Rosa Klotz

Objective: To investigate whether preoperative injection of botulinum toxin (BTX) into the sphincter of Oddi (SO) is a safe and feasible strategy to prevent postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP). Summary Background Data: POPF remains a common and potentially serious complication following DP, affecting up to 30% of patients. Pharmacologically induced sphincter relaxation by endoscopic injection of BTX into the SO has been described as a new approach to prevent POPF after DP by improved drainage of pancreatic fluid towards the duodenum. Methods: Patients scheduled for elective primary distal pancreatectomy (DP), irrespective of the underlying disease, were included in this monocenter, randomized controlled, open-label, phase-II trial with 2 parallel arms. Patients randomly assigned to the intervention group received an endoscopic injection of BTX (100 units) into the SO 3–10 days before surgery. Patients in the control group did not undergo any preoperative intervention. The combined primary endpoint was defined as the occurrence of clinically relevant postoperative pancreatic fistula (POPF grades B/C) and/or death due to any cause within 30 days following DP. Results: From March 2020 to August 2023, 50 patients were included in the trial. Subsequent to the analysis of the primary endpoint, which revealed no tendency of a beneficial effect on the rate of POPF after DP following BTX injection, even with the most favorable outcome upon further inclusion of the remaining 10 patients planned for recruitment, the recruitment was prematurely terminated. All 26 patients in the intervention group underwent successful SO BTX injection within a median of 6 (IQR of 5–8) days before surgery. DP was performed in 41 patients (82%). Postinterventional pancreatitis was not detected. Within 30 days, POPF grade B/C occurred in 6 patients in the intervention and 3 patients in the control group (28.6% vs. 15%, P =0.294). One patient in the intervention group died during the trial due to POPF-induced postpancreatectomy hemorrhage (PPH). Conclusion: Preoperative injection of BTX into the SO did not reduce clinically relevant POPF or 30-day mortality following DP, and the trial was prematurely terminated for futility. Although the intervention was safe and feasible, these findings do not support its use for the prevention of POPF after DP.

Background: Pancreatic ductal adenocarcinoma (PDAC) carries a poor prognosis, particularly in metastatic disease where surgical resection is traditionally not recommended. However, the concept of oligometastatic disease—characterized by limited metastatic spread with a presumed more favorable oncological prognosis—has prompted reconsideration of metastasis-directed therapies, including surgery, in carefully selected patients. Methods: A selective literature review was conducted using PubMed to identify studies reporting surgical treatment for oligometastatic PDAC, including synchronous or metachronous metastases. Studies were included if they reported outcomes after resection of the primary tumor and/or metastatic lesions in patients with limited metastatic burden. Results were presented in a narrative way. Results: Retrospective studies suggest that surgical resection of the primary tumor and metastases may be feasible, safe and associated with prolonged survival in selected patients with oligometastatic PDAC. Favorable prognostic factors across studies include response to systemic chemotherapy prior to resection, low tumor marker levels, limited number of metastases, and the possibility of achieving complete macroscopic resection. Patients with isolated pulmonary metastases appear to have particularly favorable outcomes. However, existing evidence is derived exclusively from retrospective analyses and is subject to considerable selection bias. Conclusions: Current evidence indicates that surgery for oligometastatic PDAC may benefit highly selected patients within a multimodal treatment strategy. The results of ongoing prospective and randomized clinical trials are expected to clarify the role of surgery in this setting. Until these results become available, treatment decisions should be individualized and made within multidisciplinary tumor boards.

