Gut microbiota influence anastomotic healing in colorectal cancer surgery through modulation of mucosal proinflammatory cytokines.

OBJECTIVE: Colorectal cancer (CRC) is the third most diagnosed cancer, and requires surgical resection and reconnection, or anastomosis, of the remaining bowel to re-establish intestinal continuity. Anastomotic leak (AL) is a major complication that increases mortality and cancer recurrence. Our objective is to assess the causal role of gut microbiota in anastomotic healing. DESIGN: The causal role of gut microbiota was assessed in a murine AL model receiving faecal microbiota transplantation (FMT) from patients with CRC collected before surgery and who later developed or not, AL. Anastomotic healing and gut barrier integrity were assessed after surgery. Bacterial candidates implicated in anastomotic healing were identified using 16S rRNA gene sequencing and were isolated from faecal samples to be tested both in vitro and in vivo. RESULTS: Mice receiving FMT from patients that developed AL displayed poor anastomotic healing. Profiling of gut microbiota of patients and mice after FMT revealed correlations between healing parameters and the relative abundance of Alistipes onderdonkii and Parabacteroides goldsteinii. Oral supplementation with A. onderdonkii resulted in a higher rate of leaks in mice, while gavage with P. goldsteinii improved healing by exerting an anti-inflammatory effect. Patients with AL and mice receiving FMT from AL patients presented upregulation of mucosal MIP-1α, MIP-2, MCP-1 and IL-17A/F before surgery. Retrospective analysis revealed that patients with AL present higher circulating neutrophil and monocyte counts before surgery. CONCLUSION: Gut microbiota plays an important role in surgical colonic healing in patients with CRC. The impact of these findings may extend to a vast array of invasive gastrointestinal procedures.

Long-term follow-up of a cohort with post sleeve gastrectomy leaks: results of endoscopic treatment and salvage surgery.

INTRODUCTION: Laparoscopic sleeve gastrectomy (LSG) is the most performed bariatric procedure worldwide. The most challenging postoperative complication is gastric leak. The objectives of this study are to examine the efficacy and morbidity of different therapeutic strategies addressing leakage, and the long-term outcomes of a cohort of LSG leaks. METHODS: A retrospective review of patients treated for LSG leaks between September 2014 and January 2023 at our high-volume bariatric surgery center was performed. RESULTS: The charts of 37 patients (29 women and 8 men) were reviewed, with a mean age of 43 years and a median follow-up of 24 months. The mean preoperative body mass index was 45.1 kg/m2. Overall, 30/37 (81%) patients were successfully treated with endoscopic management, and 7/37 (19%) ultimately underwent salvage surgery. If the leak was diagnosed earlier than 6 weeks, endoscopic treatment had a 97% success rate. The median number of endoscopic procedures was 2 per patient, and included internal pigtails, stents, septoplasty, endoluminal vacuum therapy and over-the-scope clips. Complications included stent-related ulcers (10), esophageal stenosis requiring endoscopic dilatations (4), stent migrations (2) and kinking requiring repositioning (1), and internal pigtail migration (3). Revisional surgery consisted of proximal gastrectomy and Roux-en-Y esophago-jejunal anastomosis, Roux-en-Y fistulo-jejunostomy or classic Roux-en-Y gastric bypass proximal to the gastric stricture. In 62% of the cases, the axis/caliber of the LSG was abnormal. Beyond 4 attempts, endoscopy was unsuccessful. The success rate of endoscopic management dropped to 25% when treatment was initiated more than 45 days after the index surgery. CONCLUSIONS: Purely endoscopic management was successful in 81% of cases; with 97% success rate if diagnosis earlier than 6 weeks. After four failed endoscopic procedures, a surgical approach should be considered. Delayed diagnosis appears to be a significant risk factor for failure of endoscopic treatment.

Conservative Management of Obesity in Kidney Transplant Candidates.

