Kleeberg, Manuela; Mziaut, Hassan; Knoch, Klaus Peter; Parnis, Julia; Bugliani, Marco; Siddiq, Afshan; Jörns, Anne; et al. (Diabetologia, 2017)
Pancreatic islet beta cell failure causes type 2 diabetes in humans. To identify transcriptomic changes in type 2 diabetic islets, the Innovative Medicines Initiative for Diabetes: Improving beta-cell function and identification of diagnostic biomarkers for treatment monitoring in Diabetes (IMIDIA) consortium ( www.imidia.org ) established a comprehensive, unique multicentre biobank of human islets and pancreas tissues from organ donors and metabolically phenotyped pancreatectomised patients (PPP).Affymetrix microarrays were used to assess the islet transcriptome of islets isolated either by enzymatic digestion from 103 organ donors (OD), including 84 non-diabetic and 19 type 2 diabetic individuals, or by laser capture microdissection (LCM) from surgical specimens of 103 PPP, including 32 non-diabetic, 36 with type 2 diabetes, 15 with impaired glucose tolerance (IGT) and 20 with recent-onset diabetes (<1 year), conceivably secondary to the pancreatic disorder leading to surgery (type 3c diabetes). Bioinformatics tools were used to (1) compare the islet transcriptome of type 2 diabetic vs non-diabetic OD and PPP as well as vs IGT and type 3c diabetes within the PPP group; and (2) identify transcription factors driving gene co-expression modules correlated with insulin secretion ex vivo and glucose tolerance in vivo. Selected genes of interest were validated for their expression and function in beta cells.Comparative transcriptomic analysis identified 19 genes differentially expressed (false discovery rate <=0.05, fold change >=1.5) in type 2 diabetic vs non-diabetic islets from OD and PPP. Nine out of these 19 dysregulated genes were not previously reported to be dysregulated in type 2 diabetic islets. Signature genes included TMEM37, which inhibited Ca2+-influx and insulin secretion in beta cells, and ARG2 and PPP1R1A, which promoted insulin secretion. Systems biology approaches identified HNF1A, PDX1 and REST as drivers of gene co-expression modules correlated with impaired insulin secretion or glucose tolerance, and 14 out of 19 differentially expressed type 2 diabetic islet signature genes were enriched in these modules. None of these signature genes was significantly dysregulated in islets of PPP with impaired glucose tolerance or type 3c diabetes.These studies enabled the stringent definition of a novel transcriptomic signature of type 2 diabetic islets, regardless of islet source and isolation procedure. Lack of this signature in islets from PPP with IGT or type 3c diabetes indicates differences possibly due to peculiarities of these hyperglycaemic conditions and/or a role for duration and severity of hyperglycaemia. Alternatively, these transcriptomic changes capture, but may not precede, beta cell failure.
EVALuna2:15297

T17b murine embryonal endothelial progenitor cells can be induced towards both proliferation and differentiation in a fibrin matrix - Bleiziffer, Oliver; Horch, Raymund E.; Hammon, Matthias; Arkudas, Andreas; Naschberger, Elisabeth; Rath, Subha; Pryymachuk, Galyna; Beier, Justus; Hatzopoulos, Antonis K.; Stürzl, Michael; Kneser, Ulrich (Journal of Cellular and Molecular Medicine, 2009)
Endothelial progenitor cells (EPC) may enhance blood vessel formation in a variety of clinical settings such as ischaemia and tumour angiogenesis as well as in tissue-engineered matrices. In the present study, we cultured a murine endothelial progenitor cell line, T17b, in vitro in cell culture as well as in an FDA-approved fibrin matrix and investigated cell proliferation, differentiation and secretion patterns of the angiogenic growth factor VEGF under hypoxia and differentiation. We show that T17b EPC remain viable for at least 8 days in the fibrin matrix where they proliferate and form clusters including lumen-like structures. Proliferation in fibrin clots overlayed with basal medium (BM) was confirmed morphologically and immunohistochemically by positive Ki67 staining, indicating mitotic activity. Significant cell proliferation and Ki-67 expression were absent when cells were incubated with dibutyryl-cAMP and retinoic acid (RA). Incubation with dibutyryl-cAMP and RA stimulated the expression of the EPC differentiation markers von Willebrand Factor (vWF) and VEGF receptor 2 (VEGFR-2), indicating successful differentiation in the fibrin clot. EPC differentiation induced by dibutyryl-cAMP and RA was confirmed in 2-D chamber slide cultures by positive vWF immunostaining, which was absent in BM controls. EPC chamber slides also displayed positive vWF staining when exposed to hypoxia under BM conditions, indicating EPC activation and differentiation could also be induced by hypoxia. Taken together, T17b EPC secrete increased levels of VEGF when submitted to either hypoxia or differentiation and can be differentiated into mature endothelial cells not only in cell and matrigel cultures but also in a fibrin matrix that is FDA approved for clinical application. © 2009 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.
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Keywords: Angiogenesis; Embryonal endothelial progenitor cells; Tissue engineering

Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer - Dreyer, Stephan B.; Upstill-Goddard, Rosie; Paulus-Hock, Viola; Paris, Clara; Lampraki, Eirini Maria; Dray, Eloise; Serrels, Bryan; Caligiuri, Giuseppina; Rebus, Selma; Plenker, Dennis; Galluzzo, Zachary; Brunton, Holly; et al. (Gastroenterology, 2021)
Background & Aims: Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress, and novel therapeutic response in PC to develop a biomarker-driven therapeutic strategy targeting DDR and replication stress in PC. Methods: We interrogated the transcriptome, genome, proteome, and functional characteristics of 61 novel PC patient–derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient-derived xenografts and human PC organoids. Results: Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors, including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, cosegregates with response to platinum (P <.001) and PARP inhibitor therapy (P <.001) in vitro and in vivo. We generated a novel signature of replication stress that predicts response to ATR (P <.018) and WEE1 inhibitor (P <.029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P <.001) but was not associated with DDR deficiency. Conclusions: Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR-proficient PC and after platinum therapy.
CRIS-Team Scopus Importer:2020-12-25
Keywords: DNA Damage Response; Pancreatic Cancer; Personalized Medicine; Replication Stress

Targeting Muscular Hemoglobin Content for Classification of Peripheral Arterial Disease by Noninvasive Multispectral Optoacoustic Tomography - Günther, Josefine; Knieling, Ferdinand; Träger, Anna P.; Lang, Werner; Meyer, Alexander; Regensburger, Adrian; Wagner, Alexandra; Trollmann, Regina; Wölfle, Joachim; Klett, Daniel; Uter, Wolfgang; Uder, Michael; et al. (Journal of the American College of Cardiology : Cardiovascular imaging, 2023)
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Targeting platelet-neutrophil interaction in experimental bacteremia - Wohlgemuth, L.; Traut, R.; Hagemann, B.; Knapp, C. L.; Mueller, P.; Stukan, L.; Huber-Lang, M.; Messerer, David Alexander Christian (EUROPEAN JOURNAL OF IMMUNOLOGY, 2022)
CRIS-Team WoS Importer:2023-01-27

T-cell subsets in autologous and allogeneic peripheral blood stem cell concentrates - Strobel, Joachim; Möllmer, Ina; Zingsem, Jürgen; Hauck-Dlimi, Barbara; Eckstein, Reinhold; Strasser, Erwin (Vox Sanguinis, 2015)
Regulatory T cells (Tregs) and other T-cell subsets are of importance in the setting of autologous and allogeneic stem cell transplantations. We conducted a study to assess the content of peripheral blood stem cell concentrates and related apheresis parameters in the autologous and allogeneic setting.We characterized 53 donors, patients and peripheral blood stem cell concentrates (PBSC) regarding the content of CD45(+) cells, lymphocytes, CD3(+) cells, CD3(+) CD4(+) T cells, CD3(+) CD4(+) CD25(+) T cells, CD3(+) CD4(+) CD25(+) CD127(low/negative) Tregs and CD34(+) cells and calculated cell yields, recruitment factors and collection efficiency for all cell types. We compared allogeneic data with autologous data.Autologous PBSC show significantly lower concentrations of T-cell subsets compared to allogeneic PBSC (17,112/?l CD4(+), 14,858/?l CD4(+) CD25(+) and 1579/?l CD3(+) CD4(+) CD25(+) CD127(low/negative) Tregs in autologous compared to 65,539/?l CD4(+), 44,208(+) /?l CD4(+) CD25(+) and 5040/?l CD3(+) CD4(+) CD25(+) CD127(low/negative) Tregs in allogeneic PBSC, respectively), in contrast to CD34(+) concentrations (5342/?l CD34(+) in autologous compared to 2367/?l CD34(+) in allogeneic PBSC, respectively). Accordantly, all T-cell yields are lower in the autologous setting compared to allogeneic PBSC. However, recruitment factor and collection efficiency of all cell types are higher in autologous compared to allogeneic PBSC, but not all parameters differ significantly when groups are compared.T-cell subsets and especially Tregs are a substantial part of PBSC transplantation, as considerable recruitment during apheresis occurs. In large volume apheresis, the collection efficiency of Treg is comparable to that of CD34(+) cells, while recruitment factors are even higher.
EVALuna2:15982

Teachability of multispectral optoacoustic tomography - Li, Yi; Gröhl, Janek; Haney, Briain; Caranovic, Milenko; Lorenz-Meyer, Eva; Papatheodorou, Nikolaos; Kempf, Julius; Regensburger, Adrian; Nedoschill, Emmanuel; Bühler, Adrian; Siebenlist, Gregor; Lang, Werner; et al. (Journal of Biophotonics, 2024)
To date, the appropriate training required for the reproducible operation of multispectral optoacoustic tomography (MSOT) is poorly discussed. Therefore, the aim of this study was to assess the teachability of MSOT imaging. Five operators (two experienced and three inexperienced) performed repositioning imaging experiments. The inexperienced received the following introductions: personal supervision, video meeting, or printed introduction. The task was to image the exact same position on the calf muscle for seven times on five volunteers in two rounds of investigations. In the first session, operators used ultrasound guidance during measurements while using only photoacoustic data in the second session. The performance comparison was carried out with full-reference image quality measures to quantitatively assess the difference between repeated scans. The study demonstrates that given a personal supervision and hybrid ultrasound real-time imaging in MSOT measurements, inexperienced operators are able to achieve the same level as experienced operators in terms of repositioning accuracy.
CRIS-Team Scopus Importer:2024-05-17
Keywords: MSOT; multispectral optoacoustic imaging; teachability; ultrasound

