Prognostic implications of mucinous histology in stage III colon cancer with the receipt of adjuvant chemotherapy.

BACKGROUND: There is still a debate about the survival benefit of chemotherapy in stage III mucinous colon cancer, we then conduct a comprehensive assessment of the efficacy of adjuvant chemotherapy in this population. METHODS: The data used in the current study were extracted from the Surveillance, Epidemiology and End Results (SEER) database. Chi-squared (χ2) test was used to compared patient characteristics according to the histology. The outcome of the survival analysis used in the current study was cancer-specific survival (CSS). Univariable and multivariable analyses were carried out using the Cox proportional hazards regression models to evaluate the prognostic characteristics associated with CSS of colon cancer. And the risks of mortality were presented as hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: A total of 68,976 patients diagnosed with stage III colon cancer were included in our analyses, including mucinous adenocarcinoma (MAC, N=6,592) and non-mucinous adenocarcinoma (NMA, N=62,384). In NMA, the receipt of chemotherapy had 46.0% independently decreased risk of colon cancer-specific mortality compared to non-chemotherapy group (HR =0.540, 95% CI: 0.523-0.558, P<0.001). In MAC, the receipt of chemotherapy had 37.7% independently decreased risk of colon cancer-specific mortality compared to non-chemotherapy group (HR =0.623, 95% CI: 0.566-0.685, P<0.001). CONCLUSIONS: MAC was associated with worse prognosis and was less responsive to chemotherapy compared with NMA in stage III colon cancer. However, stage III mucinous colon cancer still need to be treated with chemotherapy because of the significant survival benefit and specialized treatment plans for MAC were quite necessary in the future.

Acquired segmental sigmoid hypoganglionosis: A case report.

RATIONALE: Intestinal hypoganglionosis most commonly presents in infancy or childhood, with only a few cases reported in adults. Those are mainly diagnosed after elective surgery for long-standing constipation and megacolon. PATIENT CONCERNS: We report a case of a 48-year-old female from China who presented with symptoms of discontinuation of bowel movements for 2 months. A hard, round mass could be felt in her right lower abdomen. DIAGNOSIS: The following examination methods diagnosed acquired segmental sigmoid hypoganglionosis. An abdominal computed tomography revealed a dilatation of the colon and suspicious wall thickening of the sigmoid colon. Anorectal manometry revealed relaxation of the anal sphincter. Histological examination revealed lower numbers and the degeneration of ganglion cells. INTERVENTIONS: Sigmoidectomy and transverse colostomy. OUTCOMES: The patient recovered well from surgery. Three months after the surgery, barium enema revealed a recovery in colorectal dilatation. LESSONS: This case could help raise awareness of acquired segmental hypoganglionosis. Resection of TZ and enterostomy presents an effective remission strategy for patients at risk of anastomotic leakage due to poor intestinal conditions.

Effects of regulating gut microbiota on the serotonin metabolism in the chronic unpredictable mild stress rat model.

OBJECTIVE: This study was to inspect the antidepressant-like effect of prebiotics and probiotics, and to explore the effect of modulating gut microbiota on the serotonin (5-HT) metabolism. METHODS: Fifty rats were separated into control and other four groups randomly. The four groups underwent the chronic unpredictable mild stress (CUMS) intervention with or without prebiotics and probiotics (Bifidobacterium longum, L. rhamnosus) treatment. After weighted, the animals underwent a series of behavioral tests comprising the sucrose preference test (SPT) and the forced swimming test (FST). Central and colonic serotonin levels and relative metabolism factors were measured and analyzed. Microbiota was examined by 16S rRNA gene pyrosequencing. RESULTS: CUMS intervention caused a decrease in body weight, an increase in FST, and a decrease in SPT. Prebiotics and probiotics all ameliorated the CUMS-induced loss of weight and depressive-like behaviors to a certain extent, especially L. rhamnosus. Compared with the group of CUMS intervention, the rats of probiotics and probiotics treatment had a tendency to reduce colonic 5-HT and increase 5-HT in frontal cortex and hippocampus. However, there was no significant difference in peripheral blood 5-HT among these groups. Furthermore, CUMS caused noteworthy gut microbiota variations at the phylum and other levels in rats. Remarkably, there were considerable relations of perturbed gut microbiota with the changed metabolism of 5-HT. CONCLUSION: In conclusion, these findings implied that prebiotics and probiotics have antidepressive effects, and a considerable effect on the regulation of 5-HT metabolism, especially L. rhamnosus.

High-mobility group box-1 inhibition stabilizes intestinal permeability through tight junctions in experimental acute necrotizing pancreatitis.