OBJECTIVE: Obesity is prevalent in patients with chronic kidney disease and is associated with increased complications after kidney transplantation (KT). A body mass index limit is used in most transplant programs, though few studies have focused on conservative weight loss in KT candidates. The objective of this retrospective study is to evaluate the efficacy of a basic conservative weight management program in morbidly obese KT candidates and to perform a comprehensive nutritional evaluation. METHODS: This retrospective study included patients with a body mass index (BMI) >35 kg/m2, with grade IV or V chronic kidney disease. The conservative weight loss program consisted of anthropometric measurements every 3 months, consultation with a nutritionist, daily exercise, and counseling for healthier eating habits. Overall and quarterly BMI targets were defined. A subset of patients further underwent a comprehensive nutritional evaluation to measure socioeconomic characteristics, food intake behavior, motivation for change, and a 4-day food diary. RESULTS: Eighty patients were observed for a mean of 24 months. Successful weight loss (BMI < 35 kg/m2) was achieved in 26.3%, associated with women and those already close to the limit. The mean 1-year excess body weight loss was 8.4%. No patient with a BMI >40 kg/m2 was successful. The comprehensive nutritional evaluation was performed with 44 patients and found that only 14.6% had previously received nutritional counseling for weight loss. Cognitive restraint scored highest in the food-intake behavior. Most patients were motivated to lose weight with 66% in the action phase. There was little evidence of overeating with a recommended mean calculated daily caloric intake of 82.9%. CONCLUSION: The conservative weight loss program can have limited but non-negligible, success. Future successful nutritional interventions should take into consideration this surprising comprehensive profile of morbidly obese KT candidates.

The role of butyrate in surgical and oncological outcomes in colorectal cancer.

Butyrate is a short-chain fatty acid produced by colonic gut bacteria as a result of fermentation of dietary fibers. In the colon, butyrate is a major energy substrate and contributes to the nutritional support and proliferation of a healthy mucosa. It also promotes the intestinal barrier function by enhancing mucus production and tight junctions. In addition to its pro-proliferative effect in healthy colonocytes, butyrate inhibits the proliferation of cancer cells. The antineoplastic effect of butyrate is associated with the inhibitory effect of butyrate on histone deacetylase (HDAC) enzymes, which promote carcinogenesis. Due to the metabolic shift of cancer cells toward glycolysis, unused butyrate accumulates and inhibits procarcinogenic HDACs. In addition, recent studies suggest that butyrate may improve the healing of colonic tissue after surgery in animal models, specifically at the site of reconnection of colonic ends, anastomosis, after surgical resection. Here, we review current evidence on the impact of butyrate on epithelial integrity and colorectal cancer and present current knowledge on data that support its potential applications in surgical practice.

Oral iron supplementation after antibiotic exposure induces a deleterious recovery of the gut microbiota.

BACKGROUND: Oral iron supplementation is commonly prescribed for anemia and may play an important role in the gut microbiota recovery of anemic individuals who received antibiotic treatment. This study aims to investigate the effects of iron supplementation on gut microbiota recovery after antibiotics exposure. RESULTS: Mice were subjected to oral antibiotic treatment with neomycin and metronidazole and were fed diets with different concentrations of iron. The composition of the gut microbiota was followed throughout treatment by 16S rRNA sequencing of DNA extracted from fecal samples. Gut microbiota functions were inferred using PICRUSt2, and short-chain fatty acid concentration in fecal samples was assessed by liquid-chromatography mass spectrometry. Iron supplementation after antibiotic exposure shifted the gut microbiota composition towards a Bacteroidetes phylum-dominant composition. At the genus level, the iron-supplemented diet induced an increase in the abundance of Parasutterella and Bacteroides, and a decrease of Bilophila and Akkermansia. Parasutterella excrementihominis, Bacteroides vulgatus, and Alistipes finegoldii, were more abundant with the iron excess diet. Iron-induced shifts in microbiota composition were accompanied by functional modifications, including an enhancement of the biosynthesis of primary bile acids, nitrogen metabolism, cyanoamino acid metabolism and pentose phosphate pathways. Recovery after antibiotic treatment increased propionate levels independent of luminal iron levels, whereas butyrate levels were diminished by excess iron. CONCLUSIONS: Oral iron supplementation after antibiotic therapy in mice may lead to deleterious changes in the recovery of the gut microbiota. Our results have implications on the use of oral iron supplementation after antibiotic exposure and justify further studies on alternative treatments for anemia in these settings.

Oligosaccharides increase the genotoxic effect of colibactin produced by pks+ Escherichia coli strains.

