Short bowel syndrome is a rare complex disease that mainly develops due to extensive bowel resections and can lead to chronic intestinal failure. Due to the decreased intestinal surface absorption of macronutrient, micronutrient and/or fluids is reduced. Correspondingly manifold symptoms arise as diarrhoea, weight loss, vitamin deficiencies, chronic kidney disease, hepatopathy and others with great impact on quality of life of patients. Therapy is complex and needs interdisciplinary collaboration between dieticians, gastroenterologists, surgeons and also a dense monitoring of general practitioners. Commonly patients need permanent home-parenteral support. Therapies have to be decided individually and have to be reviewed regularly for effectivity and side effects. Furthermore, periodic monitoring of several clinical and laboratory tests should be performed. Morbidity and mortality of this disease complex is high and lead by appearance and management of complications. This practical guide should give an overview about the disease, diagnostics and management and should enable the best possible care of these complex patients.

Immune checkpoint inhibitors (ICIs) show efficacy in treatment of several solid tumors, but microsatellite-stable rectal cancer is largely resistant. Radiotherapy may enhance tumor immunogenicity and thus may make the combination of radiotherapy and ICIs a promising strategy to treat rectal cancer. While anti–programmed cell death protein 1 antibodies in neoadjuvant regimens have been linked to higher complete response rates, the added benefit of including a cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) inhibitor remains unclear. To evaluate the safety and feasibility of combining ipilimumab and nivolumab with neoadjuvant chemoradiotherapy (CRT) for rectal cancer. The CHINOREC trial was a prospective, randomized, open-label, multicenter phase 2 clinical trial conducted from June 2, 2020, to March 15, 2024, across multiple academic and tertiary medical centers in Austria. Analysis was based on intention to treat. Neoadjuvant CRT consisted of 50 Gy in 2-Gy fractions with concurrent capecitabine (1650 mg/m2/d). The experimental arm received additional intravenous ipilimumab (1 mg/kg on day 7) and nivolumab (3 mg/kg every 2 weeks starting on day 14) (CRT plus ipilimumab and nivolumab group). Surgical resection was performed 10 to 12 weeks after CRT. The primary outcome was the safety and feasibility of combining CRT with sequential ipilimumab and nivolumab, assessed by surgical complications and reoperation rates. Secondary outcomes included clinical and pathological response rates. Of the 145 patients assessed, 80 were randomized to receive either CRT alone (CRT group) (n = 30) or to the CRT plus ipilimumab and nivolumab group (n = 50) (49 male [61%]; median age, 60 [range, 36-83] years). Differences in surgical complication rates were not statistically significant between the CRT and CRT plus ipilimumab and nivolumab groups (any grade, 20 of 26 patients [77%] vs 33 of 43 [77%]; P > .99), as were reoperation rates (2 of 26 [8%] vs 3 of 43 [7%]; P > .99). Major pathological response (10 of 26 [38%] vs 16 of 43 [37%]; P > .99) and complete response (9 of 30 [30%] vs 11 of 50 [22%]; P = .44) rates were overall high in both groups. In this randomized clinical trial of patients with rectal cancer, integrating ipilimumab and nivolumab into neoadjuvant CRT was safe and feasible, with no increase in surgical complications. Although complete response rates did not significantly improve, the dual ICI regimen demonstrated promising clinical activity. These findings support further translational research to optimize timing, dosing, and fractionation of radiotherapy and ICI therapy and to guide patient selection. ClinicalTrials.gov Identifier: NCT04124601

