Molecular Profiling of Low-Grade Appendiceal Mucinous Neoplasms (LAMN).

Low-grade appendiceal mucinous neoplasia (LAMN) represents a relatively rare tumor of the appendix typically diagnosed incidentally through appendectomy for acute appendicitis. In cases where perforation occurs, mucinous content may disseminate into the abdominal cavity, leading to the development of pseudomyxoma peritonei (PMP). The primary objective of this study was to elucidate the molecular characteristics associated with various stages of LAMN and PMP. DNA was extracted from LAMN, primary PMPs, recurrent PMPs, and adenocarcinomas originating from LAMN. The subsequent analysis involved the examination of mutational hotspot regions within 50 cancer-related genes, covering over 2800 COSMIC mutations, utilizing amplicon-based next-generation sequencing (NGS). Our findings revealed activating somatic mutations within the MAPK-signaling pathway across all tumors examined. Specifically, 98.1% of cases showed mutations in KRAS, while one tumor harbored a BRAF mutation. Additionally, GNAS mutations were identified in 55.8% of tumors, with no significant difference observed between LAMN and PMP. While LAMN rarely displayed additional mutations, 42% of primary PMPs and 60% of recurrent PMPs showed additional mutations. Notably, both adenocarcinomas originating from LAMN showed mutations within TP53. Furthermore, 7.7% (4/52) of cases exhibited a potentially targetable KRAS G12C mutation. In four patients, NGS analysis was performed on both primary PMP and recurrent PMP/adenocarcinoma samples. While mutations in KRAS and GNAS were detected in almost all samples, 50% of recurrent cases displayed an additional SMAD4 mutation, suggesting a notable alteration during disease progression. Our findings indicate two key points: First, mutations within the MAPK pathway, particularly in KRAS, are evident across all tumors, along with a high frequency of GNAS mutations. Second, progression toward PMP or adenocarcinoma is associated with an accumulation of additional mutations within common oncogenic pathways.

Proficiency in bariatric surgery may shorten the learning curve for minimally-invasive D2 gastrectomy.

INTRODUCTION: Evidence from Asian studies suggests that minimally-invasive gastrectomy achieves equivalent oncological but improved perioperative outcomes compared to open surgery. Oncological gastric resections are less frequent in European countries. Index procedures may play a role for the learning curve of minimally-invasive gastrectomy. The aim of our study was to evaluate if skills acquired in bariatric surgery allow a safe and oncologically adequate implementation of minimally-invasive gastrectomy in a cohort of european patients. METHODS: In this single-center retrospective study, all patients who received primary bariatric surgery between January 2015 and December 2018 and minimally-invasive surgery for gastric cancer treated from June 2019 to January 2023 were evaluated. Primary endpoints were operation time, lymph node yield and lymph node fractions. Secondary endpoints included postoperative complications and oncological outcomes. RESULTS: Learning curves for two surgeons with 350 bariatric procedures and 44 minimally-invasive gastrectomies were analyzed. For bariatric surgery, the mean operation time decreased from initially 82 ± 27 to 45 ± 21 min and 118 ± 28 to 81 ± 36 min for sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB), while the complication rate remained within the international benchmark. For laparoscopic gastrectomy (n = 30), operation times decreased but then remained stable over time. Operation times for the robotic platform were longer (302 ± 60 vs. 390 ± 48 min; p < 0.001) with the learning curve remaining incomplete after 14 procedures. R0 status was achieved in 95.5% of patients; the mean number of lymph nodes retrieved was 37 ± 14 with no differences between the groups. Complete mesogastric excision was more frequently achieved during the later laparoscopic cases whereas it occurred earlier for the robotic group (p = 0.004). Perioperative morbidity was comparable to the European benchmark. Textbook outcome was achieved in 54.4% of the cases. CONCLUSION: In summary, we could demonstrate a successful skill transfer from bariatric surgery to minimally-invasive laparoscopic oncological gastric surgery enabling safe and oncologically adequate minimally-invasive D2 gastrectomy in a central European patient collective.