Technical considerations for isolated limb perfusion: A consensus paper - Hayes, Andrew J.; Coker, David J.; Been, Lukas; Boecxstaens, Veerle WSM; Bonvalot, Sylvie; De Cian, Franco; de la Cruz-Merino, Luis; Duarte, Carlos; Eggermont, Alexander; Farricha, Victor; Fiore, Marco; Grünhagen, Dirk; et al. (Ejso, 2024)
Background: Isolated limb perfusion (ILP) is a well-established surgical procedure for the administration of high dose chemotherapy to a limb for the treatment of advanced extremity malignancy. Although the technique of ILP was first described over 60 years ago, ILP is utilised in relatively few specialist centres, co-located with tertiary or quaternary cancer centres. The combination of high dose cytotoxic chemotherapy and the cytokine tumour necrosis factor alpha (TNFα), mandates leakage monitoring to prevent potentially serious systemic toxicity. Since the procedure is performed at relatively few specialist centres, an ILP working group was formed with the aim of producing technical consensus guidelines for the procedure to streamline practice and to provide guidance for new centres commencing the technique. Methods: Between October 2021 and October 2023 a series of face to face online and hybrid meetings were held in which a modified Delphi process was used to develop a unified consensus document. After each meeting the document was modified and recirculated and then rediscussed at subsequent meeting until a greater than 90% consensus was achieved in all recommendations. Results: The completed consensus document comprised 23 topics in which greater than 90% consensus was achieved, with 83% of recommendations having 100% consensus across all members of the working group. The consensus recommendations covered all areas of the surgical procedure including pre-operative assessment, drug dosing and administration, perfusion parameters, hyperthermia, leakage monitoring and theatre logistics, practical surgical strategies and also post-operative care, response evaluation and staff training. Conclusion: We present the first joint expert-based consensus statement with respect to the technical aspects of ILP that can serve as a reference point for both existing and new centres in providing ILP.
CRIS-Team Scopus Importer:2024-04-05

Temporärer Bauchdeckenverschluss bei Laparostoma - Wolff, Stefanie; Haupt, Werner; Croner, R. (Chirurgische Praxis, 2019)
Laparostomy is used in the treatment of abdominal compartment syndrome, abdominal trauma and severe persisting peritonitis. Since the open abdomen can lead to major surgical complications, the closure of the abdominal fascia should be achieved as soon as possible. Often a temporary closure technique has to be applied prior to definitive abdominal closure. Currently, the vacuum-assisted closure therapy is recommended for temporary abdominal closure. However, contraindication should be considered. Patients who are treated with open abdomen show an increased risk of ventral hernia and intestinal fistulas as well as an elevated mortality rate of 30 %.
CRIS-Team Scopus Importer:2021-04-20
Keywords: Abdominal compartment syndrome; Open abdomen; Temporary abdominal closure

Temporarily Transfixation of the distal interphalangeal Joint in Mallet fingers - Suffa, Nadine; Merkel, Pauline; Horch, Raymund E.; Arkudas, Andreas; Ludolph, Ingo; Stumpfe, Maximilian Christoph (Handchirurgie, Mikrochirurgie, Plastische Chirurgie, 2021)
Zusammenfassung
CRIS-Team WoS Importer:2021-10-08

Ten recommendations for sarcoma surgery: consensus of the surgical societies based on the German S3 guideline “Adult Soft Tissue Sarcomas” - Jakob, Jens; Andreou, Dimosthenis; Bedke, Jens; Denschlag, Dominik; Dürr, Hans Roland; Frese, Steffen; Gösling, Thomas; Graeter, Thomas; Grünwald, Viktor; Grützmann, Robert; Hoffmann, Jürgen; Juhasz-Boess, Ingolf; et al. (Langenbecks Archives of Surgery, 2023)
Purpose: The evidence-based (S3) guideline “Adult Soft Tissue Sarcomas” (AWMF Registry No. 032/044OL) published by the German Guideline Program in Oncology (GGPO) covers all aspects of sarcoma treatment with 229 recommendations. Representatives of all medical specialties involved in sarcoma treatment contributed to the guideline. This paper compiles the most important recommendations for surgeons selected by delegates from the surgical societies. Methods: A Delphi process was used. Delegates from the surgical societies involved in guideline process selected the 15 recommendations that were most important to them. Votes for similar recommendations were tallied. From the resulting ranked list, the 10 most frequently voted recommendations were selected and confirmed by consensus in the next step. Results: The statement “Resection of primary soft tissue sarcomas of the extremities should be performed as a wide resection. The goal is an R0 resection” was selected as the most important term. The next highest ranked recommendations were the need for a preoperative biopsy, performing preoperative MRI imaging with contrast, and discussing all cases before surgery in a multidisciplinary sarcoma committee. Conclusion: The evidence-based guideline “Adult Soft Tissue Sarcomas” is a milestone to improve the care of sarcoma patients in Germany. The selection of the top ten recommendations by surgeons for surgeons has the potential to improve the dissemination and acceptance of the guideline and thus improve the overall outcome of sarcoma patients.
CRIS-Team Scopus Importer:2023-07-21
Keywords: Delphi process; Evidence; Sarcoma guideline; Surgical recommendation

Tetramerization of human guanylate-binding protein 1 is mediated by coiled-coil formation of the C-terminal α-helices - Syguda, Adrian; Bauer, Michael; Benscheid, Utz; Ostler, Nicole; Naschberger, Elisabeth; Ince, Semra; Stürzl, Michael; Herrmann, Christian (Febs Journal, 2012)
The human guanylate-binding protein 1 (hGBP1) is a large GTP-binding protein belonging to the dynamin family, a common feature of which is nucleotide-dependent assembly to homotypic oligomers. Assembly leads to stimulation of GTPase activity, which, in the case of dynamin, is responsible for scission of vesicles from membranes. By yeast two-hybrid and biochemical experiments we addressed intermolecular interactions between all subdomains of hGBP1 and identified the C-terminal subdomain, α12/13, as a new interaction site for self-assembly. α12/13 represents a stable subdomain of hGBP1, as shown by CD spectroscopy. In addition to contacts between GTPase domains leading to dimer formation, the interaction between two α12/13 subdomains, in the course of GTP hydrolysis, results in tetramer formation of the protein. With the help of CD spectroscopy we showed coiled-coil formation of two α12/13 subdomains and concentration-dependent measurements allow estimating a value for the dissociation constant of 7.3 μm. We suggest GTP hydrolysis-driven release of the α12/13 subdomain, making it available for coiled-coil formation. Furthermore, we can demonstrate the biological relevance of hGBP1 tetramer formation in living cells by chemical cross-link experiments. © 2012 FEBS.
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Keywords: aluminum fluoride; dynamin; protein dimer; protein-protein association; self-assembly

Th17 Cell-Mediated Colitis Is Positively Regulated by Interferon Regulatory Factor 4 in a T Cell-Extrinsic Manner - Buchele, Vera; Konein, Patrick; Vogler, Tina; Kunert, Timo; Enderle, Karin; Khan, Hanif; Büttner-Herold, Maike; Lehmann, Christian; Amon, Lukas; Wirtz, Stefan; Dudziak, Diana; Neurath, Markus; et al. (Frontiers in Immunology, 2021)
Inflammatory bowel diseases (IBDs) are characterized by chronic, inflammatory gastrointestinal lesions and often require life-long treatment with immunosuppressants and repetitive surgical interventions. Despite progress in respect to the characterization of molecular mechanisms e.g. exerted by TNF-alpha, currently clinically approved therapeutics fail to provide long-term disease control for most patients. The transcription factor interferon regulatory factor 4 (IRF4) has been shown to play important developmental as well as functional roles within multiple immune cells. In the context of colitis, a T cell-intrinsic role of IRF4 in driving immune-mediated gut pathology is established. Here, we conversely addressed the impact of IRF4 inactivation in non-T cells on T cell driven colitis in vivo. Employing the CD4+CD25− naïve T cell transfer model, we found that T cells fail to elicit colitis in IRF4-deficient compared to IRF4-proficient Rag1−/− mice. Reduced colitis activity in the absence of IRF4 was accompanied by hampered T cell expansion both within the mesenteric lymph node (MLN) and colonic lamina propria (cLP). Furthermore, the influx of various myeloids, presumably inflammation-promoting cells was abrogated overall leading to a less disrupted intestinal barrier. Mechanistically, gene profiling experiments revealed a Th17 response dominated molecular expression signature in colon tissues of IRF4-proficient, colitic Rag1−/− but not in colitis-protected Rag1−/−Irf4−/− mice. Colitis mitigation in Rag1−/−Irf4−/− T cell recipients resulted in reduced frequencies and absolute numbers of IL-17a-producing T cell subsets in MLN and cLP possibly due to a regulation of conventional dendritic cell subset 2 (cDC2) known to impact Th17 differentiation. Together, extending the T cell-intrinsic role for IRF4 in the context of Th17 cell driven colitis, the provided data demonstrate a Th17-inducing and thereby colitis-promoting role of IRF4 through a T cell-extrinsic mechanism highlighting IRF4 as a putative molecular master switch among transcriptional regulators driving immune-mediated intestinal inflammation through both T cell-intrinsic and T cell-extrinsic mechanisms. Future studies need to further dissect IRF4 controlled pathways within distinct IRF4-expressing myeloid cell types, especially cDC2s, to elucidate the precise mechanisms accounting for hampered Th17 formation and, according to our data, the predominant mechanism of colitis protection in Rag1−/−Irf4−/− T cell receiving mice.
CRIS-Team Scopus Importer:2021-02-26
Keywords: inflammatory bowel disease (IBD); interferon regulatory factor 4 (IRF4); intestinal inflammation; myeloid cells; Th17

The Angiosome Concept Evaluated on the Basis of Microperfusion in Critical Limb Ischemia Patients-an Oxygen to See Guided Study - Rother, Ulrich; Kapust, Johannes; Lang, Werner; Horch, Raymund E.; Gefeller, Olaf; Meyer, Alexander (Microcirculation, 2015)
Aim of this clinical study was to evaluate the angiosome concept with regard to the microcirculation of the foot in patients with CLI and to evaluate its relevance by means of combined laser Doppler flowmetrie and white-light tissue spectrophotometry.Twenty-eight patients who underwent leg revascularization in the stage of CLI were prospectively examined. The microperfusion was assessed by light guided spectrophotometry. The measuring points were set according to the angiosome concept into direct and indirect revascularized areas of the foot. Investigations were performed pre and postinterventionally and after 4 and 12 weeks in baseline-position as well as in an elevated position of the leg.Microcirculation parameters (oxygen saturation, blood flow, velocity) of the revascularized leg showed a significant increase in elevation and baseline position compared to the preoperative values in most analyses. No significant differences between the direct and indirect revascularized angiosome were apparent.The light-guided spectrophotometry measurement proved to be feasible in terms of measuring changes in the microcirculation after leg revascularization. However, our data do not support the value of the "angiosome concept" concerning the individual changes in microperfusion of the foot in patients with CLI.
EVALuna2:5490

