Supplementary Figure S5: Impact of HITOC on tumor-infiltrating T cells.

Supplementary Figure S4: Effect of HITOC on CD4 T cell infiltration in tumors.

Supplementary Figure S1: Evaluation of the impact of heat adjunct on cisplatin cytotoxicity.

Supplementary Figure S2: Flow cytometry gating.

Objectives:Malignant bowel obstruction (MBO) caused by advanced peritoneal metastases (PM) carries a poor prognosis. Surgical intervention may be the only therapeutic option in selected cases, but operative risks must be carefully balanced against potential benefits. This study aimed to evaluate the outcomes of patients undergoing surgery for MBO secondary to PM. Methods:Single-centre retrospective analysis of consecutive patients operated for MBO of various origins between 2016 and 2021. The primary outcome was overall survival (OS). Secondary outcomes included postoperative morbidity, resumption of systemic chemotherapy, and incidence of re-obstruction. Results:A total of 27 patients (median age 64 years, 67 % female) were included. Median peritoneal cancer index (PCI) was 32, and ascites was present in 16 patients (59 %). Surgical resolution of obstruction was achieved in 24 patients (88 %) via bowel resection (n=10), internal bypass (n=7), stoma formation (n=5), or adhesiolysis (n=2). Severe morbidity occurred in 26 %, with no postoperative mortality. Five patients (19 %) required reoperation, and three (11 %) developed enterocutaneous fistulae. Median OS was 4.0 months (IQR 9.4). Survival rates at 3, 6, and 12 months were 56 , 37, and 26 %, respectively. Postoperative systemic chemotherapy was resumed in 19 patients (70 %), significantly more often among those surviving >6 months (p=0.02). Re-obstruction occurred in 14 patients (52 %). Conclusions:Surgery is a feasible and valid therapeutic option for selected patients with MBO due to advanced PM. Despite considerable morbidity, most patients are able to resume systemic chemotherapy, which may contribute to improved survival outcomes.

Supplementary Figure S6: Effect of HITOC on PD-1 and CTLA-4 expression by CD4 T cells.

Supplementary Table S1: Termination criteria used for animal experiments

Supplementary Table S2: List of antibodies used in the study

Supplementary Figure S3: Representative flow cytometry histograms.

BACKGROUND:Unwanted e-mails (UEM) constitute a futile problem for academic surgeons. However, data investigating the magnitude of this concern and its determinants are lacking. OBJECTIVE:To assess the burden UEM in academic surgery and to identify factors associated with a high burden of UEM. METHODS:Cross-sectional study conducted in a division of visceral surgery of a tertiary center, between May 1-31, 2024. Participants included physicians of the division; UEM received by the participants during the study period were collected and examined. Primary outcome was the absolute number of UEM. High burden of UEM was defined as participant UEM number ≥ percentile 75 of UEM number. RESULTS:Participants included 36 physicians (13 residents, 14 fellows and 9 consultants). A total of 2934 UEM were examined; among them, 1707 (58.2%) solicited scientific contributions, including invitations to submit manuscripts (n = 910, 31%). Number of UEM per participant was heterogenous (range 0-601), with a median of 16 (0-106). The latter also showed differences between residents 0 (0-1), fellows 34 (5-70), and consultants 147 (101-402) (p<0.001). Finally, high burden of UEM was associated with surrogates of experience and research activity, such as age (OR, 1.21; 95% CI, 1.04-1.41; p = 0.011), board certification in visceral surgery (OR, 11.50; 95% CI, 2.01-65.91; p = 0.006), number of peer-review publications (OR, 1.12; 95% CI, 1.01-1.24; p = 0.027) or H-index (OR, 1.36; 95% CI, 1.07-1.73; p = 0.012). CONCLUSIONS:UEM represent a major concern for academic surgeons. Exposure to UEM varies proportionally to professional experience and research activity.

Pleural mesothelioma is a fatal disease with limited treatment options. Recently, pleural mesothelioma management has improved with the development of immune checkpoint inhibitors (ICI). In first-line therapy, dual PD-1 and CTLA-4 blockade enhances tumor control and patient survival compared with chemotherapy. Unfortunately, only a fraction of patients is responsive to immunotherapy, and approaches to reshape the tumor immune microenvironment and make ICIs more effective are urgently required. In this study, we evaluated the effect of hyperthermic intrathoracic chemotherapy (HITOC), a treatment that combines fever-range hyperthermia with local intrapleural cisplatin chemotherapy, on the tumor immune microenvironment and response to ICIs. To do this, we developed a murine pleural mesothelioma model of HITOC. We found that HITOC significantly improved tumor control and animal survival through a mechanism involving the development of a cytotoxic immune response. Additionally, HITOC enhanced immune checkpoint expression by T lymphocytes and synergized with dual PD-1 and CTLA-4 inhibition, leading to further improvement in animal survival. Finally, the analysis of peritoneal mesothelioma patient samples treated by pressurized intraperitoneal aerosol chemotherapy revealed a similar immunomodulation. In conclusion, HITOC remodels the tumor immune microenvironment of pleural mesothelioma by promoting T-cell infiltration into the tumor and could be considered in combination with ICIs in the context of a clinical trial.

