@article{WiegeringSchmidAndresetal.2014, author = {Wiegering, Verena and Schmid, Sophie and Andres, Oliver and Wirth, Clemens and Wiegering, Armin and Meyer, Thomas and Winkler, Beate and Schlegel, Paul G. and Eyrich, Matthias}, title = {Thrombosis as a complication of central venous access in pediatric patients with malignancies: a 5-year single-center experience}, doi = {10.1186/2052-1839-14-18}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-110476}, year = {2014}, abstract = {Background Reliable central venous access (CVC) is essential for hematology-oncology patients since frequent puncture of peripheral veins—e.g., for chemotherapy, antibiotic administration, repeated blood sampling, and monitoring—can cause unacceptable pain and psychological trauma, as well as severe side effects in cases of extravasation of chemotherapy drugs. However, CVC lines still carry major risk factors, including thrombosis, infection (e.g., entry site, tunnel, and luminal infections), and catheter dislocation, leakage, or breakage. Methods Here we performed a retrospective database analysis to determine the incidence of CVC-associated thrombosis in a single-center cohort of 448 pediatric oncologic patients, and to analyze whether any subgroup of patients was at increased risk and thus might benefit from prophylactic anticoagulation. Results Of the 448 patients, 269 consecutive patients received a CVC, and 55 of these 269 patients (20\%) also had a thrombosis. Of these 55 patients, 43 had at least one CVC-associated thrombosis (total number of CVC-associated thrombosis: n = 52). Among all patients, the median duration of CVC exposure was 464 days. Regarding exposure time, no significant difference was found between patients with and without CVC-associated thrombosis. Subclavia catheters and advanced tumor stages seem to be the main risk factors for the development of CVC-associated thrombosis, whereas pharmacologic prophylaxis did not seem to have a relevant impact on the rate of thrombosis. Conclusions We conclude that pediatric surgeons and oncologists should pay close attention to ensuring optimal and accurate CVC placement, as this appears the most effective tool to minimize CVC-associated complications.}, language = {en} } @article{WiegeringRiegelWagneretal.2017, author = {Wiegering, Armin and Riegel, Johannes and Wagner, Johanna and Kunzmann, Volker and Baur, Johannes and Walles, Thorsten and Dietz, Ulrich and Loeb, Stefan and Germer, Christoph-Thomas and Steger, Ulrich and Klein, Ingo}, title = {The impact of pulmonary metastasectomy in patients with previously resected colorectal cancer liver metastases}, series = {PLoS ONE}, volume = {12}, journal = {PLoS ONE}, number = {3}, doi = {10.1371/journal.pone.0173933}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158036}, pages = {e0173933}, year = {2017}, abstract = {Background 40-50\% of patients with colorectal cancer (CRC) will develop liver metastases (CRLM) during the course of the disease. One third of these patients will additionally develop pulmonary metastases. Methods 137 consecutive patients with CRLM, were analyzed regarding survival data, clinical, histological data and treatment. Results were stratified according to the occurrence of pulmonary metastases and metastases resection. Results 39\% of all patients with liver resection due to CRLM developed additional lung metastases. 44\% of these patients underwent subsequent pulmonary resection. Patients undergoing pulmonary metastasectomy showed a significantly better five-year survival compared to patients not qualified for curative resection (5-year survival 71.2\% vs. 28.0\%; p = 0.001). Interestingly, the 5-year survival of these patients was even superior to all patients with CRLM, who did not develop pulmonary metastases (77.5\% vs. 63.5\%; p = 0.015). Patients, whose pulmonary metastases were not resected, were more likely to redevelop liver metastases (50.0\% vs 78.6\%; p = 0.034). However, the rate of distant metastases did not differ between both groups (54.5 vs.53.6; p = 0.945). Conclusion The occurrence of colorectal lung metastases after curative liver resection does not impact patient survival if pulmonary metastasectomy is feasible. Those patients clearly benefit from repeated resections of the liver and the lung metastases.}, language = {en} } @article{WiegeringPfannUtheetal.2013, author = {Wiegering, Armin and Pfann, Christina and Uthe, Friedrich Wilhelm and Otto, Christoph and Rycak, Lukas and M{\"a}der, Uwe and Gasser, Martin and Waaga-Gasser, Anna-Maria and Eilers, Martin and Germer, Christoph-Thomas}, title = {CIP2A Influences Survival in Colon Cancer and Is Critical for Maintaining Myc Expression}, series = {PLoS ONE}, journal = {PLoS ONE}, doi = {10.1371/journal.pone.0075292}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97252}, year = {2013}, abstract = {The cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncogenic factor that stabilises the c-Myc protein. CIP2A is overexpressed in several tumours, and expression levels are an independent marker for long-term outcome. To determine whether CIP2A expression is elevated in colon cancer and whether it might serve as a prognostic marker for survival, we analysed CIP2A mRNA expression by real-time PCR in 104 colon cancer samples. CIP2A mRNA was overexpressed in colon cancer samples and CIP2A expression levels correlated significantly with tumour stage. We found that CIP2A serves as an independent prognostic marker for disease-free and overall survival. Further, we investigated CIP2A-dependent effects on levels of c-Myc, Akt and on cell proliferation in three colon cancer cell lines by silencing CIP2A using small interfering (si) and short hairpin (sh) RNAs. Depletion of CIP2A substantially inhibited growth of colon cell lines and reduced c-Myc levels without affecting expression or function of the upstream regulatory kinase, Akt. Expression of CIP2A was found to be dependent on MAPK activity, linking elevated c-Myc expression to deregulated signal transduction in colon cancer.}, language = {en} } @article{WiegeringMatthesMuehlingetal.2017, author = {Wiegering, Armin and Matthes, Niels and M{\"u}hling, Bettina and Koospal, Monika and Quenzer, Anne and Peter, Stephanie and Germer, Christoph-Thomas and Linnebacher, Michael and Otto, Christoph}, title = {Reactivating p53 and Inducing Tumor Apoptosis (RITA) Enhances the Response of RITA-Sensitive Colorectal Cancer Cells to Chemotherapeutic Agents 5-Fluorouracil and Oxaliplatin}, series = {Neoplasia}, volume = {19}, journal = {Neoplasia}, number = {4}, doi = {10.1016/j.neo.2017.01.007}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-171067}, pages = {301-309}, year = {2017}, abstract = {Colorectal carcinoma (CRC) is the most common cancer of the gastrointestinal tract with frequently dysregulated intracellular signaling pathways, including p53 signaling. The mainstay of chemotherapy treatment of CRC is 5-fluorouracil (5FU) and oxaliplatin. The two anticancer drugs mediate their therapeutic effect via DNA damage-triggered signaling. The small molecule reactivating p53 and inducing tumor apoptosis (RITA) is described as an activator of wild-type and reactivator of mutant p53 function, resulting in elevated levels of p53 protein, cell growth arrest, and cell death. Additionally, it has been shown that RITA can induce DNA damage signaling. It is expected that the therapeutic benefits of 5FU and oxaliplatin can be increased by enhancing DNA damage signaling pathways. Therefore, we highlighted the antiproliferative response of RITA alone and in combination with 5FU or oxaliplatin in human CRC cells. A panel of long-term established CRC cell lines (n = 9) including p53 wild-type, p53 mutant, and p53 null and primary patient-derived, low-passage cell lines (n = 5) with different p53 protein status were used for this study. A substantial number of CRC cells with pronounced sensitivity to RITA (IC\(_{50}\)< 3.0 μmol/l) were identified within established (4/9) and primary patient-derived (2/5) CRC cell lines harboring wild-type or mutant p53 protein. Sensitivity to RITA appeared independent of p53 status and was associated with an increase in antiproliferative response to 5FU and oxaliplatin, a transcriptional increase of p53 targets p21 and NOXA, and a decrease in MYC mRNA. The effect of RITA as an inducer of DNA damage was shown by a strong elevation of phosphorylated histone variant H2A.X, which was restricted to RITA-sensitive cells. Our data underline the primary effect of RITA, inducing DNA damage, and demonstrate the differential antiproliferative effect of RITA to CRC cells independent of p53 protein status. We found a substantial number of RITA-sensitive CRC cells within both panels of established CRC cell lines and primary patient-derived CRC cell lines (6/14) that provide a rationale for combining RITA with 5FU or oxaliplatin to enhance the antiproliferative response to both chemotherapeutic agents.}, language = {en} } @article{WiegeringKorbThalheimeretal.2014, author = {Wiegering, Armin and Korb, Doreen and Thalheimer, Andreas and K{\"a}mmerer, Ulrike and Allmanritter, Jan and Matthes, Niels and Linnebacher, Michael and Schlegel, Nicolas and Klein, Ingo and Erg{\"u}n, S{\"u}leyman and Germer, Christoph-Thomas and Otto, Christoph}, title = {E7080 (Lenvatinib), a Multi-Targeted Tyrosine Kinase Inhibitor, Demonstrates Antitumor Activities Against Colorectal Cancer Xenografts}, doi = {10.1016/j.neo.2014.09.008}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-111165}, year = {2014}, abstract = {Clinical prognosis of metastasized colorectal carcinoma (CRC) is still not at desired levels and novel drugs are needed. Here, we focused on the multi-tyrosine kinase inhibitor E7080 (Lenvatinib) and assessed its therapeutic efficacy against human CRC cell lines in vitro and human CRC xenografts in vivo. The effect of E7080 on cell viability was examined on 10 humanCRCcell lines and humanendothelial cells (HUVEC). The inhibitory effect of E7080 on VEGF-induced angiogenesis was studied in an ex vivo mouse aortic ring angiogenesis assay. In addition, the efficacy of E7080 against xenografts derived fromCRC cell lines and CRC patient resection specimenswithmutated KRASwas investigated in vivo. Arelatively low cytotoxic effect of E7080 on CRC cell viabilitywas observed in vitro. Endothelial cells (HUVEC)weremore susceptible to the incubation with E7080. This is in line with the observation that E7080 demonstrated an anti-angiogenic effect in a three-dimensional ex vivo mouse aortic ring angiogenesis assay. E7080 effectively disrupted CRC cell-mediated VEGF-stimulated growth of HUVEC in vitro. Daily in vivo treatment with E7080 (5 mg/kg) significantly delayed the growth of KRAS mutated CRC xenografts with decreased density of tumor-associated vessel formations and without tumor regression. This observation is in line with results that E7080 did not significantly reduce the number of Ki67-positive cells in CRC xenografts. The results suggest antiangiogenic activity of E7080 at a dosage thatwas well tolerated by nudemice. E7080 may provide therapeutic benefits in the treatment of CRC with mutated KRAS.}, language = {en} } @article{WiegeringIsbertDietzetal.2014, author = {Wiegering, Armin and Isbert, Christoph and Dietz, Ulrich A. and Kunzmann, Volker and Ackermann, Sabine and Kerscher, Alexander and Maeder, Uwe and Flentje, Michael and Schlegel, Nicolas and Reibetanz, Joachim and Germer, Christoph-Thomas and Klein, Ingo}, title = {Multimodal therapy in treatment of rectal cancer is associated with improved survival and reduced local recurrence - a retrospective analysis over two decades}, doi = {10.1186/1471-2407-14-816}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-110606}, year = {2014}, abstract = {Background The management of rectal cancer (RC) has substantially changed over the last decades with the implementation of neoadjuvant chemoradiotherapy, adjuvant therapy and improved surgery such as total mesorectal excision (TME). It remains unclear in which way these approaches overall influenced the rate of local recurrence and overall survival. Methods Clinical, histological and survival data of 658 out of 662 consecutive patients with RC were analyzed for treatment and prognostic factors from a prospectively expanded single-institutional database. Findings were then stratified according to time of diagnosis in patient groups treated between 1993 and 2001 and 2002 and 2010. Results The study population included 658 consecutive patients with rectal cancer between 1993 and 2010. Follow up data was available for 99.6\% of all 662 treated patients. During the time period between 2002 and 2010 significantly more patients underwent neoadjuvant chemoradiotherapy (17.6\% vs. 60\%) and adjuvant chemotherapy (37.9\% vs. 58.4\%). Also, the rate of reported TME during surgery increased. The rate of local or distant metastasis decreased over time, and tumor related 5-year survival increased significantly with from 60\% to 79\%. Conclusion In our study population, the implementation of treatment changes over the last decade improved the patient's outcome significantly. Improvements were most evident for UICC stage III rectal cancer.