The association of Health-Related Quality of Life and 1-year-survival in sarcoma patients-results of a Nationwide Observational Study (PROSa) - Eichler, Martin; Singer, Susanne; Hentschel, Leopold; Richter, Stephan; Hohenberger, Peter; Kasper, Bernd; Andreou, Dimosthenis; Pink, Daniel; Jakob, Jens; Grützmann, Robert; Fung, Stephen; Wardelmann, Eva; et al. (British Journal of Cancer, 2022)
Background Sarcomas are rare cancers of high heterogeneity. Health-Related Quality of Life (HRQoL) has been shown to be a prognostic factor for survival in other cancer entities but it is unclear whether this applies to sarcoma patients. Patients and methods HRQoL was prospectively assessed in adult sarcoma patients from 2017 to 2020 in 39 German recruiting sites using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Vital status was ascertained over the course of 1 year. HRQoL domains were analysed by multivariable cox-regressions including clinical and socio-economic risk factors. Results Of 1102 patients, 126 (11.4%) died during follow-up. The hazard ratio (HR) for global health was 0.73 per 10-point increase (95% confidence interval (CI) 0.64-0.85). HR for the HRQoL-summary score was 0.74 (CI 0.64-0.85) and for physical functioning 0.82 (CI 0.74-0.89). There was also evidence that fatigue (HR 1.17, CI 1.10-1.25), appetite loss (HR 1.15, CI 1.09-1.21) and pain (HR 1.14, CI 1.08-1.20) are prognostic factors for survival. Conclusion Our study adds sarcoma-specific evidence to the existing data about cancer survival in general. Clinicians and care-givers should be aware of the relations between HRQoL and survival probability and include HRQoL in routine assessment.
CRIS-Team WoS Importer:2022-02-04

The B-cell inhibitory receptor CD22 is a major factor in host resistance to Streptococcus pneumoniae infection - Fernandes, Vitor E.; Ercoli, Giuseppe; Bénard, Alan; Brandl, Carolin; Fahnenstiel, Hannah; Müller-Winkler, Jennifer; Denny, Paul; Nitschke, Lars; Andrew, Peter W.; Weber, Georg (PLoS Pathogens, 2020)
Streptococcus pneumoniae is a major human pathogen, causing pneumonia and sepsis. Genetic components strongly influence host responses to pneumococcal infections, but the responsible loci are unknown. We have previously identified a locus on mouse chromosome 7 from a susceptible mouse strain, CBA/Ca, to be crucial for pneumococcal infection. Here we identify a responsible gene, Cd22, which carries a point mutation in the CBA/Ca strain, leading to loss of CD22 on B cells. CBA/Ca mice and gene-targeted CD22-deficient mice on a C57BL/6 background are both similarly susceptible to pneumococcal infection, as shown by bacterial replication in the lungs, high bacteremia and early death. After bacterial infections, CD22-deficient mice had strongly reduced B cell populations in the lung, including GM-CSF producing, IgM secreting innate response activator B cells, which are crucial for protection. This study provides striking evidence that CD22 is crucial for protection during invasive pneumococcal disease.
CRIS-Team Scopus Importer:2020-05-15

The clinical value of von Willebrand factor in colorectal carcinomas. - Schellerer, Vera; Müller-Bergh, Larissa; Merkel, Susanne; Zimmermann, Robert; Weiss, Dominik R.; Schlabrakowski, Anne; Naschberger, Elisabeth; Stürzl, Michael; Hohenberger, Werner; Croner, Roland S. (American Journal of Translational Research, 2011)
To identify the value of von Willebrand factor (vWF) as a clinical marker in colorectal carcinoma (CRC). Plasma levels of vWF were measured in 79 patients with UICC Stage I-IV CRC at time of operation and correlated with TNM categories, levels of the carcinoembryonic antigen (CEA), blood groups (BG) and 19 controls (CO). CO included cancer-free patients without bacterial or viral infections. For tissue analysis paraffin embedded tumour and mucosa sections of operation specimens were stained immunohistochemically for vWF and compared to vWF plasma levels as well as to TNM categories. VWF plasma levels in CRC patients were significantly dependent on blood groups (p=0.012) and elevated compared to the normal ranges as well as to controls (BG 0: p=0.668, BG A/AB/B: p=0.020). CRC-Patients over 60 years of age presented with significantly higher vWF levels than patients below 60 years (BG 0: p=0.005; BG A/AB/B: p=0.035). There was no correlation of vWF plasma levels and UICC stages in CRC. Patients with elevated vWF plasma levels also presented with elevated CEA levels, but significance was missing (p=0.080). VWF concentration within the tumour tissue was independent of concentration within normal mucosa, blood groups, histopathological characteristics and did not correlate with plasma vWF levels. VWF plasma levels are elevated in CRC patients, but not in a stage dependent manner. Besides the tumour at least blood groups and age mainly influence plasma vWF levels. In our opinion vWF as a routinely used clinical marker in CRC cannot be recommended. BACKGROUND METHODS RESULTS CONCLUSION

The contribution of systems biology and reverse genetics to the understanding of Kaposi's sarcoma-associated herpesvirus pathogenesis in endothelial cells. - Stürzl, Michael; Konrad, Andreas; Alkharsah, Khaled R.; Jochmann, Ramona; Thurau, Mathias; Marquardt, Gaby; Schulz, Thomas F. (Thrombosis and Haemostasis, 2009)
Kaposi's sarcoma-associated herpesvirus (KSHV)/human herpesvirus-8 is the causative agent of the endothelial cell-derived tumour Kaposi's sarcoma. Herpesviruses possess large complex genomes which provide many options to regulate cellular physiology during the viral life cycle and in the course of tumourigenicity. Novel techniques of systems biology and reverse genetics are increasingly applied to dissect the complex interaction of KSHV with endothelial cells. This review will outline novel results and pitfalls of these technologies in the elucidation of KSHV pathogenicity.

The Differential Diagnosis and Inter - disciplinary Treatment of Anal Carcinoma - Raptis, Dimitrios; Schneider, Ignaz Hans Friedrich; Matzel, Klaus E.; Ott, Oliver; Fietkau, Rainer; Hohenberger, Werner (Deutsches Ärzteblatt international, 2015)
Anal carcinoma accounts for 2-4% of all cases of colorectal and anorectal carcinoma. Its peak incidence is from age 58 to age 64; women are affected somewhat more commonly than men. Its incidence has risen markedly in the past three decades.This article is based on a selective review of the literature, including the guidelines of the National Comprehensive Cancer Network and the European Society of Medical Oncology.Anal carcinoma is often an incidental finding. About 85% of newly diagnosed cases are associated with an HPV infection with strain 16, 18, or 33. Radiochemotherapy with 5-fluorouracil and mitomycin C is the treatment of choice. The 5-year survival rate is 80-90%. Primary surgery with curative intent is indicated only for well-differentiated carcinoma of the anal margin (T1, N0). 10-30% of patients now undergo radical resection. The utility of endosonography and positron emission tomography for staging is debated and needs further study.The treatment of patients with anal carcinoma requires a specialized multidisciplinary approach in accordance with the current evidence-based guidelines. The potential role of prophylactic vaccination against oncogenic types of HPV in the prevention of anal carcinoma merits further investigation.
EVALuna2:15196

The Ebola virus glycoprotein and HIV-1 Vpu employ different strategies to counteract the antiviral factor tetherin. - Kühl, Annika; Banning, Carina; Marzi, Andrea; Votteler, Jörg; Steffen, Imke; Bertram, Stephanie; Glowacka, Ilona; Konrad, Andreas; Stürzl, Michael; Guo, Ju-Tao; Schubert, Ulrich; Feldmann, Heinz; et al. (Journal of Infectious Diseases, 2011)
The antiviral protein tetherin/BST2/CD317/HM1.24 restricts cellular egress of human immunodeficiency virus (HIV) and of particles mimicking the Ebola virus (EBOV), a hemorrhagic fever virus. The HIV-1 viral protein U (Vpu) and the EBOV-glycoprotein (EBOV-GP) both inhibit tetherin. Here, we compared tetherin counteraction by EBOV-GP and Vpu. We found that EBOV-GP but not Vpu counteracted tetherin from different primate species, indicating that EBOV-GP and Vpu target tetherin differentially. Tetherin interacted with the GP2 subunit of EBOV-GP, which might encode the determinants for tetherin counteraction. Vpu reduced cell surface expression of tetherin while EBOV-GP did not, suggesting that both proteins employ different mechanisms to counteract tetherin. Finally, Marburg virus (MARV)-GP also inhibited tetherin and downregulated tetherin in a cell type-dependent fashion, indicating that tetherin antagonism depends on the cellular source of tetherin. Collectively, our results indicate that EBOV-GP counteracts tetherin by a novel mechanism and that tetherin inhibition is conserved between EBOV-GP and MARV-GP.

The effect of cell concentrations from different cell populations on the viability of umbilical blood stem cells - Hauck-Dlimi, Barbara; Dlimi, Afif; Zimmermann, Robert; Eckstein, Reinhold; Zingsem, Jürgen (Clinical Laboratory, 2014)
In addition to bone marrow or peripheral blood derived stem cells, cord blood (CB) is an alternative source for hematopoietic stem cells. This report shows the impact of higher concentrations of leukocytes, mononu- clear cells (MNCs), and CD34-positive cells on the viability of CB derived stem cells after cryopreservation.Statistical analysis of data from 5520 CB units, prepared and cryopreserved from 2003 through 2011, was performed with appropriate software. Cell concentrations for leukocytes, platelets, red blood cells (RBCs), CD34-positive leukocytes, viable leukocytes, and MNCs were determined. The proliferation and differentiation capacity was assessed in cell culture assays.Content of leukocytes, CD34-positive leukocytes, and MNCs decreased after thawing. The recovery rate of colony forming units (CFUs) (29.05%) correlated significantly with leukocytes, platelets, RBCs, MNCs, CD34- positive leukocytes, and viable leukocytes. The recovery rate for erythroblasts (3.33%) correlated significantly with leukocytes, CD34-positive leukocytes, MNCs, and viable leukocytes. In the different cell concentration groups only RBCs showed a negative influence on viability. The concentrations of leukocytes, platelets, and CD34-positive leukocytes before cryopreservation correlated positively with the concentrations of leukocytes, CD34-positive leukocytes, MNCs as well as with the cell viability after thawing.Increased cell concentrations in CB do not limit the recovery of CD34-positive leukocytes nor the viability of leukocytes or the number of CFUs after thawing. On the contrary, CB units with high cell concentrations show a better outcome than units with low cell concentrations. Only RBCs seem to have a negative influence on CB quality.
EVALuna2:15987

The Effect of GPRC5a on the Proliferation, Migration Ability, Chemotherapy Resistance, and Phosphorylation of GSK-3β in Pancreatic Cancer - Liu, Bin; Yang, Hai; Pilarsky, Christian; Weber, Georg (International Journal of Molecular Sciences, 2018)
Pancreatic cancer (PaCa) is the fourth leading cause of cancer-related death, and personalized targeted cancer therapy is becoming a promising treatment strategy for PaCa. The central approach of targeted therapy is to find a targetable key and an effective targeting method. In this study, the importance of GPRC5a (the G-protein-coupled receptor family C, member 5, group A) was identified using data mining methods based on published datasets. After analysis of the basic expression of GPRC5a in normal pancreas tissue and various PaCa cell lines, gene editing of GPRC5a in the human PaCa cell line MIA PaCa-2 and the mouse PaCa cell line TB32047 was performed using CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated proteins 9) to investigate the influence of GPRC5a on the proliferation and migration of PaCa cells as well as its effects on chemotherapy drug resistance. The results showed that GPRC5a was upregulated in PaCa tissues and various PaCa cell lines. Knockout of GPRC5a reduced the proliferation and migration ability of PaCa cell lines and suppressed the chemotherapy drug resistance of gemcitabine, oxaliplatin, and fluorouracil in PaCa cells. The phosphorylation of GSK-3β (Glycogen synthase kinase-3β) was found to be upregulated in the MIA PaCa-2 and TB32047 cells after GPRC5a knockout. In conclusion, GPRC5a was upregulated in PaCa leading to an enhanced drug resistance in PaCa cells. These results provide for the first time a theoretical basis for the development of an improved PaCa targeted therapy.
EVALuna2:210711