Additional over-the-scope-clip closure can shorten endoscopic vacuum therapy for postoperative upper gastrointestinal leakage.

Background and study aims Endoscopic vacuum therapy (EVT) has become the most effective therapeutic option for upper gastrointestinal leakage. Despite its efficiency, this treatment can necessitate a long hospitalization. The aim of this study was to evaluate whether additional use of an over-the-scope-clips (OTSC) closure after successful EVT can shorten leakage therapy. Patients and methods All patients treated with EVT for leakages in the upper gastrointestinal tract at our center from 2012 to 2022 were divided into two propensity matched cohorts (EVT+OTSC vs. EVT only). The EVT+OTSC patients received OSTC application at the end of successful EVT directly after removal of the last sponge. The primary endpoint was the time interval from leakage diagnosis until discharge. Secondary endpoints included EVT efficacy, complications, and nutritional status at discharge. Results A total of 84 matched patients were analyzed. EVT efficacy was 100% in both groups. The time interval from leakage until discharge was significantly shorter in the EVT+OTSC vs. EVT group (33 [19-48] vs. 46 days [29-77] P = 0.004). No patient in the EVT+OTSC group required additional procedures for leakage management, whereas five (12%) in the EVT group needed additional stent placement ( P = 0.021). More patients could be discharged on sufficient oral nutrition in the EVT+OTSC group (98% vs. 60%; P < 0.001). Conclusions The addition of OTSCs after successful EVT is safe and has the potential to shorten leakage therapy, enabling earlier discharge along with better functional outcomes.

Chemoradiotherapy plus induction or consolidation chemotherapy as total neoadjuvant therapy for locally advanced rectal cancer: Pooled analysis of the CAO/ARO/AIO-12 and the OPRA randomized phase 2 trials.

BACKGROUND: Total neoadjuvant therapy (TNT) has been used for patients with locally advanced rectal cancer. The optimal sequence of chemoradiotherapy (CRT) and chemotherapy (CT) is a matter of debate. METHODS: We performed a pooled analysis of the CAO/ARO/AIO-12 and OPRA multicenter, randomized phase 2 trials to identify patient subsets that could benefit from one TNT sequence over the other regarding disease-free survival (DFS). Patients with stage II/III rectal cancer were randomized to CRT (50.4-54 Gy) with either induction (INCT-CRT) or consolidation CT (CRT-CNCT) with fluorouracil, leucovorin, oxaliplatin (CAO/ARO/AIO-12 and OPRA) or capecitabine and oxaliplatin (OPRA) followed by mandatory total mesorectal excision (TME) (CAO/ARO/AIO-12) or selective watch-and-wait surveillance (OPRA). 311 and 324 patients were recruited from June 15, 2015 to January 31, 2018; and from April 12, 2014 to March 30, 2020 in the two trials, respectively. Pretreatment clinical and tumor characteristics included were age, sex, ECOG, cT-category, cN-category, clinical UICC stage, location from anal verge, and tumor grade. FINDINGS: In total, 628 eligible patients were included in the pooled analysis (CAO/ARO/AIO-12, n = 304; OPRA, n = 324). Of those, 313 were randomly assigned to the INCT-CRT group, and 315 to the CRT-CNCT group. Median follow-up was 43 months (IQR, 35-49) months in the CAO/ARO/AIO-12 trial and 61,2 months (IQR, 42-68,4) in the OPRA trial. Pooled analysis of baseline clinical and tumor characteristics did not identify any subgroups of patients that would benefit by the one TNT sequence over the other with regard to DFS. INTERPRETATION: To our knowledge, this is the first pooled analysis of two randomized trials after direct head-to-head comparison of both TNT sequences. Both trials reported higher rates of complete response with CRT-CNCT, and this should be considered the preferred TNT sequence if organ preservation is a priority.

Surgical options in retrosternal oesophageal reconstruction.