BACKGROUND: Colibactin is a genotoxin that induces DNA double-strand breaks that may lead to carcinogenesis and is produced by Escherichia coli strains harboring the pks island. Human and animal studies have shown that colibactin-producing gut bacteria promote carcinogenesis and enhance the progression of colorectal cancer through cellular senescence and chromosomal abnormalities. In this study, we investigated the impact of prebiotics on the genotoxicity of colibactin-producing E. coli strains Nissle 1917 and NC101. METHODS: Bacteria were grown in medium supplemented with 20, 30 and 40 mg/mL of prebiotics inulin or galacto-oligosaccharide, and with or without 5 µM, 25 µM and 125 µM of ferrous sulfate. Colibactin expression was assessed by luciferase reporter assay for the clbA gene, essential for colibactin production, in E. coli Nissle 1917 and by RT-PCR in E. coli NC101. The human epithelial colorectal adenocarcinoma cell line, Caco-2, was used to assess colibactin-induced megalocytosis by methylene blue binding assay and genotoxicity by γ-H2AX immunofluorescence analysis. RESULTS: Inulin and galacto-oligosaccharide enhanced the expression of clbA in pks+ E. coli. However, the addition of 125 µM of ferrous sulfate inhibited the expression of clbA triggered by oligosaccharides. In the presence of either oligosaccharide, E. coli NC101 increased dysplasia and DNA double-strand breaks in Caco-2 cells compared to untreated cells. CONCLUSION: Our results suggest that, in vitro, prebiotic oligosaccharides exacerbate DNA damage induced by colibactin-producing bacteria. Further studies are necessary to establish whether oligosaccharide supplementation may lead to increased colorectal tumorigenesis in animal models colonized with pks+ E. coli.

Successful surgical weight loss with laparoscopic sleeve gastrectomy for morbid obesity prior to kidney transplantation.

Morbid obesity in kidney transplant (KT) candidates is associated with increased complications and graft failure. Multiple series have demonstrated rapid and significant weight loss after laparoscopic sleeve gastrectomy (LSG) in this population. Long-term and post-transplant weight evolutions are still largely unknown. A retrospective review was performed in eighty patients with end-stage kidney disease (ESKD) who underwent LSG in preparation for KT. From a median initial BMI of 43.7 kg/m2 , the median change at 1-year was -10.0 kg/m2 . Successful surgical weight loss (achieving a BMI < 35 kg/m2 or an excess body weight loss >50%) was attained in 76.3% and was associated with male gender, predialysis status, lower obesity class and lack of coronary artery disease. Thirty-one patients subsequently received a KT with a median delay of 16.7 months. Weight regain (increase in BMI of 5 kg/m2 postnadir) and recurrent obesity (weight regain + BMI > 35) remain a concern, occurring post-KT in 35.7% and 17.9%, respectively. Early LSG should be considered for morbidly obese patients with ESKD for improved weight loss outcomes. Early KT after LSG does not appear to affect short-term surgical weight loss. Candidates with a BMI of up to 45 kg/m2 can have a reasonable expectation to achieve the limit within 1 year.

Prospective study of the changes in pharmacokinetics of immunosuppressive medications after laparoscopic sleeve gastrectomy.

Laparoscopic sleeve gastrectomy induces weight loss via the creation of a restrictive gastric tube for early satiety and is associated with an accelerated gastric transit time. A prospective, single-dose pharmacokinetic study was performed, prior to and after laparoscopic sleeve gastrectomy, for tacrolimus, extended-release tacrolimus, mycophenolate mofetil, and enteric-coated mycophenolate sodium. The study included 12 morbidly obese patients in chronic renal failure. The median decrease in body mass index was 8.8 kg/m2 with an excess body weight loss of 54.9%. The AUC24 of all drugs were increased after laparoscopic sleeve gastrectomy by 46%, 55%, 77%, and 74%, respectively. The maximum concentrations were increased for tacrolimus, extended-release tacrolimus, and mycophenolate mofetil by 43%, 46%, and 65%. The apparent total clearances were decreased for tacrolimus, mycophenolate mofetil, and enteric-coated mycophenolate sodium by 36%, 57%, and 38%. Laparoscopic sleeve gastrectomy can be associated with significant changes in pharmacokinetics of the drugs evaluated. The mechanism is likely decreased apparent drug clearance due to an increased drug exposure (from a more distal site of intestinal absorption with decreased intestinal metabolism), or decreased clearance (liver metabolism). Adapting the monitoring of immunosuppression will be important to avoid overdosing and potential side effects.