The effect of targeted hyperoxemia in a randomized controlled trial employing a long-term resuscitated, model of combined acute subdural hematoma and hemorrhagic shock in swine with coronary artery disease: An exploratory, hypothesis-generating study - Datzmann, Thomas; Messerer, David Alexander Christian; Münz, Franziska; Hoffmann, Andrea; Gröger, Michael; Mathieu, René; Mayer, Simon; Gässler, Holger; Zink, Fabian; McCook, Oscar; Merz, Tamara; Scheuerle, Angelika; et al. (Frontiers in Medicine, 2022)
Controversial evidence is available regarding suitable targets for the arterial O2 tension (PaO2) after traumatic brain injury and/or hemorrhagic shock (HS). We previously demonstrated that hyperoxia during resuscitation from hemorrhagic shock attenuated cardiac injury and renal dysfunction in swine with coronary artery disease. Therefore, this study investigated the impact of targeted hyperoxemia in a long-term, resuscitated model of combined acute subdural hematoma (ASDH)-induced brain injury and HS. The prospective randomized, controlled, resuscitated animal investigation consisted of 15 adult pigs. Combined ASDH plus HS was induced by injection of 0.1 ml/kg autologous blood into the subdural space followed by controlled passive removal of blood. Two hours later, resuscitation was initiated comprising re-transfusion of shed blood, fluids, continuous i.v. noradrenaline, and either hyperoxemia (target PaO2 200 – 250 mmHg) or normoxemia (target PaO2 80 – 120 mmHg) during the first 24 h of the total of 54 h of intensive care. Systemic hemodynamics, intracranial and cerebral perfusion pressures, parameters of brain microdialysis and blood biomarkers of brain injury did not significantly differ between the two groups. According to the experimental protocol, PaO2 was significantly higher in the hyperoxemia group at the end of the intervention period, i.e., at 24 h of resuscitation, which coincided with a higher brain tissue PO2. The latter persisted until the end of observation period. While neurological function as assessed using the veterinary Modified Glasgow Coma Score progressively deteriorated in the control group, it remained unaffected in the hyperoxemia animals, however, without significant intergroup difference. Survival times did not significantly differ in the hyperoxemia and control groups either. Despite being associated with higher brain tissue PO2 levels, which were sustained beyond the intervention period, targeted hyperoxemia exerted neither significantly beneficial nor deleterious effects after combined ASDH and HS in swine with pre-existing coronary artery disease. The unavailability of a power calculation and, thus, the limited number of animals included, are the limitations of the study.
CRIS-Team Scopus Importer:2022-09-30
Keywords: GFAP; MAP-2; mitochondrial respiration; multimodal brain monitoring; neuron-specific enolase; oxidative stress hyperoxemia after acute subdural hematoma and hemorrhagic shock; protein S100β; traumatic brain injury

The effects of an overnight holding of whole blood at room temperature on haemoglobin modification and in vitro markers of red blood cell aging - Eckstein, Markus; Zimmermann, Rüdiger; Roth, T.; Hauck-Dlimi, B.; Strasser, E. F.; Xiang, Wei (Vox Sanguinis, 2015)
Some effects of the red blood cell (RBC) storage lesion are well documented whereas others are not. Whether a period of room temperature hold (RTH) during RBC production enhances the RBC storage lesion has remained controversial. In this study, we compared whole blood (WB)-derived RBCs produced after 24-h RTH with rapidly cooled (RC) RBCs and tested them for classical metabolic markers and signs of oxidative damage.SAGM-RBCs were prepared from mixed and split pairs (n = 12) of WB units. RBCs prepared after a 24-h period of RTH on day+1 after collection (RTH-RBCs) were compared with RC-RBCs. All RBCs were stored at 4°C for 42 days with assay of in vitro variables on days+1, +15, +22, +29 and +42. The study examined standard quality parameters, glutathione, catalase and superoxide dismutase (SOD) activities, and indicative markers of oxidative cell damage including post-translational haemoglobin modification, malondialdehyde (MDA), and phosphatidylserine expression.RTH-RBCs exhibited decreased levels of potassium (1·98 ± 0·26 vs. 5·23 ± 0·65 mmol/l) and of 2,3-diphosphoglycerate (2,3-DPG) on day+1 compared with RC-RBCs. Haemolysis rate on day+42 was higher in RTH-RBCs than in RC-RBCs (0·52 ± 0·13 vs. 0·37 ± 0·12%). The phosphatidylserine expression amounted to 0·25 ± 0·20% in RTH-RBCs and 0·07 ± 0·12% in RC-RBCs. Haemoglobin modification was not different between both RBC groups. RTH-RBCs showed slightly higher MDA concentration on days +29 and +42.RC-RBCs and RTH-RBCs show only small differences of classical in vitro parameters and no relevant differences in antioxidative metabolism and oxidative haemoglobin modification. These findings do not explain the loss observed in in vivo survival studies with RBCs.
EVALuna2:4710

The effects of iloprost on colonic anastomotic healing in rats under obstructive ileus conditions - Galanopoulos, Georgios; Raptis, Dimitrios; Pramateftakis, Manousos-Georgios; Mantzoros, Ioannis; Kanellos, Ioannis; Lazarides, Charalambos (Journal of Surgical Research, 2014)
The aim of this study was to investigate the effects of iloprost, on colonic anastomotic healing in rats, under obstructive ileus conditions.Eighty male Albino rats were randomized into four groups of 20 animals each. They underwent colonic resection followed by an inverted anastomosis. The rats of group 1 (control) and group 2 (ileus) received 3 mL of saline 0.9% intraperitoneally and those of group 3 (iloprost), and group 4 (ileus + iloprost) iloprost (2 ?g/kg of body weight), immediately postoperatively and daily until the day of sacrifice. Each group was further divided into two equal subgroups, depending on the day of sacrifice. The animals of subgroup "a" were sacrificed on the fourth postoperative day, whereas those of "b" on the eighth day. Macroscopic and histologic assessment was performed, whereas anastomotic bursting pressures and the tissue concentrations in hydroxyproline and collagenase I were evaluated.Means of bursting pressure, neoangiogenesis, fibroblast activity, and hydroxyproline concentration were significantly increased in group 4 compared with group 2. In addition, on the fourth postoperative day, the inflammatory cell infiltration and the collagenase I concentration were significantly decreased in group 4 compared with group 2. Moreover, on the eighth postoperative day, collagen deposition was significantly increased in group 4 compared with group 2.Iloprost after intraperitoneal administration reverses the negative effect of obstructive ileus. It promotes not only the angiogenic activity but also collagen formation, resulting in increased bursting pressures on the fourth and eighth postoperative days.
EVALuna2:15193

The EMT-activator Zeb1 is a key factor for cell plasticity and promotes metastasis in pancreatic cancer - Krebs, Angela M.; Mitschke, Julia; Losada, Maria Lasierra; Schmalhofer, Otto; Boerries, Melanie; Busch, Hauke; Böttcher, Martin; Mougiakakos, Dimitrios; Reichardt, Wilfried; Bronsert, Peter; Brunton, Valerie G.; Pilarsky, Christian; et al. (Nature Cell Biology, 2017)
Metastasis is the major cause of cancer-associated death. Partial activation of the epithelial-to-mesenchymal transition program (partial EMT) was considered a major driver of tumour progression from initiation to metastasis. However, the role of EMT in promoting metastasis has recently been challenged, in particular concerning effects of the Snail and Twist EMT transcription factors (EMT-TFs) in pancreatic cancer. In contrast, we show here that in the same pancreatic cancer model, driven by Pdx1-cre-mediated activation of mutant Kras and p53 (KPC model), the EMT-TF Zeb1 is a key factor for the formation of precursor lesions, invasion and notably metastasis. Depletion of Zeb1 suppresses stemness, colonization capacity and in particular phenotypic/metabolic plasticity of tumour cells, probably causing the observed in vivo effects. Accordingly, we conclude that different EMT-TFs have complementary subfunctions in driving pancreatic tumour metastasis. Therapeutic strategies should consider these potential specificities of EMT-TFs to target these factors simultaneously.

The ephrin receptor tyrosine kinase A2 is a cellular receptor for Kaposi's sarcoma-associated herpesvirus - Hahn, Alexander; Kaufmann, Johanna K.; Wies, Effi; Naschberger, Elisabeth; Panteleev-Ivlev, Julia; Schmidt, Katharina; Holzer, Angela; Schmidt, Martin; Chen, Jin; Koenig, Simone; Enßer, Armin; Myoung, Jinjong; et al. (Nature Medicine, 2012)
Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi's sarcoma, a highly vascularized tumor originating from lymphatic endothelial cells, and of at least two different B cell malignancies. A dimeric complex formed by the envelope glycoproteins H and L (gH-gL) is required for entry of herpesviruses into host cells. We show that the ephrin receptor tyrosine kinase A2 (EphA2) is a cellular receptor for KSHV gH-gL. EphA2 co-precipitated with both gH-gL and KSHV virions. Infection of human epithelial cells with a GFP-expressing recombinant KSHV strain, as measured by FACS analysis, was increased upon overexpression of EphA2. Antibodies against EphA2 and siRNAs directed against EphA2 inhibited infection of endothelial cells. Pretreatment of KSHV with soluble EphA2 resulted in inhibition of KSHV infection by up to 90%. This marked reduction of KSHV infection was seen with all the different epithelial and endothelial cells used in this study. Similarly, pretreating epithelial or endothelial cells with the soluble EphA2 ligand ephrinA4 impaired KSHV infection. Deletion of the gene encoding EphA2 essentially abolished KSHV infection of mouse endothelial cells. Binding of gH-gL to EphA2 triggered EphA2 phosphorylation and endocytosis, a major pathway of KSHV entry. Quantitative RT-PCR and in situ histochemistry revealed a close correlation between KSHV infection and EphA2 expression both in cultured cells derived from human Kaposi's sarcoma lesions or unaffected human lymphatic endothelium, and in situ in Kaposi's sarcoma specimens, respectively. Taken together, our results identify EphA2, a tyrosine kinase with known functions in neovascularization and oncogenesis, as an entry receptor for KSHV. © 2012 Nature America, Inc. All rights reserved.
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The EZ-blocker for one-lung ventilation in patients undergoing thoracic surgery: clinical applications and experience in 100 cases in a routine clinical setting - Moritz, Andreas; Irouschek, Andrea; Birkholz, Torsten; Prottengeier, Johannes; Sirbu, Horia; Schmidt, Joachim (Journal of Cardiothoracic Surgery, 2018)
BACKGROUND: In certain clinical situations the insertion of a double-lumen tube (DLT) for one-lung ventilation (OLV) is not feasible or unfavorable. In these cases, the EZ-Blocker (EZB) may serve as an alternative. The aim of our analysis was to report on the clinical applications and our experience with the EZB for one-lung ventilation in 100 patients undergoing thoracic surgery. METHODS: All anesthetic records from patients older than 18 years of age undergoing general anesthesia in the department of thoracic surgery with intraoperative use of an EZB for OLV at the University Hospital of Erlangen in four consecutive years were analyzed retrospectively. RESULTS: Most frequently, EZB was used in difficult airway (27%) and for surgical procedures with high risk for left recurrent laryngeal nerve injury (21%), followed by application in intubated (12%) or tracheostomized (11%) patients. 11% of the patients had an increased risk of gastric regurgitation. Almost all EZBs were placed free of complications (99%). Clinically sufficient lung collapse was achieved in all patients. No serious airway injuries or immediate complications were documented. CONCLUSIONS: The EZB is an efficient, easy-to-use and safe airway device and enables OLV in several clinical situations, when conventional DLTs are not feasible or less favorable. Three major applications were depicted from the data: expected difficult airway, surgical procedures with necessity of intraoperative recurrent laryngeal nerve monitoring and already intubated or tracheostomized patients.
EVALuna2:35112

