[Cowden syndrome in a male patient with metachronous triple cancers and various clinical features:a case report].

A 66-year-old male patient with a thyroid and nasopharyngeal cancer history visited our hospital because of a positive fecal occult blood test. Total colonoscopy detected sessile or subpedunculated polyps in the ascending colon, sigmoid colon, and rectum. These polyps were endoscopically resected, and the rectal polyp was pathologically diagnosed as adenocarcinoma in adenoma and the others as adenomas. Additionally, multiple sessile lesions were revealed in the sigmoid colon and rectum. A complete gastrointestinal tract examination revealed multiple foci of glycogenic acanthosis in the esophagus, multiple sessile lesions in the stomach, multiple sessile lesions, clubbings (rod-shaped lesions), and venous malformations in the small bowel. Mucocutaneous examination indicated hemangiomas on the body trunk, patchy pigmentation on the glans penis, and keratotic papules in the inguinal region. The National Comprehensive Cancer Network diagnostic criteria for Cowden syndrome were used in this case. The patient met four major and two minor criteria;thus, Cowden syndrome was diagnosed. Moreover, the patient was had phosphatase and tensin homolog deleted on chromosome 10 gene mutation. This is the first reported case of metachronal triple cancers in a male patient with Cowden syndrome, and our results indicate the importance of cancer surveillance.

Arginase 2 attenuates ulcerative colitis by antioxidant effects of spermidine.

BACKGROUND: Spermidine suppress oxidative stress and is involved in various disease pathogenesis including ulcerative colitis (UC). Arginase 2 (ARG2) plays a central role in the synthesis of spermidine. This study aimed to clarify the effect of endogenously produced spermidine on colitis. METHODS: The physiological role of ARG2 and spermidine was investigated using Arg2-deficient mice with reduced spermidine. Immunohistochemical staining of the rectum was used to analyze ARG2 expression and spermidine levels in healthy controls and UC patients. RESULTS: In mice with dextran sulfate sodium-induced colitis, ARG2 and spermidine levels were increased in the rectal epithelium. Spermidine protects colonic epithelial cells from oxidative stress and Arg2 knockdown cells reduced antioxidant activity. Organoids cultured from the small intestine and colon of Arg2-deficient mice both were more susceptible to oxidative stress. Colitis was exacerbated in Arg2-deficient mice compared to wild-type mice. Supplementation with spermidine result in comparable severity of colitis in both wild-type and Arg2-deficient mice. In the active phase of UC, rectal ARG2 expression and spermidine accumulation were increased compared to remission. ARG2 and spermidine levels were similar in healthy controls and UC remission patients. CONCLUSIONS: ARG2 produces spermidine endogenously in the intestinal epithelium and has a palliative effect on ulcerative colitis. ARG2 and spermidine are potential novel therapeutic targets for UC.

Use of endoscopic hand-suturing to treat refractory bleeding from a gastric ulcer in a patient with a left ventricular assist device.

We herein describe a 49-year-old man with severe heart failure due to fulminant myocarditis who underwent left ventricular assist device implantation and received clopidogrel and warfarin as antithrombotic agents. The patient developed anemia secondary to chronic bleeding gastric hyperplastic polyps, necessitating endoscopic mucosal resection. Despite attempts to manage post-endoscopic mucosal resection bleeding from a gastric ulcer by endoscopic hemostasis using hemostatic forceps, local hemostatic agents, and polyglycolic acid sheets, the bleeding persisted. Hemostasis of the refractory bleeding was finally achieved by endoscopic hand-suturing of the ulcer. One month later, the ulcer was almost completely scarred. This case has important clinical value in that it demonstrates the efficacy of endoscopic hand-suturing even in challenging cases such as refractory bleeding gastric ulcers in patients with left ventricular assist devices.

Duodenal microbiome in chronic kidney disease.

BACKGROUND: The intestinal microbiome is involved in the pathogenesis of chronic kidney disease (CKD). Despite its importance, the microbiome of the small intestinal mucosa has been little studied due to sampling difficulties, and previous studies have mainly focused on fecal sources for microbiome studies. We aimed to characterize the small intestinal microbiome of CKD patients by studying the microbiome collected from duodenal and fecal samples of CKD patients and healthy controls. METHODS: Overall, 28 stage 5 CKD patients and 21 healthy participants were enrolled. Mucosal samples were collected from the deep duodenum during esophagogastroduodenoscopy and fecal samples were also collected. The 16S ribosomal RNA gene sequencing using Qiime2 was used to investigate and compare the microbial structure and metagenomic function of the duodenal and fecal microbiomes. RESULTS: The duodenal flora of CKD patients had decreased alpha diversity compared with the control group. On the basis of taxonomic composition, Veillonella and Prevotella were significantly reduced in the duodenal flora of CKD patients. The tyrosine and tryptophan metabolic pathways were enhanced in the urea toxin-related metabolic pathways based on the Kyoto Encyclopedia of Genes and Genomes database. CONCLUSION: The small intestinal microbiome in CKD patients is significantly altered, indicating that increased intestinal permeability and production of uremic toxin may occur in the upper small intestine of CKD patients.