}, language = {en} } @article{WidderKelmReibetanzetal.2022, author = {Widder, Anna and Kelm, Matthias and Reibetanz, Joachim and Wiegering, Armin and Matthes, Niels and Germer, Christoph-Thomas and Seyfried, Florian and Flemming, Sven}, title = {Robotic-assisted versus laparoscopic left hemicolectomy — postoperative inflammation status, short-term outcome and cost effectiveness}, series = {International Journal of Environmental Research and Public Health}, volume = {19}, journal = {International Journal of Environmental Research and Public Health}, number = {17}, issn = {1660-4601}, doi = {10.3390/ijerph191710606}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-286203}, year = {2022}, abstract = {Robotic-assisted colon surgery may contain advantages over the laparoscopic approach, but clear evidence is sparse. This study aimed to analyze postoperative inflammation status, short-term outcome and cost-effectiveness of robotic-assisted versus laparoscopic left hemicolectomy. All consecutive patients who received minimal-invasive left hemicolectomy at the Department of Surgery I at the University Hospital of Wuerzburg in 2021 were prospectively included. Importantly, no patient selection for either procedure was carried out. The robotic-assisted versus laparoscopic approaches were compared head to head for postoperative short-term outcomes as well as cost-effectiveness. A total of 61 patients were included, with 26 patients having received a robotic-assisted approach. Baseline characteristics did not differ among the groups. Patients receiving a robotic-assisted approach had a significantly decreased length of hospital stay as well as lower rates of complications in comparison to patients who received laparoscopic surgery (n = 35). In addition, C-reactive protein as a marker of systemic stress response was significantly reduced postoperatively in patients who were operated on in a robotic-assisted manner. Consequently, robotic-assisted surgery could be performed in a cost-effective manner. Thus, robotic-assisted left hemicolectomy represents a safe and cost-effective procedure and might improve patient outcomes in comparison to laparoscopic surgery.}, language = {en} } @article{WallaschekReuterSilkenatetal.2021, author = {Wallaschek, Nina and Reuter, Saskia and Silkenat, Sabrina and Wolf, Katharina and Niklas, Carolin and {\"O}zge, Kayisoglu and Aguilar, Carmen and Wiegering, Armin and Germer, Christoph-Thomas and Kircher, Stefan and Rosenwald, Andreas and Shannon-Lowe, Claire and Bartfeld, Sina}, title = {Ephrin receptor A2, the epithelial receptor for Epstein-Barr virus entry, is not available for efficient infection in human gastric organoids}, series = {PLoS Pathogens}, volume = {17}, journal = {PLoS Pathogens}, number = {2}, doi = {10.1371/journal.ppat.1009210}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259206}, pages = {e1009210}, year = {2021}, abstract = {Epstein-Barr virus (EBV) is best known for infection of B cells, in which it usually establishes an asymptomatic lifelong infection, but is also associated with the development of multiple B cell lymphomas. EBV also infects epithelial cells and is associated with all cases of undifferentiated nasopharyngeal carcinoma (NPC). EBV is etiologically linked with at least 8\% of gastric cancer (EBVaGC) that comprises a genetically and epigenetically distinct subset of GC. Although we have a very good understanding of B cell entry and lymphomagenesis, the sequence of events leading to EBVaGC remains poorly understood. Recently, ephrin receptor A2 (EPHA2) was proposed as the epithelial cell receptor on human cancer cell lines. Although we confirm some of these results, we demonstrate that EBV does not infect healthy adult stem cell-derived gastric organoids. In matched pairs of normal and cancer-derived organoids from the same patient, EBV only reproducibly infected the cancer organoids. While there was no clear pattern of differential expression between normal and cancer organoids for EPHA2 at the RNA and protein level, the subcellular location of the protein differed markedly. Confocal microscopy showed EPHA2 localization at the cell-cell junctions in primary cells, but not in cancer cell lines. Furthermore, histologic analysis of patient tissue revealed the absence of EBV in healthy epithelium and presence of EBV in epithelial cells from inflamed tissue. These data suggest that the EPHA2 receptor is not accessible to EBV on healthy gastric epithelial cells with intact cell-cell contacts, but either this or another, yet to be identified receptor may become accessible following cellular changes induced by inflammation or transformation, rendering changes in the cellular architecture an essential prerequisite to EBV infection.}, language = {en} } @article{WagnerEikenHaubitzetal.2019, author = {Wagner, Johanna and Eiken, Barbara and Haubitz, Imme and Lichthardt, Sven and Matthes, Niels and L{\"o}b, Stefan and Klein, Ingo and Germer, Christoph-Thomas and Wiegering, Armin}, title = {Suprapubic bladder drainage and epidural catheters following abdominal surgery—a risk for urinary tract infections?}, series = {PLoS ONE}, volume = {14}, journal = {PLoS ONE}, number = {1}, doi = {10.1371/journal.pone.0209825}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177731}, pages = {e0209825}, year = {2019}, abstract = {Background Epidural catheters are state of the art for postoperative analgesic in abdominal surgery. Due to neurolysis it can lead to postoperative urinary tract retention (POUR), which leads to prolonged bladder catheterization, which has an increased risk for urinary tract infections (UTI). Our aim was to identify the current perioperative management of urinary catheters and, second, to identify the optimal time of suprapubic bladder catheter removal in regard to the removal of the epidural catheter. Methods We sent a questionnaire to 102 German hospitals and analyzed the 83 received answers to evaluate the current handling of bladder drainage and epidural catheters. Then, we conducted a retrospective study including 501 patients, who received an epidural and suprapubic catheter after abdominal surgery at the University Hospital W{\"u}rzburg. We divided the patients into three groups according to the point in time of suprapubic bladder drainage removal in regard to the removal of the epidural catheter and analyzed the onset of a UTI. Results Our survey showed that in almost all hospitals (98.8\%), patients received an epidural catheter and a bladder drainage after abdominal surgery. The point in time of urinary catheter removal was equally distributed between before, simultaneously and after the removal of the epidural catheter (respectively: ~28-29\%). The retrospective study showed a catheter-associated UTI in 6.7\%. Women were affected significantly more often than men (10,7\% versus 2,5\%, p<0.001). There was a non-significant trend to more UTIs when the suprapubic catheter was removed after the epidural catheter (before: 5.7\%, after: 8.4\%). Conclusion The point in time of suprapubic bladder drainage removal in relation to the removal of the epidural catheter does not seem to correlate with the rate of UTIs. The current handling in Germany is inhomogeneous, so further studies to standardize treatment are recommended.}, language = {en} } @article{WagnerWetzWiegeringetal.2021, author = {Wagner, Johanna C. and Wetz, Anja and Wiegering, Armin and Lock, Johan F. and L{\"o}b, Stefan and Germer, Christoph-Thomas and Klein, Ingo}, title = {Successful surgical closure of infected abdominal wounds following preconditioning with negative pressure wound therapy}, series = {Langenbeck's Archives of Surgery}, volume = {406}, journal = {Langenbeck's Archives of Surgery}, number = {7}, issn = {1435-2451}, doi = {10.1007/s00423-021-02221-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-267541}, pages = {2479-2487}, year = {2021}, abstract = {Purpose Traditionally, previous wound infection was considered a contraindication to secondary skin closure; however, several case reports describe successful secondary wound closure of wounds "preconditioned" with negative pressure wound therapy (NPWT). Although this has been increasingly applied in daily practice, a systematic analysis of its feasibility has not been published thus far. The aim of this study was to evaluate secondary skin closure in previously infected abdominal wounds following treatment with NPWT. Methods Single-center retrospective analysis of patients with infected abdominal wounds treated with NPWT followed by either secondary skin closure referenced to a group receiving open wound therapy. Endpoints were wound closure rate, wound complications (such as recurrent infection or hernia), and perioperative data (such as duration of NPWT or hospitalization parameters). Results One hundred ninety-eight patients during 2013-2016 received a secondary skin closure after NPWT and were analyzed and referenced to 67 patients in the same period with open wound treatment after NPWT. No significant difference in BMI, chronic immunosuppressive medication, or tobacco use was found between both groups. The mean duration of hospital stay was 30 days with a comparable duration in both patient groups (29 versus 33 days, p = 0.35). Interestingly, only 7.7\% of patients after secondary skin closure developed recurrent surgical site infection and in over 80\% of patients were discharged with closed wounds requiring only minimal outpatient wound care. Conclusion Surgical skin closure following NPWT of infected abdominal wounds is a good and safe alternative to open wound treatment. It prevents lengthy outpatient wound therapy and is expected to result in a higher quality of life for patients and reduce health care costs.}, language = {en} } @article{UttingerRiedmeierReibetanzetal.2022, author = {Uttinger, Konstantin L. and Riedmeier, Maria and Reibetanz, Joachim and Meyer, Thomas and Germer, Christoph Thomas and Fassnacht, Martin and Wiegering, Armin and Wiegering, Verena}, title = {Adrenalectomies in children and adolescents in Germany - a diagnose related groups based analysis from 2009-2017}, series = {Frontiers in Endocrinology}, volume = {13}, journal = {Frontiers in Endocrinology}, issn = {1664-2392}, doi = {10.3389/fendo.2022.914449}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-282280}, year = {2022}, abstract = {Background Adrenalectomies are rare procedures especially in childhood. So far, no large cohort study on this topic has been published with data on to age distribution, operative procedures, hospital volume and operative outcome. Methods This is a retrospective analysis of anonymized nationwide hospital billing data (DRG data, 2009-2017). All adrenal surgeries (defined by OPS codes) of patients between the age 0 and 21 years in Germany were included. Results A total of 523 patient records were identified. The mean age was 8.6 ± 7.7 years and 262 patients were female (50.1\%). The majority of patients were between 0 and 5 years old (52\% overall), while 11.1\% were between 6 and 11 and 38.8\% older than 12 years. The most common diagnoses were malignant neoplasms of the adrenal gland (56\%, mostly neuroblastoma) with the majority being younger than 5 years. Benign neoplasms in the adrenal gland (D350) account for 29\% of all cases with the majority of affected patients being 12 years or older. 15\% were not defined regarding tumor behavior. Overall complication rate was 27\% with a clear higher complication rate in resection for malignant neoplasia of the adrenal gland. Bleeding occurrence and transfusions are the main complications, followed by the necessary of relaparotomy. There was an uneven patient distribution between hospital tertiles (low volume, medium and high volume tertile). While 164 patients received surgery in 85 different "low volume" hospitals (0.2 cases per hospital per year), 205 patients received surgery in 8 different "high volume" hospitals (2.8 cases per hospital per year; p<0.001). Patients in high volume centers were significant younger, had more extended resections and more often malignant neoplasia. In multivariable analysis younger age, extended resections and open procedures were independent predictors for occurrence of postoperative complications. Conclusion Overall complication rate of adrenalectomies in the pediatric population in Germany is low, demonstrating good therapeutic quality. Our analysis revealed a very uneven distribution of patient volume among hospitals.}, language = {en} } @article{SuratVogelWiegeringetal.2021, author = {Surat, G{\"u}zin and Vogel, Ulrich and Wiegering, Armin and Germer, Christoph-Thomas and Lock, Johan Friso}, title = {Defining the scope of antimicrobial stewardship interventions on the prescription quality of antibiotics for surgical intra-abdominal infections}, series = {Antibiotics}, volume = {10}, journal = {Antibiotics}, number = {1}, issn = {2079-6382}, doi = {10.3390/antibiotics10010073}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-223034}, year = {2021}, abstract = {Background: The aim of this study was to assess the impact of antimicrobial stewardship interventions on surgical antibiotic prescription behavior in the management of non-elective surgical intra-abdominal infections, focusing on postoperative antibiotic use, including the appropriateness of indications. Methods: A single-center quality improvement study with retrospective evaluation of the impact of antimicrobial stewardship measures on optimizing antibacterial use in intra-abdominal infections requiring emergency surgery was performed. The study was conducted in a tertiary hospital in Germany from January 1, 2016, to January 30, 2020, three years after putting a set of antimicrobial stewardship standards into effect. Results: 767 patients were analyzed (n = 495 in 2016 and 2017, the baseline period; n = 272 in 2018, the antimicrobial stewardship period). The total days of therapy per 100 patient days declined from 47.0 to 42.2 days (p = 0.035). The rate of patients receiving postoperative therapy decreased from 56.8\% to 45.2\% (p = 0.002), comparing both periods. There was a significant decline in the rate of inappropriate indications (17.4\% to 8.1 \%, p = 0.015) as well as a significant change from broad-spectrum to narrow-spectrum antibiotic use (28.8\% to 6.5\%, p ≤ 0.001) for postoperative therapy. The significant decline in antibiotic use did not affect either clinical outcomes or the rate of postoperative wound complications. Conclusions: Postoperative antibiotic use for intra-abdominal infections could be significantly reduced by antimicrobial stewardship interventions. The identification of inappropriate indications remains a key target for antimicrobial stewardship programs.