Myositis is a rare (<1%) but potentially severe immune-related adverse event (irAE) of immune checkpoint inhibitors (ICIs), with a 40%-50% fatality rate. Its incidence and pathology in curative, neoadjuvant settings, particularly with chemoradiotherapy (CRT), remain poorly defined. Given the severity, stringent diagnostic and therapeutic approaches may be warranted in curative patients. In the CHINOREC trial, 50 rectal cancer (RC) patients receiving neoadjuvant CRT with ipilimumab (IPI) and nivolumab (NIVO) were prospectively monitored for myotoxicity biomarkers, including creatine kinase (CK) and cardiac troponins (cTnT, cTnI). Patients with CK and cTnT levels above the upper limit normal with or without overt clinical symptoms underwent muscle biopsy and guideline-adapted treatment (glucocorticoids, immunoglobulin, infliximab, plasma exchange). Six patients (12%) developed biopsy-confirmed myositis. Elevated cTnT, but not cTnI, distinguished skeletal from cardiac involvement, aligning with normal cardiac magnetic resonance imaging (CMR) findings. Immunohistochemistry showed a predominant CD8+ T cell infiltrate and patchy human leukocyte antigen (HLA) Class I upregulation. Despite myositis, all patients underwent successful tumor resection with normalized CK levels and no residual cardiac dysfunction. ICI-induced myositis may be more frequent in neoadjuvant-treated RC patients receiving CRT+ICI than in palliative settings. Comprehensive biomarker monitoring and early T cell-directed intervention are essential for mitigating life-threatening irAEs while preserving oncologic outcomes.

B cells have important functions in gut homeostasis, and dysregulated B cell populations are frequently observed in patients with inflammatory bowel diseases, including both ulcerative colitis (UC) and Crohn's disease (CD). How these B cell perturbations contribute to disease remains largely unknown. Here, we perform deep sequencing of the B cell receptor (BCR) repertoire in four cohorts of patients with CD, together with healthy controls and patients with UC. We identify BCR clones that are shared between patients with CD but not found in healthy individuals nor in patients with UC, indicating CD-associated B cell immune responses. Shared clones are present in the inflamed gut mucosa, draining intestinal lymph nodes and blood, suggesting the presence of common CD-associated antigens that drive B cell responses in CD patients.

139 Background: Immune checkpoint inhibitors (ICIs) seem only effective in a primed tumor immune microenvironment (TIME). Neoadjuvant radiotherapy (RT) has been shown to induce an immunogenic cell death (ICD) and thereby restores the susceptibility to ICI. This study evaluates the safety of neoadjuvant chemoradiotherapy (CRT) with concomitant ipilimumab (IPI) and nivolumab (NIVO) in curative rectal cancer (RC) patients. Methods: The CHINOREC study (ClinicalTrials.gov identifier NCT04124601) is a prospective, randomized (ratio 50:30), open-label, multicenter, phase II investigator-initiated trial (IIT). Patients with RC received neoadjuvant CRT (50 Gy in 2 Gy fractions with concurrent capecitabine 1650 mg/m 2 /d) alone or in combination with IPI (1 mg/kg IV at day 7), following 3 cycles of NIVO (3 mg/kg IV Q2W, starting on day 14). Surgical resection was performed 10-12 weeks post CRT. The primary endpoint was surgical safety and feasibility (Clavien-Dindo Classification) of neoadjuvant CRT with sequential IPI and NIVO following surgical resection. Secondary outcome was complete response rate (clinical and pathological). Results: Between June 2020 and November 2023, 145 patients were screened and 80 randomly assigned to CRT (n=30) or CRT+IPI/NIVO (n=50). The primary endpoint (any surgical complication) did not differ between the 2 groups (78% vs. 77%). The reoperation rate (≥Grade IIIb) was comparable low in both groups (8% vs. 7%). No new safety signals were identified. The rate of major pathological response (MPR) and complete response (CR) was also comparable high in both arms (38% vs. 37% and 30% vs. 22%, respectively). Conclusions: Neoadjuvant IPI/NIVO can be safely applied concomitant with CRT in patients with RC, as it does not increase the rate of reoperation or surgical complications. The validity of the encouraging CR rate needs to be elucidated over time. Further translational analyses will elucidate mechanistic insight regarding improved fraction, dosing and timing of CRT and ICI. Clinical trial information: NCT04124601 .