BACKGROUND: In acute necrotizing pancreatitis (ANP), bacterial translocation (BT) from the gastrointestinal tract is the essential pathogenesis in the development of septic complications. Although high-mobility group box-1 (HMGB1) is associated with BT and organ dysfunction in ANP, the mechanism of HMGB1 in the intestinal barrier dysfunction and BT has not been well addressed. In this study, we intend to address the role of HMGB1 in ANP involving BT and intestinal barrier dysfunction. METHODS: Experimental ANP was achieved in male Sprague-Dawley rats through a retrograde injection of taurocholate into the common biliopancreatic duct following a laparotomy operation. HMGB1 blockade intervention was conducted with a subcutaneous injection of anti-HMGB1 antibody immediately before the laparotomy procedure. Twenty-four hours after ANP induction, pancreatic and intestinal tissues and blood samples were collected for a histopathological assessment and lipid peroxidation or glutathione (GSH) evaluation. AP-induced barrier dysfunction was determined by an intestinal permeability assessment. Tight junction proteins and autophagy regulators were investigated by western blotting, immunohistological analysis and confocal immunofluorescence imaging. RESULTS: ANP developed as indicated by microscopic parenchymal necrosis and fat necrosis, which were associated with intestinal mucosal barrier dysfunction. HMGB1 inhibition played a protective role in intestinal mucosal barrier dysfunction, protected against microbiome changes in ANP, and relieved intestinal oxidative stress. Additionally, HMGB1 inhibition attenuated intestinal permeability; preserved the expression of TJs, such as claudin-2 and occludin; and decreased autophagy. Furthermore, the autophagy regulator LC3 and TJ protein claudin-2 were both upregulated in ANP according to dual immunofluorescence analysis. CONCLUSION: HMGB1 inhibition ameliorated the severity of experimental ANP though beneficial effects on BT, mainly involving in TJ function.

Autophagy Strengthens Intestinal Mucosal Barrier by Attenuating Oxidative Stress in Severe Acute Pancreatitis.

BACKGROUND: Intestinal mucosal barrier dysfunction can be caused by severe acute pancreatitis (SAP). It is normally associated with changes to mucosal autophagy and oxidative stress. OBJECTIVE: The aim of this study was to investigate the correlation between autophagy and oxidative stress on the intestinal mucosal barrier of SAP rat model. METHODS: SAP was induced by retrograde injection of sodium taurocholate (5%) into the biliopancreatic duct. Bacterial translocation (BT) was detected by 16S rDNA sequencing analysis. Morphological alterations in the pancreas and gut were determined by hematoxylin-eosin staining. Oxidative stress status was determined by measuring the level of intestinal malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPx). Western blot, RT-PCR, and immunofluorescent staining were preformed to analyze the expression of tight junction and autophagy proteins. RESULTS: According to the sequencing analysis, rats in SAP group were divided into BT (+) group (n = 9) and BT (-) group (n = 8). Pancreatic and intestinal injuries in SAP group were significantly higher than sham operation group. The content of MDA was clearly elevated, and SOD as well as GPx activities were decreased in BT (+) group as compared with BT (-) group. The expression of LC3II and Beclin1 in BT (-) group was higher than that observed in BT (+). In contrast, BT (+) group had a higher level of claudin-2 and a lower level of zonula occluden-1, occludin, and claudin-1. CONCLUSION: These results suggest that activated autophagy may attenuate intestinal mucosal barrier dysfunction by preventing and reducing the oxidative stress in SAP.

Effect of intestinal epithelial autophagy on bacterial translocation in severe acute pancreatitis.

BACKGROUND AND OBJECTIVE: We examined the impact of autophagy activation on bacterial translocation (BT) and tight junction (TJ) proteins in the intestinal mucosa of patients with severe acute pancreatitis (SAP). METHODS: Thirty-one SAP patients were divided into two groups, BT(+) and BT(-), according to the presence of BT in the blood, as detected by 16S rDNA sequencing. Eight healthy individuals were included in the control group. Serum endotoxin levels were measured by ELISA. Colonic mucosal tissue was obtained by endoscopy, and the TJ proteins and phosphatidylethanolamine-conjugated microtubule-associated protein light chain 3 (LC3-II) were analyzed using immunofluorescence and Western blotting. RESULTS: The expression of LC3II in patients with SAP was higher than that observed in healthy controls. Patients who tested positive for the presence of BT had a higher level of claudins-2 (CL-2) and a lower level of occludin and Zonula occluden-1 (ZO-1) than BT(-) patients. Moreover, the levels of LC3II in BT(-) patients was higher than that found in BT(+) patients, and occludin and ZO-1 were positively correlated with LC3II. CONCLUSIONS: Autophagy activation in the intestinal epithelial cells of patients with SAP and its effects on BT may act through enhancing para-cellular TJs.