Implantation of sigmoid colon cancer into the endoscopic resection site of intramucosal rectal cancer: A case report.

A 70-year-old woman was diagnosed with intramucosal rectal cancer and advanced sigmoid colon cancer at the same time. First, the intramucosal rectal cancer was curatively resected by endoscopic submucosal dissection, and surgery was subsequently performed for sigmoid colon cancer. After 20 months, a follow-up colonoscopy revealed a tumor growth at the ulcer scar of the endoscopic submucosal dissection. Histological findings and KRAS mutation analysis suggested implantation of sigmoid colon cancer to the post-endoscopic submucosal dissection site of intramucosal rectal cancer.

Palliative stenting for malignant colorectal stenosis in the elderly.

Objectives: Self-expandable metal stents are widely used for the treatment of malignant colorectal stenosis (MCS). In elderly individuals with MCS, self-expandable metal stents are often used as a palliative treatment, but prophylactic stent placement is not recommended. We investigated the efficacy and safety of self-expandable metal stents for the elderly in a palliative setting, specifically in a prophylactic setting. Methods: Elderly patients with MCS who received a palliative stent (the stent group) or palliative stoma (the stoma group) were retrospectively enrolled between April 2017 and June 2022, and the prognosis and complication rates were assessed. Additionally, patients in the stent group were divided into symptomatic and asymptomatic subgroups, and prognosis, stent patency, and complication rates were evaluated. Results: During the study period, 31 patients with a mean age of 85.4 years and 12 patients with a mean age of 82.0 years were enrolled in the stent and stoma groups, respectively. While overall survival and complication rates were comparable, the length of hospital stay was significantly shorter in the stent group. Of the 31 patients in the stent group, 16 asymptomatic patients received prophylactic stenting, which was not associated with increased complication rates. Conclusions: Palliative stents for MCS appear to be effective and safe even in the elderly, and thus, prophylactic stents can be considered for asymptomatic patients.

Update on gut microbiota in gastrointestinal diseases.

The human gut is a complex microbial ecosystem comprising approximately 100 trillion microbes collectively known as the "gut microbiota". At a rough estimate, the human gut microbiome contains almost 3.3 million genes, which are about 150 times more than the total human genes present in the human genome. The vast amount of genetic information produces various enzymes and physiologically active substances. Thus, the gut microbiota contributes to the maintenance of host health; however, when healthy microbial composition is perturbed, a condition termed "dysbiosis", the altered gut microbiota can trigger the development of various gastrointestinal diseases. The gut microbiota has consequently become an extremely important research area in gastroenterology. It is also expected that the results of research into the gut microbiota will be applied to the prevention and treatment of human gastrointestinal diseases. A randomized controlled trial conducted by a Dutch research group in 2013 showed the positive effect of fecal microbiota transplantation (FMT) on recurrent Clostridioides difficile infection (CDI). These findings have led to the development of treatments targeting the gut microbiota, such as probiotics and FMT for inflammatory bowel diseases (IBD) and other diseases. This review focuses on the association of the gut microbiota with human gastrointestinal diseases, including CDI, IBD, and irritable bowel syndrome. We also summarize the therapeutic options for targeting the altered gut microbiota, such as probiotics and FMT.

Gurvits syndrome: a case of acute esophageal necrosis associated with diabetic ketoacidosis.

BACKGROUND: Acute esophageal necrosis (AEN), commonly referred to as Gurvits syndrome or "black esophagus", is a rare clinical disease. We present a case of AEN associated with diabetic ketoacidosis (DKA). CASE PRESENTATION: A 66-year-old male came to our hospital with coffee-ground emesis, dyspnea, and general malaise. He was treated for type 2 diabetes mellitus using insulin and had not been taking his medication, including insulin, for several days. Laboratory analysis revealed severe hyperglycemia (730 mg/dL), normocytic anemia (hemoglobin level, 7.7 g/dL; mean corpuscular volume, 100.4 fL), high serum potassium (7.6 mEq/L), and a high level of blood urea (98.7 mg/dL). Ketones and glucose were detected in the urine, and serum ß-hydroxybutyrate was elevated (2132 µmol/L). Arterial blood gas analysis confirmed metabolic acidosis (pH, 7.29; HCO3, 10.5 mmol/L). Collectively, the patient was diagnosed with DKA and upper gastrointestinal bleeding. The patient's condition improved with intravenous fluids, and he received intravenous insulin to treat DKA. According to these findings, the patient was diagnosed with DKA and upper gastrointestinal bleeding. The patient underwent esophagogastroduodenoscopy (EGD) which revealed a circumferential necrosis of the middle and distal esophagus, immediately proximal to the gastroesophageal junction. The patient was then treated with an intravenous proton pump inhibitor. The patient continued to improve with conservative treatment and was subsequently discharged in a stable condition. An EGD repeated 14 days after discharge showed complete healing of the necrotic-like mucosal change without stricture formation of the esophagus. CONCLUSIONS: AEN is rare but potentially life-threatening case of upper gastrointestinal bleeding. Therefore, a clinician should be aware of AEN as a potential cause of upper gastrointestinal bleeding in elderly patients with poorly controlled diabetes and significant comorbidities.

