Concept: Large intestine
To explore whether patients with a defective ileocecal valve (ICV)/cecal distension reflex have small intestinal bacterial overgrowth.
Intussusception is uncommon in adults. To our knowledge, synchronous colocolic intussusceptions have never been reported in the literature. Here we described the case of a 59-year-old female of synchronous colocolic intussusceptions presenting as acute abdomen that was diagnosed by CT preoperatively. Laparotomy with radical right hemicolectomy and sigmoidectomy was undertaken without reduction of the invagination due to a significant risk of associated malignancy. The final diagnosis was synchronous adenocarcinoma of proximal transverse colon and sigmoid colon without lymph nodes or distant metastasis. The patient had an uneventful recovery. The case also emphasizes the importance of thorough exploration during surgery for bowel invagination since synchronous events may occur.
Extracellular ATP is released from live cells in controlled conditions, as well as dying cells in inflammatory conditions, and, thereby, regulates T cell responses, including Th17 cell induction. The level of extracellular ATP is closely regulated by ATP hydrolyzing enzymes, such as ecto-nucleoside triphosphate diphosphohydrolases (ENTPDases). ENTPDase1/CD39, which is expressed in immune cells, was shown to regulate immune responses by downregulating the ATP level. In this study, we analyzed the immunomodulatory function of ENTPDase7, which is preferentially expressed in epithelial cells in the small intestine. The targeted deletion of Entpd7 encoding ENTPDase7 in mice resulted in increased ATP levels in the small intestinal lumen. The number of Th17 cells was selectively increased in the small intestinal lamina propria in Entpd7(-/-) mice. Th17 cells were decreased by oral administration of antibiotics or the ATP antagonist in Entpd7(-/-) mice, indicating that commensal microbiota-dependent ATP release mediates the enhanced Th17 cell development in the small intestinal lamina propria of Entpd7(-/-) mice. In accordance with the increased number of small intestinal Th17 cells, Entpd7(-/-) mice were resistant to oral infection with Citrobacter rodentium. Entpd7(-/-) mice suffered from severe experimental autoimmune encephalomyelitis, which was associated with increased numbers of CD4(+) T cells producing both IL-17 and IFN-γ. Taken together, these findings demonstrate that ENTPDase7 controls the luminal ATP level and, thereby, regulates Th17 cell development in the small intestine.
Angiosarcoma is a rare disease with a poor prognosis; significantly, patients with intestinal angiosarcomas who survive over 1 year after diagnosis are extraordinarily rare. This article describes the case of a 33-year-old gentleman who presented with abdominal pain of 4 months duration, which had increased in severity 2 weeks prior to presentation. After a complicated diagnostic and therapeutic process, the diagnosis of primary angiosarcoma of the small intestine with metastasis to the liver was made by pathological and immunohistochemical examinations. We reviewed previous cases of angiosarcoma described in the English literature to determine their risk factors, diagnosis and treatment, and we found that angiosarcoma is extremely rare, especially in the small intestine. To the best of our knowledge, this may be the youngest case of primary angiosarcoma of the small intestine with metastasis to the liver reported in the English literature.
Ulcerative colitis (UC) is a chronic relapsing-remitting form of inflammatory bowel disease (IBD) that increases the risk of colorectal cancer, the third most common malignancy in humans. Oxidative stress is a risk factor for the development of UC. The Keap1-Nrf2-ARE pathway is one of the most important defensive mechanisms against oxidative and/or electrophilic stresses. In this study, we identified CPUY192018 as a potent small-molecule inhibitor of the Keap1-Nrf2 PPI, investigated the cyto-protective effects of CPUY192018 on the NCM460 colonic cells and evaluated whether treatment with the inhibitor of the Keap1-Nrf2 PPI exerts protection on an established experimental model of UC induced by dextran sodium sulfate (DSS). Our study clearly demonstrated that CPUY192018 had a cytoprotective effect against DSS in both NCM460 cells and mouse colon via the activation of Nrf2 signaling. These results suggested that activation of Nrf2 by directly inhibiting the Keap1-Nrf2 PPI may be beneficial as a treatment for UC.
The appendix may modulate colon microbiota and bowel inflammation. We investigated whether appendectomy alters colorectal cancer risk.
The increased risks conferred by inflammatory bowel disease (IBD) to the development of colorectal cancer (CRC) gave rise to the term “colitis-associated cancer” and the concept that inflammation promotes colon tumorigenesis. A condition more common than IBD is low-grade inflammation, which correlates with altered gut microbiota composition and metabolic syndrome, both present in many cases of CRC. Recent findings suggest that low-grade inflammation in the intestine is promoted by consumption of dietary emulsifiers, a ubiquitous component of processed foods which alter the composition of gut microbiota. Here, we demonstrate in a pre-clinical model of colitis-induced CRC that regular consumption of dietary emulsifiers carboxymethylcellulose or polysorbate-80 exacerbated tumor development. Enhanced tumor development was associated with an altered microbiota metagenome characterized by elevated levels of lipopolysaccharide and flagellin. We found that emulsifier-induced alterations in the microbiome were necessary and sufficient to drive alterations in major proliferation and apoptosis signaling pathways thought to govern tumor development. Overall, our findings support the concept that perturbations in host-microbiota interactions that cause low-grade gut inflammation can promote colon carcinogenesis.
