TY - JOUR A1 - Diers, Johannes A1 - Acar, Laura A1 - Wagner, Johanna C. A1 - Baum, Philip A1 - Hankir, Mohammed A1 - Flemming, Sven A1 - Kastner, Carolin A1 - Germer, Christoph-Thomas A1 - L’hoest, Helmut A1 - Marschall, Ursula A1 - Lock, Johan Friso A1 - Wiegering, Armin T1 - 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 JF - Cancer Communications N2 - No abstract available. KW - cancer diagnosis KW - COVID-19 pandemic KW - Germany Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-312862 VL - 42 IS - 7 ER - TY - JOUR A1 - Diers, Johannes A1 - Baum, Philip A1 - Lehmann, Kai A1 - Uttinger, Konstatin A1 - Baumann, Nikolas A1 - Pietryga, Sebastian A1 - Hankir, Mohammed A1 - Matthes, Niels A1 - Lock, Johann F. A1 - Germer, Christoph-Thomas A1 - Wiegering, Armin T1 - Disproportionately high failure to rescue rates after resection for colorectal cancer in the geriatric patient population - A nationwide study JF - Cancer Medicine N2 - 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. KW - colorectal cancer KW - geriatric KW - octogenerians KW - surgery Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-312858 VL - 11 IS - 22 ER - TY - JOUR A1 - Jurowich, Christian A1 - Lichthardt, Sven A1 - Kastner, Caroline A1 - Haubitz, Imme A1 - Prock, Andre A1 - Filser, Jörg A1 - Germer, Christoph-Thomas A1 - Wiegering, Armin T1 - Laparoscopic versus open right hemicolectomy in colon carcinoma: A propensity score analysis of the DGAV StuDoQ|ColonCancer registry JF - PLoS ONE N2 - 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. KW - Laparoscopy KW - Lymph nodes KW - Minimally invasive surgery KW - Surgical oncology KW - Oncology KW - Surgical and invasive medical procedures Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202184 VL - 14 IS - 6 ER - TY - JOUR A1 - Kastner, Carolin A1 - Hendricks, Anne A1 - Deinlein, Hanna A1 - Hankir, Mohammed A1 - Germer, Christoph-Thomas A1 - Schmidt, Stefanie A1 - Wiegering, Armin T1 - Organoid Models for Cancer Research — From Bed to Bench Side and Back JF - Cancers N2 - 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. KW - cancer KW - tumor disease KW - organoid KW - patient-derived organoid (PDOs) KW - patient-derived tumor organoid (PDTO) Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-246307 SN - 2072-6694 VL - 13 IS - 19 ER - TY - JOUR A1 - Köhler, Franziska A1 - Reese, Lena A1 - Hendricks, Anne A1 - Kastner, Carolin A1 - Müller, Sophie A1 - Lock, Johan F. A1 - Germer, Christoph-Thomas A1 - Wiegering, Armin T1 - 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) JF - Langenbeck’s Archives of Surgery N2 - 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 für 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. KW - LAMN KW - low-grade mucinous neoplasm KW - appendix KW - epidemiology KW - ZfKD KW - Germany Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-323919 VL - 407 IS - 8 ER - TY - JOUR A1 - Köhler, Franziska A1 - Reese, Lena A1 - Kastner, Carolin A1 - Hendricks, Anne A1 - Müller, Sophie A1 - Lock, Johan F. A1 - Germer, Christoph-Thomas A1 - Wiegering, Armin T1 - Surgical site infection following single-port appendectomy: a systematic review of the literature and meta-analysis JF - Frontiers in Surgery N2 - 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. KW - appendicitis KW - appendectomy KW - surgical site infection KW - single-port appendectomy KW - conventional laparoscopic appendectomy KW - wound infection KW - SSI Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-276943 SN - 2296-875X VL - 9 ER - TY - JOUR A1 - Lichthardt, Sven A1 - Kerscher, Alexander A1 - Dietz, Ulrich A. A1 - Jurowich, Christian A1 - Kunzmann, Volker A1 - von Rahden, Burkhard H. A. A1 - Germer, Christoph-Thomas A1 - Wiegering, Armin T1 - Original article: role of adjuvant chemotherapy in a perioperative chemotherapy regimen for gastric cancer JF - BMC Cancer N2 - 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. KW - gastric cancer KW - chemotherapy KW - neoadjuvant KW - multimodal KW - complication KW - adjuvant KW - risk factor KW - survival Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-147743 VL - 16 IS - 650 ER - TY - JOUR A1 - Lichthardt, Sven A1 - Wagner, Johanna A1 - Löb, Stefan A1 - Matthes, Niels A1 - Kastner, Caroline A1 - Anger, Friedrich A1 - Germer, Christoph-Thomas A1 - Wiegering, Armin T1 - 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 JF - BMC Cancer N2 - 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. KW - Rectal cancer KW - Surgery KW - Radiochemotherapy KW - Time interval Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229334 VL - 20 IS - 1 ER - TY - JOUR A1 - Matthes, Niels A1 - Diers, Johannes A1 - Schlegel, Nicolas A1 - Hankir, Mohammed A1 - Haubitz, Imme A1 - Germer, Christoph-Thomas A1 - Wiegering, Armin T1 - Validation of MTL30 as a quality indicator for colorectal surgery JF - PLoS One N2 - 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. KW - surgical care KW - discharge definition KW - definition KW - mortality KW - pancreatectomy KW - complications KW - superior KW - capture Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230530 VL - 15 IS - 8 ER - TY - JOUR A1 - Meir, Michael A1 - Kannapin, Felix A1 - Diefenbacher, Markus A1 - Ghoreishi, Yalda A1 - Kollmann, Catherine A1 - Flemming, Sven A1 - Germer, Christoph-Thomas A1 - Waschke, Jens A1 - Leven, Patrick A1 - Schneider, Reiner A1 - Wehner, Sven A1 - Burkard, Natalie A1 - Schlegel, Nicolas T1 - Intestinal epithelial barrier maturation by enteric glial cells is GDNF-dependent JF - International Journal of Molecular Sciences N2 - Enteric glial cells (EGCs) of the enteric nervous system are critically involved in the maintenance of intestinal epithelial barrier function (IEB). The underlying mechanisms remain undefined. Glial cell line-derived neurotrophic factor (GDNF) contributes to IEB maturation and may therefore be the predominant mediator of this process by EGCs. Using GFAP\(^{cre}\) x Ai14\(^{floxed}\) mice to isolate EGCs by Fluorescence-activated cell sorting (FACS), we confirmed that they synthesize GDNF in vivo as well as in primary cultures demonstrating that EGCs are a rich source of GDNF in vivo and in vitro. Co-culture of EGCs with Caco2 cells resulted in IEB maturation which was abrogated when GDNF was either depleted from EGC supernatants, or knocked down in EGCs or when the GDNF receptor RET was blocked. Further, TNFα-induced loss of IEB function in Caco2 cells and in organoids was attenuated by EGC supernatants or by recombinant GDNF. These barrier-protective effects were blunted when using supernatants from GDNF-deficient EGCs or by RET receptor blockade. Together, our data show that EGCs produce GDNF to maintain IEB function in vitro through the RET receptor. KW - enteric glial cells KW - neurotrophic factors KW - intestinal epithelial barrier KW - GDNF5 KW - RET6 KW - inflammatory bowel disease KW - enteric nervous system KW - gut barrier KW - intercellular junctions Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-258913 SN - 1422-0067 VL - 22 IS - 4 ER -