BACKGROUND: Retrosternal oesophageal reconstructions with collar anastomoses can become necessary when the stomach is either unavailable for oesophageal replacement, or orthotopic reconstruction is deemed impractical. Our aim was to analyse our results regarding technical approaches and outcomes. MATERIALS AND METHODS: All patients undergoing primary and secondary oesophageal retrosternal reconstructions with collar anastomoses at our centre (2019-2023) were retrospectively analysed and individual surgical reconstruction options were presented. RESULTS: Overall, twelve patients received primary (n = 5; 42.7%) or secondary (n = 7; 58.3%) reconstructions; ten with colonic interposition and two with gastric pull-up. Male/female ratio was 4:8; median age 66 years (30-87). Charlson-Comorbidity-Score (CCS) was 5 (1-7); 8/12 patients (67%) had ASA-classification score ≥ 3. We observed no conduit necrosis, but one patient (8.3%) with a leakage of the oesophago-colonostomy which was successfully treated by endoscopic vacuum therapy. Four patients (33.3%) acquired nosocomial pneumonia. Additional drainages for pleural fluid collections were necessary in three patients (25%). Overall comprehensive-complication-index (CCI) was 26.2 (0-44.9). Length-of-stay (LOS) was 22 days median (15-40). There was no 90-days mortality. Overall, CCI during the follow-up (FU) period at median 26 months (16-50) was 33.7 (0-100). 10 out of 12 patients were on sufficient oral nutrition at 12 months FU. CONCLUSION: Primary and secondary oesophageal retrosternal reconstructions encompass diverse entities and typically requires tailored decision-making. These procedures, though rare, are feasible with acceptable complication rates and positive functional outcomes when performed in experienced hands.

Optimal Treatment Strategies for cT2 Staged Adenocarcinoma of the Esophagus and the Gastroesophageal Junction: A Multinational, High-volume Center Retrospective Cohort Analysis.

OBJECTIVE: A multi-national high-volume center study was undertaken to evaluate outcomes after primary surgery (PS) or neoadjuvant treatment followed by surgery (NAT/S) in cT2 staged adenocarcinomas of the esophagus (EAC) and gastroesophageal junction (GEJ). BACKGROUND: Optimal treatment approach with either NAT/S or PS for clinically staged cT2cNany or cT2N0 EAC and GEJ remains unknown due to the lack of randomized controlled trials. METHODS: Retrospective analysis of prospectively maintained databases from ten centers was performed. Between 01/2012-08/2023 645 patients who fulfilled inclusion criteria of GEJ Siewert type I, II or EAC with cT2 status at diagnosis underwent PS or NAT/S with curative intent. Primary endpoint was overall survival (OS). RESULTS: In the cT2cNany cohort 192 patients (29.8%) underwent PS and 453 (70.2%) underwent NAT/S. In all cT2cN0 patients (n=333), NAT/s remained the more frequent treatment (56.2%). Patients undergoing PS were in both cT2 cohorts older (P<0.001) and had a higher ASA classification (P<0.05). R0 resection showed no differences between NAT/S and PS in both cT2 cohorts (P>0.4).Median OS was 51.0 months in the PS group (95% CI 31.6-70.4) versus 114.0 months (95% CI 53.9-174.1) in the NAT/S group (P=0.003) of cT2cNany patients. For cT2cN0 patients NAT/S was associated with longer OS (P=0.002) and disease-free survival (DFS) (P=0.001). After propensity score matching of cT2N0 patients, survival benefit for NAT/S remained (P=0.004). Histopathology showed that 38.1% of cT2cNany and 34.2% of cT2cN0 patients were understaged. CONCLUSIONS: Due to unreliable identification of cT2N0 disease, all patients should be offered a multimodal therapeutic approach.

Availability in ECMO Reduces the Failure to Rescue in Patients With Pulmonary Embolism After Major Surgery: A Nationwide Analysis of 2.4 Million Cases.