In 2012, the Department of Visceral Surgery of the Lausanne University Hospital CHUV implemented a dedicated high-resolution anoscopy (HRA) outpatient clinic for surveillance and follow-up purposes. This 10-year longitudinal study analyzed 537 patients (2214 visits) using a structured screening protocol. Dysplastic lesions were detected in 49% of patients, predominantly low-grade squamous intraepithelial lesions (LSILs, 74%). Among LSIL cases, 6% progressed to high-grade squamous intraepithelial lesions (HSILs) within 24 months, reaching 25% cumulative progression at 36 months. Of HSIL patients, 3% developed carcinoma in situ after 48 months. Notably, no invasive carcinoma was observed during the follow-up. Four patients diagnosed with squamous cell carcinoma at initial screening were treated with chemoradiotherapy, and one required salvage surgery. Independent risk factors for the presence of higher-stage precancerous lesions (≥HSILs) were the presence of high-risk HPV genotypes (OR 14.5, 95% CI 5-42.2, p < 0.001), detectable HIV viral load (OR 5.4, 95% CI 1.8-16.7, p = 0.003), and symptoms at the first screening visit (OR 3.2, 95% CI 1.1-9.9, p = 0.04). HIV-positive status was associated with a trend towards an increased risk of progression (OR 2.79, p = 0.073). These findings highlight the importance of systematic follow-up and early intervention in high-risk populations to prevent anal cancer progression.

Abstract Objective Acute diverticulitis is a frequent clinical conditions encountered in emergency settings. Despite recent international guidelines, management of acute diverticulitis (AD) varies and is not standardized. The aim of the study was to achieve a Swiss nationwide consensus on clinical management of acute diverticulitis. Methods A three-staged consensus meeting according to the Delphi method was performed in 2020 involving 78 Swiss surgeons from 40 hospitals. A steering-group drafted the questionnaires, gathered best available evidence which was presented and discussed in meetings prior answering the questions. Consensus was defined as ≥70% of agreement. Results 57 surgeons answered all the 3 rounds and 28 (53%) performed > 50 colorectal resections per year. On initial workup in the emergency setting, performing leucocytes count (87%), CRP (98%) and CT imaging (98%) reached consensus for the diagnosis, but no uniform classification system of AD was retained. Signs of generalized peritonitis (100%), requiring intravenous pain medication (98%), inability to tolerate oral intake (95%), lack of adequate social support (86%), immunosuppression (96%), and complicated AD on CT (84%) were criteria for hospitalization. Persisting symptoms (95%) and immunosuppression (89%) were criteria for elective colonic resection, while the number of AD episodes were not (27%). In case of abscess, a size ≥ 4 cm reached consensus for percutaneous drainage (88%). No consensus were reached for surgical approach and techniques in the emergency settings, apart from damage control surgery for instable patients (70%). In the follow-up, recommendation for dietary restrictions or lifestyle habits did not reach reach consensus. Conclusion Swiss colorectal surgeons reached consensus for several diagnostics, hospitalization, and elective surgery criterias. However, emergency surgical management and follow-up are less standardized. These variations should be further assessed, and particularly in the context the latest published recommendations.

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.

Abstract Objectives Cytology of ascites or peritoneal washing is a routine part of staging of peritoneal metastases (PM). We aim to determine value of cytology in patients undergoing pressurized intraperitoneal aerosol chemotherapy (PIPAC). Methods Single-center retrospective cohort study included consecutive patients having PIPAC for PM of different primary between January 2015 and January 2020. Results A total of 75 patients (median 63 years (IQR 51–70), 67 % female) underwent a total of 144 PIPAC. At PIPAC 1 59 % patients had positive and 41 % patients had negative cytology. Patients with negative and positive cytology only differed in terms of symptoms of ascites (16% vs. 39 % respectively, p=0.04), median ascites volume (100 vs. 0 mL, p=0.01) and median PCI (9 vs. 19, p<0.01). Among 20 patients who completed 3 PIPACs (per protocol), cytology changed in one from positive to negative, and in two from negative to positive. Median overall survival was 30.9 months in the per protocol group and 12.9 months in patients having <3 PIPACs (=0.519). Conclusions Positive cytology under PIPAC treatment is more frequently encountered in patients with higher PCI and symptomatic ascites. Cytoversion was rarely observed and cytology status had no impact on treatment decisions in this cohort.