The gammaherpesviruses Kaposi's sarcoma-associated herpesvirus and murine gammaherpesvirus 68 modulate the Toll-like receptor-induced proinflammatory cytokine response - Bussey, Kendra A.; Reimer, Elisa; Todt, Helene; Denker, Brigitte; Gallo, Antonio; Konrad, Andreas; Ottinger, Matthias; Adler, Heiko; Stuerl, Michael; Brune, Wolfram; Brinkmann, Melanie M. (Journal of Virology, 2014)
The human pathogen Kaposi's sarcoma-associated herpesvirus (KSHV), the etiological agent of Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease, establishes lifelong latency upon infection. Murine gammaherpesvirus 68 (MHV68) is a well-established model for KSHV. Toll-like receptors (TLRs) play a crucial role for the innate immune response to pathogens. Although KSHV and MHV68 are detected by TLRs, studies suggest they modulate TLR4 and TLR9 signaling, respectively. In this study, we show that in bone marrow-derived macrophages (BMDMs), MHV68 did not induce a detectable proinflammatory cytokine response. Furthermore, MHV68 abrogated the response to TLR2, -4, -7, and -9 agonists in BMDMs. Similarly to observations with MHV68, infection with KSHV efficiently inhibited TLR2 signaling in THP-1 monocytes. Using a KSHV open reading frame (ORF) library, we found that K4.2, ORF21, ORF31, and the replication and transcription activator protein (RTA)/ORF50 inhibited TLR2-dependent nuclear factor kappa B (NF-?B) activation in HEK293 TLR2-yellow fluorescent protein (YFP)- and Flag-TLR2-transfected HEK293T cells. Of the identified ORFs, RTA/ORF50 strongly downregulated TLR2 and TLR4 signaling by reducing TLR2 and TLR4 protein expression. Confocal microscopy revealed that TLR2 and TLR4 were no longer localized to the plasma membrane in cells expressing RTA/ORF50. In this study, we have shown that the gammaherpesviruses MHV68 and KSHV efficiently downmodulate TLR signaling in macrophages and have identified a novel function of RTA/ORF50 in modulation of the innate immune response.The Toll-like receptors (TLRs) are an important class of pattern recognition receptors of the innate immune system. They induce a potent proinflammatory cytokine response upon detection of a variety of pathogens. In this study, we found that the gammaherpesviruses murine gammaherpesvirus 68 (MHV68) and Kaposi's sarcoma-associated herpesvirus (KSHV) efficiently inhibit the TLR-mediated innate immune response. We further identified the KSHV-encoded replication and transcription activator protein (RTA) as a novel modulator of TLR signaling. Our data suggest that the gammaherpesviruses MHV68 and KSHV prevent activation of the innate immune response by targeting TLR signaling.
EVALuna2:15172

The glycan CA19-9 promotes pancreatitis and pancreatic cancer in mice - Engle, Dannielle D.; Tiriac, Herve; Rivera, Keith D.; Pommier, Arnaud; Whalen, Sean; Oni, Tobiloba E.; Alagesan, Brinda; Lee, Eun Jung; Yao, Melissa A.; Lucito, Matthew S.; Spielman, Benjamin; Da Silva, Brandon; et al. (Science, 2019)
Glycosylation alterations are indicative of tissue inflammation and neoplasia, but whether these alterations contribute to disease pathogenesis is largely unknown. To study the role of glycan changes in pancreatic disease, we inducibly expressed human fucosyltransferase 3 and b1,3-galactosyltransferase 5 in mice, reconstituting the glycan sialyl-Lewisa, also known as carbohydrate antigen 19-9 (CA19-9). Notably, CA19-9 expression in mice resulted in rapid and severe pancreatitis with hyperactivation of epidermal growth factor receptor (EGFR) signaling. Mechanistically, CA19-9 modification of the matricellular protein fibulin-3 increased its interaction with EGFR, and blockade of fibulin-3, EGFR ligands, or CA19-9 prevented EGFR hyperactivation in organoids. CA19-9–mediated pancreatitis was reversible and could be suppressed with CA19-9 antibodies. CA19-9 also cooperated with the KrasG12D oncogene to produce aggressive pancreatic cancer. These findings implicate CA19-9 in the etiology of pancreatitis and pancreatic cancer and nominate CA19-9 as a therapeutic target.
CRIS-Team Scopus Importer:2019-07-09

The glycan CA19-9 promotes pancreatitis and pancreatic cancer in mice - Engle, Dannielle; Tiriac, Herve; Rivera, Keith; Pommier, Arnaud; Whalen, Sean; Oni, Tobiloba; Alagesan, Brinda; Lee, Eun; Yao, Melissa; Lucito, Matthew; Spielman, Benjamin; Yu, Kenneth; et al. (CANCER RESEARCH, 2019)
CRIS-Team WoS Importer:2020-05-02

The G Protein-Coupled Receptor RAI3 Is an Independent Prognostic Factor for Pancreatic Cancer Survival and Regulates Proliferation via STAT3 Phosphorylation - Jahny, Elisabeth; Yang, Hai; Liu, Bin; Jahnke, Beatrix; Lademann, Franziska; Knoesel, Thomas; Ruemmele, Petra; Grützmann, Robert; Aust, Daniela; Pilarsky, Christian; Denz, Axel (PLoS ONE, 2017)
Pancreatic Ductal Adenocarcinoma (PDAC) is one of the deadliest tumors worldwide. Understanding the function of gene expression alterations is a prerequisite for developing new strategies in diagnostic and therapy. GPRC5A (RAI3), coding for a seven transmembrane G protein-coupled receptor is known to be overexpressed in pancreatic cancer and might be an interesting candidate for therapeutic intervention. Expression levels of RAI3 were compared using a tissue microarray of 435 resected patients with pancreatic cancer as well as 209 samples from chronic pancreatitis (CP), intra-ductal papillary mucinous neoplasm (IPMN) and normal pancreatic tissue. To elucidate the function of RAI3 overexpression, siRNA based knock-down was used and transfected cells were analyzed using proliferation and migration assays. Pancreatic cancer patients showed a statistically significant overexpression of RAI3 in comparison to normal and chronic pancreatitis tissue. Especially the loss of apical RAI3 expression represents an independent prognostic parameter for overall survival of patients with pancreatic cancer. Suppression of GPRC5a results in decreased cell growth, proliferation and migration in pancreatic cancer cell lines via a STAT3 modulated pathway, independent from ERK activation.
EVALuna2:6846

The guanylate binding protein-1 GTPase controls the invasive and angiogenic capability of endothelial cells through inhibition of MMP-1 expression - Naschberger, Elisabeth; Stürzl, Michael; et al. (EMBO Journal, 2003)
Expression of the large GTPase guanylate binding protein-1 (GBP-1) is induced by inflammatory cytokines (ICs) in endothelial cells (ECs), and the helical domain of the molecule mediates the repression of EC proliferation by ICs. Here we show that the expression of GBP-1 and of the matrix metalloproteinase-1 (MMP-1) are inversely related in vitro and in vivo, and that GBP-1 selectively inhibits the expression of MMP-1 in ECs, but not the expression of other proteases. The GTPase activity of GBP-1 was necessary for this effect, which inhibited invasiveness and tube-forming capability of ECs in three-dimensional collagen-I matrices. A GTPase-deficient mutant (D184N-GBP-1) operated as a transdominant inhibitor of wild-type GBP-1 and rescued MMP-1 expression in the presence of ICs. Expression of D184N-GBP-1, as well as paracrine supplementation of MMP-1, restored the tube-forming capability of ECs in the presence of wild-type GBP-1. The latter finding indicated that the inhibition of capillary formation is specifically due to the repression of MMP-1 expression by GBP-1, and is not affected by the anti-proliferative activity of the helical domain of GBP-1. These findings substantiate the role of GBP-1 as a major regulator of the anti-angiogenic response of ECs to ICs.
Created from Fastlane, Scopus look-up
Keywords: Angiogenesis; Collagenase; Inflammation; Invasion; MMP

The H2S Donor Sodium Thiosulfate (Na2S2O3) Does Not Improve Inflammation and Organ Damage After Hemorrhagic Shock in Cardiovascular Healthy Swine - Messerer, David Alexander Christian; Gaessler, Holger; Hoffmann, Andrea; Groeger, Michael; Benz, Kathrin; Huhn, Aileen; Hezel, Felix; Calzia, Enrico; Radermacher, Peter; Datzmann, Thomas (Frontiers in Immunology, 2022)
We previously demonstrated marked lung-protective properties of the H2S donor sodium thiosulfate (Na2S2O3, STS) in a blinded, randomized, controlled, long-term, resuscitated porcine model of swine with coronary artery disease, i.e., with decreased expression of the H2S-producing enzyme cystathionine-gamma-lyase (CSE). We confirmed these beneficial effects of STS by attenuation of lung, liver and kidney injury in mice with genetic CSE deletion (CSE-ko) undergoing trauma-and-hemorrhage and subsequent intensive care-based resuscitation. However, we had previously also shown that any possible efficacy of a therapeutic intervention in shock states depends both on the severity of shock as well as on the presence or absence of chronic underlying co-morbidity. Therefore, this prospective, randomized, controlled, blinded experimental study investigated the effects of the STS in cardiovascular healthy swine. After anesthesia and surgical instrumentation, 17 adult Bretoncelles-Meishan-Willebrand pigs were subjected to 3 hours of hemorrhage by removal of 30% of the blood volume and titration of the mean arterial pressure (MAP) approximate to 40 +/- 5 mmHg. Afterwards, the animals received standardized resuscitation including re-transfusion of shed blood, fluids, and, if needed, continuous i.v. noradrenaline to maintain MAP at pre-shock values. Animals were randomly allocated to either receive Na2S2O3 or vehicle control starting 2 hours after initiation of shock until 24 hours of resuscitation. The administration of Na2S2O3 did not alter survival during the observation period of 68 hours after the initiation of shock. No differences in cardio-circulatory functions were noted despite a significantly higher cardiac output, which coincided with significantly more pronounced lactic acidosis at 24 hours of resuscitation in the Na2S2O3 group. Parameters of liver, lung, and kidney function and injury were similar in both groups. However, urine output was significantly higher in the Na2S2O3 group at 24 hours of treatment. Taken together, this study reports no beneficial effect of Na2S2O3 in a clinically relevant model of hemorrhagic shock-and-resuscitation in animals without underlying chronic cardiovascular co-morbidity.
CRIS-Team WoS Importer:2022-07-08