Objective: Postoperative pulmonary embolism (PE) is a rare but potentially life-threatening complication, which can be treated with extracorporeal membrane oxygenation (ECMO) therapy, a novel therapy option for acute cardiorespiratory failure. We postulate that hospitals with ECMO availability have more experienced staff, technical capabilities, and expertise in treating cardiorespiratory failure. Design: A retrospective analysis of surgical procedures in Germany between 2012 and 2019 was performed using hospital billing data. High-risk surgical procedures for postoperative PE were analyzed according to the availability of and expertise in ECMO therapy and its effect on outcome, regardless of whether ECMO was used in patients with PE. Methods: Descriptive, univariate, and multivariate analyses were applied to identify possible associations and correct for confounding factors (complications, complication management, and mortality). Results: A total of 13,976,606 surgical procedures were analyzed, of which 2,407,805 were defined as high-risk surgeries. The overall failure to rescue (FtR) rate was 24.4% and increased significantly with patient age, as well as type of surgery. The availability of and experience in ECMO therapy (defined as at least 20 ECMO applications per year; ECMO centers) are associated with a significantly reduced FtR in patients with PE after high-risk surgical procedures. In a multivariate analysis, the odds ratio (OR) for FtR after postoperative PE was significantly lower in ECMO centers (OR, 0.75 [0.70-0.81], P < 0.001). Conclusions: The availability of and expertise in ECMO therapy lead to a significantly reduced FtR rate of postoperative PE. This improved outcome is independent of the use of ECMO in these patients.

Improved Learning Gain in Medical Students by Using Animated Whiteboard-Videos in Comparison to Textbooks in Surgery.

BACKGROUND: Animated videos have become popular in teaching medical students, although there is a certain lack of evidence concerning its efficacy. Surgery seems to be an ideal field for its application, since animations are very helpful to understand anatomic structures and complex procedures. The aim of this study was to investigate the effects of animated videos compared to textbooks on learning gain. METHODS: A prospective 2-arm cohort study with 5th-year medical students was conducted during their 2-week surgical training module. The initial cohort of students received textbook sections on 3 major topics in visceral surgery as learning medium (text cohort). During the following semester, the second cohort of students received 3 animated whiteboard videos (animated videos) containing equivalent content (video cohort). All participants completed a multiple-choice test consisting of 15 questions on the learning content at baseline (pre-test) and after the learning period (post-test) and answered an additional evaluation questionnaire. RESULTS: Both cohorts were similar in their descriptive data and demonstrated significant learning gain during the 2-week learning period. The video cohort achieved better results (80% vs 73% correct answers; P = .028) and a higher learning gain (17% vs 11%; P = .034) in the post-test compared to the text cohort. The estimated learning time was longer in the video cohort (62 min vs 37 min; P < .001) and watching the videos resulted in higher learning gain (21% vs 6%; P < .001). Subgroups with higher learning gain by video learning were female gender (20% vs 11%; P = .040), native German speakers (18% vs 11%; P = .009), students without prior surgical experience (19% vs 12%; P = .033) and those undecided concerning a surgical career (22% vs 9%; P = .020). Interestingly, "low digital orientation" students benefited from videos (22% vs 13%; P = .021), whereas "high digital orientation" students did not. CONCLUSIONS: Animated videos increase medical students' learning gain and interest in surgery.

Perioperative Enhanced Recovery Concepts Significantly Improve Postoperative Outcome in Patients with Crohn`s Disease.