}, language = {en} } @article{SchmidtDenkWiegering2020, author = {Schmidt, Stefanie and Denk, Sarah and Wiegering, Armin}, title = {Targeting protein synthesis in colorectal cancer}, series = {Cancers}, volume = {12}, journal = {Cancers}, number = {5}, issn = {2072-6694}, doi = {10.3390/cancers12051298}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-206014}, year = {2020}, abstract = {Under physiological conditions, protein synthesis controls cell growth and survival and is strictly regulated. Deregulation of protein synthesis is a frequent event in cancer. The majority of mutations found in colorectal cancer (CRC), including alterations in the WNT pathway as well as activation of RAS/MAPK and PI3K/AKT and, subsequently, mTOR signaling, lead to deregulation of the translational machinery. Besides mutations in upstream signaling pathways, deregulation of global protein synthesis occurs through additional mechanisms including altered expression or activity of initiation and elongation factors (e.g., eIF4F, eIF2α/eIF2B, eEF2) as well as upregulation of components involved in ribosome biogenesis and factors that control the adaptation of translation in response to stress (e.g., GCN2). Therefore, influencing mechanisms that control mRNA translation may open a therapeutic window for CRC. Over the last decade, several potential therapeutic strategies targeting these alterations have been investigated and have shown promising results in cell lines, intestinal organoids, and mouse models. Despite these encouraging in vitro results, patients have not clinically benefited from those advances so far. In this review, we outline the mechanisms that lead to deregulated mRNA translation in CRC and highlight recent progress that has been made in developing therapeutic strategies that target these mechanisms for tumor therapy.}, language = {en} } @article{RiedmeierDecarolisHaubitzetal.2021, author = {Riedmeier, Maria and Decarolis, Boris and Haubitz, Imme and M{\"u}ller, Sophie and Uttinger, Konstantin and B{\"o}rner, Kevin and Reibetanz, Joachim and Wiegering, Armin and H{\"a}rtel, Christoph and Schlegel, Paul-Gerhardt and Fassnacht, Martin and Wiegering, Verena}, title = {Adrenocortical carcinoma in childhood: a systematic review}, series = {Cancers}, volume = {13}, journal = {Cancers}, number = {21}, issn = {2072-6694}, doi = {10.3390/cancers13215266}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-248507}, year = {2021}, abstract = {Adrenocortical tumors are rare in children. This systematic review summarizes the published evidence on pediatric adrenocortical carcinoma (ACC) to provide a basis for a better understanding of the disease, investigate new molecular biomarkers and therapeutic targets, and define which patients may benefit from a more aggressive therapeutic approach. We included 137 studies with 3680 ACC patients (~65\% female) in our analysis. We found no randomized controlled trials, so this review mainly reflects retrospective data. Due to a specific mutation in the TP53 gene in ~80\% of Brazilian patients, that cohort was analyzed separately from series from other countries. Hormone analysis was described in 2569 of the 2874 patients (89\%). Most patients were diagnosed with localized disease, whereas 23\% had metastasis at primary diagnosis. Only 72\% of the patients achieved complete resection. In 334 children (23\%), recurrent disease was reported: 81\% — local recurrence, 19\% (n = 65) — distant metastases at relapse. Patients < 4 years old had a different distribution of tumor stages and hormone activity and better overall survival (p < 0.001). Although therapeutic approaches are typically multimodal, no consensus is available on effective standard treatments for advanced ACC. Thus, knowledge regarding pediatric ACC is still scarce and international prospective studies are needed to implement standardized clinical stratifications and risk-adapted therapeutic strategies.}, language = {en} } @article{ReibetanzKelmUttingeretal.2022, author = {Reibetanz, Joachim and Kelm, Matthias and Uttinger, Konstantin L. and Reuter, Miriam and Schlegel, Nicolas and Hankir, Mohamed and Wiegering, Verena and Germer, Christoph-Thomas and Fassnacht, Martin and Lock, Johan Friso and Wiegering, Armin}, title = {Differences in morbidity and mortality between unilateral adrenalectomy for adrenal Cushing's syndrome and bilateral adrenalectomy for therapy refractory extra-adrenal Cushing's syndrome}, series = {Langenbeck's Archives of Surgery}, volume = {407}, journal = {Langenbeck's Archives of Surgery}, number = {6}, doi = {10.1007/s00423-022-02568-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-323947}, pages = {2481-2488}, year = {2022}, abstract = {Purpose In selected cases of severe Cushing's syndrome due to uncontrolled ACTH secretion, bilateral adrenalectomy appears unavoidable. Compared with unilateral adrenalectomy (for adrenal Cushing's syndrome), bilateral adrenalectomy has a perceived higher perioperative morbidity. The aim of the current study was to compare both interventions in endogenous Cushing's syndrome regarding postoperative outcomes. Methods We report a single-center, retrospective cohort study comparing patients with hypercortisolism undergoing bilateral vs. unilateral adrenalectomy during 2008-2021. Patients with adrenal Cushing's syndrome due to adenoma were compared with patients with ACTH-dependent Cushing's syndrome (Cushing's disease and ectopic ACTH production) focusing on postoperative morbidity and mortality as well as long-term survival. Results Of 83 patients with adrenalectomy for hypercortisolism (65.1\% female, median age 53 years), the indication for adrenalectomy was due to adrenal Cushing's syndrome in 60 patients (72.2\%; 59 unilateral and one bilateral), and due to hypercortisolism caused by Cushing's disease (n = 16) or non-pituitary uncontrolled ACTH secretion of unknown origin (n = 7) (27.7\% of all adrenalectomies). Compared with unilateral adrenalectomy (n = 59), patients with bilateral adrenalectomy (n = 24) had a higher rate of severe complications (0\% vs. 33\%; p < 0.001) and delayed recovery (median: 10.2\% vs. 79.2\%; p < 0.001). Using the MTL30 marker, patients with bilateral adrenalectomy fared worse than patients after unilateral surgery (MTL30 positive: 7.2\% vs. 25.0\% p < 0.001). Postoperative mortality was increased in patients with bilateral adrenalectomy (0\% vs. 8.3\%; p = 0.081). Conclusion While unilateral adrenalectomy for adrenal Cushing's syndrome represents a safe and definitive therapeutic option, bilateral adrenalectomy to control ACTH-dependent extra-adrenal Cushing's syndrome or Cushing's disease is a more complicated intervention with a mortality of nearly 10\%.}, language = {en} } @article{RamserBaurKelleretal.2021, author = {Ramser, Michaela and Baur, Johannes and Keller, Nicola and Kukleta, Jan F. and D{\"o}rfer, J{\"o}rg and Wiegering, Armin and Eisner, Lukas and Dietz, Ulrich A.}, title = {Robotische Hernienchirurgie I: Robotische Leistenhernienversorgung (r‑TAPP). Videobeitrag und Ergebnisse einer Kohortenstudie an 302 operierten Hernien}, series = {Der Chirurg}, volume = {92}, journal = {Der Chirurg}, number = {8}, doi = {10.1007/s00104-021-01425-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-264883}, pages = {707-720}, year = {2021}, abstract = {Die Versorgung von Leistenhernien mit offenen und minimal-invasiven Verfahren hat in den vergangenen 30 Jahren einen vom Ergebnis her gesehen hohen Standard erreicht. Allerdings besteht noch Bedarf an einer weiteren Reduktion der postoperativen Serome, chronischen Schmerzen und des Rezidivs. In diesem Videobeitrag wird die endoskopische Anatomie der Leiste im Hinblick auf die robotische transabdominelle pr{\"a}peritoneale Patchplastik (r‑TAPP) dargestellt und die Operationsschritte der r‑TAPP als Video illustriert. Es werden die Ergebnisse einer Kohortenstudie an 302 konsekutiven Hernien, die mittels r‑TAPP operiert wurden, vorgestellt und hinsichtlich des Mehrwerts der robotischen Technik - auch in der Weiterbildung - diskutiert. Die r‑TAPP ist die nat{\"u}rliche Weiterentwicklung der konventionellen TAPP und hat das Potenzial, bei zunehmender Ger{\"a}teverf{\"u}gbarkeit und Reduktion der Materialkosten zu einem neuen Standard zu werden. K{\"u}nftige Studien werden den vielseitigen Mehrwert der r‑TAPP auch mit neuen Parametern verfeinern m{\"u}ssen.}, language = {de} } @article{RamserBaurKelleretal.2021, author = {Ramser, Michaela and Baur, Johannes and Keller, Nicola and Kukleta, Jan F. and D{\"o}rfer, J{\"o}rg and Wiegering, Armin and Eisner, Lukas and Dietz, Ulrich A.}, title = {Robotic hernia surgery I. English version}, series = {Der Chirurg}, volume = {92}, journal = {Der Chirurg}, number = {Suppl 1}, doi = {10.1007/s00104-021-01446-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-323934}, pages = {S1-S13}, year = {2021}, abstract = {The treatment of inguinal hernias with open and minimally invasive procedures has reached a high standard in terms of outcome over the past 30 years. However, there is still need for further improvement, mainly in terms of reduction of postoperative seroma, chronic pain, and recurrence. This video article presents the endoscopic anatomy of the groin with regard to robotic transabdominal preperitoneal patch plasty (r‑TAPP) and illustrates the surgical steps of r‑TAPP with respective video sequences. The results of a cohort study of 302 consecutive hernias operated by r‑TAPP are presented and discussed in light of the added value of the robotic technique, including advantages for surgical training. r‑TAPP is the natural evolution of conventional TAPP and has the potential to become a new standard as equipment availability increases and material costs decrease. Future studies will also have to refine the multifaceted added value of r‑TAPP with new parameters.}, language = {en} } @article{PeterBultinckMyantetal.2014, author = {Peter, Stefanie and Bultinck, Jennyfer and Myant, Kevin and Jaenicke, Laura A. and Walz, Susanne and M{\"u}ller, Judith and Gmachl, Michael and Treu, Matthias and Boehmelt, Guido and Ade, Casten P. and Schmitz, Werner and Wiegering, Armin and Otto, Christoph and Popov, Nikita and Sansom, Owen and Kraut, Norbert and Eilers, Martin}, title = {H Tumor cell-specific inhibition of MYC function using small molecule inhibitors of the HUWE1 ubiquitin ligase}, series = {EMBO Molecular Medicine}, volume = {6}, journal = {EMBO Molecular Medicine}, number = {12}, issn = {1757-4684}, doi = {10.15252/emmm.201403927}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-118132}, pages = {1525-41}, year = {2014}, abstract = {Deregulated expression of MYC is a driver of colorectal carcinogenesis, necessitating novel strategies to inhibit MYC function. The ubiquitin ligase HUWE1 (HECTH9, ARF-BP1, MULE) associates with both MYC and the MYC-associated protein MIZ1. We show here that HUWE1 is required for growth of colorectal cancer cells in culture and in orthotopic xenograft models. Using high-throughput screening, we identify small molecule inhibitors of HUWE1, which inhibit MYC-dependent transactivation in colorectal cancer cells, but not in stem and normal colon epithelial cells. Inhibition of HUWE1 stabilizes MIZ1. MIZ1 globally accumulates on MYC target genes and contributes to repression of MYC-activated target genes upon HUWE1 inhibition. Our data show that transcriptional activation by MYC in colon cancer cells requires the continuous degradation of MIZ1 and identify a novel principle that allows for inhibition of MYC function in tumor cells.}, language = {en} } @article{PelzWagnerLichthardtetal.2018, author = {Pelz, J{\"o}rg O. W. and Wagner, Johanna and Lichthardt, Sven and Baur, Johannes and Kastner, Caroline and Matthes, Niels and Germer, Christoph-Thomas and Wiegering, Armin}, title = {Laparoscopic right-sided colon resection for colon cancer - has the control group so far been chosen correctly?