Background: Complete surgical resection (R0 resection) is crucial for overall and disease-free survival in patients with pancreatic cancer undergoing curative surgery. The radical antegrade modular pancreatosplenectomy (RAMPS) procedure was developed to increase achievement of R0 resection margins for tumour resections of the pancreatic body and tail. By extending the posterior dissection plane, a more radical surgical resection can be achieved, as this is the most frequent site of positive margins in conventional left pancreatectomy. RAMPS includes a standardized lymph node dissection and early control of the splenic vessels. Feasibility and safety have already been demonstrated and retrospective studies have shown promising results regarding higher proportions of R0 resection and lymph node counts. To date, high-quality evidence from randomized clinical trials investigating the oncological benefit of RAMPS (that is, resection margin status, disease-free and overall survival) for this patient cohort is lacking. Methods: The RAMPS trial is a multicentre, randomized clinical, patient and assessor-blinded, confirmatory, superiority trial. In all, 122 patients with an indication for left pancreatectomy due to malignancy of the pancreatic body or tail will be required in each study arm to achieve 80% power at a significance level of 0.025; patients will be randomized to either the RAMPS approach or conventional left pancreatectomy in a 1 : 1 ratio. Patients will be recruited over a 30-month enrolment period. The primary outcome will be the achievement of R0 resections. Secondary outcomes include survival and surgical, functional, and patient-reported outcomes with a 3-year follow-up. Conclusion: The primary objective of the RAMPS trial is to demonstrate the superiority of the RAMPS approach over standard left pancreatectomy in improving the achievement of R0 resection and, consequently, long-term oncological patient outcomes. RAMPS could be established as the new surgical standard for tumour resection in patients with pancreatic cancer in the body or tail of the pancreas. Registration number: DRKS00033031 (https://www.bfarm.de/EN/BfArM/Tasks/German-Clinical-Trials-Register/_node.html).

Introduction: Randomised controlled trials (RCTs) are central to generating high-quality evidence in the surgical field but face unique methodological and practical challenges, including recruitment, follow-up, blinding and ensuring patient-centred outcomes. Patient and public involvement (PPI) has emerged as a promising strategy to enhance the relevance, quality and impact of surgical research by actively involving patients throughout the whole research process. Despite growing recognition of its value, the integration and reporting of PPI in surgical RCTs remain inconsistent, and no systematic evaluation has yet addressed its application within general and abdominal surgery. Methods and analysis: RCTs in general and abdominal surgery published since 2014 will be identified through systematic searches of the databases MEDLINE, Web of Science and CENTRAL. This systematic review and primary (meta-epidemiological) statistical analysis will assess the reporting prevalence, implementation extent and quality of PPI over time. The Guidance for Reporting Involvement of Patients and the Public 2 (GRIPP2)-SF checklist and Cochrane Risk of Bias V.2.0 tool will be used to evaluate PPI reporting and study quality. To enable a comparison between studies reporting PPI and those that do not, propensity score matching will be performed to identify non-PPI studies with similar population and design characteristics. Subsequently, regression analyses will be employed to investigate potential associations between PPI reporting and various trial characteristics, including patient recruitment and retention, outcome selection and methodological quality. The Patient Advisory Board of the Study Centre of the German Society of Surgery is actively engaged in all phases of the systematic review. Ethics and dissemination: This systematic review does not require ethical approval. Results will be published in an international peer-reviewed scientific journal, as well as distributed in a lay format to the patient community and to the broader public. PROSPERO registration number: CRD42024524426.

Introduction Neoadjuvant (chemo)radiotherapy (n(C)RT) followed by resection with total mesorectal excision (TME) constitutes the standard treatment for patients with locally advanced rectal cancer of the middle and lower third. However, n(C)RT has demonstrated no significant impact on overall survival but is associated with adverse effects, including impaired sphincter and sexual function. We hypothesise that omitting n(C)RT in selected patients with a clear circumferential resection margin (CRM) >1 mm as determined through preoperative MRI is not inferior regarding local recurrence rate within 3 years after surgery. That treatment approach may show fewer adverse effects and be more cost-effective. Methods and analysis Selective neoadjuvant therapy of rectal cancer patients (SELREC) is a randomised controlled, parallel-group, open, multicentre, non-inferiority trial. The experimental intervention involves performing TME surgery without n(C)RT. In contrast, the control intervention adheres to German S3-guidelines, incorporating neoadjuvant radiotherapy (nRT) with a dosage of 5×5 Gy or a total of 50.4 Gy. Additionally, if applicable, concomitant chemotherapy (CT) based on 5-fluorouracil is administered, followed by TME surgery within less than 12 weeks. Adjuvant treatment according to guidelines is allowed depending on the (y)pTNM stage. The inclusion criteria for this study encompass adult patients with primary adenocarcinoma of the rectum in whom the main tumour mass is located less than 12 cm away from the anal verge, as assessed via proctoscopy. Additionally, eligible participants are required to have a preoperative tumour stage determined by MRI of either T1 or T2 with lymph node involvement (N1) or T3 with no lymph node involvement (N0) or with lymph node involvement (N1) and no distant metastases (M0). The assessment of a clear CRM >1 mm, based on MRI, is another prerequisite for inclusion. A total of 1074 patients in approximately 35 centres are planned to be allocated to the trial. The primary endpoint of the trial is local recurrence within 3 years after surgery. The primary estimand is based on the full analysis set using a logistic mixed model (margin 3%). The first secondary endpoint is no/minor low anterior resection syndrome (LARS) score at 2 years after surgery, and further secondary endpoints include survival outcomes and quality of life. Safety analysis involves describing the frequencies of major intervention-specific complications, such as the acute toxicity of n(C)RT according to CTCAE and perioperative morbidity and mortality according to Clavien-Dindo criteria. SELREC is financially supported by the German Federal Ministry of Education and Research. Ethics and dissemination This trial has been prospectively registered in the German Clinical Trials Register. Previously, the study had been approved by the responsible ethics committee of Heidelberg and the local ethics committees of the collaborating institutions before patient enrolment. Any protocol deviation that has an impact on relevant parameters such as study design, endpoints or patient safety will be reported to the responsible ethics committees. The results will be published in a peer-reviewed scientific journal and on institutional websites. Trial registration number German Clinical Trials Register DRKS00030567.