BACKGROUND AND AIMS: Despite recent advancements in medical and surgical techniques in patients suffering from Crohn`s Disease (CD), postoperative morbidity remains relevant due to a long-standing, non-curable disease burden. As demonstrated for oncological patients, perioperative enhanced recovery concepts provide great potential to improve postoperative outcome. However, robust evidence about the effect of perioperative enhanced recovery concepts in the specific cohort of CD patients is lacking. METHODS: In a prospective single-center study, all patients receiving ileocecal resection due to CD between 2020 and 2023 were included. A specific perioperative enhanced recovery concept (ERC) was implemented and patients were divided into two groups (before and after implementation). The primary outcome focused on postoperative complications as measured by the Comprehensive Complication Index (CCI), secondary endpoints were severe complications, length of hospital stay, and rates of re-admission. RESULTS: 83 patients were analyzed of which 33 patients participated in the enhanced recovery program (postERC). While patient characteristics were comparable between both groups, ERC resulted in significantly decreased rates of overall and severe postoperative complications (CCI: 21.4 versus 8.4, p=0.0036; Clavien Dindo >2: 38% versus 3.1%, p=0.0002). Additionally, postERC-patients were earlier ready for discharge (6.5 days versus 5 days, p=0.001) and rates of re-admission were significantly lower (20% versus 3.1%, p=0.03). In a multivariate analysis, the recovery concept was identified as independent factor to reduce severe postoperative complications (p=0.019). CONCLUSION: A specific perioperative enhanced recovery concept significantly improves the postoperative outcome of patients suffering from Crohn`s Disease.

The impact of surgical timing on outcome in acute appendicitis in adults: a retrospective observational population-based cohort study.

BACKGROUND: Acute appendicitis is a global disease with high incidence. The main objective was to assess the association between time from admission to surgery (TAS) and surgery during emergency hours with operative outcome in light of conflicting evidence. METHODS: This is a retrospective population-wide analysis of hospital billing data (2010-2021) of all adult patient records of surgically treated cases of acute appendicitis in Germany by TAS. The primary outcome was a composite clinical endpoint (CCE; prolonged length of stay, surgical site infection, interventional draining after surgery, revision surgery, ICU admission and/or in-hospital mortality). Cases of complicated appendicitis were identified using diagnosis (ICD-10) and procedural codes (resection beyond appendectomy). RESULTS: 855 694 patient records were included, of which 27·6% (236,481) were complicated cases of acute appendicitis. 49·0% (418,821) were females and median age was 37 (interquartile range 22·5-51·5). Age, male sex, and comorbidity were associated with an increased proportion of CCE and in-hospital mortality. TAS was associated with a clinically relevant increase of CCE after 12 h in complicated appendicitis [Odd's ratio (OR), 1·19, 95% CI: 1·14-1·21] and after 24 h in uncomplicated appendicitis (OR 1·10, 95% CI: 1·02-1·19). Beyond the primary endpoint, the proportion of complicated appendicitis increased after TAS of 72 h. Surgery during emergency hours (6 pm-6.59 am) was associated with an increase of CCE and mortality (OR between 1·14 and 1·49). Age, female sex, night-time admission, weekend admission, a known previous surgery, obesity, and therapeutic anticoagulation were associated with delayed performance of surgery. CONCLUSION: This work found an increase of a CCE after TAS of 12 h for complicated appendicitis and an increase of the CCE after TAS of 24 h for uncomplicated appendicitis with a stable proportion of complicated appendicitis in these time windows. Both CCE and mortality were increased if appendectomy was performed during emergency hours.

Positive resection margins in Crohn's disease are a relevant risk factor for postoperative disease recurrence.

Postoperative disease recurrence in Crohn's disease represents a relevant issue despite recent advancements in surgical and medical therapies. Additional criteria are necessary to improve the identification of patients at risk and to enable selective therapeutic approaches. The role of resection margins on disease recurrence remains unclear and general recommendations are lacking. A single-center retrospective analysis was performed including all patients who received ileocecal resection due to Crohn's disease. Resection margins were analyzed by two independent pathologists and defined by histopathological criteria based on previous consensus reports. 158 patients were included for analysis with a median follow up of 35 months. While postoperative morbidity was not affected, positive resection margins resulted in significantly increased rates of severe endoscopic recurrence at 6 months (2.0% versus 15.6%, p = 0.02) and overall (4.2% versus 19.6%, p = 0.001), which resulted in significantly increased numbers of surgical recurrence (0% versus 4.5%, p = 0.04). Additionally, positive margins were identified as independent risk factor for severe endoscopic disease recurrence in a multivariate analysis. Based on that, positive margins represent an independent risk factor for postoperative endoscopic and surgical disease recurrence. Prospective studies are required to determine whether extended resection or postoperative medical prophylaxis is beneficial for patients with positive resection margins.