Anastomotic leakage still represents the most feared complication in colorectal surgery. However, there is limited data focusing on management and how this affects outcome in case of leakage following open versus laparoscopic right colectomy. We, therefore, performed an observational multicenter study addressing this issue. Data of patients undergoing elective right colectomy for benign and malignant disease using an open or laparoscopic approach were collected in seven colorectal units among Austria between January 2010 and December 2019. Patients undergoing emergency surgery or suffering from Crohn’s disease with chronic anastomotic fistula were excluded. Demographic, peri- and postoperative data were analyzed retrospectively. During the study, a total of 3446 patients were operated on using an open (n = 2282, 66.2

Importance:Immune checkpoint inhibitors (ICIs) show efficacy in treatment of several solid tumors, but microsatellite-stable rectal cancer is largely resistant. Radiotherapy may enhance tumor immunogenicity and thus may make the combination of radiotherapy and ICIs a promising strategy to treat rectal cancer. While anti-programmed cell death protein 1 antibodies in neoadjuvant regimens have been linked to higher complete response rates, the added benefit of including a cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor remains unclear. Objective:To evaluate the safety and feasibility of combining ipilimumab and nivolumab with neoadjuvant chemoradiotherapy (CRT) for rectal cancer. Design, Setting, and Participants:The CHINOREC trial was a prospective, randomized, open-label, multicenter phase 2 clinical trial conducted from June 2, 2020, to March 15, 2024, across multiple academic and tertiary medical centers in Austria. Analysis was based on intention to treat. Intervention:Neoadjuvant CRT consisted of 50 Gy in 2-Gy fractions with concurrent capecitabine (1650 mg/m2/d). The experimental arm received additional intravenous ipilimumab (1 mg/kg on day 7) and nivolumab (3 mg/kg every 2 weeks starting on day 14) (CRT plus ipilimumab and nivolumab group). Surgical resection was performed 10 to 12 weeks after CRT. Main Outcome and Measures:The primary outcome was the safety and feasibility of combining CRT with sequential ipilimumab and nivolumab, assessed by surgical complications and reoperation rates. Secondary outcomes included clinical and pathological response rates. Results:Of the 145 patients assessed, 80 were randomized to receive either CRT alone (CRT group) (n = 30) or to the CRT plus ipilimumab and nivolumab group (n = 50) (49 male [61%]; median age, 60 [range, 36-83] years). Differences in surgical complication rates were not statistically significant between the CRT and CRT plus ipilimumab and nivolumab groups (any grade, 20 of 26 patients [77%] vs 33 of 43 [77%]; P > .99), as were reoperation rates (2 of 26 [8%] vs 3 of 43 [7%]; P > .99). Major pathological response (10 of 26 [38%] vs 16 of 43 [37%]; P > .99) and complete response (9 of 30 [30%] vs 11 of 50 [22%]; P = .44) rates were overall high in both groups. Conclusions and Relevance:In this randomized clinical trial of patients with rectal cancer, integrating ipilimumab and nivolumab into neoadjuvant CRT was safe and feasible, with no increase in surgical complications. Although complete response rates did not significantly improve, the dual ICI regimen demonstrated promising clinical activity. These findings support further translational research to optimize timing, dosing, and fractionation of radiotherapy and ICI therapy and to guide patient selection. Trial Registration:ClinicalTrials.gov Identifier: NCT04124601.

Sphincter-preserving techniques like autologous compound platelet-rich fibrin foam have gained popularity, offering potential for better functional outcomes in anal fistula treatment. The present study aimed to evaluate the efficacy and safety of Obsidian RFT®. The study conducted a retrospective analysis from January 2018 to December 2022 on patients who received anal fistula closure with Obsidian RTF® at the Department of General Surgery, Medical University of Vienna. Clinical diagnosis, complemented by radiographic imaging, was employed to confirm inconclusive cases. Demographic and fistula characteristics and postoperative data were collected from electronic records following STROCSS criteria. Fifteen patients received Obsidian RFT® treatment for anal fistulas. We found no intra- and postoperative complications. The median hospital stay was 3 days. After a median follow-up of 32 months, a closure rate of 53.3

