Can we predict the risk of esophageal stricture after caustic injury?

Nonoperative management of severe caustic injuries has demonstrated its feasibility, avoiding the need for emergency esogastric resection and resulting in low mortality rates. However, leaving superficial necrosis in place could increase the risk of esophageal stricture development. Data on the risk factors of esophageal stricture secondary to caustic ingestion are scarce. The aim of our study was to identify the risk factors for esophageal strictures after caustic ingestion at admission. From February 2015 to March 2021, all consecutive patients with esophageal or gastric caustic injury score ≥ II according to the Zargar classification were retrospectively analyzed. For each patient, we collected over 50 criteria at admission to the emergency room and then selected among them 20 criteria with the best clinical relevance and limited missing data for risk factor analyses. Among the 184 patients included in this study, 37 developed esophageal strictures (cumulative rate 29.4%). All esophageal strictures occurred within 3 months. In multivariate analyses, the risk factors for esophageal strictures were voluntary ingestion (cause-specific hazard ratio 5.92; 95% confidence interval 1.76-19.95, P = 0.004), Zargar's esophageal score ≥ III (cause-specific hazard ratio 14.30; 95% confidence interval 6.07-33.67, P < 0.001), and severe ear, nose, and throat lesions (cause-specific hazard ratio 2.15; 95% confidence interval 1.09-4.22, P = 0.027). Intentional ingestion, severe endoscopic grade, and severe ENT lesions were identified as risk factors for esophageal stricture following caustic ingestion. Preventive measures for this population require further evaluation.

Changes in HLA-B27 Transgenic Rat Fecal Microbiota Following Tofacitinib Treatment and Ileocecal Resection Surgery: Implications for Crohn's Disease Management.

The therapeutic management of Crohn's disease (CD), a chronic relapsing-remitting inflammatory bowel disease (IBD), is highly challenging. Surgical resection is sometimes a necessary procedure even though it is often associated with postoperative recurrences (PORs). Tofacitinib, an orally active small molecule Janus kinase inhibitor, is an anti-inflammatory drug meant to limit PORs in CD. Whereas bidirectional interactions between the gut microbiota and the relevant IBD drug are crucial, little is known about the impact of tofacitinib on the gut microbiota. The HLA-B27 transgenic rat is a good preclinical model used in IBD research, including for PORs after ileocecal resection (ICR). In the present study, we used shotgun metagenomics to first delineate the baseline composition and determinants of the fecal microbiome of HLA-B27 rats and then to evaluate the distinct impact of either tofacitinib treatment, ileocecal resection or the cumulative effect of both interventions on the gut microbiota in these HLA-B27 rats. The results confirmed that the microbiome of the HLA-B27 rats was fairly different from their wild-type littermates. We demonstrated here that oral treatment with tofacitinib does not affect the gut microbial composition of HLA-B27 rats. Of note, we showed that ICR induced an intense loss of bacterial diversity together with dramatic changes in taxa relative abundances. However, the oral treatment with tofacitinib neither modified the alpha-diversity nor exacerbated significant modifications in bacterial taxa induced by ICR. Collectively, these preclinical data are rather favorable for the use of tofacitinib in combination with ICR to address Crohn's disease management when considering microbiota.

Failure to rescue following proctectomy for rectal cancer: the additional benefit of laparoscopic approach in a nationwide observational study of 44,536 patients.