The gut barrier as a gatekeeper in colorectal cancer treatment.

Colorectal cancer (CRC) is highly prevalent and is a major cause of cancer-related deaths worldwide. The incidence rate of CRC remains alarmingly high despite screening measures. The main curative treatment for CRC is a surgical resection of the diseased bowel segment. Postoperative complications usually involve a weakened gut barrier and a dissemination of bacterial proinflammatory lipopolysaccharides. Herein we discuss how gut microbiota and microbial metabolites regulate basal inflammation levels in the gut and the healing process of the bowel after surgery. We further elaborate on the restoration of the gut barrier function in patients with CRC and how this potentially impacts the dissemination and implantation of CRC cells in extracolonic tissues, contributing therefore to worse survival after surgery.

Modulating Gut Microbiota Prevents Anastomotic Leak to Reduce Local Implantation and Dissemination of Colorectal Cancer Cells after Surgery.

PURPOSE: Anastomotic leak (AL) is a major complication in colorectal cancer surgery and consists of the leakage of intestinal content through a poorly healed colonic wound. Colorectal cancer recurrence after surgery is a major determinant of survival. We hypothesize that AL may allow cancer cells to escape the gut and lead to cancer recurrence and that improving anastomotic healing may prevent local implantation and metastatic dissemination of cancer cells. EXPERIMENTAL DESIGN: We investigated the association between AL and postoperative outcomes in patients with colorectal cancer. Using mouse models of poor anastomotic healing, we assessed the processes of local implantation and dissemination of cancer cells. The effect of dietary supplementation with inulin and 5-aminosalicylate (5-ASA), which activate PPAR-γ in the gut, on local anastomotic tumors was assessed in mice undergoing colonic surgery. Inulin and 5-ASA were also assessed in a mouse model of liver metastasis. RESULTS: Patients experiencing AL displayed lower overall and oncologic survival than non-AL patients. Poor anastomotic healing in mice led to larger anastomotic and peritoneal tumors. The microbiota of patients with AL displays a lower capacity to activate the antineoplastic PPAR-γ in the gut. Modulation of gut microbiota using dietary inulin and 5-ASA reinforced the gut barrier and prevented anastomotic tumors and metastatic spread in mice. CONCLUSIONS: Our findings reinforce the hypothesis that preventing AL is paramount to improving oncologic outcomes after colorectal cancer surgery. Furthermore, they pave the way toward dietary targeting of PPAR-γ as a novel way to enhance healing and diminish cancer recurrence.

Putrescine Supplementation Limits the Expansion of pks+ Escherichia coli and Tumor Development in the Colon.

Escherichia coli that harbor the polyketide synthase (pks) genomic island produce colibactin and are associated with sporadic colorectal cancer development. Given the considerable prevalence of pks+ bacteria in healthy individuals, we sought to identify strategies to limit the growth and expansion of pks+ E. coli. We found that culture supernatants of the probiotic strain E. coli Nissle 1917 were able to inhibit the growth of the murine pathogenic strain pks+ E. coli NC101 (EcNC101). We performed a nontargeted analysis of the metabolome in supernatants from several E. coli strains and identified putrescine as a potential postbiotic capable of suppressing EcNC101 growth in vitro. The effect of putrescine supplementation was then evaluated in the azoxymethane/dextran sulfate sodium mouse model of colorectal cancer in mice colonized with EcNC101. Putrescine supplementation inhibited the growth of pks+ E. coli, reduced the number and size of colonic tumors, and downmodulated the release of inflammatory cytokines in the colonic lumen. Additionally, putrescine supplementation led to shifts in the composition and function of gut microbiota, characterized by an increase in the Firmicutes/Bacteroidetes ratio and enhanced acetate production. The effect of putrescine was further confirmed in vitro using a pks+ E. coli strain isolated from a patient with colorectal cancer. These results suggest that probiotic-derived metabolites can be used as an alternative to live bacteria in individuals at risk of developing colorectal cancer due to the presence of pks+ bacteria in their colon. SIGNIFICANCE: Putrescine supplementation inhibits the growth of cancer-promoting bacteria in the gut, lowers inflammation, and reduces colon cancer development. The consumption of healthy foods rich in putrescine may be a potential prophylactic approach for individuals at risk of developing colorectal cancer due to the presence of pks+ bacteria in their colon.