The health-related quality of life of sarcoma patients and survivors in germany—cross-sectional results of a nationwide observational study (Prosa) - Eichler, Martin; Hentschel, Leopold; Richter, Stephan; Hohenberger, Peter; Kasper, Bernd; Andreou, Dimosthenis; Pink, Daniel; Jakob, Jens; Singer, Susanne; Grützmann, Robert; Fung, Stephen; Wardelmann, Eva; et al. (Cancers, 2020)
Sarcomas are rare cancers with high heterogeneity in terms of type, location, and treatment. The health-related quality of life (HRQoL) of sarcoma patients has rarely been investigated and is the subject of this analysis. Adult sarcoma patients and survivors were assessed between September 2017 and February 2019 in 39 study centers in Germany using standardized, validated questionnaires (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)). Associated factors were analyzed exploratively using multivariable linear regressions. Among 1113 patients, clinically important limitations and symptoms were most pronounced in emotional (63%, 95% CI 60–66%), physical (60%, 95% CI 57–62%), role functioning (51%, 95% CI 48–54%), and pain (56%, 95% CI 53–59%) and fatigue (51%, 95% CI 48–54%). HRQoL differed between tumor locations with lower extremities performing the worst and sarcoma types with bone sarcoma types being most affected. Additionally, female gender, higher age, lower socioeconomic status, recurrent disease, not being in retirement, comorbidities, and being in treatment were associated with lower HRQoL. Sarcoma patients are severely restricted in their HRQoL, especially in functioning scales. The heterogeneity of sarcomas with regard to type and location is reflected in HRQoL outcomes. During treatment and follow-up, close attention has to be paid to the reintegration of the patients into daily life as well as to their physical abilities and emotional distress.
CRIS-Team Scopus Importer:2020-12-11
Keywords: Clinically important restrictions and symptoms; Health-related quality of life; Observational study; Rare disease; Sarcoma

The health-related quality of life of sarcoma patients treated with neoadjuvant versus adjuvant radiotherapy – Results of a multi-center observational study - Singer, Susanne; Semrau, Sabine; Golcher, Henriette; Fechner, Katja; Kallies, Annett; Zapata Bonilla, Sergio; Grützmann, Robert; Fietkau, Rainer; Kluba, Torsten; Jentsch, Christina; Andreou, Dimosthenis; Bornhäuser, Martin; et al. (Radiotherapy and Oncology, 2023)
Aim: The sequence of radiotherapy and resection in patients with soft tissue sarcomas is usually discussed on an individual basis. Better understanding of potential differences of health-related quality of life (QoL) between patients undergoing adjuvant (ART) versus neoadjuvant radiotherapy (NART) is therefore helpful for clinical decision making. Methods: Adult sarcoma patients from 39 hospitals completed the European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30). Differences in global QoL, physical functioning, role functioning, fatigue, pain, and insomnia between ART versus NART were investigated with multivariate regression, adjusting for age, gender, chemotherapy, grading, stage, tumor location, recurrence/distant metastasis, sarcoma type, time since last treatment, and treatment status using validated thresholds. Results: A total of 1110 patients participated. Of them, 340 had received radiotherapy (NART: n = 95, 28%; ART: n = 245, 72%). Global QoL was 59.3 on average after NART and 60.5 after ART (Badj = 1.0, p = 0.74). Physical functioning was 65.9 compared to 70.5 (Badj = 4.2; p = 0.16), role function 48.8 vs. 56.7 (Badj = 7.0, p = 0.08), fatigue 47.5 vs. 45.4 (Badj = -1.2; p = 0.71), pain 40.2 vs. 34.1 (Badj = -6.8; p = 0.08), and insomnia 33.7 vs. 41.6 (Badj = 5.5, p = 0.16). Among patients with NART, clinically relevant QoL impairments were less frequent 2 years after treatment compared to < 2 years thereafter (n = 6 vs. n = 4 on average). Conclusion: There is little evidence for QoL differences in most domains and overall QoL between the two irradiation groups. However, patients after NART might experience worse role functioning and pain but fewer problems with insomnia compared to patients after ART.
CRIS-Team Scopus Importer:2023-10-20
Keywords: Leiomyosarcoma; Liposarcoma; Neoadjuvant Therapy; Neoplasms; Connective and Soft Tissue; Patient Reported Outcome Measures; Radiotherapy; Adjuvant

The helical domain of GBP-1 mediates the inhibition of endothelial cell proliferation by inflammatory cytokines. - Guenzi, Eric; Töpolt, Kristin; Cornali, Emmanuelle; Lubeseder‐Martellato, Clara; Jörg, Anita; Matzen, Kathrin; Zietz, Christian; Kremmer, Elisabeth; Nappi, Filomena; Schwemmle, Martin; Hohenadl, Christine; Barillari, Giovanni; et al. (EMBO Journal, 2001)
Inflammatory cytokines (IC) activate endothelial cell adhesiveness for monocytes and inhibit endothelial cell growth. Here we report the identification of the human guanylate binding protein-1 (GBP-1) as the key and specific mediator of the anti-proliferative effect of IC on endothelial cells. GBP-1 expression was induced by IC, downregulated by angiogenic growth factors, and inversely related to cell proliferation both in vitro in microvascular and macrovascular endothelial cells and in vivo in vessel endothelial cells of Kaposi's sarcoma. Experimental modulation of GBP-1 expression demonstrated that GBP-1 mediates selectively the anti-proliferative effect of IC, without affecting endothelial cell adhesiveness for monocytes. GBP-1 anti-proliferative activity did not affect ERK-1/2 activation, occurred in the absence of apoptosis, was found to be independent of the GTPase activity and isoprenylation of the molecule, but was specifically mediated by the C-terminal helical domain of the protein. These results define GBP-1 as an important tool for dissection of the complex activity of IC on endothelial cells, and detection and specific modulation of the IC-activated non-proliferating phenotype of endothelial cells in vascular diseases.

The Histone Demethylase Jumonji Domain-Containing Protein 3 (JMJD3) As Central Mediator of Fibroblast Activation - Bergmann, Christina; Brandt, Adrian; Dees, Clara; Zhang, Yun; Chen, Chih-Wei; Mallano, Tatjana; Wohlfahrt, Thomas; Liang, Ruifang; Kagwiria, Rosebeth; Bozec, Aline; Rieker, Ralf; Abraham, David; et al. (2017)
EVALuna2:33428

The histone demethylase Jumonji domain-containing protein 3 (JMJD3) regulates fibroblast activation in systemic sclerosis - Bergmann, Christina; Brandt, Adrian; Merlevede, Benita; Hallenberger, Ludwig; Dees, Clara; Wohlfahrt, Thomas; Pötter, Sebastian; Zhang, Yun; Chen, Chih-Wei; Mallano, Tatjana; Liang, Ruifang; Kagwiria, Rosebeth; et al. (Annals of the Rheumatic Diseases, 2017)
Systemic sclerosis (SSc) fibroblasts remain activated even in the absence of exogenous stimuli. Epigenetic alterations are thought to play a role for this endogenous activation. Trimethylation of histone H3 on lysine 27 (H3K27me3) is regulated by Jumonji domain-containing protein 3 (JMJD3) and ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX) in a therapeutically targetable manner. The aim of this study was to explore H3K27me3 demethylases as potential targets for the treatment of fibrosis.JMJD3 was inactivated by small interfering RNA-mediated knockdown and by pharmacological inhibition with GSKJ4. The effects of targeted inactivation of JMJD3 were analysed in cultured fibroblasts and in the murine models of bleomycin-induced and topoisomerase-I (topoI)-induced fibrosis. H3K27me3 at the FRA2 promoter was analysed by ChIP.The expression of JMJD3, but not of UTX, was increased in fibroblasts in SSc skin and in experimental fibrosis in a transforming growth factor beta (TGF?)-dependent manner. Inactivation of JMJD3 reversed the activated fibroblast phenotype in SSc fibroblasts and prevented the activation of healthy dermal fibroblasts by TGF?. Pharmacological inhibition of JMJD3 ameliorated bleomycin-induced and topoI-induced fibrosis in well-tolerated doses. JMJD3 regulated fibroblast activation in a FRA2-dependent manner: Inactivation of JMJD3 reduced the expression of FRA2 by inducing accumulation of H3K27me3 at the FRA2 promoter. Moreover, the antifibrotic effects of JMJD3 inhibition were reduced on knockdown of FRA2.We present first evidence for a deregulation of JMJD3 in SSc. JMJD3 modulates fibroblast activation by regulating the levels of H3K27me3 at the promoter of FRA2. Targeted inhibition of JMJD3 limits the aberrant activation of SSc fibroblasts and exerts antifibrotic effects in two murine models.
EVALuna2:13457

The impact of body mass index on prognosis in patients with colon carcinoma - Fuchs, Julian; Schellerer, Vera S.; Brunner, Maximilian; Geppert, Carol-Immanuel; Grützmann, Robert; Weber, Klaus; Merkel, Susanne (International Journal of Colorectal Disease, 2022)
Background: The impact of body mass index (BMI) on prognosis in patients with curatively resected stage I–III colon carcinoma was analyzed. Methods: The prospectively collected data of 694 patients who underwent complete mesocolic excision between 2003 and 2014 were analyzed. BMI was classified into four categories: underweight (BMI < 18.5 kg/m2; n = 13), normal weight (BMI 18.5 to 24.9 kg/m2; n = 221), overweight (BMI 25.0 to 29.9 kg/m2; n = 309), and obese (BMI ≥ 30.0 kg/m2; n = 151). Univariate and multivariate analyses for comparison of prognosis were performed. Results: The 5-year rate of locoregional recurrence in all 694 patients was 2.1%, and no differences were found with respect to BMI (p = 0.759). For distant metastasis, the 5-year rate for all patients was 13.4%, and BMI did not have a significant impact (p = 0.593). The 5-year rate of disease-free survival for all 694 patients was 72.4%. The differences with respect to BMI were not found to be significant in univariate analysis (p = 0.222). In multivariate Cox regression analysis, disease-free survival was significantly better in obese patients (HR 0.7; p = 0.034). Regarding overall survival, the 5-year rate for all patients was 78.1%. In univariate analyses, no significant differences were found for BMI (p = 0.094). In the Cox regression analysis, overweight and obese patients had significantly better survival (overweight: HR 0.7; p = 0.027; obese: HR 0.6; p = 0.019). Conclusion: The better survival of overweight and obese patients in multivariate analyses must be interpreted with caution. It is influenced by several factors and seems to correspond to the phenomenon of the obesity paradox.
CRIS-Team Scopus Importer:2022-04-22
Keywords: Body mass index; Colon carcinoma; Obesity paradox; Overall survival; Prognosis