Prospective compliance assessment of surgical site infection prevention measures in colorectal surgery Philip Deslarzes, Jonas Jurt, Martin Hübner, Dieter Hahnloser, Daniel Clerc , Laurence Senn, Nicolas Demartines and Fabian Grass* Department of Visceral Surgery, Lausanne University Hospital, Centre Hospitalier Universitaire Vaudois, University of Lausanne (UNIL), Lausanne, Switzerland Infection Prevention and Control Unit, Department of Infectious Diseases, Lausanne University Hospital, Centre Hospitalier Universitaire Vaudois, University of Lausanne (UNIL), Lausanne, Switzerland

Postoperative ileus is a common and distressing complication after intestinal surgery. It presents clinically as impairment of intestinal motility, characterized by abdominal pain, vomiting, and delayed recovery of defaecatory function. For patients, this increases the risk of serious complications, such as pneumonia, venous thromboembolic events, and malnutrition. For healthcare systems, it leads to a substantial economic burden associated with increased medical, nursing, dietitian, and laboratory costs. Accordingly, postoperative ileus is now recognized as a research priority by expert and public stakeholder groups. Numerous clinical interventions have been evaluated in efforts to prevent postoperative ileus, but few have led to meaningful patient benefit. A key challenge for researchers is the absence of a standardized and agreed framework to describe the effectiveness of new interventions in clinical studies. Common outcomes include the time taken until first passage of flatus/stool, time until tolerance of oral diet, and the return of bowel sounds. It remains unclear, however, whether these are sufficiently relevant to patients and healthcare professionals when evaluating new treatments and implementing them in clinical practice. A solution to this problem is the development of an agreed core outcome set developed through patient–clinician consensus. Core outcome sets provide a minimum set of outcomes that should be reported in all studies of a defined clinical condition and are supported by the Core OutcomeMeasures in Effective Trials (COMET) Initiative. The present report describes the international development and final content of an agreed core outcome set for postoperative ileus relevant to patients undergoing intestinal surgery.

The key priority for obstructed colon cancer (OCC) is urgent resolution of the large bowel obstruction with ideally no compromise of oncological outcomes and low initial and permanent ostomy rates. Proactive management is pivotal to decrease the risk of perforation and septic shock. Staged procedures have an important place to provide optimal treatment and offer similar treatment and outcomes as in the elective setting. The approach is tailored to the patient's condition, the oncological situation and expertise of the available surgical team. This overview concludes by proposing a comprehensive treatment algorithm for individualized treatment of OCC.

Abstract Objective Anastomotic leakage (AL) is one of the most feared complications of colorectal surgery. Despite surgical improvements, AL incidence remains significant and guidance on its prevention and management is lacking. The aim of the study was to achieve a Swiss nationwide consensus on clinical prevention and management of AL. Methods A three-step Delphi consensus meeting was performed in 2020 involving 78 Swiss surgeons from 40 centers. A steering-group drafted the questions, gathered best available evidence which was discussed in meetings prior answering the questions. Consensus was defined as ≥70% of agreement. Results The three consensus meetings were attended by 66, 57 and 37 surgeons, respectively. Surgeons’ median experience was 14 years, with 47% performing >50 colorectal resections yearly. Consensus was reached on routine use of preoperative nutritional screening (100%) using nutritional scores (88%) and >10% weight loss (95%). but not low BMI (63%) or low albumin (64%). Consensus was reached for no bowel preparation (BP) prior to right colectomy (RC) (76%) and for mechanical BP with oral antibiotics prior anterior resections (AR) (70%). No consensus was found on BP prior left colectomy (LC). Respondents favored a side-to-side anastomosis (76%) after RC, with extra-corporeal confection (70%), without consensus on the anastomosis being stapled or hand-sewn; an end-to-end (73%), stapled (80%) anastomosis after LC and a stapled anastomosis (86%) after AR, irrespective of the anastomosis configuration type. Anastomotic control with transanal leak-test was supported by 92%, while ICG control did not reached consensus (67%). After TME, routine diversion was favored (73%), irrespective of neoadjuvant therapy (94%) or not (70%). Consensus was reached on routine postoperative CRP monitoring (94%). CT-scan with rectal contrast enema was the preferred investigation for suspected AL after RC or LC (82%) and AR (76%). Conservative management of AL, provided appropriate clinical state, was an acceptable option after LC (72%), AR with stoma (95%), but not after RC (59%) or AR without stoma (53%). Conclusion Consensus was reached on several clinical aspects for prevention and management of AL among Swiss colorectal surgeons, providing national guidance. Further data is required on intraoperative aspects of anastomosis confection and control to ensure broader consensus.

Awareness of climate change grows in the population and people develop eco-responsible habits in their daily and professional life. The health care system is nowadays responsible for 4.6% of global greenhouse gases emissions, and most of them comes from hospital activity. The operating room is one of the greatest contributors of the overall energetic cost and generates a large amount of hospital waste. As an example, all laparoscopic procedures in the US has an energy cost similar to an 80'000 inhabitants city during one year. A better understanding of the environmental impact of surgery is necessary to identify what can be done to limit the ecological impact of surgery without compromising standards of care.