Recent studies suggest small intestine bacterial overgrowth (SIBO) is common among developing world children. SIBO’s pathogenesis and effect in the developing world are unclear. Our objective was to determine the prevalence of SIBO in Bangladeshi children and its association with malnutrition. Secondary objectives included determination of SIBO’s association with sanitation, diarrheal disease, and environmental enteropathy. We performed a cross-sectional analysis of 90 Bangladeshi 2-year-olds monitored since birth from an impoverished neighborhood. SIBO was diagnosed via glucose hydrogen breath testing, with a cutoff of a 12-ppm increase over baseline used for SIBO positivity. Multivariable logistic regression was performed to investigate SIBO predictors. Differences in concomitant inflammation and permeability between SIBO-positive and -negative children were compared with multiple comparison adjustment. A total of 16.7% (15/90) of the children had SIBO. The strongest predictors of SIBO were decreased length-for-age Z score since birth (odds ratio [OR], 0.13; 95% confidence interval [CI], 0.03 to 0.60) and an open sewer outside the home (OR, 4.78; 95% CI, 1.06 to 21.62). Recent or frequent diarrheal disease did not predict SIBO. The markers of intestinal inflammation fecal Reg 1β (116.8 versus 65.6 µg/ml; P = 0.02) and fecal calprotectin (1,834.6 versus 766.7 µg/g; P = 0.004) were elevated in SIBO-positive children. Measures of intestinal permeability and systemic inflammation did not differ between the groups. These findings suggest linear growth faltering and poor sanitation are associated with SIBO independently of recent or frequent diarrheal disease. SIBO is associated with intestinal inflammation but not increased permeability or systemic inflammation.
In 2009, an estimated 565,000 Americans had Crohn’s disease (1), an inflammatory bowel disorder that can affect any part of the gastrointestinal tract. Symptoms include persistent diarrhea, abdominal cramps and pain, constipation leading to bowel obstruction, and rectal bleeding.* Symptoms sometimes intensify in severity and require hospitalization and surgeries of the small intestine, colon, or rectum (2). Hospital discharge data from the National Inpatient Sample (NIS) of the Healthcare Cost and Utilization Project (HCUP) were used to estimate U.S. hospitalizations(†) for Crohn’s disease as both the first-listed and any-listed(§) discharge diagnosis and common surgical procedures during hospitalizations with Crohn’s disease as first-listed diagnosis from 2003 to 2013, the most recent decade of data. Despite new therapies that were expected to improve remission and reduce hospitalizations, estimated numbers (and age-adjusted rates per 100,000 U.S. population) of hospitalizations for Crohn’s disease as the first-listed diagnosis did not change significantly from 2003 to 2013. The proportion of these hospitalizations during which small bowel resection was performed decreased from 4.9% in 2003 to 3.9% in 2013 (p<0.05); however, colorectal resection and fistula repair rates remained stable. Hospital stays for any-listed Crohn's disease increased from >120,000 (44.2 per 100,000) in 2003 to >196,000 (59.7 per 100,000) in 2013 (p<0.05). Patient education initiatives should focus on increasing awareness of exacerbating factors and medication compliance to prevent hospitalizations.
In view of the wide-spread deficiency of iron and zinc in populations dependent on plant foods, it is desirable to improve the bioavailability of the same. Specific dietary spices may alter the ultrastructure and permeability characteristics of intestines. Groups of Wistar rats were fed piperine, capsaicin and ginger containing diets for 8 weeks in order to examine their possible influence on intestinal absorption of iron, zinc and calcium. Everted segments of duodenum, jejunum and ileum portions of small intestines isolated from these rats were examined for ex vivo uptake of iron, zinc and calcium from incubations containing digesta of finger millet. Higher uptake of iron, zinc and calcium by the intestinal segments from spice-fed animals was observed. The increase in the mineral uptake was the highest for calcium with >100% in some cases. The positive influence of dietary capsaicin was more pronounced on zinc uptake as compared to that of iron. Uptake of the glutamic acid standard was 87% and 62% higher in the case of jejunal segments of rats fed piperine and ginger. The higher intestinal uptake of iron and zinc as a result of consumption of pungent spices could encourage a strategy to reduce deficiency of these trace elements prevalent in population dependent on plant based foods.