}, series = {World Journal of Surgical Oncology}, volume = {16}, journal = {World Journal of Surgical Oncology}, number = {117}, doi = {10.1186/s12957-018-1417-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176186}, year = {2018}, abstract = {Background: The treatment strategies for colorectal cancer located in the right side of the colon have changed dramatically during the last decade. Due to the introduction of complete mesocolic excision (CME) with central ligation of the vessels and systematic lymph node dissection, the long-term survival of affected patients has increased significantly. It has also been proposed that right-sided colon resection can be performed laparoscopically with the same extent of resection and equal long-term results. Methods: A retrospective evaluation of a prospectively expanded database on right-sided colorectal cancer or adenoma treated at the University Hospital of Wuerzburg between 2009 and 2016 was performed. All patients underwent CME. This data was analyzed alone and in comparison to the published data describing laparoscopic right-sided colon resection for colon cancer. Results: The database contains 279 patients, who underwent right-sided colon resection due to colorectal cancer or colorectal adenoma (255 open; 24 laparoscopic). Operation data (time, length of stay, time on ICU) was equal or superior to laparoscopy, which is comparable to the published results. Surprisingly, the surrogate parameter for correct CME (the number of removed lymph nodes) was significantly higher in the open group. In a subgroup analysis only including patients who were feasible for laparoscopic resection and had been operated with an open procedure by an experienced surgeon, operation time was significantly shorter and the number of removed lymph nodes is significantly higher in the open group. Conclusion: So far, several studies demonstrate that laparoscopic right-sided colon resection is comparable to open resection. Our data suggests that a consequent CME during an open operation leads to significantly more removed lymph nodes than in laparoscopically resected patients and in several so far published data of open control groups from Europe. Further prospective randomized trials comparing the long-term outcome are urgently needed before laparoscopy for right-sided colon resection can be recommended ubiquitously.}, language = {en} } @article{OttoKastnerSchmidtetal.2022, author = {Otto, Christoph and Kastner, Carolin and Schmidt, Stefanie and Uttinger, Konstantin and Baluapuri, Apoorva and Denk, Sarah and Rosenfeldt, Mathias T. and Rosenwald, Andreas and Roehrig, Florian and Ade, Carsten P. and Schuelein-Voelk, Christina and Diefenbacher, Markus E. and Germer, Christoph-Thomas and Wolf, Elmar and Eilers, Martin and Wiegering, Armin}, title = {RNA polymerase I inhibition induces terminal differentiation, growth arrest, and vulnerability to senolytics in colorectal cancer cells}, series = {Molecular Oncology}, volume = {16}, journal = {Molecular Oncology}, number = {15}, doi = {10.1002/1878-0261.13265}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312806}, pages = {2788-2809}, year = {2022}, abstract = {Ribosomal biogenesis and protein synthesis are deregulated in most cancers, suggesting that interfering with translation machinery may hold significant therapeutic potential. Here, we show that loss of the tumor suppressor adenomatous polyposis coli (APC), which constitutes the initiating event in the adenoma carcinoma sequence for colorectal cancer (CRC), induces the expression of RNA polymerase I (RNAPOL1) transcription machinery, and subsequently upregulates ribosomal DNA (rDNA) transcription. Targeting RNAPOL1 with a specific inhibitor, CX5461, disrupts nucleolar integrity, and induces a disbalance of ribosomal proteins. Surprisingly, CX5461-induced growth arrest is irreversible and exhibits features of senescence and terminal differentiation. Mechanistically, CX5461 promotes differentiation in an MYC-interacting zinc-finger protein 1 (MIZ1)- and retinoblastoma protein (Rb)-dependent manner. In addition, the inhibition of RNAPOL1 renders CRC cells vulnerable towards senolytic agents. We validated this therapeutic effect of CX5461 in murine- and patient-derived organoids, and in a xenograft mouse model. These results show that targeting ribosomal biogenesis together with targeting the consecutive, senescent phenotype using approved drugs is a new therapeutic approach, which can rapidly be transferred from bench to bedside.}, language = {en} } @article{OttoHahlbrockEichetal.2016, author = {Otto, Christoph and Hahlbrock, Theresa and Eich, Kilian and Karaaslan, Ferdi and J{\"u}rgens, Constantin and Germer, Christoph-Thomas and Wiegering, Armin and K{\"a}mmerer, Ulrike}, title = {Antiproliferative and antimetabolic effects behind the anticancer property of fermented wheat germ extract}, series = {BMC Complementary and Alternative Medicine}, volume = {16}, journal = {BMC Complementary and Alternative Medicine}, number = {160}, doi = {10.1186/s12906-016-1138-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146013}, year = {2016}, abstract = {Background Fermented wheat germ extract (FWGE) sold under the trade name Avemar exhibits anticancer activity in vitro and in vivo. Its mechanisms of action are divided into antiproliferative and antimetabolic effects. Its influcence on cancer cell metabolism needs further investigation. One objective of this study, therefore, was to further elucidate the antimetabolic action of FWGE. The anticancer compound 2,6-dimethoxy-1,4-benzoquinone (DMBQ) is the major bioactive compound in FWGE and is probably responsible for its anticancer activity. The second objective of this study was to compare the antiproliferative properties in vitro of FWGE and the DMBQ compound. Methods The IC\(_{50}\) values of FWGE were determined for nine human cancer cell lines after 24 h of culture. The DMBQ compound was used at a concentration of 24 μmol/l, which is equal to the molar concentration of DMBQ in FWGE. Cell viability, cell cycle, cellular redox state, glucose consumption, lactic acid production, cellular ATP levels, and the NADH/NAD\(^+\) ratio were measured. Results The mean IC\(_{50}\) value of FWGE for the nine human cancer cell lines tested was 10 mg/ml. Both FWGE (10 mg/ml) and the DMBQ compound (24 μmol/l) induced massive cell damage within 24 h after starting treatment, with changes in the cellular redox state secondary to formation of intracellular reactive oxygen species. Unlike the DMBQ compound, which was only cytotoxic, FWGE exhibited cytostatic and growth delay effects in addition to cytotoxicity. Both cytostatic and growth delay effects were linked to impaired glucose utilization which influenced the cell cycle, cellular ATP levels, and the NADH/NAD\(^+\) ratio. The growth delay effect in response to FWGE treatment led to induction of autophagy. Conclusions FWGE and the DMBQ compound both induced oxidative stress-promoted cytotoxicity. In addition, FWGE exhibited cytostatic and growth delay effects associated with impaired glucose utilization which led to autophagy, a possible previously unknown mechanism behind the influence of FWGE on cancer cell metabolism.}, language = {en} } @article{MuellerKoehlerHendricksetal.2021, author = {M{\"u}ller, Sophie and K{\"o}hler, Franziska and Hendricks, Anne and Kastner, Carolin and B{\"o}rner, Kevin and Diers, Johannes and Lock, Johan F. and Petritsch, Bernhard and Germer, Christoph-Thomas and Wiegering, Armin}, title = {Brain metastases from colorectal cancer: a systematic review of the literature and meta-analysis to establish a guideline for daily treatment}, series = {Cancers}, volume = {13}, journal = {Cancers}, number = {4}, issn = {2072-6694}, doi = {10.3390/cancers13040900}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228883}, year = {2021}, abstract = {Colorectal cancer (CRC) is the third most common malignancy worldwide. Most patients with metastatic CRC develop liver or lung metastases, while a minority suffer from brain metastases. There is little information available regarding the presentation, treatment, and overall survival of brain metastases (BM) from CRC. This systematic review and meta-analysis includes data collected from three major databases (PubMed, Cochrane, and Embase) based on the key words "brain", "metastas*", "tumor", "colorectal", "cancer", and "malignancy". In total, 1318 articles were identified in the search and 86 studies matched the inclusion criteria. The incidence of BM varied between 0.1\% and 11.5\%. Most patients developed metastases at other sites prior to developing BM. Lung metastases and KRAS mutations were described as risk factors for additional BM. Patients with BM suffered from various symptoms, but up to 96.8\% of BM patients were asymptomatic at the time of BM diagnosis. Median survival time ranged from 2 to 9.6 months, and overall survival (OS) increased up to 41.1 months in patients on a multimodal therapy regimen. Several factors including age, blood levels of carcinoembryonic antigen (CEA), multiple metastases sites, number of brain lesions, and presence of the KRAS mutation were predictors of OS. For BM diagnosis, MRI was considered to be state of the art. Treatment consisted of a combination of surgery, radiation, or systemic treatment.}, language = {en} } @article{MeirMaurusKuperetal.2021, author = {Meir, Michael and Maurus, Katja and Kuper, Jochen and Hankir, Mohammed and Wardelmann, Eva and Rosenwald, Andreas and Germer, Christoph-Thomas and Wiegering, Armin}, title = {The novel KIT exon 11 germline mutation K558N is associated with gastrointestinal stromal tumor, mastocytosis, and seminoma development}, series = {Genes, Chromosomes \& Cancer}, volume = {60}, journal = {Genes, Chromosomes \& Cancer}, number = {12}, doi = {10.1002/gcc.22988}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257476}, pages = {827-832}, year = {2021}, abstract = {Familial gastrointestinal stromal tumors (GIST) are dominant genetic disorders that are caused by germline mutations of the type III receptor tyrosine kinase KIT. While sporadic mutations are frequently found in mastocytosis and GISTs, germline mutations of KIT have only been described in 39 families until now. We detected a novel germline mutation of KIT in exon 11 (p.Lys-558-Asn; K558N) in a patient from a kindred with several GISTs harboring different secondary somatic KIT mutations. Structural analysis suggests that the primary germline mutation alone is not sufficient to release the autoinhibitory region of KIT located in the transmembrane domain. Instead, the KIT kinase module becomes constitutively activated when K558N combines with different secondary somatic mutations. The identical germline mutation in combination with an additional somatic KIT mutation was detected in a second patient of the kindred with seminoma while a third patient within the family had a cutaneous mastocytosis. These findings suggest that the K558N mutation interferes with the juxtamembranous part of KIT, since seminoma and mastocystosis are usually not associated with exon 11 mutations.}, language = {en} } @article{MatthesDiersSchlegeletal.2020, author = {Matthes, Niels and Diers, Johannes and Schlegel, Nicolas and Hankir, Mohammed and Haubitz, Imme and Germer, Christoph-Thomas and Wiegering, Armin}, title = {Validation of MTL30 as a quality indicator for colorectal surgery}, series = {PLoS One}, volume = {15}, journal = {PLoS One}, number = {8}, doi = {10.1371/journal.pone.0238473}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230530}, year = {2020}, abstract = {Background Valid indicators are required to measure surgical quality. These ideally should be sensitive and selective while being easy to understand and adjust. We propose here the MTL30 quality indicator which takes into account 30-day mortality, transfer within 30 days, and a length of stay of 30 days as composite markers of an uneventful operative/postoperative course. Methods Patients documented in the StuDoQ|Colon and StuDoQ|Rectal carcinoma register of the German Society for General and Visceral Surgery (DGAV) were analyzed with regard to the effects of patient and tumor-related risk factors as well as postoperative complications on the MTL30. Results In univariate analysis, the MTL30 correlated significantly with patient and tumor-related risk factors such as ASA score (p<0.001), age (p<0.001), or UICC stage (p<0.001). There was a high sensitivity for the postoperative occurrence of complications such as re-operations (p<0.001) or subsequent bleeding (p<0.001), as well as a significant correlation with the CDC classification (p<0.001). In multivariate analysis, patient-related risk factors and postoperative complications significantly increased the odds ratio for a positive MTL30. A negative MTL30 showed a high specify for an uneventful operative and postoperative course. Conclusion The MTL30 is a valid indicator of colorectal surgical quality.