Inulin impacts tumorigenesis promotion by colibactin-producing Escherichia coli in ApcMin/+ mice.

Introduction: The prebiotic inulin has previously shown both protective and tumor-promoting effects in colorectal cancer (CRC). These inconsistencies may be due to the gut microbial composition as several bacteria have been associated with CRC. Specifically, polyketide synthase-positive (pks+) Escherichia coli promotes carcinogenesis and facilitates CRC progression through the production of colibactin, a genotoxin that induces double-strand DNA breaks (DSBs). We investigated whether colibactin-producing Escherichia coli changed the protection conferred by inulin against tumor growth and progression using the ApcMin/+ mouse model of CRC. Methods: Mice received a 2% dextran sodium sulfate (DSS) solution followed by oral gavage with the murine pks + E. coli strain NC101 (EcNC101) and were fed a diet supplemented with 10% cellulose as control or 10% inulin for 4 weeks. Results: Inulin supplementation led to increase EcNC101 colonization compared to mice receiving the control diet. The increased colonization of EcNC101 resulted in more DSBs, tumor burden, and tumor progression in ApcMin/+ mice. The tumorigenic effect of EcN101 in ApcMin/+ mice mediated by inulin was dependent on colibactin production. Pasteurized E. coli Nissle 1917 (EcN), a probiotic, suppressed the inulin-driven EcNC101 expansion and impacted tumor progression. Discussion: Our results suggest that the presence of pks + E. coli influences the outcome of inulin supplementation in CRC and that microbiota-targeted interventions may mitigate this effect. Given the prevalence of pks + E. coli in both healthy and CRC populations and the importance of a fiber-rich diet, inulin supplementation in individuals colonized with pks + bacteria should be considered with caution.

Assessment of Gut Barrier Integrity in Mice Using Fluorescein-Isothiocyanate-Labeled Dextran.

Gut barrier integrity is a hallmark of intestinal health. While gut barrier integrity can be assessed using indirect markers such as the measurement of plasma inflammatory markers and bacterial translocation to the spleen and lymph nodes, the gold standard directly quantifies the ability of selected molecules to traverse the gut mucosal layer toward systemic circulation. This article uses a non-invasive, cost-effective, and low-burden technique to quantify and follow in real time the intestinal permeability in mice using fluorescein-isothiocyanate-labeled dextran (FITC-dextran). Prior to oral supplementation with FITC-dextran, the mice are fasted. They are then gavaged with FITC-dextran diluted in phosphate-buffered saline (PBS). One hour after the gavage, the mice are subjected to general anesthesia using isoflurane, and the in vivo fluorescence is visualized in an imaging chamber. This technique aims to assess residual fluorescence in the abdominal cavity and the hepatic uptake, which is suggestive of portal migration of the fluorescent probe. Blood and stool samples are collected 4 h after oral gavage, and the mice are sacrificed. Plasma and fecal samples diluted in PBS are then plated, and the fluorescence is recorded. The concentration of FITC-dextran is then calculated using a standard curve. In previous research, in vivo imaging has shown that fluorescence rapidly spreads to the liver in mice with a weaker gut barrier induced by a low-fiber diet, while in mice supplemented with fiber to strengthen the gut barrier, the fluorescent signal is retained mostly in the gastrointestinal tract. In addition, in this study, control mice had elevated plasma fluorescence and reduced fluorescence in the stool, while inversely, inulin-supplemented mice had higher levels of fluorescence signals in the gut and low levels in the plasma. In summary, this protocol provides qualitative and quantitative measurements of intestinal permeability as a marker for gut health.

Cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy for small bowel neuroendocrine tumors with peritoneal metastasis.