[Watch and Wait for Rectal Cancer]. / Surveillance bei Watch-and-Wait nach neoadjuvanter Therapie beim Rektumkarzinom.

About one third of all colorectal carcinomas (CRC) are localised in the rectum. As part of a multimodal therapy concept, neoadjuvant therapy achieves downstaging of the tumour in 50-60% of cases and a so-called complete clinical response (cCR), defined as clinically (and radiologically) undetectable residual tumour after completion of neoadjuvant therapy, in 10-30% of cases.In view of the perioperative morbidity and mortality associated with radical rectal resection, including the occurrence of a symptom complex known as low anterior resection syndrome (LARS) and the need for deviation, at least temporarily, the question of the risk-benefit balance of organ resection in the presence of cCR has been raised. In this context, the therapeutic concept of a "watch-and-wait" approach with omission of immediate organ resection and inclusion in a structured surveillance regime, has emerged.For a safe, oncological implementation of this option, it is necessary to develop standards in the definition of a suitable patient clientele and the implementation of the concept. In addition to the initial correct selection of the patient group that is suitable for a primarily non-surgical procedure, the inherent goal is the early and sufficient detection of tumour recurrence (so-called local regrowth) during the "watch-and-wait" phase (surveillance).In this context, in this paper we address the questions of: 1. the optimal timing of initial re-staging, 2. the criteria for assessing the clinical response and selecting the appropriate patient clientele, 3. the rhythm and design of the surveillance protocol.

Clinical Management of Major Postoperative Bleeding After Bariatric Surgery.

INTRODUCTION: Major postoperative bleeding (mPOB) is the most common complication after bariatric surgery. Its intesity varies from self-limiting to life-threatening situations. Comprehensive decision-making and treatment strategies are mandatory but not established yet. METHODS: We retrospectively analyzied our prospectively collected database of our bariatric patients during 2012-2022. The primary study endpoint was major postoperative bleeding (mPOB) defined as hemoglobin drop > 2 g/dl or clinically relevant bleeding requiring intervention (transfusion, endoscopy or surgery). Secondary endpoints were overall complications according to Clavien-Dindo-Classification and comprehensive-complication-index (CCI). RESULTS: We identified 1017 patients, of whom 667 underwent gastric bypass (GB) and 350 sleeve gastrectomy (SG). Major postoperative bleeding occured in 39 patients (total 3.8%; 5.1% after GB and 2.3% after SG). Patients with mPOB were more often diagnosed with type 2 diabetes (p = 0.039), chronic kidney failure (p = 0.013) or received antiplatelet drug treatment (p = 0.003). The interval from detection to intervention within 24 h was 92.1% (35/39). Blood transfusions were necessary in 20/39 cases (total 51.3%; 45.2% after GB and 75% after SG; p = 0.046). Luminal bleeding only occured after GB (19/31; 61.3%), while all mPOB after SG were intraabdominal (p = 0.002). Reoperations were performed in 21/39 (total 53.8%; 48.4% after GB and 75% after SG; p = 0.067). CCI in patients with mPOB was 34.7 overall, with 31.2 after GB and 47.9 after SG (p = 0.005). CONCLUSION: The clinical appearance of mPOB depends on the type of surgery with severe bleedings after SG. We suggest a surgery first approach for mPOB after SG and an endoscopy first approach after GB.

Diverticulitis patient care during the Covid-19 pandemic in Germany-a retrospective nationwide population-based cohort study.