Combined endoscopic stenting and laparoscopic stent fixation for benign gastric tube stricture after esophagectomy: a case report.

BACKGROUND: There are several options for the treatment of gastrointestinal stricture, including endoscopic stent placement and bypass surgery. However, a benign stricture is difficult to manage in a reconstructed gastric tube in the thoracic cavity owing to the technical difficulty of bypass surgery, and the possibility of stent migration. CASE PRESENTATION: A 78-year-old woman was admitted to our hospital for treatment for her inability to eat. She had undergone video-assisted subtotal esophagectomy with retromediastinal gastric tube reconstruction 7 years earlier. At the current admission, there was a severely dilated gastric tube in the thoracic cavity with a soft stricture immediately anterior to the spine. Conservative therapy was ineffective; therefore, endoscopic stenting was performed. However, the stent migrated to the upper side of the stricture because the stricture was mild, and the stent was not fixed in the gastric tube. Next, endoscopic stent placement followed by laparoscopic stent fixation was performed. The stent was patent and worked well, and the patient's body weight increased. However, the stent collapsed 2 years later, with recurrence of symptoms. Stent-in-stent placement with an over-the-scope clip was performed, and the second stent was also patent and worked well. CONCLUSIONS: Laparoscopic stent fixation with endoscopic stent placement could be an effective option for patients with a benign stricture in the reconstructed gastric tube.

One-year clinical efficacy and safety of indigo naturalis for active ulcerative colitis: a real-world prospective study.

BACKGROUND/AIMS: Recent studies suggested a favorable effect of indigo naturalis (IN) in inducing remission for refractory ulcerative colitis (UC), however, the maintenance effect of IN for patients with UC remains unknown. Therefore, we conducted a prospective uncontrolled open-label study to analyze the efficacy and safety of IN for patients with UC. METHODS: Patients with moderate to severe active UC (clinical activity index [CAI] ≥ 8) took 2 g/day of IN for 52 weeks. CAI at weeks 0, 4, 8, and 52 and Mayo endoscopic subscore (MES) and Geboes score (GS) at weeks 0, 4, and 52 were assessed. Clinical remission (CAI ≤ 4), mucosal healing (MES ≤ 1), and histological healing (GS ≤ 1) rates at each assessment were evaluated. Overall adverse events (AEs) during study period were also evaluated. The impact of IN on mucosal microbial composition was assessed using 16S ribosomal RNA gene sequences. RESULTS: Thirty-three patients were enrolled. The rates of clinical remission at weeks 4, 8, and 52 were 67%, 76%, and 73%, respectively. The rates of mucosal healing at weeks 4 and 52 were 48% and 70%, respectively. AEs occurred in 17 patients (51.5%) during follow-up. Four patients (12.1%) showed severe AEs, among whom 3 manifested acute colitis. No significant alteration in the mucosal microbial composition was observed with IN treatment. CONCLUSIONS: One-year treatment of moderate to severe UC with IN was effective. IN might be a promising therapeutic option for maintaining remission in UC, although the relatively high rate of AEs should be considered.

The Compositional Structure of the Small Intestinal Microbial Community via Balloon-Assisted Enteroscopy.

INTRODUCTION: An association has been found between human-gut microbiota and various diseases (e.g., metabolic disease) by analyzing fecal or colonic microbiota. Despite the importance of the small intestinal microbiota, sampling difficulties prevent its full analysis. We investigated the composition and metagenomic functions of microbiota along the small intestine and compared them with the microbiota from feces and from other gastrointestinal (GI) sites. METHODS: Mucosal samples from the six GI sites (stomach, duodenum, distal jejunum, proximal ileum, terminal ileum, and rectum) were collected under balloon-assisted enteroscopy. Fecal samples were collected from all participants. The microbial structures and metagenomic functions of the small intestinal mucosal microbiota were compared with those from feces and other GI sites using 16S ribosomal RNA gene sequencing. RESULTS: We analyzed 133 samples from 29 participants. Microbial beta diversity analysis showed that the jejunum and ileum differed significantly from the lower GI tract and the feces (p < 0.001). Jejunal and duodenal microbiotas formed similar clusters. Wide clusters spanning the upper and lower GI tracts were observed with the ileal microbiota, which differed significantly from the jejunal microbiota (p < 0.001). Veillonella and Streptococcus were abundant in the jejunum but less so in the lower GI tract and feces. The metagenomic functions associated with nutrient metabolism differed significantly between the small intestine and the feces. CONCLUSIONS: The fact that the compositional structures of small intestinal microbiota differed from those of fecal and other GI microbiotas reveals that analyzing the small intestinal microbiota is necessary for association studies on metabolic diseases and gut microbiota.