}, language = {en} } @article{LichthardtWagnerLoebetal.2020, author = {Lichthardt, Sven and Wagner, Johanna and L{\"o}b, Stefan and Matthes, Niels and Kastner, Caroline and Anger, Friedrich and Germer, Christoph-Thomas and Wiegering, Armin}, title = {Pathological complete response due to a prolonged time interval between preoperative chemoradiation and surgery in locally advanced rectal cancer: analysis from the German StuDoQ|Rectalcarcinoma registry}, series = {BMC Cancer}, volume = {20}, journal = {BMC Cancer}, number = {1}, doi = {10.1186/s12885-020-6538-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229334}, year = {2020}, abstract = {Background Preoperative chemoradiotherapy is the recommended standard of care for patients with local advanced rectal cancer. However, it remains unclear, whether a prolonged time interval to surgery results in an increased perioperative morbidity, reduced TME quality or better pathological response. Aim of this study was to determine the time interval for best pathological response and perioperative outcome compared to current recommended interval of 6 to 8 weeks. Methods This is a retrospective analysis of the German StuDoQ|Rectalcarcinoma registry. Patients were grouped for the time intervals of "less than 6 weeks", "6 to 8 weeks", "8 to 10 weeks" and "more than 10 weeks". Primary endpoint was pathological response, secondary endpoint TME quality and complications according to Clavien-Dindo classification. Results Due to our inclusion criteria (preoperative chemoradiation, surgery in curative intention, M0), 1.809 of 9.560 patients were suitable for analysis. We observed a trend for increased rates of pathological complete response (pCR: ypT0ypN0) and pathological good response (pGR: ypT0-1ypN0) for groups with a prolonged time interval which was not significant. Ultimately, it led to a steady state of pCR (16.5\%) and pGR (22.6\%) in "8 to 10" and "more than 10" weeks. We were not able to observe any differences between the subgroups in perioperative morbidity, proportion of rectal extirpation (for cancer of the lower third) or difference in TME quality. Conclusion A prolonged time interval between neoadjuvant chemoradiation can be performed, as the rate of pCR seems to be increased without influencing perioperative morbidity.}, language = {en} } @article{LichthardtKerscherDietzetal.2016, author = {Lichthardt, Sven and Kerscher, Alexander and Dietz, Ulrich A. and Jurowich, Christian and Kunzmann, Volker and von Rahden, Burkhard H. A. and Germer, Christoph-Thomas and Wiegering, Armin}, title = {Original article: role of adjuvant chemotherapy in a perioperative chemotherapy regimen for gastric cancer}, series = {BMC Cancer}, volume = {16}, journal = {BMC Cancer}, number = {650}, doi = {10.1186/s12885-016-2708-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-147743}, year = {2016}, abstract = {Background Multimodal treatment strategies - perioperative chemotherapy (CTx) and radical surgery - are currently accepted as treatment standard for locally advanced gastric cancer. However, the role of adjuvant postoperative CTx (postCTx) in addition to neoadjuvant preoperative CTx (preCTx) in this setting remains controversial. Methods Between 4/2006 and 12/2013, 116 patients with locally advanced gastric cancer were treated with preCTx. 72 patients (62 \%), in whom complete tumor resection (R0, subtotal/total gastrectomy with D2-lymphadenectomy) was achieved, were divided into two groups, one of which receiving adjuvant therapy (n = 52) and one without (n = 20). These groups were analyzed with regard to survival and exclusion criteria for adjuvant therapy. Results Postoperative complications, as well as their severity grade, did not correlate with fewer postCTx cycles administered (p = n.s.). Long-term survival was shorter in patients receiving postCTx in comparison to patients without postCTx, but did not show statistical significance. In per protocol analysis by excluding two patients with perioperative death, a shorter 3-year survival rate was observed in patients receiving postCTx compared to patients without postCTx (3-year survival: 71.2 \% postCTx group vs. 90.0 \% non-postCTx group; p = 0.038). Conclusion These results appear contradicting to the anticipated outcome. While speculative, they question the value of post-CTx. Prospectively randomized studies are needed to elucidate the role of postCTx.}, language = {en} } @article{LenschowFussKircheretal.2021, author = {Lenschow, Christina and Fuss, Carmina Teresa and Kircher, Stefan and Buck, Andreas and Kickuth, Ralph and Reibetanz, Joachim and Wiegering, Armin and Stenzinger, Albrecht and H{\"u}bschmann, Daniel and Germer, Christoph Thomas and Fassnacht, Martin and Fr{\"o}hling, Stefan and Schlegel, Nicolas and Kroiss, Matthias}, title = {Case Report: Abdominal Lymph Node Metastases of Parathyroid Carcinoma: Diagnostic Workup, Molecular Diagnosis, and Clinical Management}, series = {Frontiers in Endocrinology}, volume = {12}, journal = {Frontiers in Endocrinology}, issn = {1664-2392}, doi = {10.3389/fendo.2021.643328}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-233362}, year = {2021}, abstract = {Parathyroid carcinoma (PC) is an orphan malignancy accounting for only ~1\% of all cases with primary hyperparathyroidism. The localization of recurrent PC is of critical importance and can be exceedingly difficult to diagnose and sometimes futile when common sites of recurrence in the neck and chest cannot be confirmed. Here, we present the diagnostic workup, molecular analysis and multimodal therapy of a 46-year old woman with the extraordinary manifestation of abdominal lymph node metastases 12 years after primary diagnosis of PC. The patient was referred to our endocrine tumor center in 2016 with the aim to localize the tumor causative of symptomatic biochemical recurrence. In view of the extensive previous workup we decided to perform [18F]FDG-PET-CT. A pathological lymph node in the liver hilus showed slightly increased FDG-uptake and hence was suspected as site of recurrence. Selective venous sampling confirmed increased parathyroid hormone concentration in liver veins. Abdominal lymph node metastasis was resected and histopathological examination confirmed PC. Within four months, the patient experienced biochemical recurrence and based on high tumor mutational burden detected in the surgical specimen by whole exome sequencing the patient received immunotherapy with pembrolizumab that led to a biochemical response. Subsequent to disease progression repeated abdominal lymph node resection was performed in 10/2018, 01/2019 and in 01/2020. Up to now (12/2020) the patient is biochemically free of disease. In conclusion, a multimodal diagnostic approach and therapy in an interdisciplinary setting is needed for patients with rare endocrine tumors. Molecular analyses may inform additional treatment options including checkpoint inhibitors such as pembrolizumab.}, language = {en} } @article{LehmannKlingerDiersetal.2021, author = {Lehmann, Kai S. and Klinger, Carsten and Diers, Johannes and Buhr, Heinz-Johannes and Germer, Christoph-Thomas and Wiegering, Armin}, title = {Safety of anastomoses in colorectal cancer surgery in octogenarians: a prospective cohort study with propensity score matching}, series = {BJS Open}, volume = {5}, journal = {BJS Open}, number = {6}, doi = {10.1093/bjsopen/zrab102}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265044}, year = {2021}, abstract = {Background Up to 20 per cent of all operations for patients with colorectal cancer (CRC) are performed in octogenarians. Anastomotic leakage is a leading cause of morbidity and death after resection for CRC. The aim of this study was to assess the rate of anastomosis creation, the risk of anastomotic leakage and death in surgery for left-sided CRC in elderly patients. Methods This prospective cohort study compared patients less than 80 and 80 or more years with left-sided CRC resection performed between 2013 and 2019. Data were provided from a risk-adjusted surgical quality-assessment system with 219 participating centres in Germany. Outcome measures were the rate of anastomoses, anastomotic leakages, death at 30 days and 2-year overall survival (OS). Propensity score matching was used to control for selection bias and compare subgroups of patients of less than 80 and 80 or more years. Results Out of 18 959 patients, some 3169 (16.7 per cent) were octogenarians. Octogenarians were less likely to receive anastomoses (82.0 versus 92.9 per cent, P < 0.001; odds ratio 0.50 (95 per cent c.i. 0.44 to 0.58), P < 0.001). The rate of anastomotic leakages did not differ between age groups (8.6 versus 9.7 per cent, P = 0.084), but 30-day mortality rate after leakage was significantly higher in octogenarians (15.8 versus 3.5 per cent, P < 0.001). Overall, anastomotic leakage was the strongest predictor for death (odds ratio 4.95 (95 per cent c.i. 3.66 to 6.66), P < 0.001). In the subgroup with no leakage, octogenarians had a lower 2-year OS rate than younger patients (71 versus 87 per cent, P < 0.001), and in the population with anastomotic leakage, the 2-year OS was 80 per cent in younger and 43 per cent in elderly patients (P < 0.001). After propensity score matching, older age remained predictive for not receiving an anastomosis (odds ratio 0.54 (95 per cent c.i. 0.46 to 0.63), P < 0.001) and for death (odds ratio 2.60 (95 per cent c.i. 1.78 to 3.84), P < 0.001), but not for the occurrence of leakages (odds ratio 0.94 (95 per cent c.i. 0.76 to 1.15), P = 0.524). Conclusion Anastomotic leakage is not more common in octogenarians, but an age of 80 years or older is an independent factor for not receiving an anastomosis in surgery for left-sided CRC. The mortality rate in the case of leakage in octogenarians was reported to exceed 15 per cent.}, language = {en} } @article{KoehlerReeseKastneretal.2022, author = {K{\"o}hler, Franziska and Reese, Lena and Kastner, Carolin and Hendricks, Anne and M{\"u}ller, Sophie and Lock, Johan F. and Germer, Christoph-Thomas and Wiegering, Armin}, title = {Surgical site infection following single-port appendectomy: a systematic review of the literature and meta-analysis}, series = {Frontiers in Surgery}, volume = {9}, journal = {Frontiers in Surgery}, issn = {2296-875X}, doi = {10.3389/fsurg.2022.919744}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-276943}, year = {2022}, abstract = {Introduction Surgical site infections (SSIs) are one of the most common postoperative complications after appendectomy leading to recurrent surgery, prolonged hospital stay, and the use of antibiotics. Numerous studies and meta-analyses have been published on the effect of open versus conventional laparoscopic appendectomy (CLA) reporting faster postoperative recovery and less postoperative pain for CLA. A development from CLA has been the single-port appendectomy (SPA), associated with a better cosmesis but seemingly having a higher risk of wound infections. The aim of this systematic literature review and meta-analysis is to investigate whether reduced port or SPA alters the ratio of SSIs. Methods Pubmed, Embase, and Cochrane databases were screened for suitable articles. All articles published between January 1, 2002, and March 23, 2022, were included. Articles regarding children below the age of 18 were excluded as well as manuscripts that investigated solemnly open appendectomies. Articles were screened for inclusion criteria by two independent authors. Incidence of SSI was the primary outcome. Duration of operation and length of hospital stay were defined as secondary outcomes. Results A total of 25 studies were found through a database search describing 5484 patients. A total of 2749 patients received SPA and 2735 received CLA. There was no statistical difference in the rate of SSI (P = 0.98). A total of 22 studies including 4699 patients reported the duration of operation (2223 SPA and 2476 CLA). There was a significantly shorter operation time seen in CLA. The length of hospital stay was reported in 23 studies (4735 patients: 2235 SPA and 2500 CLA). A shorter hospital stay was seen in the SPA group (P < 0.00001). Separately performed analysis of randomized controlled trials could not confirm this effect (P = 0.29). Discussion SPA is an equally safe procedure considering SSI compared to CLA and does not lead to an increased risk of SSI. A longer operation time for SPA and a minor difference in the length of stay does lead to the use of SPA in selected patients only.}, language = {en} } @article{KoehlerReeseHendricksetal.2022, author = {K{\"o}hler, Franziska and Reese, Lena and Hendricks, Anne and Kastner, Carolin and M{\"u}ller, Sophie and Lock, Johan F. and Germer, Christoph-Thomas and Wiegering, Armin}, title = {Low-grade mucinous neoplasms (LAMN) of the appendix in Germany between 2011 and 2018: a nationwide analysis based on data provided by the German Center for Cancer Registry Data (ZfKD) at the Robert Koch Institute (RKI)}, series = {Langenbeck's Archives of Surgery}, volume = {407}, journal = {Langenbeck's Archives of Surgery}, number = {8}, doi = {10.1007/s00423-022-02639-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-323919}, pages = {3615-3622}, year = {2022}, abstract = {Introduction Low-grade appendiceal mucinous neoplasms (LAMN) are semi-malignant tumors of the appendix which are incidentally found in up to 1\% of appendectomy specimen. To this day, no valid descriptive analysis on LAMN is available for the German population. Methods Data of LAMN (ICD-10: D37.3) were collected from the population-based cancer registries in Germany, provided by the German Center for Cancer Registry Data (Zentrum f{\"u}r Krebsregisterdaten—ZfKD). Data was anonymized and included gender, age at diagnosis, tumor staging according to the TNM-classification, state of residence, information on the performed therapy, and survival data. Results A total of 612 cases were reported to the ZfKD between 2011 and 2018. A total of 63.07\% were female and 36.93\% were male. Great inhomogeneity in reporting cases was seen in the federal states of Germany including the fact that some federal states did not report any cases at all. Age distribution showed a mean age of 62.03 years (SD 16.15) at diagnosis. However, data on tumor stage was only available in 24.86\% of cases (n = 152). A total of 49.34\% of these patients presented with a T4-stage. Likewise, information regarding performed therapy was available in the minority of patients: 269 patients received surgery, 22 did not and for 312 cases no information was available. Twenty-four patients received chemotherapy, 188 did not, and for 400 cases, no information was available. Overall 5-year survival was estimated at 79.52\%. Patients below the age of 55 years at time of diagnosis had a significantly higher 5-year survival rate compared to patients above the age of 55 years (85.77\% vs. 73.27\%). Discussion In this study, we observed an incidence of LAMN in 0.13\% of all appendectomy specimen in 2018. It seems likely that not all cases were reported to the ZfKD; therefore, case numbers may be considered underestimated. Age and gender distribution goes in line with international studies with females being predominantly affected. Especially regarding tumor stage and therapy in depth information cannot be provided through the ZfKD-database. This data analysis emphasizes the need for further studies and the need for setting up a specialized registry for this unique tumor entity to develop guidelines for the appropriate treatment and follow-up.