BACKGROUND: There is growing evidence that failure to rescue (FTR) is an important factor of postoperative mortality (POM) after rectal cancer surgery and surgical approach modified post-operative outcomes. However, the impact of laparoscopy on FTR after proctectomy for rectal cancer remains unknown. The aim of this study was to compare the rates of postoperative complications and FTR after laparoscopy vs open proctectomy for cancer. METHODS: All patients who underwent proctectomy for rectal cancer between 2012 and 2016 were included. FTR was defined as the 90-day POM rate among patients with major complications. Outcomes of patients undergoing open or laparoscopic rectal cancer surgery were compared after 1:1 propensity score matching by year of surgery, hospital volume, sex, age, Charlson score, neoadjuvant chemotherapy, tumor localization and type of anastomosis. RESULTS: Overall, 44,536 patients who underwent proctectomy were included, 7043 of whom (15.8%) developed major complications. The rates of major complications, POM and FTR were significantly higher in open compared to laparoscopic procedure (major complications: 19.2% vs 13.7%, p < 0.001; POM: 5.4% vs 2.3%, p < 0.001; FTR: 13.6% vs 8.3%, p < 0.001; respectively). After matching, open and laparoscopic groups were comparable. Multivariate analysis showed that age, Charlson score, sphincter-preserving procedure and surgical approach were predictive factors for FTR. Open proctectomy was found to be a risk factor for FTR (OR 1.342, IC95% [1.066; 1.689], p = 0.012) compared to laparoscopic procedure. CONCLUSION: When complications occurred, patients operated on by open proctectomy were more likely to die.

Hospital surgical volume-outcome relationship of postoperative morbidity for ileocolic resection in Crohn's disease: A French nationwide study of 4,205 patients.

BACKGROUND AND AIMS: Despite the development of medical therapy, nearly 50% of patients with Crohn's disease (CD) undergo surgery during their lifetime. Several studies have suggested some risk factors for postoperative morbidity (POM) after ileocolic resection (ICR). However, the impact of surgical hospital volume on POM in CD has not been extensively studied. This study aimed to assess the impact of surgical hospital volume on POM after ICR for CD. METHODS: All patients with CD who underwent ICR in France between 2013 and 2022 were identified in the French Database, Programme de Médicalisation des Systèmes d'Information. Using the Chi-square automatic interaction detector, we determined the cut-off value to split high-surgical volume (≥6 ICR/year) and low-surgical volume centers (<6 ICR/year). The primary outcome was the evaluation of major POM during hospitalization. POM was evaluated according to the surgical volume center. The Elixhauser comorbidity index (ECI) was used to categorize the comorbidities of patients. RESULTS: A total of 4,205 patients were identified, and the major POM during hospitalization was significantly (p = 0.0004) lower in the high-surgical volume (6.2%) compared to low-surgical volume centers (9.1%). After multivariate analysis, independent factors associated with major POM were surgical hospital volume (P = 0.024), male sex (P = 0.029), ECI ≥1 (P < 0.001), and minor POM (P < 0.001). CONCLUSION: Major POM after ICR for CD is closely associated with surgical hospital volume. Centralization of surgery for CD is desirable, especially in patients with major comorbidities.

