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In the colorectal cancer (CRC) niche, the transcription factors signal transducer and activator of transcription 3 (STAT3) and nuclear factor-κB (NF-κB) are hyperactivated in both malignant cells and tumor-infiltrating leukocytes (TILs) and cooperate to maintain cancer cell proliferation/survival and drive protumor inflammation. Through drug repositioning studies, the anthelmintic drug rafoxanide has recently emerged as a potent and selective antitumor molecule for different types of cancer, including CRC. Here, we investigate whether rafoxanide could negatively modulate STAT3/NF-κB and inflammation-associated CRC. The antineoplastic effect of rafoxanide was explored in a murine model of CRC resembling colitis-associated disease. Cell proliferation and/or STAT3/NF-κB activation were evaluated in colon tissues taken from mice with colitis-associated CRC, human CRC cells, and CRC patient-derived explants and organoids after treatment with rafoxanide. The STAT3/NF-κB activation and cytokine production/secretion were assessed in TILs isolated from CRC specimens and treated with rafoxanide. Finally, we investigated the effects of TIL-derived supernatants cultured with or without rafoxanide on CRC cell proliferation and STAT3/NF-κB activation. The results showed that rafoxanide restrains STAT3/NF-κB activation and inflammation-associated colon tumorigenesis in vivo without apparent effects on normal intestinal cells. Rafoxanide markedly reduces STAT3/NF-κB activation in cultured CRC cells, CRC-derived explants/organoids, and TILs. Finally, rafoxanide treatment impairs the ability of TILs to produce protumor cytokines and promote CRC cell proliferation. We report the novel observation that rafoxanide negatively affects STAT3/NF-κB oncogenic activity at multiple levels in the CRC microenvironment. Our data suggest that rafoxanide could potentially be deployed as an anticancer drug in inflammation-associated CRC., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

This article is the second in a series of two publications on the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the management of Crohn's disease. The first article covers medical management; the present article addresses surgical management, including preoperative aspects and drug management before surgery. It also provides technical advice for a variety of common clinical situations. Both articles together represent the evidence-based recommendations of the ECCO for Crohn's disease and an update of prior ECCO Guidelines., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: Patients with ulcerative colitis (UC) receiving liver transplantation (LT) due to primary sclerosing cholangitis (PSC) have higher risk of developing colorectal cancers (CRC). Aim of this systematic review was to define the patients' features, immunosuppressive management, and oncological outcomes of LT recipients with UC-PSC developing CRC., Methods: Searches were conducted in PubMed (MEDLINE), Cochrane Library, Web of Science for all English articles published until September 2023. Inclusion criteria were original articles including patients specifying outcomes of interest. Primary endpoints comprised incidence of CRC, disease free survival (DFS), overall survival (OS) and cancer recurrence. Secondary endpoints were patient's and tumor characteristics, graft function, immunosuppressive management and PSC recurrence. PROSPERO CRD42022369190., Results: Fifteen studies included, 88 patients were identified. Patients (mean age: 50 years) had a long history of UC (20 years), mainly with active colitis (79%), and developed tumor within the first 3 years from LT, while receiving a double or triple immunosuppressive therapy. Cumulative incidence of tumor was 5.5%. At one, two and three years, DFS was 92%, 82% and 75%, while OS was 87%, 81% and 79% respectively. Disease progression rate was 15%. After CRC surgery, 94% of patients maintained a good graft functionality, with no reported cases of PSC recurrence., Conclusions: After LT, patients with PSC and UC have an increased risk of CRC, especially in presence of long history of UC and active colitis. Surgical resection guarantees satisfactory mid-term oncological outcomes, but samples are limited, and long-term data are lacking. National and international registry are auspicial to evaluate long-term oncological outcomes and to optimize clinical management., (© 2024. The Author(s).)

Purpose: Routine use of abdominal drain or prolonged antibiotic prophylaxis is no longer part of current clinical practice in colorectal surgery. Nevertheless, in patients undergoing laparoscopic right hemicolectomy with intracorporeal anastomosis (ICA), it may reduce perioperative abdominal contamination. Furthermore, in cancer patients, prolonged surgery with extensive dissection such as central vascular ligation and complete mesocolon excision with D3 lymphadenectomy (altogether radical right colectomy RRC) is called responsible for affecting postoperative ileus. The aim was to evaluate postoperative resumption of gastrointestinal functions in patients undergoing right hemicolectomy for cancer with ICA and standard D2 dissection or RRC, with or without abdominal drain and prolonged antibiotic prophylaxis., Methods: Monocentric factorial parallel arm randomized pilot trial including all consecutive patients undergoing laparoscopic right hemicolectomy and ICA for cancer, in 20 months. Patients were randomized on a 1:1:1 ratio to receive abdominal drain, prolonged antibiotic prophylaxis or neither (I level), and 1:1 to receive RRC or D2 colectomy (II level). Patients were not blinded. The primary aim was the resumption of gastrointestinal functions (time to first gas and stool, time to tolerated fluids and food). Secondary aims were length of stay and complications' rate., Clinicaltrials: gov no. NCT04977882., Results: Fifty-seven patients were screened; according to sample size, 36 were randomized, 12 for each arm for postoperative management, and 18 for each arm according to surgical techniques. A difference in time to solid diet favored the group without drain or antibiotic independently from standard or RRC. Furthermore, when patients were divided with respect to surgical technique and into matched cohorts, no differences were seen for primary and secondary outcomes., Conclusion: Abdominal drainage and prolonged antibiotic prophylaxis in patients undergoing right hemicolectomy for cancer with ICA seem to negatively affect the resumption of a solid diet after laparoscopic right hemicolectomy with ICA for cancer. RRC does not seem to influence gastrointestinal function recovery., (© 2024. The Author(s).)