Can control of gut microbiota be a future therapeutic option for inflammatory bowel disease?

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract encompassing two main clinical entities, Crohn's disease and ulcerative colitis. Accumulated evidence indicates that an aberrant immune activation caused by the interplay of genetic susceptibility and environmental impact on the gut microbiota may be involved in the pathogenesis of IBD. Rapid advances in next-generation sequencing technology have enabled a number of studies to identify the alteration of the gut microbiota, termed dysbiosis, in IBD. Moreover, the alteration in the metabolites derived from the gut microbiota in IBD has also been described in many studies. Therefore, microbiota-based interventions such as fecal microbiota transplantation (FMT) have attracted attention as a novel therapeutic option in IBD. However, in clinical trials, the efficacy of FMT for IBD remains controversial. Additional basic and clinical studies are required to validate whether FMT can assume a complementary role in the treatment of IBD. The present review provides a synopsis on dysbiosis in IBD and on the association between the gut microbiota and the pathogenesis of IBD. In addition, we summarize the use of probiotics in IBD and the results of current clinical trials of FMT for IBD.

Targeted deletion of Atg5 in intestinal epithelial cells promotes dextran sodium sulfate-induced colitis.

Autophagy-associated genes have been identified as susceptible loci for inflammatory bowel disease. We investigated the role of a core autophagy factor, Atg5, in the development of dextran sodium sulfate (DSS)-induced colitis. Intestinal epithelial cell (IEC)-specific Atg5 gene deficient mice (Atg5 ΔIEC mice) were generated by cross of Atg5-floxed mice (Atg5 fl/fl ) with transgenic mice expressing Cre-recombinase driven by the villin promotor. Mice were given three cycles of 1.5% DSS in drinking water for 5 days and regular water for 14 days over a 60-day period. The dysfunction of autophagy characterized by a marked accumulation of p62 protein, a substrate for autophagy degradation, was detected in epithelial cells in the non-inflamed and inflamed mucosa of inflammatory bowel disease patients. DSS-colitis was exacerbated in Atg5 ΔIEC mice compared to control Atg5 fl/fl mice. Phosphorylation of inositol-requiring transmembrane kinase/endonuclease1α (IRE1α), a sensor for endoplasmic reticulum stress, and c-Jun N-terminal kinase, a downstream target of IRE1α, were significantly enhanced in IECs in DSS-treated Atg5 ΔIEC mice. Accumulation of phosphorylated IRE1α was enhanced by the treatment with chloroquine, an autophagy inhibitor. Apoptotic IECs were more abundant in DSS-treated Atg5 ΔIEC mice. These findings suggest that Atg5 suppresses endoplasmic reticulum stress-induced apoptosis of IECs via the degradation of excess p-IRE1α.

Analysis of endoscopic brush samples identified mucosa-associated dysbiosis in inflammatory bowel disease.