}, language = {en} } @article{KoehlerHendricksKastneretal.2021, author = {K{\"o}hler, Franziska and Hendricks, Anne and Kastner, Carolin and M{\"u}ller, Sophie and Boerner, Kevin and Wagner, Johanna C. and Lock, Johan F. and Wiegering, Armin}, title = {Laparoscopic appendectomy versus antibiotic treatment for acute appendicitis-a systematic review}, series = {International Journal of Colorectal Disease}, volume = {36}, journal = {International Journal of Colorectal Disease}, number = {10}, issn = {1432-1262}, doi = {10.1007/s00384-021-03927-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-266616}, pages = {2283-2286}, year = {2021}, abstract = {Background Over the last years, laparoscopic appendectomy has progressively replaced open appendectomy and become the current gold standard treatment for suspected, uncomplicated appendicitis. At the same time, though, it is an ongoing discussion that antibiotic therapy can be an equivalent treatment for patients with uncomplicated appendicitis. The aim of this systematic review was to determine the safety and efficacy of antibiotic therapy and compare it to the laparoscopic appendectomy for acute, uncomplicated appendicitis. Methods The PubMed database, Embase database, and Cochrane library were scanned for studies comparing laparoscopic appendectomy with antibiotic treatment. Two independent reviewers performed the study selection and data extraction. The primary endpoint was defined as successful treatment of appendicitis. Secondary endpoints were pain intensity, duration of hospitalization, absence from work, and incidence of complications. Results No studies were found that exclusively compared laparoscopic appendectomy with antibiotic treatment for acute, uncomplicated appendicitis. Conclusions To date, there are no studies comparing antibiotic treatment to laparoscopic appendectomy for patients with acute uncomplicated appendicitis, thus emphasizing the lack of evidence and need for further investigation.}, language = {en} } @article{KaemmererGiresPfetzeretal.2015, author = {K{\"a}mmerer, Ulrike and Gires, Olivier and Pfetzer, Nadja and Wiegering, Armin and Klement, Rainer Johannes and Otto, Christoph}, title = {TKTL1 expression in human malign and benign cell lines}, series = {BMC Cancer}, volume = {15}, journal = {BMC Cancer}, number = {2}, doi = {10.1186/1471-2407-15-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-126397}, year = {2015}, abstract = {Background Overexpression of transketolase-like 1 protein TKTL1 in cancer cells has been reported to correlate with enhanced glycolysis and lactic acid production. Furthermore, enhanced TKTL1 expression was put into context with resistance to chemotherapy and ionizing radiation. Here, a panel of human malign and benign cells, which cover a broad range of chemotherapy and radiation resistance as well as reliance on glucose metabolism, was analyzed in vitro for TKTL1 expression. Methods 17 malign and three benign cell lines were characterized according to their expression of TKTL1 on the protein level with three commercially available anti-TKTL1 antibodies utilizing immunohistochemistry and Western blot, as well as on mRNA level with three published primer pairs for RT-qPCR. Furthermore, sensitivities to paclitaxel, cisplatin and ionizing radiation were assessed in cell survival assays. Glucose consumption and lactate production were quantified as surrogates for the "Warburg effect". Results Considerable amounts of tktl1 mRNA and TKTL1 protein were detected only upon stable transfection of the human embryonic kidney cell line HEK293 with an expression plasmid for human TKTL1. Beyond that, weak expression of endogenous tktl1 mRNA was measured in the cell lines JAR and U251. Western blot analysis of JAR and U251 cells did not detect TKTL1 at the expected size of 65 kDa with all three antibodies specific for TKTL1 protein and immunohistochemical staining was observed with antibody JFC12T10 only. All other cell lines tested here revealed expression of tktl1 mRNA below detection limits and were negative for TKTL1 protein. However, in all cell lines including TKTL1-negative HEK293-control cells, antibody JFC12T10 detected multiple proteins with different molecular weights. Importantly, JAR and U251 did neither demonstrate an outstanding production of lactic acid nor increased resistance against chemotherapeutics or to ionizing radiation, respectively. Conclusion Using RT-qPCR and three different antibodies we observed only exceptional occurrence of TKTL1 in a panel of malignant human cell lines in vitro. The presence of TKTL1 was unrelated to either the rate of glucose consumption/lactic acid production or resistance against chemo- and radiotherapy.}, language = {en} } @article{KastnerHendricksDeinleinetal.2021, author = {Kastner, Carolin and Hendricks, Anne and Deinlein, Hanna and Hankir, Mohammed and Germer, Christoph-Thomas and Schmidt, Stefanie and Wiegering, Armin}, title = {Organoid Models for Cancer Research — From Bed to Bench Side and Back}, series = {Cancers}, volume = {13}, journal = {Cancers}, number = {19}, issn = {2072-6694}, doi = {10.3390/cancers13194812}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-246307}, year = {2021}, abstract = {Simple Summary Despite significant strides in multimodal therapy, cancers still rank within the first three causes of death especially in industrial nations. A lack of individualized approaches and accurate preclinical models are amongst the major barriers that limit the development of novel therapeutic options and drugs. Recently, the 3D culture system of organoids was developed which stably retains the genetic and phenotypic characteristics of the original tissue, healthy as well as diseased. In this review, we summarize current data and evidence on the relevance and reliability of such organoid culture systems in cancer research, focusing on their role in drug investigations (in a personalized manner). Abstract Organoids are a new 3D ex vivo culture system that have been applied in various fields of biomedical research. First isolated from the murine small intestine, they have since been established from a wide range of organs and tissues, both in healthy and diseased states. Organoids genetically, functionally and phenotypically retain the characteristics of their tissue of origin even after multiple passages, making them a valuable tool in studying various physiologic and pathophysiologic processes. The finding that organoids can also be established from tumor tissue or can be engineered to recapitulate tumor tissue has dramatically increased their use in cancer research. In this review, we discuss the potential of organoids to close the gap between preclinical in vitro and in vivo models as well as clinical trials in cancer research focusing on drug investigation and development.}, language = {en} } @article{JurowichLichthardtKastneretal.2019, author = {Jurowich, Christian and Lichthardt, Sven and Kastner, Caroline and Haubitz, Imme and Prock, Andre and Filser, J{\"o}rg and Germer, Christoph-Thomas and Wiegering, Armin}, title = {Laparoscopic versus open right hemicolectomy in colon carcinoma: A propensity score analysis of the DGAV StuDoQ|ColonCancer registry}, series = {PLoS ONE}, volume = {14}, journal = {PLoS ONE}, number = {6}, doi = {10.1371/journal.pone.0218829}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-202184}, pages = {e0218829}, year = {2019}, abstract = {Objective To assess whether laparoscopy has any advantages over open resection for right-sided colon cancer. Summary background data Right hemicolectomy can be performed using either a conventional open or a minimally invasive laparoscopic technique. It is not clear whether these different access routes differ with regard to short-term postoperative outcomes. Methods Patients documented in the German Society for General and Visceral Surgery StuDoQ|ColonCancer registry who underwent right hemicolectomy were analyzed regarding early postoperative complications according to Clavien-Dindo (primary endpoint), operation (OP) time, length of postoperative hospital stay (LOS), MTL30 and number of lymph nodes retrieved (secondary endpoints). Results A total of 4.997 patients were identified as undergoing oncological right hemicolectomy without additional interventions. Of these, 4.062 (81.3\%) underwent open, 935 (18.7\%) laparoscopic surgery. Propensity score analysis showed a significantly shorter LOS (OR: 0.55 CI 95\%0.47-.64) and a significantly longer OP time (OR2.32 CI 1.98-2.71) for the laparoscopic route. Risk factors for postoperative complications, anastomotic insufficiency, ileus, reoperation and positive MTL30 were higher ASA status, higher age and increasing BMI. The surgical access route (open / lap) had no influence on these factors, but the laparoscopic group did have markedly fewer lymph nodes retrieved. Conclusion The present registry-based analysis could detect no relevant advantages for the minimally invasive laparoscopic access route. Further oncological analyses are needed to clarify the extent to which the smaller lymph node harvest in the laparoscopic group is accompanied by a poorer oncological outcome.}, language = {en} } @article{HendricksMuellerFassnachtetal.2022, author = {Hendricks, Anne and M{\"u}ller, Sophie and Fassnacht, Martin and Germer, Christoph-Thomas and Wiegering, Verena A. and Wiegering, Armin and Reibetanz, Joachim}, title = {Impact of lymphadenectomy on the oncologic outcome of patients with adrenocortical carcinoma — a systematic review and meta-analysis}, series = {Cancers}, volume = {14}, journal = {Cancers}, number = {2}, issn = {2072-6694}, doi = {10.3390/cancers14020291}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-254798}, year = {2022}, abstract = {(1) Background: Locoregional lymphadenectomy (LND) in adrenocortical carcinoma (ACC) may impact oncological outcome, but the findings from individual studies are conflicting. The aim of this systematic review and meta-analysis was to determine the oncological value of LND in ACC by summarizing the available literature. (2) Methods: A systematic search on studies published until December 2020 was performed according to the PRISMA statement. The primary outcome was the impact of lymphadenectomy on overall survival (OS). Two separate meta-analyses were performed for studies including patients with localized ACC (stage I-III) and those including all tumor stages (I-IV). Secondary endpoints included postoperative mortality and length of hospital stay (LOS). (3) Results: 11 publications were identified for inclusion. All studies were retrospective studies, published between 2001-2020, and 5 were included in the meta-analysis. Three studies (N = 807 patients) reported the impact of LND on disease-specific survival in patients with stage I-III ACC and revealed a survival benefit of LND (hazard ratio (HR) = 0.42, 95\% confidence interval (95\% CI): 0.26-0.68). Based on results of studies including patients with ACC stage I-IV (2 studies, N = 3934 patients), LND was not associated with a survival benefit (HR = 1.00, 95\% CI: 0.70-1.42). None of the included studies showed an association between LND and postoperative mortality or LOS. (4) Conclusion: Locoregional lymphadenectomy seems to offer an oncologic benefit in patients undergoing curative-intended surgery for localized ACC (stage I-III).}, language = {en} } @article{HendricksMeirHankiretal.2022, author = {Hendricks, Anne and Meir, Michael and Hankir, Mohammed and Lenschow, Christina and Germer, Christoph-Thomas and Schneider, Michael and Wiegering, Armin and Schlegel, Nicolas}, title = {Suppurative thyroiditis caused by ingested fish bone in the thyroid gland: a case report on its diagnostics and surgical therapy}, series = {BMC Surgery}, volume = {22}, journal = {BMC Surgery}, number = {1}, doi = {10.1186/s12893-022-01542-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-299775}, year = {2022}, abstract = {Background Accidental ingestion of fish bone is a common cause of otolaryngological emergency. Migration of the ingested bone into the thyroid gland, however, occurs very rarely. The associated clinical presentation, symptoms and duration of discomfort are also highly variable between patients and can be diagnostically challenging. Case presentation Here, we report the case of a 71-year-old female patient presenting with an ingested fish bone that migrated into the right thyroid lobe as a rare cause of suppurative thyroiditis with the clinical features of sepsis. We outline the diagnostic approach, peri- and intraoperative management as well as complications. It is proposed that besides endoscopy, imaging methods such as ultrasound or computed tomography may be necessary to verify the diagnosis and location of an ingested fish bone. Prompt surgical removal of the foreign body and resection of the infectious focus is recommended to minimize the risk of local inflammation, recurrent nerve lesions and septic complications arising from the spread of infection. Conclusion Fish bone migration into the thyroid gland is an extremely rare event, the successful detection and surgical management of which can be achieved through a careful interdisciplinary approach.