BACKGROUND Bariatric surgery (BS) has a lower percentage of complications than other abdominal surgeries. Hemorrhage in one of the most common complications and can be life-threatening. Hereditary factor XI (FXI) deficiency is a coagulation disorder that can result in excessive bleeding requiring intervention to restore hemostasis. Risks over benefits in patients with morbid obesity with BS indication, as well as those with FXI deficiency, should be carefully evaluated. This article reports the case of an obese woman with FXI deficiency -undergoing SG. CASE REPORT A 49-year-old woman with a BMI of 51 kg/m² was diagnosed as having severe FXI deficiency during preoperative exams prior to bariatric surgery. Virus-inactivated homo-group plasma 10 ml/kg infusion was administrated 1 h before surgery, during the entire procedure, and continuing until postoperative day (POD) 4. A very low-calorie ketogenic diet (VLCKD) was proposed to the patient 4 weeks before surgery. Laparoscopic sleeve gastrectomy was performed with staple-line reinforcement by oversewing the seromuscular layer using continuous suture. Subcutaneous enoxaparin 4000 U.I. was administered from POD 1 until POD 25 to prevent any thromboembolic event. The patient was discharged on POD 5 in good clinical condition. CONCLUSIONS Risks of bleeding andor thromboembolic events before or after BS are increased in patient with FXI deficiency. Bariatric surgery in these patients is safe in experienced BS centers, and the risks associated with the obesity seem to exceed those of the coagulopathy and surgery. Careful preoperative counseling, extensive hematological checks, and meticulous surgery are essential to reduce BS risks. Sleeve gastrectomy oversewing the stapler line seems a reasonable choice.

Background: Although complete mesocolic excision (CME) is supposed to be associated with a higher lymph node (LN) yield, decreased local recurrence, and survival improvement, its implementation currently is debated because the evidence level of these data is rather low and still not supported by randomized controlled trials., Method: This is a multicenter, randomized, superiority trial (NCT04871399). The 3-year disease-free survival (DFS) was the primary end point of the study. The secondary end points were safety (duration of operation, perioperative complications, hospital length of stay), oncologic outcomes (number of LNs retrieved, 3- and 5-year overall survival, 5-year DFS), and surgery quality (specimen length, area and integrity rate of mesentery, length of ileocolic and middle-colic vessels). The trial design required the LN yield to be higher in the CME group at interim analysis., Results: Interim data analysis is presented in this report. The study enrolled 258 patients in nine referral centers. The number of LNs retrieved was significantly higher after CME (25 vs. 20; p = 0.012). No differences were observed with respect to intra- or post-operative complications, postoperative mortality, or duration of surgery. The hospital stay was even shorter after CME (p = 0.039). Quality of surgery indicators were higher in the CME arm of the study. Survival data still were not available., Conclusions: Interim data show that CME for right colon cancer in referral centers is safe and feasible and does not increase perioperative complications. The study documented with evidence that quality of surgery and LN yield are higher after CME, and this is essential for continuation of patient recruitment and implementation of an optimal comparison. Trial registration The trial was registered at ClinicalTrials.gov with the code NCT04871399 and with the acronym CoME-In trial., (© 2023. The Author(s).)

Introduction: The role of robotic lateral pelvic lymph node dissection (LPLND) for lateral pelvic nodal disease (LPND) in rectal cancer has yet to be investigated in the Western hemisphere. This study aims to investigate the safety and feasibility of robotic LPLND by utilising a well-established totally robotic TME protocol., Methods: We conducted a retrospective study on 17 consecutive patients who underwent robotic LPLND for LPND ± TME for rectal cancer between 2015 and 2021. A single docking totally robotic approach from the left hip with full splenic mobilisation was performed using the X/Xi da Vinci platform. All patients underwent a tri-compartmental robotic en bloc excision of LPND with preservation of the obturator nerve and pelvic nerve plexus, leaving a well-skeletonised internal iliac vessel and its branches., Results: The median operative time was 280 min, which was 40 min longer than our standard robotic TME. The median BMI was 26, and there were no conversions. The median inpatient stay was 7 days with no Clavien-Dindo > 3 complications. One patient (6%) developed local recurrence and metastatic disease within 5 months. The proportion of histologically confirmed LPND was 41%, of which 94% were well to moderately differentiated adenocarcinoma. Median pre-operative lateral pelvic node size was significantly higher in positive nodes (14 mm vs. 8 mm ( p = 0.01)). All patients had clear resection margins on histology., Discussion: Robotic LPLND is safe and feasible with good peri-operative and short-term outcomes, with the ergonomic advantages of a robotic TME docking protocol readily transferrable in LPLND.