BACKGROUND: The mucosa-associated gut microbiota directly modulates epithelial and mucosal function. In this study, we investigated the mucosa-associated microbial community in patients with inflammatory bowel disease (IBD), using endoscopic brush samples. METHODS: A total of 174 mucus samples from 43 patients with ulcerative colitis (UC), 26 with Crohn's disease (CD) and 14 non-IBD controls were obtained by gentle brushing of mucosal surfaces using endoscopic cytology brushes. The gut microbiome was analyzed using 16S rRNA gene sequencing. RESULTS: There were no significant differences in microbial structure among different anatomical sites (the ileum, cecum and sigmoid colon) within individuals. There was, however, a significant difference in microbial structure between CD, UC and non-IBD controls. The difference between CD and non-IBD controls was more marked than that between UC patients and non-IBD controls. α-Diversity was significantly lower in UC and CD patients than non-IBD controls. When comparing CD patients with non-IBD controls, the phylum Proteobacteria was significantly increased and the phyla Firmicutes and Bacteroidetes were significantly reduced. These included a significant increase in the genera Escherichia, Ruminococcus (R. gnavus), Cetobacterium, Actinobacillus and Enterococcus, and a significant decrease in the genera Faecalibacterium, Coprococcus, Prevotella and Roseburia. Comparisons between CD and UC patients revealed a greater abundance of the genera Escherichia, Ruminococcus (R. gnavus), Clostridium, Cetobacterium, Peptostreptococcus in CD patients, and the genera Faecalibacterium, Blautia, Bifidobacterium, Roseburia and Citrobacter in UC patients. CONCLUSIONS: Mucosa-associated dysbiosis was identified in IBD patients. CD and UC may be distinguishable from the mucosa-associated microbial community structure.

Nanoparticle curcumin ameliorates experimental colitis via modulation of gut microbiota and induction of regulatory T cells.

BACKGROUND AND AIMS: Curcumin is a hydrophobic polyphenol derived from turmeric, a traditional Indian spice. Curcumin exhibits various biological functions, but its clinical application is limited due to its poor absorbability after oral administration. A newly developed nanoparticle curcumin shows improved absorbability in vivo. In this study, we examined the effects of nanoparticle curcumin (named Theracurmin) on experimental colitis in mice. METHODS: BALB/c mice were fed with 3% dextran sulfate sodium (DSS) in water. Mucosal cytokine expression and lymphocyte subpopulation were analyzed by real-time PCR and flow cytometry, respectively. The profile of the gut microbiota was analyzed by real-time PCR. RESULTS: Treatment with nanoparticle curcumin significantly attenuated body weight loss, disease activity index, histological colitis score and significantly improved mucosal permeability. Immunoblot analysis showed that NF-κB activation in colonic epithelial cells was significantly suppressed by treatment with nanoparticle curcumin. Mucosal mRNA expression of inflammatory mediators was significantly suppressed by treatment with nanoparticle curcumin. Treatment with nanoparticle curcumin increased the abundance of butyrate-producing bacteria and fecal butyrate level. This was accompanied by increased expansion of CD4+ Foxp3+ regulatory T cells and CD103+ CD8α- regulatory dendritic cells in the colonic mucosa. CONCLUSIONS: Treatment with nanoparticle curcumin suppressed the development of DSS-induced colitis potentially via modulation of gut microbial structure. These responses were associated with induction of mucosal immune cells with regulatory properties. Nanoparticle curcumin is one of the promising candidates as a therapeutic option for the treatment of IBD.

Expression of Interleukin-26 is upregulated in inflammatory bowel disease.

AIM: To investigate interleukin (IL)-26 expression in the inflamed mucosa of patients with inflammatory bowel disease (IBD) and the function of IL-26. METHODS: Human colonic subepithelial myofibroblasts (SEMFs) were isolated from colon tissue surgically resected. The expression of IL-26 protein and its receptor complex was analyzed by immunohistochemistry. The gene expression induced by IL-26 was evaluated by real-time polymerase chain reaction. Intracellular signaling pathways were evaluated by immunoblotting and specific small interfering (si) RNA transfection. RESULTS: The mRNA and protein expression of IL-26 were significantly enhanced in the inflamed mucosa of patients with IBD. IL-26 receptor complex was expressed in colonic SEMFs in vivo and in vitro. IL-26 stimulated the mRNA expression of IL-6 and IL-8 in colonic SEMFs. The inhibitors of mitogen-activated protein kinases and phosphoinositide 3-kinase, and siRNAs for signal transducers and activator of transcription 1/3, nuclear factor-kappa B and activator protein-1 significantly reduced the mRNA expression of IL-6 and IL-8 induced by IL-26. CONCLUSION: These results suggest that IL-26 plays a role in the pathophysiology of IBD through induction of inflammatory mediators.