Background: Short bowel syndrome with intestinal failure (SBS-IF) is a rare but devastating medical condition. An absolute loss of bowel length forces the patients into parenteral support dependency and a variety of medical sequelae, resulting in increased morbidity and mortality. Interdisciplinary treatment may include therapy with the effective but expensive intestinotrophic peptide teduglutide. Objectives: A time -discrete Markov model was developed to simulate the treatment effect [lifetime costs, quality -adjusted life years (QALYs), and life years (LYs)] of teduglutide plus best supportive care compared with best supportive care alone in patients with SBS-IF. Methods: The health status of the model was structured around the number of days on PS. Clinical data from 3 data sets were used: 1 ) an Austrian observational study (base case), 2 ) pooled observational cohort studies, and 3 ) a prospective study of teduglutide effectiveness in parenteral nutritiondependent short bowel syndrome subjects. Direct and indirect costs were derived from published sources. QALYs, LYs, and costs were discounted (3% per annum). Results: Under the base case assumption, teduglutide is associated with costs of 2,296,311 per patient and 10.78 QALYs (13.74 LYs) over a lifetime horizon. No teduglutide is associated with 1,236,816 and 2.24 QALYs (8.57 LYs). The incremental cost -utility ratio (ICUR) amounts to 123,945 . In case of the pooled clinical data set, the ICUR increases to 184,961 . If clinical data based on the study of teduglutide effectiveness in parenteral nutritiondependent short bowel syndrome subjects were used, the ICUR increased to 235,612 Conclusions: Teduglutide in treating patients with SBS-IF meets the traditional cost-effectiveness criteria from a European societal perspective. Nevertheless, the varying concentrations of teduglutide efficacy leave a degree of uncertainty in the calculations.

Background: Anastomotic leak rates after colorectal surgery remain high. In most left-sided colon and rectal resection surgeries, a circular stapler is utilized to create the primary bowel anastomosis. However, it remains unclear whether a relationship between circular stapler technology and anastomotic leak in left-sided colorectal surgery exists. Methods: A post-hoc analysis was conducted using a prospectively collected data set of patients from the 2017 European Society of Coloproctology snapshot audit who underwent elective left-sided resection (left hemicolectomy, sigmoid colectomy, or rectal resection) with a manual circular stapled anastomosis. Rates of anastomotic leak and unplanned intensive care unit stay in association with manual circular stapling were assessed. Patient-, disease-, geographical-, and surgeon-related factors as well as stapler brand were explored using multivariable regression models to identify predictors of adverse outcomes. Results: Across 3305 procedures, 8.0% of patients had an anastomotic leak and 2.1% had an unplanned intensive care unit stay. Independent predictors of anastomotic leak were male sex, minimal-access surgery converted to open surgery, and anastomosis height C11 (lower third rectum) (all P < 0.050). Independent predictors of unplanned intensive care unit stay were minimal-access surgery converted to open surgery and American Society of Anesthesiologists grade IV (all P < 0.050). Stapler device brand was not a predictor of anastomotic leak or unplanned intensive care unit stay in multivariable regression analysis. There were no differences in rates of anastomotic leak and unplanned intensive care unit stay according to stapler head diameter, geographical region, or surgeon experience. Conclusion: In patients undergoing left-sided bowel anastomosis, choice of manual circular stapler, in terms of manufacturer or head diameter, is not associated with rates of anastomotic leak and unplanned intensive care unit stay.

Summary Objective A clear relationship between higher surgeon volume and improved outcomes has not been convincingly established in rectal cancer surgery. The aim of this study was to evaluate the impact of individual surgeon’s caseload and hospital volume on perioperative outcome. Methods We retrospectively analyzed 336 consecutive patients undergoing oncological resection for rectal cancer at two Viennese hospitals between 1 January 2015 and 31 December 2020. The effect of baseline characteristics as well as surgeons’ caseloads (low volume: 0–5 cases per year, high volume > 5 cases per year) on postoperative complication rates (Clavien-Dindo Classification groups of < 3 and ≥ 3) were evaluated. Results No differences in baseline characteristics were found between centers in terms of sex, smoking status, or comorbidities of patients. Interestingly, only 14.7% of surgeons met the criteria to be classified as high-volume surgeons, while accounting for 66.3% of all operations. There was a significant difference in outcomes depending on the treating center in univariate and multivariate binary logistic regression analysis (odds ratio (OR) = 2.403, p = 0.008). Open surgery was associated with lower complication rates than minimally invasive approaches in univariate analysis (OR = 0.417, p = 0.003, 95%CI = 0.232–0.739) but not multivariate analysis. This indicated that the center’s policy rather than surgeon volume or mode of surgery impact on postoperative outcomes. Conclusion Treating center standards impacted on outcome, while individual caseload of surgeons or mode of surgery did not independently affect complication rates in this analysis. The majority of rectal cancer resections are performed by a small number of surgeons in Viennese hospitals.