PURPOSE: Coronavirus disease 2019 (COVID-19) impacted health care systems around the world. Despite a decrease in emergency admissions, an increased number of complicated forms of diverticulitis was reported. It was the aim of this study to analyze the pandemic impact on diverticulitis management in Germany. METHODS: This is a retrospective population-wide analysis of hospital billing data (2012-2021) of diverticulitis in Germany. Patients were identified based on diagnosis (ICD10) and procedural codes to stratify by conservative and operative management. Primary outcome of interest was admission rates, secondary outcomes were rates of surgical vs conservative treatment and fraction of complicated clinical courses during the pandemic. RESULTS: Of a total of 991,579 cases, 66,424 (6.7%) were admitted during pandemic lockdowns. Conservative treatment was the most common overall (66.9%) and higher during lockdowns (70.7%). Overall admissions and population adjusted rates of surgically treated patients decreased, the latter by 12.7% and 11.3%, corrected to estimated rates, in the two lockdowns. Surgery after emergency presentation decreased by 7.1% (p=0.053) and 11.1% (p=0.002) in the two lockdowns with a higher rate of ostomy and/or revision (+5.6%, p=0.219, and +10.2%, p=0.030). In-hospital mortality was increased in lockdown periods (1.64% vs 1.49%). In detail, mortality was identical in case of conservative treatment during lockdown periods (0.5%) but was higher in surgically treated patients (4.4% vs 3.6%). CONCLUSION: During lockdowns, there was an overall decrease of admissions for diverticulitis, especially non-emergency admissions in Germany, and treatment was more likely to be conservative. In case of surgery, however, there was increased risk of a complicated course (ostomy, re-surgery), possibly due to patient selection.

Human organoids are superior to cell culture models for intestinal barrier research.

Loss of intestinal epithelial barrier function is a hallmark in digestive tract inflammation. The detailed mechanisms remain unclear due to the lack of suitable cell-based models in barrier research. Here we performed a detailed functional characterization of human intestinal organoid cultures under different conditions with the aim to suggest an optimized ex-vivo model to further analyse inflammation-induced intestinal epithelial barrier dysfunction. Differentiated Caco2 cells as a traditional model for intestinal epithelial barrier research displayed mature barrier functions which were reduced after challenge with cytomix (TNFα, IFN-γ, IL-1ß) to mimic inflammatory conditions. Human intestinal organoids grown in culture medium were highly proliferative, displayed high levels of LGR5 with overall low rates of intercellular adhesion and immature barrier function resembling conditions usually found in intestinal crypts. WNT-depletion resulted in the differentiation of intestinal organoids with reduced LGR5 levels and upregulation of markers representing the presence of all cell types present along the crypt-villus axis. This was paralleled by barrier maturation with junctional proteins regularly distributed at the cell borders. Application of cytomix in immature human intestinal organoid cultures resulted in reduced barrier function that was accompanied with cell fragmentation, cell death and overall loss of junctional proteins, demonstrating a high susceptibility of the organoid culture to inflammatory stimuli. In differentiated organoid cultures, cytomix induced a hierarchical sequence of changes beginning with loss of cell adhesion, redistribution of junctional proteins from the cell border, protein degradation which was accompanied by loss of epithelial barrier function. Cell viability was observed to decrease with time but was preserved when initial barrier changes were evident. In summary, differentiated intestinal organoid cultures represent an optimized human ex-vivo model which allows a comprehensive reflection to the situation observed in patients with intestinal inflammation. Our data suggest a hierarchical sequence of inflammation-induced intestinal barrier dysfunction starting with loss of intercellular adhesion, followed by redistribution and loss of junctional proteins resulting in reduced barrier function with consecutive epithelial death.

Surgical treatment of internal hernia after Roux-en-Y gastric bypass - impact of institutional standards and surgical approach.