The Impact of Chronic Kidney Disease on Mid-Term Outcomes after Revascularisation of Peripheral Arterial Occlusive Disease: Results from a Prospective Cohort Study - Kotov, Artur; Blasche, Deven A.; Peters, Frederik; Pospiech, Philip; Rother, Ulrich; Stavroulakis, Konstantinos; Remig, Juergen; Schmidt-Lauber, Christian; Zeller, Thomas; Goertz, Hartmut; Tessarek, Jorg; Behrendt, Christian-Alexander (Journal of Clinical Medicine, 2022)
Objective: The current study aimed to determine the relationship between chronic kidney disease (CKD) and major 12-month outcomes for patients with in-hospital treatment for symptomatic peripheral arterial occlusive disease (PAOD). Methods: An analysis of the prospective longitudinal multicentric cohort study with 12-month follow-up was conducted including patients who underwent endovascular or open surgery for symptomatic PAOD at 35 German vascular centres (initial study protocol: NCT03098290). Severity of CKD was grouped into four stages combining information about the estimated glomerular filtration rate (eGFR) at baseline and dialysis dependency. Outcomes included overall mortality as well as the two composite endpoints of amputation or death, and of major cardiovascular events (MACE). 12-month incidences and adjusted hazard ratios were estimated using the Kaplan-Meier function and Cox proportional hazard models. Results: A total of 4354 patients (32% female, 69 years mean age, 68% intermittent claudication, 69% percutaneous endovascular revascularisation) were included and followed for 244 days in median. Thereof, 22% had any CKD and 5% had end stage kidney disease (ESKD) at baseline. The 12-month overall mortality rate was 3.6% (95% CI 2.3-4.9) with 96 events in the entire cohort: 147 were amputated or died (5.3%, 95% CI 5.2-5.3), and 277 had a MACE (9.5%, 95% CI 9.4-9.5). When compared with patients without kidney disease, ESKD was significantly associated with overall mortality (HR 1.9; 95% CI 1.1-3.5), amputation or death (HR 2.4; 95% CI 1.4-4.1), and MACE (HR 2.0; 95% CI 1.3-3.2). Conclusions: In the current study on mid-term outcomes after invasive revascularisation for symptomatic PAOD, one out of five patients suffered from any CKD while those few with ESKD had twice the odds of death, of amputation or death, and of major adverse cardiovascular events after twelve months. These results emphasise that concomitant CKD and its impact on outcomes should be considered by severity while mild and moderate grades should not lead to ineffectual treatment strategies.
CRIS-Team WoS Importer:2022-09-09

The impact of surgical experience and frequency of practice on perioperative outcomes in pancreatic surgery - Krautz, Christian; Haase, Elisabeth; Elshafei, Moustafa; Saeger, Hans Detlev; Distler, Marius; Grützmann, Robert; Weber, Georg (BMC Surgery, 2019)
Objective: We aimed to determine the impact of surgical experience and frequency of practice on perioperative morbidity and mortality in pancreatic surgery. Methods: 1281 patients that underwent pancreatic resections from 1993 to 2013 were retrospectively analyzed using logistic regression models. All cases were stratified according to the surgeon's level of experience, which was based on the number of previously performed pancreatic resections and the extent of received supervision (novice: N < 20/intensive; intermediate: N = 21-90/decreasing; and experienced surgeon: N > 90/none). Additional stratification was based on the frequency of practice (sporadic: 3 resections > 6 weeks, frequent: 3 resections ≤6 weeks). Results: The novice and experienced categories were related to a decreased risk of postoperative pancreatic fistulas (odds ratio [OR] 0.46, 95% confidence interval [CI] 0.26-0.82 and 0.54, 95% CI 0.36-0.82) and in-hospital mortality (OR 0.45, 95% CI 0.17-1.16 and 0.42, 95% CI 0.21-0.83) compared to the intermediate category. Frequent practice was associated with a significantly lower risk of delayed gastric emptying (OR 0.56, 95% CI 0.38-0.83), postpancreatectomy hemorrhage (OR 0.64, 95% CI 0.42-0.98) and in-hospital mortality (OR 0.45, 95% CI 0.24-0.87). Conclusions: Our results emphasize the importance of supervision within a pancreatic surgery training program. In addition, our data underline the need of a sufficient patient caseload to ensure frequent practice.
CRIS-Team Scopus Importer:2019-08-27
Keywords: Frequency of practice; In-hospital mortality; Pancreatic surgery; Perioperative outcomes; Surgical experience; Volume-outcome relationship

The impact of surgical quality on prognosis in patients undergoing rectal carcinoma surgery after preoperative chemoradiation - Kiehlmann, Marcus; Weber, Klaus; Göhl, Jonas; Fietkau, Rainer; Agaimy, Abbas; Hohenberger, Werner; Merkel, Susanne (International Journal of Colorectal Disease, 2016)
The aim of the study was to analyse the impact of surgical quality on the prognosis of rectal carcinoma patients who underwent preoperative long-term chemoradiation and TME surgery.In a total of 314 patients, four quality indicators, including plane of surgery, pathological circumferential resection margin (pCRM), intraoperative local tumour cell dissemination and anastomotic leakage, were analysed with respect to locoregional recurrence, distant metastasis and overall survival.In 260 (82.8 %) of the patients, all four quality indicators were fulfilled. In 30 (9.6 %) of the patients, at least one quality indicator was not fulfilled; in 24 (7.6 %) of the patients, the data were not complete. Locoregional recurrence was significantly increased in patients who underwent surgery in the muscularis propria plane, who had a pCRM <= 1 mm or who experienced local tumour cell dissemination. In patients who had at least one quality indicator that was not fulfilled (suboptimal surgical quality), the 5-year rate of locoregional recurrence in those patients was 23.1 % compared to 4.8 % in patients who underwent optimal surgery (P = 0.001). In multivariate analysis, suboptimal surgery (hazard ratio (HR) 3.9; P = 0.020), abdominoperineal excision (HR 4.7; P = 0.003) and poor regression of primary tumours (HR 8.5; P < 0.001) were identified as independent prognostic factors for locoregional recurrence. In contrast to type of surgical treatment, ypT, ypN and regression grade, the quality of surgery did not significantly influence distant metastasis or overall survival.Even after preoperative chemoradiation, the surgical quality still has a strong impact on local control in patients with rectal carcinoma.
EVALuna2:6711

The importance of pancreatic inflammation in endosonographic diagnostics of solid pancreatic masses - Vitali, Francesco; Strobel, Deike; Frulloni, Luca; Heinrich, Marc Christopher; Pfeifer, Lukas; Görtz, Rüdiger; Hundorfean, Gheorghe; Wachter, David Lukas; Wachter, David; Grützmann, Robert; Bernatik, Thomas; Neurath, Markus; et al. (Medical Ultrasonography, 2018)
AIMS: Endosonography (EUS) is one of the main diagnostic tools for the differential diagnosis of pancreatic masses. The aim of our study was to describe the value of this technique in the work-up of solid pancreatic lesions, considering the influence of the morphological evidence of pancreatic inflammation in the diagnostic process. MATERIAL AND METHODS: Retrospective analysis of prospectively collected data in our tertiary University center. From March 2007 to October 2015, 218 patients underwent EUS for a suspected solid pancreatic neoplasm (based on previous cross-sectional imaging results, idiopatic acute pancreatitis, weight loss, pancreatic hyperenzymemia, painless jaundice or elevated Ca 19-9 values). RESULTS: Malignant lesions were diagnosed in 98 (45%) patients. Sensitivity of EUS for malignancy was 91% and specificity 89.2%. Signs of pancreatic inflammation in the surrounding pancreatic parenchyma around the focal lesion were present in 97 patients (44.4%)(more often in men, smokers and drinkers, and the most common etiology was focal chronic pancreatitis) and in these patients the sensitivity and sensibility dropped to 44% and 87.1%, respectively. In patients without signs of pancreatic inflammation, the pancreatic focal lesions were adenocarcinoma, neuroendocrine tumor, ventral/dorsal split, non-pancreatic pathology, pancreatic lipomatosis and autoimmune pancreatitis. CONCLUSION: Pancreatic inflammation (either focal or involving the whole gland) lowers the diagnostic sensibility of EUS in the work- up of pancreatic masses suspected for cancer, requiring further invasive diagnostic methods. Focal autoimmune pancreatitis and paraduodenal pancreatitis are still confused with pancreatic cancer, even in the absence of pancreatic inflammation.
EVALuna2:35194

The Influence of Body Mass Index on Long-Term Prognosis in Patients with Colon Carcinomas - Merkel, Susanne; Fuchs, Julian; Schellerer, Vera; Brunner, Maximilian; Geppert, Carol-Immanuel; Grützmann, Robert; Weber, Klaus (ONCOLOGY RESEARCH AND TREATMENT, 2020)
CRIS-Team WoS Importer:2020-03-20

The influence of expectations on recovery, quality of life, and treatment satisfaction in surgical patients - Weiss, Maren; Siassi, Ramin Michael; Hohenberger, Werner; Lösel, Friedrich (Psychology of Expectations, 2010)

The influence of four different anticoagulants on dynamic light scattering of platelets - Raczat, Tatjana; Kraemer, L.; Gall, Christine; Weiss, D. R.; Eckstein, Reinhold; Ringwald, J. (Vox Sanguinis, 2014)
For testing of dynamic light scattering of platelets with ThromboLUX (TLX) in platelet-rich plasma (PRP) derived from venous whole blood (vWB), anticoagulation is needed. We compared TLX score in PRPs containing citrate, ethylene-diamine-tetraacetic-acid (EDTA), citrate-phosphate-dextrose-adenine (CPDA) or citrate-theophylline-adenosine-dipyridamole. Initial and late TLX scores were measured after 30-120 min or four to six hours, respectively. Compared with citrate, mean differences in initial TLX score were only significant for CPDA. Also, mean differences between initial and late TLX scores were only significant for CPDA. TLX failed to detect EDTA-induced platelet alterations. The clinical relevance of TLX needs further studies.
EVALuna2:5452