Continuing use of antithrombotic medications for patients with bleeding gastroduodenal ulcer requiring endoscopic hemostasis: a case-control study.

OBJECTIVE: The aim of this study was to compare clinical characteristics and outcomes of bleeding gastroduodenal ulcer between patients taking antithrombotic medications and those not taking antithrombotic medications. METHODS: We performed a case-control study of 346 patients with endoscopically verified bleeding gastroduodenal ulcer, which included 173 cases taking antithrombotic medications throughout peri-bleeding period and 173 age- and sex-matched controls not taking antithrombotic medications. RESULTS: The cases showed less frequent Helicobacter pylori (H. pylori) infections (45.1% versus 60.7%, p = .005), more frequent duodenal location (31.8% versus 19.1%, p = .009), and more frequent rebleeding (13.9% versus 5.8%, p = .02) than the controls. Multivariate analysis revealed that duodenal location (odds ratio [OR] 3.01, 95% confidence interval [CI] 1.37-6.65) and use of antithrombotic medications (OR 2.47, 95% CI 1.13-5.77) were independent factors for rebleeding. However, there were no differences in clinical outcomes, including final successful endoscopic hemostasis, need for surgical intervention, and mortality between cases and controls. Thromboembolic events did not occur in any cases and controls during the periendoscopic period. CONCLUSIONS: Low prevalence of H. pylori infection, frequent duodenal location, and high rebleeding rate are characteristics of patients with bleeding gastroduodenal ulcer under antithrombotic medications. Continuation of antithrombotic medications can be accepted for bleeding gastroduodenal ulcer.

Whipple's disease diagnosed using electron microscopy and polymerase chain reaction.

A 50-year-old man presented with bloody diarrhea and 25-kg weight loss over 3 months. Upper and lower endoscopy showed diffuse shaggy white villi in the duodenum and terminal ileum. In addition, capsule endoscopy and double-balloon enteroscopy revealed shaggy white villi in the entire small intestine. Histological examination of biopsy specimens found the lamina propria of the duodenal and intestinal mucosa to be densely infiltrated by rich foamy macrophages that were periodic acid-Schiff-positive. Electron microscopy showed numerous bacilli in the lamina propria. Tropheryma whipplei DNA was detected in the specimens by polymerase chain reaction. Based on these findings, the patient was diagnosed with Whipple's disease. He was treated with a 2-week course of ceftriaxone followed by trimethoprim-sulfamethoxazole. At the 2-month follow up, diffuse white shaggy villi improved dramatically.

Time trends of the impact of Helicobacter pylori infection and nonsteroidal anti-inflammatory drugs on peptic ulcer bleeding in Japanese patients.

BACKGROUND/AIMS: Helicobacter pylori infection and the use of nonsteroidal anti-inflammatory drugs (NSAIDs) are the main causes of peptic ulcers. The purpose of the present study was to elucidate the time trends of the impact of H. pylori infection and use of NSAIDs and/or antithrombotic agents on peptic ulcer bleeding (PUB) in Japanese patients. METHODS: We retrospectively reviewed 719 patients who had received endoscopic hemostasis for PUB between 2002 and 2013. Subjects were divided into either the first-half group (2002-2007, n = 363) or the second-half group (2008-2013, n = 356). The clinical characteristics of the patients, including the prevalence of H. pylori infection and use of NSAIDs and antithrombotic agents, were compared between the two groups. RESULTS: Compared to the first-half group, patients in the second-half group were characterized by older age (proportion of the patients above 60 years old, 63.9 vs. 76.7%, p = 0.0002), less frequent H. pylori infection (71.6 vs. 57.9%, p < 0.001) and more frequent NSAID intake (39.9 vs. 48.6%, p = 0.02). No significant difference was observed regarding the use of antithrombotic agents between the two groups (18.6 vs. 23.3%, p = 0.13). The prevalence of H. pylori infection and proportion of patients above 60 years old were significantly different between the two groups in a multivariate analysis. CONCLUSION: The main cause of PUB has clearly shifted from H. pylori infection to the use of NSAIDs over the last decade.