INTRODUCTION: Internal hernia is one of the most frequent long-term complications after laparoscopic gastric bypass surgery (RYGB). Surgical treatment of an internal hernia itself has risks that can largely be avoided by the implementation of institutional standards and a structured approach. MATERIAL AND METHODS: From 2012 until 2022, we extracted all consecutive bariatric cases from the prospectively collected national database (StuDoQ). Data from all patients undergoing internal hernia repair were then collected from our hospital information management system and retrospectively analyzed. We compared patient characteristics and surgical outcome of patients before and after the implementation of standard operating procedures for institutional and perioperative aspects (first vs. second time span). RESULTS: Overall, 37 patients were identified (median age 43 years, 86.5% female). Internal hernia was diagnosed after substantial weight loss (17.2 kg/m2) and on average about 34 months after RYGB. Baseline characteristics (age, sex, BMI, achieved total weight loss% and time interval to index surgery were comparable between the two groups). After local standardization, the conversion rate decreased from 52.6 to 5.6% (p = 0.007); duration of surgery from 92 to 39 min (p = 0.003), and length of stay from 7.7 to 2.8 days (p = 0.019). CONCLUSION: In this study, we could demonstrate that the surgical therapy of internal hernia after gastric bypass can be significantly improved by implementing institutional and surgical standards. The details described (including a video) may provide valuable information for non-specialized surgeons to avoid pitfalls and improve surgical outcomes.

Nationwide volume-outcome relationship concerning in-hospital mortality and failure-to-rescue in surgery of sigmoid diverticulitis.

PURPOSE: A correlation between the hospital volume and outcome is described for multiple entities of oncological surgery. To date, this has not been analyzed for the surgical treatment of sigmoid diverticulitis. The aim of this study was to explore the impact of the annual caseload per hospital of colon resection on the postoperative incidence of complications, failure to rescue, and mortality in patients with diverticulitis. METHODS: Patients receiving colorectal resection independent from the diagnosis from 2012 to 2017 were selected from a German nationwide administrative dataset. The hospitals were grouped into five equal caseload quintiles (Q1-Q5 in ascending caseload order). The outcome analysis was focused on patients receiving surgery for sigmoid diverticulitis. RESULTS: In total, 662,706 left-sided colon resections were recorded between 2012 and 2017. Of these, 156,462 resections were performed due to sigmoid diverticulitis and were included in the analysis. The overall in-house mortality rate was 3.5%, ranging from 3.8% in Q1 (mean of 9.5 procedures per year) to 3.1% in Q5 (mean 62.8 procedures per year; p < 0.001). Q5 hospitals revealed a risk-adjusted odds ratio of 0.85 (95% CI 0.78-0.94; p < 0.001) for in-hospital mortality compared to Q1 during multivariable logistic regression analysis. High-volume centers showed overall lower complication rates, whereas the failure-to-rescue did not differ significantly. CONCLUSION: Surgical treatment of sigmoid diverticulitis in high-volume colorectal centers shows lower postoperative mortality rates and fewer postoperative complications.

Neoplasms of the Appendix.

BACKGROUND: Neoplasms of the vermiform appendix are rare. They comprise a heterogeneous group of entities requiring differentkinds of treatment. METHODS: This review is based on publications retrieved by a selective literature search in the PubMed, Embase, and Cochranedatabases. RESULTS: 0.5% of all tumors of the gastrointestinal tract arise in the appendix. Their treatment depends on their histopathologicalclassification and tumor stage. The mucosal epithelium gives rise to adenomas, sessile serrated lesions, adenocarcinomas,goblet-cell adenocarcinomas, and mucinous neoplasms. Neuroendocrine neoplasms originate in neuroectodermal tissue. Adenomasof the appendix can usually be definitively treated by appendectomy. Mucinous neoplasms, depending on their tumorstage, may require additional cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC). Adeno -carcinomas and goblet-cell adenocarcinomas can metastasize via the lymphatic vessels and the bloodstream and should thereforebe treated by oncological right hemicolectomy. Approximately 80% of neuroendocrine tumors are less than 1 cm in diameterwhen diagnosed and can therefore be adequately treated by appendectomy; right hemicolectomy is recommended if the patienthas risk factors for metastasis via the lymphatic vessels. Systemic chemotherapy has not been shown to be beneficial forappendiceal neoplasms in prospective, randomized trials; it is recommended for adenocarcinomas and goblet-cell adenocarcinomasof stage III or higher, in analogy to the treatment of colorectal carcinoma.