Chitin-glucan improves important pathophysiological features of irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is one of the most frequent and debilitating conditions leading to gastroenterological referrals. However, recommended treatments remain limited, yielding only limited therapeutic gains. Chitin-glucan (CG) is a novel dietary prebiotic classically used in humans at a dosage of 1.5-3.0 g/d and is considered a safe food ingredient by the European Food Safety Authority. To provide an alternative approach to managing patients with IBS, we performed preclinical molecular, cellular, and animal studies to evaluate the role of chitin-glucan in the main pathophysiological mechanisms involved in IBS. AIM: To evaluate the roles of CG in visceral analgesia, intestinal inflammation, barrier function, and to develop computational molecular models. METHODS: Visceral pain was recorded through colorectal distension (CRD) in a model of long-lasting colon hypersensitivity induced by an intra-rectal administration of TNBS [15 milligrams (mg)/kilogram (kg)] in 33 Sprague-Dawley rats. Intracolonic pressure was regularly assessed during the 9 wk-experiment (weeks 0, 3, 5, and 7) in animals receiving CG (n = 14) at a human equivalent dose (HED) of 1.5 g/d or 3.0 g/d and compared to negative control (tap water, n = 11) and positive control (phloroglucinol at 1.5 g/d HED, n = 8) groups. The anti-inflammatory effect of CG was evaluated using clinical and histological scores in 30 C57bl6 male mice with colitis induced by dextran sodium sulfate (DSS) administered in their drinking water during 14 d. HT-29 cells under basal conditions and after stimulation with lipopolysaccharide (LPS) were treated with CG to evaluate changes in pathways related to analgesia (µ-opioid receptor (MOR), cannabinoid receptor 2 (CB2), peroxisome proliferator-activated receptor alpha, inflammation [interleukin (IL)-10, IL-1b, and IL-8] and barrier function [mucin 2-5AC, claudin-2, zonula occludens (ZO)-1, ZO-2] using the real-time PCR method. Molecular modelling of CG, LPS, lipoteichoic acid (LTA), and phospholipomannan (PLM) was developed, and the ability of CG to chelate microbial pathogenic lipids was evaluated by docking and molecular dynamics simulations. Data were expressed as the mean ± SEM. RESULTS: Daily CG orally-administered to rats or mice was well tolerated without including diarrhea, visceral hypersensitivity, or inflammation, as evaluated at histological and molecular levels. In a model of CRD, CG at a dosage of 3 g/d HED significantly decreased visceral pain perception by 14% after 2 wk of administration (P < 0.01) and reduced inflammation intensity by 50%, resulting in complete regeneration of the colonic mucosa in mice with DSS-induced colitis. To better reproduce the characteristics of visceral pain in patients with IBS, we then measured the therapeutic impact of CG in rats with TNBS-induced inflammation to long-lasting visceral hypersensitivity. CG at a dosage of 1.5 g/d HED decreased visceral pain perception by 20% five weeks after colitis induction (P < 0.01). When the CG dosage was increased to 3.0 g/d HED, this analgesic effect surpassed that of the spasmolytic agent phloroglucinol, manifesting more rapidly within 3 wk and leading to a 50% inhibition of pain perception (P < 0.0001). The underlying molecular mechanisms contributing to these analgesic and anti-inflammatory effects of CG involved, at least in part, a significant induction of MOR, CB2 receptor, and IL-10, as well as a significant decrease in pro-inflammatory cytokines IL-1b and IL-8. CG also significantly upregulated barrier-related genes including muc5AC, claudin-2, and ZO-2. Molecular modelling of CG revealed a new property of the molecule as a chelator of microbial pathogenic lipids, sequestering gram-negative LPS and gram-positive LTA bacterial toxins, as well as PLM in fungi at the lowesr energy conformations. CONCLUSION: CG decreased visceral perception and intestinal inflammation through master gene regulation and direct binding of microbial products, suggesting that CG may constitute a new therapeutic strategy for patients with IBS or IBS-like symptoms.

Efficacy and tolerability of chitin-glucan combined with simethicone (GASTRAP® DIRECT) in irritable bowel syndrome: A prospective, open-label, multicenter study.

BACKGROUND: Irritable bowel syndrome (IBS), defined according to the Rome IV diagnostic criteria, is a chronic functional gastrointestinal disorder characterized by recurrent abdominal pain related to altered bowel habits. First-line recommended treatments are limited to combining drugs targeting predominant symptoms, particularly pain (antispasmodics), constipation (laxatives), and diarrhea (loperamide), yielding only a limited therapeutic gain. GASTRAP® DIRECT is a class IIa medical formulation composed of a combination of chitin-glucan and simethicone indicated for the symptomatic treatment of gas-related gastrointestinal disorders by combining different mechanisms of action. AIM: To evaluate the efficacy, tolerability, and safety of 4-week GASTRAP® DIRECT treatment in patients with IBS. METHODS: In this prospective, multicenter, open-label trial, 120 patients with IBS received three sticks of GASTRAP® DIRECT (1.5 g/d of chitin-glucan and 0.75 mg/d of simethicone) per day for 4 weeks. The primary endpoint was the responder rate, defined as the number of patients whose abdominal pain score decreased by ≥ 30% from baseline to week (W) 4. The analysis was performed using the per-protocol set. Cardinal symptoms, impact of global symptoms on daily life, change in stool consistency, and improvement in defecatory disorders were evaluated. RESULTS: Overall, 100 patients were evaluated. At W4, 67% (95%CI: 57-75) showed improvement in abdominal pain (score: 5.8 ± 2.4 vs 2.9 ± 2.0, P < 0.0001). Similar improvements were observed for bloating [8.0 ± 1.7 vs 4.7 ± 2.9, P < 0.0001; 60% (95%CI: 50-70) responders], abdominal distension [7.2 ± 2.1 vs 4.4 ± 3.1, P < 0.0001; 53% (95%CI: 43-63) responders], and impact of global symptoms on daily life [7.1 ± 2.0 vs 4.6 ± 2.9, P < 0.0001; 54% (95%CI: 44-64) responders]. Stool consistency improved in most patients (90% and 57% for patients with liquid and hard stools, respectively). Overall, 42% of patients with defecatory disorders reported very much/considerable improvements by W2. No severe adverse event occurred, and tolerability was rated "good" or "very good" by 93% of patients. CONCLUSION: GASTRAP® DIRECT is safe and well tolerated, alleviating IBS symptoms rapidly in 2 weeks. This open-label study suggests that the combination of chitin-glucan and simethicone could be beneficial in patients with IBS.