Abstract Background One of the hallmarks of Crohn’s disease (CD) is mesenteric thickening, accompanied by enlarged draining lymph nodes (LNs) in the affected areas. Descriptive studies imply that lymphatic architecture is altered in affected areas. Additionally, an altered IgA and IgG response towards commensal bacteria in CD patients compared to healthy controls has been described. Thus, we set out to investigate the B cell response in draining lymph nodes of patients with CD undergoing surgery. Methods We prospectively collected draining lymph nodes and serum samples in patients with Crohn’s disease during intestinal resections. LNs of affected and adjacent unaffected intestinal segments were processed for phenotyping by flowcytometry (n=18) and B cell receptor (BCR) sequencing (n=24). Histological analysis was performed to investigate size and number of germinal centers in affected and unaffected areas (n=10). Serum samples were collected from patients with CD undergoing surgery (n=18), and healthy individuals (n=16). The study was approved by the local ethics committee (EK #1480/2016) and all patients prospectively gave their written informed consent to participate in the study. Results Affected draining LNs showed a significantly increased fraction of CD45+CD19+ B cells (p=0.0055) compared to unaffected LNs. Fractions of double negative B cells (p=0.0394) and plasmablasts (p=0.0126) were significantly increased, and memory B cells significantly decreased (p=0.0127) in affected draining lymph nodes, respectively. Histological analysis revealed no difference in the numbers of germinal centers per high power field, but a significantly increased germinal center size (p<0.001). BCR sequencing demonstrated a reduction in IGHA (p<0.001) and IGHE (p=0.031), and a significant increase in IGHG1/2 (p<0.001) in affected LNs compared to unaffected LNs. Analysis of somatic hypermutation of BCRs and diversity analysis showed no significant increase in somatic hypermutation in IGHG1/2, and diversity analysis indicated significant diversity in specificity. Serum IgA of patients with CD recognized a significantly greater fraction of commensals in CD patients, and IgG binding towards commensals was almost universally detectable in CD patients but absent in healthy controls. Conclusion Our data indicate that a pathological IgG response in patients with severe disease is directed towards a broad set of antigens, most likely stemming from commensals. Additionally, expansion only at the site of inflammation may indicate a triggered immune response due to a leaky intestinal barrier. The relevance of pathological IgG antibodies on disease recurrence following surgery needs to be addressed in future studies.

Key Clinical MessageAmyloidosis is a heterogeneous disease characterized by tissue deposition of abnormally folded fibrillary proteins that can manifest itself by a wide variety of symptoms depending on the affected organs. GI involvement among amyloidosis patients is common. Its clinical manifestation often presents with nonspecific symptoms such as weight loss, diarrhea, and malabsorption. With no specific treatment existing for GI amyloidosis, therapy focuses on impeding amyloid deposition and managing the patients' symptoms with supportive measures. Here, we present an AL‐amyloidosis patient with GI involvement and intestinal failure (IF) who was successfully treated with the glucagon‐like peptide‐2 (GLP‐2) analogue teduglutide. Over the course of treatment with teduglutide, the patient was able to achieve independence from parenteral nutrition and experienced a significant improvement in quality of life (QoL) as stool frequency and consistency improved, urinary output was stabilized and body weight as well as body composition improved over the course of teduglutide therapy. With no longer being exposed to the burden and associated risks of parenteral nutrition, we were able to reduce the potential morbidity and mortality rate as well as to improve the patient's overall QoL. Intestinal tissue biopsy workup revealed a histopathological correlate for the clinical response; Congo‐Red‐positive intestinal depositions almost completely disappeared within 6 months of teduglutide therapy. Implementing intestinotrophic GLP‐2 analogue teduglutide may enrich the spectrum of treatment options for amyloidosis patients with IF who are dependent on parenteral support.