BACKGROUND: Up to 20% of patients with small-bowel neuroendocrine tumors (SB-NETs) may present with peritoneal carcinomatosis (PM). Surgical cytoreduction (CRS) has been proposed as an adequate management as it confers a survival benefit in selected patients. The addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to CRS in this context may be an option but data on its added benefits is lacking. METHODS: A search was performed in the prospective multicenter international collaborative database of the Peritoneal Surface Oncology Group International (PSOGI) and BIG-RENAPE working groups, and patients who underwent a surgical treatment (CRS or CRS with HIPEC) for a SB-NET with PM were identified and compared. RESULTS: Between 2002 and 2016, a total of 67 patients were identified as having a CRS for SB-NET, with 36 receiving HIPEC during surgery. Median postoperative follow-up was 34 months. The peritoneal cancer index (PCI) and the completeness of cytoreduction score (CCR-score) were higher in the CRS-HIPEC group. More grade III-IV complications occurred in this group as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0. Despite a tendency toward a better progression/recurrence-free survival in patients receiving HIPEC, no significant differences were noted between the CRS and CRS-HIPEC groups in terms of postoperative recurrence. CONCLUSIONS: HIPEC does not seem to provide additional benefits in terms of postoperative evolution and survival in patients with SB-NET undergoing CRS. It is associated with higher morbidity. It may possibly lead to an improved recurrence-free survival, but further reports are required to confirm this assumption.

Prevalence of pks + bacteria and enterotoxigenic Bacteroides fragilis in patients with colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is the third most diagnosed cancer and the second most common cause of cancer deaths worldwide. CRC patients present with an increase in pathogens in their gut microbiota, such as polyketide synthase-positive bacteria (pks +) and enterotoxigenic Bacteroides fragilis (ETBF). The pks + Escherichia coli promotes carcinogenesis and facilitates CRC progression through the production of colibactin, a genotoxin that induces double-strand DNA breaks (DSBs). ETBF is a procarcinogenic bacterium producing the B. fragilis toxin (bft) that promotes colorectal carcinogenesis by modulating the mucosal immune response and inducing epithelial cell changes. METHODS: Fecal samples were collected from healthy controls (N = 62) and CRC patients (N = 94) from the province of Québec (Canada), and a bacterial DNA extraction was performed. Fecal DNA samples were then examined for the presence of the pks island gene and bft using conventional qualitative PCR. RESULTS: We found that a high proportion of healthy controls are colonized by pks + bacteria (42%) and that these levels were similar in CRC patients (46%). bft was detected in 21% of healthy controls and 32% of CRC patients, while double colonization by both pks + bacteria and ETBF occurred in 8% of the healthy controls and 13% of the CRC patients. Most importantly, we found that early-onset CRC (< 50 years) patients were significantly less colonized with pks + bacteria (20%) compared to late-onset CRC patients (52%). CONCLUSIONS: Healthy controls had similar levels of pks + bacteria and ETBF colonization as CRC patients, and their elevated levels may place both groups at greater risk of developing CRC. Colonization with pks + bacteria was less prevalent in early-compared to late-onset CRC.

The concurrence of an enterocutaneous fistula and granulomatosis with polyangiitis: The role of immunosuppression as a bridge to definitive surgical treatment.

BACKGROUND AND AIM: Granulomatosis with polyangiitis (GPA) is a systemic disease that consists of vasculitis and granulomatous inflammation, and that usually affects the respiratory tract, the ear, nose, and throat sphere, and the kidneys. GPA may also cause skin manifestations that include ulcerations, nodules, or papules. An enterocutaneous fistula (ECF) is an abnormal tract that connects the skin surface to the gastrointestinal system. METHODS: We report the first case of an ECF as a concurrent clinical manifestation during a new-onset GPA in a 68-year-old male patient. RESULTS: The patient presented with an abdominal cutaneous wound with subcutaneous abscess that evolved into an ECF with spontaneous enteric drainage. He also complained of nasal crusting, epistaxis, and cough, with further investigation revealing bilateral pulmonary nodules. Transthoracic biopsy was performed and was suggestive of necrotizing vasculitis. A diagnosis of autoimmune vasculitis was highly suspected, and an immunosuppressive regimen of corticosteroid and intravenous cyclophosphamide was initiated. Significant improvement was noted in nasal manifestations, cough, and the output of the ECF. Definitive surgical management of the ECF was performed successfully. CONCLUSION: To the best of our knowledge, the presentation of a GPA with an ECF has not been previously reported and poses major challenges to medical and surgical treatment, as it constitutes a dilemma as to how to address an autoimmune process requiring immunosuppression in the context of an infectious condition. This presentation suggests that immunosuppression in these patients may still be considered. RELEVANCE FOR PATIENTS: The concomitant presence of an ECF with abscess, an infectious process, and of an autoimmune disorder requiring immunosuppression is a major medical challenge. This case suggests that immunosuppression may still be considered in these patients to promote a better control of the concomitant ECF before definitive surgical therapy.