The Influence of Liver Resection on Intrahepatic Tumor Growth - Brandt, Hannes; Nissler, Valerie; Croner, Roland S. (Journal of Visualized Experiments, 2016)
The high incidence of tumor recurrence after resection of metastatic liver lesions remains an unsolved problem. Small tumor cell deposits, which are not detectable by routine clinical imaging, may be stimulated by hepatic regeneration factors after liver resection. It is not entirely clear, however, which factors are crucial for tumor recurrence. The presented mouse model may be useful to explore the mechanisms that play a role in the development of recurrent malignant lesions after liver resection. The model combines the easy-to-perform and reproducible techniques of defined amounts of liver tissue removal and tumor induction (by injection) in mice. The animals were treated with either a single laparotomy, a 30% liver resection, or a 70% liver resection. All animals subsequently received a tumor cell injection into the remaining liver tissue. After two weeks of observation, the livers and tumors were evaluated for size and weight and examined by immunohistochemistry. After a 70% liver resection, the tumor volume and weight were significantly increased compared to a laparotomy alone (p <0.05). In addition, immunohistochemistry (Ki67) showed an increased tumor proliferation rate in the resection group (p <0.05). These findings demonstrate the influence of hepatic regeneration mechanisms on intrahepatic tumor growth. Combined with methods like histological workup or RNA analysis, the described mouse model could serve as foundation for a close examination of different factors involved in tumor growth and metastatic disease recurrence within the liver. A considerable number of variables like the length of postoperative observation, the cell line used for injection or the timing of injection and liver resection offer multiple angles when exploring a specific question in the context of post-hepatectomy metastases. The limitations of this procedure are the authorization to perform the procedure on animals, access to an appropriate animal testing facility and acquisition of certain equipment.
EVALuna2:15242

The influence of postoperative complications on long-term prognosis in patients with colorectal carcinoma - Beck, Clemens; Weber, Klaus; Brunner, Maximilian; Agaimy, Abbas; Semrau, Sabine; Grützmann, Robert; Schellerer, Vera; Merkel, Susanne (International Journal of Colorectal Disease, 2020)
Background: The impact of postoperative complications (POCs) on the long-term prognosis of patients with colorectal carcinoma was analysed with respect to their severity according to the Clavien-Dindo classification (CDC). Methods: The prospectively collected data of 2158 patients who underwent curative resection of a colorectal carcinoma (1168 rectal carcinomas, 990 colon carcinomas) without distant metastases from 1995 to 2014 were analysed. The POCs were documented in a standardized form and graded with the CDC. Patients who died postoperatively (CDC grade V, 1.7%) were excluded. Results: In total, 467 patients (21.6%) had POCs: CDC I, 141 (6.5%); CDC II, 162 (7.5%); CDC III, 112 (5.2%); and CDC IV, 52 (2.4%). More POCs and higher CDC grades were found in men, ASA III-IV patients, rectal carcinoma patients, and patients who underwent abdominoperineal excisions or multivisceral resections. The 5-year locoregional recurrence rate was 5.3% in patients without POCs and 6.6% in patients with POCs. It was highest in CDC III patients (12.9%), which was confirmed in multivariate analysis (HR 2.2; p = 0.005). The 5-year distant metastasis rate was 15.9% in CDC 0 patients and 19.5% in CDC I–IV patients. In multivariate analysis, distant metastasis was highest in CDC III patients (HR 1.7; p = 0.020). The 5-year overall survival rate was 83.5% in patients without POCs and 73.5% in patients with POCs. It was worst in CDC IV patients (63.1%), which was confirmed by multivariate analysis (HR 1.9; p = 0.001). Conclusion: Patients with POCs after colorectal surgery have a poor long-term prognosis. As the CDC grade increases, survival deteriorates.
CRIS-Team Scopus Importer:2020-04-14
Keywords: Clavien-Dindo classification; Colorectal carcinoma; Postoperative complications; Prognosis

The Influence of Postoperative Complications on Long-Term Prognosis in Patients with Colorectal Carcinomas - Beck, Clemens; Schellerer, Vera; Weber, Klaus; Brunner, Maximilian; Agaimy, Abbas; Semrau, Sabine; Grützmann, Robert; Merkel, Susanne (ONCOLOGY RESEARCH AND TREATMENT, 2020)
CRIS-Team WoS Importer:2020-03-20

The influence of pre-analytical conditions on platelet-derived microparticles - Eckstein, Fabian; Xiang, Wei; Weiss, Dominik R; Zimmermann, Robert; Strasser, Erwin F (Clinical Laboratory, 2014)
Microparticles (MP) have recently become a focus of both research and clinical investigations. As pre-analytical conditions frequently remain unpublished, further studies are needed to analyze their impact on MP release.This prospective study investigated the effect of sequential storage under three different sets of conditions (fresh; storage at 4 degrees C for 24 hours, SC1; storage at -70 degrees C for 24 hours, SC2) and agitation on platelet-derived MP (PMP) in 11 healthy blood donors (6 male, 5 female). PMP were quantified using flow cytometry (FCM) for analysis of all events positive for both CD41a-PE and Annexin-V-FITC. Newly developed calibration beads for FCM (size of 0.3 - 0.9 microm) were applied for FCM. For functional testing a phospholipid-dependent clotting assay (XACT) was used.PMP concentration increased 1.7-fold in platelet-poor plasma (PPP) under SC1 and further increased 1.6-fold (p < 0.001) under SC2 (p = 0.005). Overall, samples of SC2 had a 5.5-fold increased count of large PMP (0.5 - 0.9 microm) compared to baseline. Results in samples of SC2 ranged from 40.1 seconds to 80.3 seconds but on average the CT was also shortened compared to the CT for SC1 and fresh samples. Additional agitation before PPP preparation reduced the PMP concentration by around 50% (p = 0.025). 135% more small PMP were detected with recently developed calibration beads. Compared to CT (XACT) flow cytometry using Megamix Plus calibration beads is able to reveal significant differences between the analyzed preanalytical conditions.Fresh blood samples should be used for standardizing PMP analysis. Calibration beads for FCM (size of 0.3 - 0.9 microm) have shown to be a reliable tool for PMP quantification especially for PMP of smaller sizes up to 300 nm. Agitation of blood samples before PMP analysis should be avoided. The application of XACT is limited for the analysis of preanalytical conditions.
EVALuna2:4693

The influence of tumour site on prognosis in metastatic colorectal carcinomas with primary tumour resection - Merkel, Susanne; Schellerer, Vera; Wein, Axel; Semrau, Sabine; Geppert, Carol-Immanuel; Göhl, Jonas; Hohenberger, Werner; Weber, Klaus; Grützmann, Robert (International Journal of Colorectal Disease, 2018)
PURPOSE: The aim of our study was to compare the characteristics and prognosis between right- and left-sided metastatic colorectal carcinomas. METHODS: Data from 937 patients with stage IV colorectal carcinomas (synchronous distant metastasis) who had a resection of the primary tumour between 1985 and 2014 were analysed. Carcinomas in the caecum to transverse colon were defined as right-sided (n = 250; 26.7%). They were compared to tumours located from the splenic flexure to the rectum categorised as left-sided (n = 687; 73.3%). RESULTS: In right-sided carcinomas, we observed significantly more female patients (50.8 vs 36.2%; p < 0.001), more unfavourable histological types (24.0 vs 8.6%; p < 0.001), more M1c carcinomas (metastases to the peritoneum ± others; 32.0 vs 14.4%; p < 0.001) and more emergencies (11.6 vs 7.1%; p = 0.029), while multimodal treatment was utilised in fewer patients (51.6 vs 63.8%; p = 0.001) and curative resections were less frequently (24.1 vs 35.4%; p = 0.002). Prognosis was significantly worse in patients with right-sided carcinomas (2-year-survival 27.2 vs 44.6%, p < 0.01). This difference was more pronounced after R2 resection (15.3 vs 29.7%; p < 0.001), than after macroscopic curative resection (2-year-survival 63.9 vs 71.9%; p = 0.106). In multivariate Cox regression analysis, tumour site was found to be an independent prognostic factor for overall survival (HR 1.2; 95% CI 1.0-1.5; p = 0.012). During the three 10-year periods, the prognosis improved equally in patients with right- and left-sided carcinomas, while the differences in survival remained identical. CONCLUSIONS: In a surgical patient cohort undergoing primary tumour resection, significant differences in prognosis were observed between patients with metastatic right- and left-sided colorectal carcinomas.
EVALuna2:35146

The Intratumoral and Intestinal Microbiome in Pancreatic Cancer - Langheinrich, Melanie; Wirtz, Stefan; Grützmann, Robert; Kersting, Stephan; Weber, Georg (ONCOLOGY RESEARCH AND TREATMENT, 2020)
CRIS-Team WoS Importer:2020-03-20

The large GTPase AtGBPL3 links nuclear envelope formation and morphogenesis to transcriptional repression - Reimann, Theresa; Müdsam, Christina; Schachtler, Christina; Ince, Semra; Sticht, Heinrich; Herrmann, Christian; Stürzl, Michael; Kost, Benedikt (Nature Plants, 2023)
Guanylate binding proteins (GBPs) are prominent regulators of immunity not known to be required for nuclear envelope formation and morphogenesis. Here we identify the Arabidopsis GBP orthologue AtGBPL3 as a lamina component with essential functions in mitotic nuclear envelope reformation, nuclear morphogenesis and transcriptional repression during interphase. AtGBPL3 is preferentially expressed in mitotically active root tips, accumulates at the nuclear envelope and interacts with centromeric chromatin as well as with lamina components transcriptionally repressing pericentromeric chromatin. Reduced expression of AtGBPL3 or associated lamina components similarly altered nuclear morphology and caused overlapping transcriptional deregulation. Investigating the dynamics of AtGBPL3-GFP and other nuclear markers during mitosis (1) revealed that AtGBPL3 accumulation on the surface of daughter nuclei precedes nuclear envelope reformation and (2) uncovered defects in this process in roots of AtGBPL3 mutants, which cause programmed cell death and impair growth. AtGBPL3 functions established by these observations are unique among dynamin-family large GTPases.
CRIS-Team WoS Importer:2023-05-26

The long-term influence of hospital and surgeon volume on local control and survival in the randomized German Rectal Cancer Trial CAO/ARO/AIO-94 - Sprenger, Thilo; Beissbarth, Tim; Sauer, Rolf; Tschmelitsch, Joerg; Fietkau, Rainer; Hohenberger, Werner; Staib, Ludger; Raab, Hans-Rudolf; Roedel, Claus; Ghadimi, Michael (Surgical Oncology-Oxford, 2020)
Background: The association of treatment volume and oncological outcome of rectal cancer patients undergoing multidisciplinary treatment is subject of an ongoing debate. Prospective data on long-term local control and overall survival (OS) are not available so far. This study investigated the long-term influence of hospital and surgeon volume on local recurrence (LR) and OS in patients with locally advanced rectal cancers.
CRIS-Team WoS Importer:2021-01-08

The Mesentery-Past, Present, and Future - Coffey, J. Calvin; Hohenberger, Werner; Heald, R. (Clinics in Colon and Rectal Surgery, 2022)
This article summarizes the events that shaped our current understanding of the mesentery and the abdomen. The story of how this evolved is intriguing at several levels. It speaks to considerable personal commitment on the part of the pioneers involved. It explains how scientific and clinical fields went different directions with respect to anatomy and clinical practice. It demonstrates that it is no longer acceptable to adhere unquestioningly to models of abdominal anatomy and surgery. The article concludes with a brief description of the Mesenteric Model of abdominal anatomy, and of how this now presents an opportunity to unify scientific and clinical approaches to the latter.
CRIS-Team Scopus Importer:2022-09-02
Keywords: history; mesentery; surgery