}, language = {en} } @article{FussOtherHeinzeetal.2021, author = {Fuss, Carmina Teresa and Other, Katharina and Heinze, Britta and Landwehr, Laura-Sophie and Wiegering, Armin and Kalogirou, Charis and Hahner, Stefanie and Fassnacht, Martin}, title = {Expression of the chemokine receptor CCR7 in the normal adrenal gland and adrenal tumors and its correlation with clinical outcome in adrenocortical carcinoma}, series = {Cancers}, volume = {13}, journal = {Cancers}, number = {22}, issn = {2072-6694}, doi = {10.3390/cancers13225693}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250112}, year = {2021}, abstract = {Background: The chemokine receptor CCR7 is crucial for an intact immune function, but its expression is also associated with clinical outcome in several malignancies. No data exist on the expression of CCR7 in adrenocortical tumors. Methods: CCR7 expression was investigated by qRT-PCR and immunohistochemistry in 4 normal adrenal glands, 59 adrenocortical adenomas, and 181 adrenocortical carcinoma (ACC) samples. Results: CCR7 is highly expressed in the outer adrenocortical zones and medulla. Aldosterone-producing adenomas showed lower CCR7 protein levels (H-score 1.3 ± 1.0) compared to non-functioning (2.4 ± 0.5) and cortisol-producing adenomas (2.3 ± 0.6), whereas protein expression was variable in ACC (1.8 ± 0.8). In ACC, CCR7 protein expression was significantly higher in lymph node metastases (2.5 ± 0.5) compared to primary tumors (1.8±0.8) or distant metastases (2.0 ± 0.4; p < 0.01). mRNA levels of CCR7 were not significantly different between ACCs, normal adrenals, and adrenocortical adenomas. In contrast to other tumor entities, neither CCR7 protein nor mRNA expression significantly impacted patients' survival. Conclusion: We show that CCR7 is expressed on mRNA and protein level across normal adrenals, benign adrenocortical tumors, as well as ACCs. Given that CCR7 did not influence survival in ACC, it is probably not involved in tumor progression, but it could play a role in adrenocortical homeostasis.}, language = {en} } @article{FlemmingHankirKusanetal.2021, author = {Flemming, Sven and Hankir, Mohammed K. and Kusan, Simon and Krone, Manuel and Anger, Friedrich and Germer, Christoph-Thomas and Wiegering, Armin}, title = {Safety of elective abdominal and vascular surgery during the COVID-19 pandemic: a retrospective single-center study}, series = {European Journal of Medical Research}, volume = {26}, journal = {European Journal of Medical Research}, doi = {10.1186/s40001-021-00583-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-264975}, year = {2021}, abstract = {Background Patients with coronavirus disease 2019 (COVID-19) who undergo surgery have impaired postoperative outcomes and increased mortality. Consequently, elective and semi-urgent operations on the increasing number of patients severely affected by COVID-19 have been indefinitely postponed.in many countries with unclear implications on disease progression and overall survival. The purpose of this study was to evaluate whether the establishment of a standardized screening program for acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is sufficient to ensure high-quality medical and surgical treatment of COVID-19 and non-COVID-19 patients while minimizing in-hospital SARS-CoV-2 transmission. Methods The screening program comprised polymerase chain reaction (PCR) testing of nasopharyngeal swabs and a standardized questionnaire about potential symptoms for SARS-CoV-2 infection. All elective and emergency patients admitted to the surgical department of a tertiary-care hospital center in Lower Franconia, Germany, between March and May 2020 were included and their characteristics were recorded. Results Out of the study population (n = 657), 509 patients (77.5\%) had at least one risk factor for a potentially severe course of COVID-19 and 164 patients (25\%) were active smokers. The average 7-day incidence in Lower Franconia was 24.0/100,000 during the observation period. Preoperative PCR testing revealed four asymptomatic positive patients out of the 657 tested patients. No postoperative SARS-CoV-2 infection or transmission could be detected. Conclusion The implementation of a standardized preoperative screening program to both COVID-19 and non-COVID-19 patients can ensure high-quality surgical care while minimizing infection risk for healthcare workers and potential in-hospital transmission.}, language = {en} } @article{DietzKudsiGarciaUrenaetal.2021, author = {Dietz, Ulrich A. and Kudsi, O. Yusef and Garcia-Ure{\~n}a, Miguel and Baur, Johannes and Ramser, Michaela and Maksimovic, Sladjana and Keller, Nicola and D{\"o}rfer, J{\"o}rg and Eisner, Lukas and Wiegering, Armin}, title = {Robotische Hernienchirurgie III: Robotische Inzisionalhernienversorgung mit „transversus abdominis release" (r-TAR). Videobeitrag und Ergebnisse einer Kohortenstudie}, series = {Der Chirurg}, volume = {92}, journal = {Der Chirurg}, number = {10}, doi = {10.1007/s00104-021-01480-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265172}, pages = {936-947}, year = {2021}, abstract = {Das Prinzip der gezielten Trennung bzw. Schw{\"a}chung einzelner Komponenten der Bauchdecke zur Spannungsentlastung der Medianlinie bei großen abdominellen Rekonstruktionen ist seit {\"u}ber 30 Jahren als anteriore Komponentenseparation (aKS) bekannt und ein etabliertes Verfahren. Auf der Suche nach Alternativen mit geringerer Komplikationsrate wurde die posteriore Komponentenseparation (pKS) entwickelt; der „transversus abdominis release" (TAR) ist eine nervenschonende Modifikation der pKS. Mit den ergonomischen Ressourcen der Robotik (z. B. abgewinkelte Instrumente) kann der TAR minimal-invasiv durchgef{\"u}hrt werden (r-TAR): Bruchl{\"u}cken von bis zu 14 cm lassen sich verschließen und ein großes extraperitoneales Netz implantieren. In diesem Videobeitrag wird die Versorgung großer Inzisionalhernien in der r‑TAR-Technik pr{\"a}sentiert. Exemplarisch werden die Ergebnisse einer Kohortenstudie an 13 konsekutiven Patienten vorgestellt. Der Eingriff ist anspruchsvoll, die eigenen Ergebnisse sind - wie auch die Berichte aus der Literatur - ermutigend. Der r‑TAR entwickelt sich zur K{\"o}nigsdisziplin der Bauchdeckenrekonstruktion.}, language = {de} } @article{DietzKudsiGarciaUrenaetal.2021, author = {Dietz, Ulrich A. and Kudsi, O. Yusef and Garcia-Ure{\~n}a, Miguel and Baur, Johannes and Ramser, Michaela and Maksimovic, Sladjana and Keller, Nicola and D{\"o}rfer, J{\"o}rg and Eisner, Lukas and Wiegering, Armin}, title = {Robotic hernia repair III. English version}, series = {Der Chirurg}, volume = {92}, journal = {Der Chirurg}, number = {Suppl 1}, doi = {10.1007/s00104-021-01500-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-323896}, pages = {S28-S39}, year = {2021}, abstract = {The principle of targeted separation or weakening of individual components of the abdominal wall to relieve tension in the median line during major abdominal reconstruction has been known for over 30 years as anterior component separation (aCS) and is an established procedure. In search of alternatives with lower complication rates, posterior component separation (pCS) was developed; transversus abdominis release (TAR) is a nerve-sparing modification of pCS. With the ergonomic resources of robotics (e.g., angled instruments), TAR can be performed in a minimally invasive manner (r-TAR): hernia gaps of up to 14 cm can be closed and a large extraperitoneal mesh implanted. In this video article, the treatment of large incisional hernias using the r‑TAR technique is presented. Exemplary results of a cohort study in 13 consecutive patients are presented. The procedure is challenging, but our own results—as well as reports from the literature—are encouraging. The r‑TAR is becoming the pinnacle procedure for abdominal wall reconstruction.}, language = {en} } @misc{DietzKudsiGarciaUrenaetal.2021, author = {Dietz, Ulrich A. and Kudsi, O. Yusef and Garcia-Ure{\~n}a, Miguel and Baur, Johannes and Ramser, Michaela and Maksimovic, Sladjana and Keller, Nicola and D{\"o}rfer, J{\"o}rg and Eisner, Lukas and Wiegering, Armin}, title = {Erratum to: Robotic hernia repair III. English version}, series = {Der Chirurg}, volume = {92}, journal = {Der Chirurg}, number = {Suppl 1}, doi = {10.1007/s00104-021-01564-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-329360}, pages = {40}, year = {2021}, abstract = {No abstract available.}, language = {en} } @article{DiersBaumLehmannetal.2022, author = {Diers, Johannes and Baum, Philip and Lehmann, Kai and Uttinger, Konstatin and Baumann, Nikolas and Pietryga, Sebastian and Hankir, Mohammed and Matthes, Niels and Lock, Johann F. and Germer, Christoph-Thomas and Wiegering, Armin}, title = {Disproportionately high failure to rescue rates after resection for colorectal cancer in the geriatric patient population - A nationwide study}, series = {Cancer Medicine}, volume = {11}, journal = {Cancer Medicine}, number = {22}, doi = {10.1002/cam4.4784}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312858}, pages = {4256-4264}, year = {2022}, abstract = {Background Colorectal cancer incidence increases with patient age. The aim of this study was to assess, at the nationwide level, in-hospital mortality, and failure to rescue in geriatric patients (≥ 80 years old) with colorectal cancer arising from postoperative complications. Methods All patients receiving surgery for colorectal cancer in Germany between 2012 and 2018 were identified in a nationwide database. Association between age and in-hospital mortality following surgery and failure to rescue, defined as death after complication, were determined in univariate and multivariate analyses. Results Three lakh twenty-eight thousands two hundred and ninety patients with colorectal cancer were included of whom 77,287 were 80 years or older. With increasing age, a significant relative increase in right hemicolectomy was observed. In general, these patients had more comorbid conditions and higher frailty. In-hospital mortality following colorectal cancer surgery was 4.9\% but geriatric patients displayed a significantly higher postoperative in-hospital mortality of 10.6\%. The overall postoperative complication rate as well as failure to rescue increased with age. In contrast, surgical site infection (SSI) and anastomotic leakage (AL) did not increase in geriatric patients, whereas the associated mortality increased disproportionately (13.3\% for SSI and 29.9\% mortality for patients with AI, both p < 0.001). Logistic regression analysis adjusting for confounders showed that geriatric patients had almost five-times higher odds for death after surgery than the baseline age group below 60 (OR 4.86; 95\%CI [4.45-5.53], p < 0.001). Conclusion Geriatric patients have higher mortality after colorectal cancer surgery. This may be partly due to higher frailty and disproportionately higher rates of failure to rescue arising from postoperative complications.}, language = {en} } @article{DiersAcarWagneretal.2022, author = {Diers, Johannes and Acar, Laura and Wagner, Johanna C. and Baum, Philip and Hankir, Mohammed and Flemming, Sven and Kastner, Carolin and Germer, Christoph-Thomas and L'hoest, Helmut and Marschall, Ursula and Lock, Johan Friso and Wiegering, Armin}, title = {Cancer diagnosis is one quarter lower than the expected cancer incidence in the first year of COVID-19 pandemic in Germany: A retrospective register-based cohort study}, series = {Cancer Communications}, volume = {42}, journal = {Cancer Communications}, number = {7}, doi = {10.1002/cac2.12314}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312862}, pages = {673-676}, year = {2022}, abstract = {No abstract available.}, language = {en} } @article{DewulfDietzMontgomeryetal.2022, author = {Dewulf, Maxime and Dietz, Ulrich A. and Montgomery, Agneta and Pauli, Eric M. and Marturano, Matthew N. and Ayuso, Sullivan A. and Augenstein, Vedra A. and Lambrecht, Jan R. and K{\"o}hler, Gernot and Keller, Nicola and Wiegering, Armin and Muysoms, Filip}, title = {Robotische Hernienchirurgie Teil IV : Roboterassistierte endoskopische parastomale Hernienversorgung. Videobericht und Ergebnisse}, series = {Chirurgie}, volume = {93}, journal = {Chirurgie}, number = {11}, doi = {10.1007/s00104-022-01715-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-323882}, pages = {1051-1062}, year = {2022}, abstract = {Die chirurgische Behandlung parastomaler Hernien gilt als komplex und ist bekanntermaßen komplikationstr{\"a}chtig. In der Vergangenheit wurden diese Hernien durch die Relokation des Stomas oder Nahtverfahren der Austrittstelle versorgt. In den letzten Jahren wurden verschiedene netzbasierte Techniken vorgeschlagen, die heute in der minimal-invasiven Chirurgie eingesetzt werden. Mit der Verbreitung der roboterassistierten Hernienchirurgie wurden die Netzverfahren weiterentwickelt und die Ergebnisse f{\"u}r die Patienten erheblich verbessert. In diesem Beitrag wird ein {\"U}berblick {\"u}ber die verf{\"u}gbaren Techniken der roboterassistierten Versorgung parastomaler Hernien pr{\"a}sentiert. Es werden technische {\"U}berlegungen und erste Ergebnisse des roboterassistierten modifizierten Sugarbaker-Verfahrens, der roboterassistierten Pauli-Technik und der Verwendung des trichterf{\"o}rmigen Netzes IPST vorgestellt. Dar{\"u}ber hinaus werden die Herausforderungen bei der roboterassistierten Versorgung parastomaler Hernien am Ileum-Conduit diskutiert. Die Operationstechniken werden durch Foto- und Videomaterial veranschaulicht.