High-grade neuroendocrine small-cell carcinoma of the anal canal: Long-term remission with chemoradiotherapy.

Primary small-cell carcinoma of the anal canal is an exceedingly rare tumor with a poor prognosis even when aggressive therapy is initiated. We present the case of a 53-year-old male patient who presented with chronic anal pain. Examination under general anesthesia revealed the presence of a mass in the anal canal. A biopsy was performed, and histopathological examination showed a high-grade neuroendocrine small-cell carcinoma. Assessment with endoscopic ultrasound showed an invasion of the internal anal sphincter. The patient was treated with a chemoradiotherapy (CRT) regimen consisting of cisplatin and etoposide, combined to radiotherapy. The patient achieved long-term remission with CRT. This is one of the first reports in the literature of a case of a high-grade neuroendocrine small-cell carcinoma of the anal canal where long-term remission was achieved with non-surgical management of a tumor invading the anal sphincter. This favorable evolution with CRT suggests that remission could still be achieved with anal small-cell carcinomas. More cases are however required to validate this approach. RELEVANCE FOR PATIENTS: This case presentation suggests that long-term remission can still be achieved using CRT and without an extensive surgical resection in patients with small-cell carcinoma of the anal canal.

Improvement of colonic healing and surgical recovery with perioperative supplementation of inulin and galacto-oligosaccharides.

BACKGROUND AND AIMS: Anastomotic leak (AL) is a major complication in colorectal surgery. Recent evidence suggests that the gut microbiota may affect healing and may cause or prevent AL. Butyrate is a beneficial short-chain fatty acid (SCFA) that is produced as a result of bacterial fermentation of dietary oligosaccharides and has been described as beneficial in the maintenance of colonic health. To assess the impact of oligosaccharides on colonic anastomotic healing in mice, we propose to modulate the microbiota with oligosaccharides to increase butyrate production via enhancement of butyrate-producing bacteria and, consequently, improve anastomotic healing in mice. METHODS: Animal experiments were conducted in mice that were subjected to diets supplemented with inulin, galacto-oligosaccharides (GOS) or cellulose, as a control, for two weeks before undergoing a surgical colonic anastomosis. Macroscopic and histological assessment of the anastomosis was performed. Extent of epithelial proliferation was assessed by Ki-67 immunohistochemistry. Gelatin zymography was used to evaluate the extent of matrix metalloproteinase (MMP) hydrolytic activity. RESULTS: Inulin and GOS diets were associated with increased butyrate production and better anastomotic healing. Histological analysis revealed an enhanced mucosal continuity, and this was associated with an increased re-epithelialization of the wound as determined by increased epithelial proliferation. Collagen concentration in peri-anastomotic tissue was higher with inulin and GOS diets and MMP activity, a marker of collagen degradation, was lower with both oligosaccharides. Inulin and GOS diets were further associated with lower bacterial translocation. CONCLUSIONS: Dietary supplementation with inulin and GOS may improve anastomotic healing and reinforce the gut barrier in mice.

Minimally invasive management of a paraduodenal hernia with intestinal malrotation.

Paraduodenal hernias (PDHs) are rare entities that may present with acute or subacute symptoms, and which pose challenges to prompt diagnosis and treatment. The minimally invasive management of these hernias is emerging as a new compelling approach to optimize surgical recovery. We present the case of a 42-year-old female patient who presented with acute abdominal pain and symptoms of bowel obstruction. Abdominal imaging suggested the presence of a left PDH. Laparoscopic exploration was performed. Intestinal malrotation was noted with incarceration of a small bowel loop in the Landzert fossa. The incarcerated bowel loop was freed and primary repair of the hernial defect was performed. PDHs are usually congenital and involve a herniation of abdominal content into the left mesocolon, between the mesocolon and the posterior abdominal wall. Minimally invasive treatment, consisting of adhesiolysis and repair of the hernial defect, seems to be a valid and safe option.