Introduction: Colon cancer in ulcerative colitis patients with liver transplant (UCCOLT) due to primary sclerosing cholangitis carries significant treatment challenges. Aim of this literature search is to review management strategies and provide a framework to facilitate the decisional process in this clinical setting., Methods: PRISMA-compliant systematic search was followed by critical expert commentary of the results and development of a surgical management algorithm. Endpoints included surgical management, operative strategies, functional and survival outcomes. Technical and strategics aspects with particular regard to the choice of reconstruction were evaluated to tentatively develop an integrated algorithm., Results: Ten studies reporting treatment of 20 UCCOLT patients were identified after screening. Nine patients underwent proctocolectomy and end-ileostomy (PC) and eleven had restorative ileal pouch-anal anastomosis (IPAA). Reported results for perioperative outcomes, oncological outcomes, and graft loss were comparable for both procedures. There were no reports of subtotal colectomies and ileo-rectal anastomosis (IRA)., Conclusions: Literature in the field is scarce and decision-making is particularly complex. PC and IPAA have been reported with good results. Nevertheless, IRA may also be considered in UCCOLT patients in selected cases, reducing the risks of sepsis, OLT and pouch failure; furthermore, in young patients, it has the advantage of preserving fertility or sexual function. The proposed treatment algorithm may represent a valuable support in guiding surgical strategy., Competing Interests: Declaration of competing interest The authors have no conflict of interest or financial disclosures., (Copyright © 2023 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

A higher frequency of mucinous and signet-ring cell colonic adenocarcinoma has been reported in inflammatory bowel disease (IBD). The primary aim was to investigate the frequency of mucinous and signet-ring cell colorectal adenocarcinoma in patients with IBD (Cases) versus age-matched non-IBD Controls. The secondary aims were to compare the characteristics of these two histotypes of colorectal cancer (CRC) in IBD patients vs. Controls and to search for specific risk factors in IBD. In a case-control study, all IBD patients with CRC diagnosed from 2000 to 2022 were enrolled and matched for age (1:2) with non-IBD Controls with CRC. The study population included 120 CRC patients (40 IBD, 80 Controls). In IBD, CRC included standard adenocarcinoma in 23 (57.5%) patients mucinous/signet-ring cell adenocarcinoma in 17 (42.5%) patients. The proportion of mucinous/signet-ring cell adenocarcinoma was higher in IBD than in Controls (17 [42.5%] vs. 18 [22.5%]; p = 0.03). In rectal CRC, the proportion of mucinous/signet-ring cell adenocarcinoma was higher than standard adenocarcinoma in IBD (8 [47.1%] vs. 4 [17.4%]; p = 0.04) but not in Controls (4 [22.2%] vs. 20 [32.2%]; p = 0.59). In rectal CRC, the proportion of these two histotypes was higher in Cases than in Controls (8/12 [66.6%] vs. 4/24 [16.6%]; p = 0.008), with no risk factors identified in IBD. CRC was more frequently represented by mucinous/signet-ring cell adenocarcinoma in IBD than in age-matched non-IBD Controls. In IBD, these two CRC histotypes were more frequent in the rectum.

Aim: Ambulatory laparoscopic colectomy (ALC), meaning discharge within 24 h of surgical colonic resection, has recently been proposed in a few, selected patients. This systematic review was performed with the aim of reviewing protocols for ALC and assessing feasibility, safety and outcomes after ALC., Method: A PRISMA-compliant systematic review and pooled analysis was performed searching all English studies published until October 2022 in PubMed, Cochrane Library, Web of Science (PROSPERO, CRD42022334463). Inclusion criteria were original articles including patients undergoing ALC, specifying at least one outcome of interest. Exclusion criteria were articles reporting a robotic-assisted procedure; unable to retrieve patient data from articles; the same patient series included in different studies. Primary outcomes were success, overall complications and readmission rates. Secondary outcomes included mortality and specific complications such us surgical site infection, anastomotic leak, ileus, bleeding, rate of ALC acceptance, and unscheduled consultation and reoperation rate., Results: Among 1087 studies imported for screening, 11 were included (1296 patients). The success rate was 47% with an overall morbidity of 14%. Readmission and reoperation rates were 5% and 1%, respectively. No mortality was recorded. Protocols of ALC differ significantly among published studies., Conclusions: Overall, ALC appears to be safe and feasible in selected cases with an acceptable success rate and a low risk of readmission after hospital discharge. Future studies should evaluate patients' benefits and discharge criteria, as well as uniformity and standardization of eligibility criteria. This systematic review may help inform on ALC adoption in clinical practice., (© 2023 Association of Coloproctology of Great Britain and Ireland.)