Objective: The DELORES trial investigated whether laparoscopic resection rectopexy (LRR) is superior to Delorme’s procedure (DP) in full-thickness rectal prolapse. Background: Multiple perineal and transabdominal procedures are current practice for rectal prolapse surgery. Evidence from adequately designed randomized studies addressing the question of which of these procedures are superior in terms of recurrence and bowel function is lacking. Methods: DELORES was a randomized, observer-blinded, expertise-based multicenter trial. Patients with full-thickness rectal prolapse were eligible. The primary outcome was time to recurrence of full-thickness rectal prolapse within 24 months after primary surgery. The main secondary endpoints were morbidity, hospital stay, quality of life, constipation, and fecal incontinence (DRKS00000482). Results: A total of 358 patients were screened between September 2010 and January 2016. Based on screening, 70 patients were randomized and 65 were included in the analysis (33 LRR and 32 DP procedures). The median follow-up was 23.9 months. Analysis of the primary outcome showed that LRR was superior to DP ( P =0.0012). During the 24-month follow-up, 8.2% of patients in the LRR group had a full-thickness prolapse recurrence versus 42.8% in the DP group. The median time to recurrence was 17.8 months for LRR and 8.2 months for DP. The median duration of surgery was 212 min (LRR) versus 77 min (DP). Overall postoperative morbidity was low. The reoperation rate was higher for DP (0% LRR vs. 33.3% DP). Quality of life (FIQL) and incontinence scores (Wexner) were more favorable for LRR at 24-month follow-up. Conclusions: LRR is superior to DP in terms of recurrence and has favorable functional results.

Background: The risk of postoperative pancreatic fistula (POPF), one of the most dreaded complications after pancreatic surgery, can be predicted from preoperative imaging and tabular clinical routine data. However, existing studies suffer from limited clinical applicability due to a need for manual data annotation and a lack of external validation. We propose AutoFRS (automated fistula risk score software), an externally validated end-to-end prediction tool for POPF risk stratification based on multimodal preoperative data. Materials and methods: We trained AutoFRS on preoperative contrast-enhanced computed tomography imaging and clinical data from 108 patients undergoing pancreatic head resection and validated it on an external cohort of 61 patients. Prediction performance was assessed using the area under the receiver operating characteristic curve (AUC) and balanced accuracy. In addition, model performance was compared to the updated alternative fistula risk score (ua-FRS), the current clinical gold standard method for intraoperative POPF risk stratification. Results: AutoFRS achieved an AUC of 0.81 and a balanced accuracy of 0.72 in internal validation and an AUC of 0.79 and a balanced accuracy of 0.70 in external validation. In a patient subset with documented intraoperative POPF risk factors, AutoFRS (AUC: 0.84 ± 0.05) performed on par with the uaFRS (AUC: 0.85 ± 0.06). The AutoFRS web application facilitates annotation-free prediction of POPF from preoperative imaging and clinical data based on the AutoFRS prediction model. Conclusion: POPF can be predicted from multimodal clinical routine data without human data annotation, automating the risk prediction process. We provide additional evidence of the clinical feasibility of preoperative POPF risk stratification and introduce a software pipeline for future prospective evaluation. Export