}, language = {de} } @article{DewulfDietzMontgomeryetal.2022, author = {Dewulf, Maxime and Dietz, Ulrich A. and Montgomery, Agneta and Pauli, Eric M. and Marturano, Matthew N. and Ayuso, Sullivan A. and Augenstein, Vedra A. and Lambrecht, Jan R. and K{\"o}hler, Gernot and Keller, Nicola and Wiegering, Armin and Muysoms, Filip}, title = {Robotic hernia surgery IV. English version}, series = {Chirurgie}, volume = {93}, journal = {Chirurgie}, number = {Suppl 2}, doi = {10.1007/s00104-022-01779-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-323875}, pages = {S129-S140}, year = {2022}, abstract = {The surgical treatment of parastomal hernias is considered complex and is known to be prone to complications. Traditionally, this condition was treated using relocation techniques or local suture repairs. Since then, several mesh-based techniques have been proposed and are nowadays used in minimally invasive surgery. Since the introduction of robot-assisted surgery to the field of abdominal wall surgery, several adaptations to these techniques have been made, which may significantly improve patient outcomes. In this contribution, we provide an overview of available techniques in robot-assisted parastomal hernia repair. Technical considerations and preliminary results of robot-assisted modified Sugarbaker repair, robot-assisted Pauli technique, and minimally invasive use of a funnel-shaped mesh in the treatment of parastomal hernias are presented. Furthermore, challenges in robot-assisted ileal conduit parastomal hernia repair are discussed. These techniques are illustrated by photographic and video material. Besides providing a comprehensive overview of robot-assisted parastomal hernia repair, this article focuses on the specific advantages of robot-assisted techniques in the treatment of this condition.}, language = {en} } @article{BaurRamserKelleretal.2021, author = {Baur, Johannes and Ramser, Michaela and Keller, Nicola and Muysoms, Filip and D{\"o}rfer, J{\"o}rg and Wiegering, Armin and Eisner, Lukas and Dietz, Ulrich A.}, title = {Robotische Hernienchirurgie II: Robotische prim{\"a}r ventrale und inzisionale Hernienversorgung (rv-TAPP und r-Rives/r-TARUP). Videobeitrag und Ergebnisse einer Kohortenstudie an 118 Patienten}, series = {Der Chirurg}, volume = {92}, journal = {Der Chirurg}, number = {9}, doi = {10.1007/s00104-021-01450-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-264912}, pages = {809-821}, year = {2021}, abstract = {Die endoskopische Versorgung von Umbilikal- und Inzisionalhernien hat sich in den vergangenen 30 Jahren an die Limitationen der konventionellen laparoskopischen Instrumente angepasst. Dazu geh{\"o}rt die Entwicklung von Netzen f{\"u}r die intraperitoneale Lage (intraperitoneales Onlay-Mesh, IPOM) mit antiadh{\"a}siven Beschichtungen; allerdings kommt es bei einem betr{\"a}chtlichen Teil dieser Patienten doch zu Adh{\"a}sionen. Minimal-invasive Verfahren f{\"u}hren zu weniger perioperativen Komplikationen, bei einer etwas h{\"o}heren Rezidivrate. Mit den ergonomischen Ressourcen der Robotik, die abgewinkelte Instrumente anbietet, besteht erstmals die M{\"o}glichkeit, Netze minimal-invasiv in unterschiedliche Bauchdeckenschichten zu implantieren und gleichzeitig eine morphologische und funktionelle Rekonstruktion der Bauchdecke zu erreichen. In diesem Videobeitrag wird die Versorgung von Ventral- und Inzisionalhernien mit Netzimplantation in den pr{\"a}peritonealen Raum (robotische ventrale transabdominelle pr{\"a}peritoneale Patchplastik, rv-TAPP) sowie in den retrorektalen Raum (r-Rives bzw. robotische transabdominelle retromuskul{\"a}re umbilikale Patchplastik [r-TARUP]) pr{\"a}sentiert. Es werden die Ergebnisse einer Kohortenstudie an 118 konsekutiven Patienten vorgestellt und im Hinblick auf den Mehrwert der robotischen Technik in der Extraperitonealisierung der Netze und in der Weiterbildung diskutiert.}, language = {de} } @article{BaurRamserKelleretal.2021, author = {Baur, Johannes and Ramser, Michaela and Keller, Nicola and Muysoms, Filip and D{\"o}rfer, J{\"o}rg and Wiegering, Armin and Eisner, Lukas and Dietz, Ulrich A.}, title = {Robotic hernia repair II. English version}, series = {Der Chirurg}, volume = {92}, journal = {Der Chirurg}, number = {Suppl 1}, doi = {10.1007/s00104-021-01479-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-323866}, pages = {S15-S26}, year = {2021}, abstract = {Endoscopic management of umbilical and incisional hernias has adapted to the limitations of conventional laparoscopic instruments over the past 30 years. This includes the development of meshes for intraperitoneal placement (intraperitoneal onlay mesh, IPOM), with antiadhesive coatings; however, adhesions do occur in a significant proportion of these patients. Minimally invasive procedures result in fewer perioperative complications, but with a slightly higher recurrence rate. With the ergonomic resources of robotics, which offers angled instruments, it is now possible to implant meshes in a minimally invasively manner in different abdominal wall layers while achieving morphologic and functional reconstruction of the abdominal wall. This video article presents the treatment of ventral and incisional hernias with mesh implantation into the preperitoneal space (robot-assisted transabdominal preperitoneal ventral hernia repair, r‑ventral TAPP) as well as into the retrorectus space (r-Rives and robotic transabdominal retromuscular umbilical prosthetic repair, r‑TARUP, respectively). The results of a cohort study of 118 consecutive patients are presented and discussed with regard to the added value of the robotic technique in extraperitoneal mesh implantation and in the training of residents.}, language = {en} } @article{BaurMatheGesierichetal.2017, author = {Baur, Johannes and Mathe, Katrin and Gesierich, Anja and Weyandt, Gerhard and Wiegering, Armin and Germer, Christoph-Thomas and Gasser, Martin and Pelz, J{\"o}rg O. W.}, title = {Morbidity and oncologic outcome after saphenous vein-sparing inguinal lymphadenectomy in melanoma patients}, series = {World Journal of Surgical Oncology}, volume = {15}, journal = {World Journal of Surgical Oncology}, number = {99}, doi = {10.1186/s12957-017-1164-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157687}, year = {2017}, abstract = {Background: Inguinal lymph node dissection (LND) is a surgical procedure with a high morbidity rate. Variations in surgical procedure, such as sparing of the saphenous vein, have been proposed to reduce surgical morbidity. While sparing of the saphenous vein has shown promising results in earlier studies, data for this procedure in melanoma patients are rare. In this retrospective study, we report 10-year findings on the effects of saphenous vein-sparing LND on surgical morbidity and oncologic outcomes in melanoma patients. Methods: A retrospective analysis of melanoma patients receiving inguinal LND in our facility between 2003 and 2013 was performed. Patients were divided into two groups: the saphenous vein resection group and the vein sparing group. Surgical morbidity, including wound infection, lymphatic fistula, severe bleeding, neurological complications, and chronic lymphedema, as well as regional recurrence-free survival were investigated. Results: A total of 106 patients were included in this study; of these, the saphenous vein was spared in 41 patients (38.7\%). The rate of lymphatic fistula was 51.6 vs. 48.8\%, wound infection occurred in 31.3 vs. 24.4\%, and patients suffered from chronic lymphedema in 30.0 vs. 26.5\% in V. saphena magna resection vs. sparing group. Differences observed, however, were not significant. No difference in regional recurrence-free survival between the two study groups was detected. Conclusions: The results of our retrospective analysis could not confirm the promising results reported in earlier studies. Thus, sparing of the saphenous vein appears to be optional.}, language = {en} } @article{AngerLockKleinetal.2022, author = {Anger, Friedrich and Lock, Johan Friso and Klein, Ingo and Hartlapp, Ingo and Wiegering, Armin and Germer, Christoph-Thomas and Kunzmann, Volker and L{\"o}b, Stefan}, title = {Does concurrent cholestasis alter the prognostic value of preoperatively elevated CA19-9 serum levels in patients with pancreatic head adenocarcinoma?}, series = {Annals of Surgical Oncology}, volume = {29}, journal = {Annals of Surgical Oncology}, number = {13}, doi = {10.1245/s10434-022-12460-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-323854}, pages = {8523-8533}, year = {2022}, abstract = {Background Pancreatic adenocarcinoma (PDAC) patients with preoperative carbohydrate antigen 19-9 (CA19-9) serum levels higher than 500 U/ml are classified as biologically borderline resectable (BR-B). To date, the impact of cholestasis on preoperative CA19-9 serum levels in these patients has remained unquantified. Methods Data on 3079 oncologic pancreatic resections due to PDAC that were prospectively acquired by the German Study, Documentation and Quality (StuDoQ) registry were analyzed in relation to preoperative CA19-9 and bilirubin serum values. Preoperative CA19-9 values were adjusted according to the results of a multivariable linear regression analysis of pathologic parameters, bilirubin, and CA19-9 values. Results Of 1703 PDAC patients with tumor located in the pancreatic head, 420 (24.5 \%) presented with a preoperative CA19-9 level higher than 500 U/ml. Although receiver operating characteristics (ROC) analysis failed to determine exact CA19-9 cut-off values for prognostic indicators (R and N status), the T, N, and G status; the UICC stage; and the number of simultaneous vein resections increased with the level of preoperative CA19-9, independently of concurrent cholestasis. After adjustment of preoperative CA19-9 values, 18.5 \% of patients initially staged as BR-B showed CA19-9 values below 500 U/ml. However, the postoperative pathologic results for these patients did not change compared with the patients who had CA19-9 levels higher than 500 U/ml after bilirubin adjustment. Conclusions In this multicenter dataset of PDAC patients, elevation of preoperative CA19-9 correlated with well-defined prognostic pathologic parameters. Bilirubin adjustment of CA19-9 is feasible but does not affect the prognostic value of CA19-9 in jaundiced patients.}, language = {en} } @article{AngerDoeringvanDametal.2021, author = {Anger, Friedrich and D{\"o}ring, Anna and van Dam, Jacob and Lock, Johann Frisco and Klein, Ingo and Bittrich, Max and Germer, Christoph-Thomas and Wiegering, Armin and Kunzmann, Volker and van Eijck, Casper and L{\"o}b, Stefan}, title = {Impact of Borderline Resectability in Pancreatic Head Cancer on Patient Survival: Biology Matters According to the New International Consensus Criteria}, series = {Annals of Surgical Oncology}, volume = {28}, journal = {Annals of Surgical Oncology}, number = {4}, issn = {1068-9265}, doi = {10.1245/s10434-020-09100-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235251}, pages = {2325-2336}, year = {2021}, abstract = {Background International consensus criteria (ICC) have redefined borderline resectability for pancreatic ductal adenocarcinoma (PDAC) according to three dimensions: anatomical (BR-A), biological (BR-B), and conditional (BR-C). The present definition acknowledges that resectability is not just about the anatomic relationship between the tumour and vessels but that biological and conditional dimensions also are important. Methods Patients' tumours were retrospectively defined borderline resectable according to ICC. The study cohort was grouped into either BR-A or BR-B and compared with patients considered primarily resectable (R). Differences in postoperative complications, pathological reports, overall (OS), and disease-free survival were assessed. Results A total of 345 patients underwent resection for PDAC. By applying ICC in routine preoperative assessment, 30 patients were classified as stage BR-A and 62 patients as stage BR-B. In total, 253 patients were considered R. The cohort did not contain BR-C patients. No differences in postoperative complications were detected. Median OS was significantly shorter in BR-A (15 months) and BR-B (12 months) compared with R (20 months) patients (BR-A vs. R: p = 0.09 and BR-B vs. R: p < 0.001). CA19-9, as the determining factor of BR-B patients, turned out to be an independent prognostic risk factor for OS. Conclusions Preoperative staging defining surgical resectability in PDAC according to ICC is crucial for patient survival. Patients with PDAC BR-B should be considered for multimodal neoadjuvant therapy even if considered anatomically resectable.}, language = {en} }