Saccharomyces cerevisiae prevents postoperative recurrence of Crohn's disease modeled by ileocecal resection in HLA-B27 transgenic rats.

BACKGROUND: Postoperative recurrence (POR) after ileocecal resection (ICR) affects most Crohn's disease patients within 3-5 years after surgery. Adherent-invasive Escherichia coli (AIEC) typified by the LF82 strain are pathobionts that are frequently detected in POR of Crohn's disease and have a potential role in the early stages of the disease pathogenesis. Saccharomyces cerevisiae CNCM I-3856 is a probiotic yeast reported to inhibit AIEC adhesion to intestinal epithelial cells and to favor their elimination from the gut. AIM: To evaluate the efficacy of CNCM I-3856 in preventing POR induced by LF82 in an HLA-B27 transgenic (TgB27) rat model. METHODS: Sixty-four rats [strain F344, 38 TgB27, 26 control non-Tg (nTg)] underwent an ICR at the 12th wk (W12) of life and were sacrificed at the 18th wk (W18) of life. TgB27 rats were challenged daily with oral administration of LF82 (109 colony forming units (CFUs)/day (d), n = 8), PBS (n = 5), CNCM I-3856 (109 CFUs/d, n = 7) or a combination of LF82 and CNCM I-3856 (n = 18). nTg rats receiving LF82 (n = 5), PBS (n = 5), CNCM I-3856 (n = 7) or CNCM I-3856 and LF82 (n = 9) under the same conditions were used as controls. POR was analyzed using macroscopic (from 0 to 4) and histologic (from 0 to 6) scores. Luminal LF82 quantifications were performed weekly for each animal. Adherent LF82 and inflammatory/regulatory cytokines were quantified in biopsies at W12 and W18. Data are expressed as the median with the interquartile range. RESULTS: nTg animals did not develop POR. A total of 7/8 (87%) of the TgB27 rats receiving LF82 alone had POR (macroscopic score ≥ 2), which was significantly prevented by CNCM I-3856 administration [6/18 (33%) TgB27 rats, P = 0.01]. Macroscopic lesions were located 2 cm above the anastomosis in the TgB27 rats receiving LF82 alone and consisted of ulcerations with a score of 3.5 (2 - 4). Seven out of 18 TgB27 rats (39%) receiving CNCM I-3856 and LF82 had no macroscopic lesions. Compared to untreated TgB27 animals receiving LF82 alone, coadministration of CNCM I-3856 and LF82 significantly reduced the macroscopic [3.5 (2 - 4) vs 1 (0 - 3), P = 0.002] and histological lesions by more than 50% [4.5 (3.3 - 5.8) vs 2 (1.3 - 3), P = 0.003]. The levels of adherent LF82 were correlated with anastomotic macroscopic scores in TgB27 rats (r = 0.49, P = 0.006), with a higher risk of POR in animals having high levels of luminal LF82 (71.4% vs 25%, P = 0.02). Administration of CNCM I-3856 significantly reduced the levels of luminal and adherent LF82, increased the production of interleukin (IL)-10 and decreased the production of IL-23 and IL-17 in TgB27 rats. CONCLUSION: In a reliable model of POR induced by LF82 in TgB27 rats, CNCM I-3856 prevents macroscopic POR by decreasing LF82 infection and gut inflammation.