Abstract Background Myositis is an infrequent (<1%) but potentially life-threatening (case fatality rate 40-50%) immune-related adverse event (irAEs) of immune checkpoint inhibitors (ICI), such as ipilimumab (IPI) and nivolumab (NIVO). The true incidence is likely to be underestimated and may not be representative for curative neoadjuvant treatment approaches in gastrointestinal (GI) cancers, especially in combination with chemoradiotherapy (CRT). Currently, the summary of product characteristics (SmPC) does not suggest any pre-emptive screening or surveillance. Methods The CHINOREC study is an ongoing prospective, randomized, open-label, multicenter, phase II investigator-initiated trial (IIT). Patients with intermediate to locally advanced rectal cancer (LARC) receive either neoadjuvant CRT alone or in combination with a single dose of IPI and 3 cycles of NIVO, following surgical resection. Patients are monitored at baseline and throughout the whole study period for myotoxicity biomarkers, including cardiac troponin T (cTnT) and cardiac troponin I (cTnI). Findings From 06/2020 to 11/2023, 80 patients have been enrolled of whom 50 patients were randomized to the CRT+IPI/NIVO arm. Six patients (12%) developed biopsy-verified myositis. Myositis treatment was promptly implemented using a pragmatic step-up approach. Patients received glucocorticoids (GC) with concomitant intravenous immunoglobulin (IVIG). If myotoxicity biomarkers did not improve, patients received infliximab (INFLIXI) and/or plasma exchange (PLEX). Although all patients had strikingly elevated cTnT (median peak 284 ng/L, 95% CI 39-3097), cTnI levels remained largely normal, correlating with a negative cardiac magnetic resonance (CMR). All patients underwent successful tumor surgery without any major surgical complication. As of today, all patients' creatine kinase (CK) and myoglobin (MB) levels have normalized and they are tumor free without any major sequela. Interpretation Longitudinal biomarker screening (cTnT/cTnI) for ICI-induced myotoxicities is pivotal in curative neoadjuvant-treated cancer patients to initiate an early counter treatment in a holistic step-up approach, without compromising oncological principles.

Das Kurzdarmsyndrom ist eine Form von chronisch intestinalem Versagen, ein sehr seltenes und komplexes Krankheitsbild mit großer Auswirkung auf andere Organe und stark eingeschränkter Lebensqualität. Während andere Organversagen wie Leberversagen oder Herzinsuffizienz weithin bekannt sind, ist das Versagen des Dünndarmes ein unterschätztes und unterdiagnostiziertes Krankheitsbild. Es tritt als Folge von ausgeprägten Darmresektionen (Dünndarmrestlänge <2m) auf, seltener aufgrund angeborener Darmatresie oder hoher Fistulierung, und ist gekennzeichnet durch die Notwendigkeit von parenterale Unterstützung. Der Mangel an Mikro-, Makro-Nährstoffen und/oder Flüssigkeit führt zu vielfältigen Symptomen und Problemen und bedarf individueller Therapiekonzepte in enger Zusammenarbeit mit Diätolog*innen und Chirurg*innen. Aufgrund der Seltenheit dieser Erkrankung (Inzidenz von ca 20-40/Million Einwohner) sollten die Patienten an Zentren mit Expertise in Kooperation mit dem Hausärzte-Netzwerk betreut werden. Dieser Leitfaden zielt darauf ab, Hausärzt*innen und anderen Ärzt*innen sowie Patient*innen einen Anhalt zur Diagnostik und Therapie zu geben. Dies ist insbesondere wichtig, da die Mortalität und Morbidität durch die Beherrschung der Komplikationen stark reduziert werden kann ([Table 1]).