Predictive factors for intractability to endoscopic hemostasis in the treatment of bleeding gastroduodenal peptic ulcers in Japanese patients.

BACKGROUND/AIMS: Despite improvements in endoscopic hemostasis and pharmacological therapies, upper gastrointestinal (UGI) ulcers repeatedly bleed in 10% to 20% of patients, and those without early endoscopic reintervention or definitive surgery might be at a high risk for mortality. This study aimed to identify the risk factors for intractability to initial endoscopic hemostasis. METHODS: We analyzed intractability among 428 patients who underwent emergency endoscopy for bleeding UGI ulcers within 24 hours of arrival at the hospital. RESULTS: Durable hemostasis was achieved in 354 patients by using initial endoscopic procedures. Sixty-nine patients with Forrest types Ia, Ib, IIa, and IIb at the second-look endoscopy were considered intractable to the initial endoscopic hemostasis. Multivariate analysis indicated that age ≥70 years (odds ratio [OR], 2.06; 95% confidence interval [CI], 1.07 to 4.03), shock on admission (OR, 5.26; 95% CI, 2.43 to 11.6), hemoglobin <8.0 mg/dL (OR, 2.80; 95% CI, 1.39 to 5.91), serum albumin <3.3 g/dL (OR, 2.23; 95% CI, 1.07 to 4.89), exposed vessels with a diameter of ≥2 mm on the bottom of ulcers (OR, 4.38; 95% CI, 1.25 to 7.01), and Forrest type Ia and Ib (OR, 2.21; 95% CI, 1.33 to 3.00) predicted intractable endoscopic hemostasis. CONCLUSIONS: Various factors contribute to intractable endoscopic hemostasis. Careful observation after endoscopic hemostasis is important for patients at a high risk for incomplete hemostasis.

G protein-coupled receptor 43 moderates gut inflammation through cytokine regulation from mononuclear cells.

BACKGROUND: Short-chain fatty acids (SCFAs), which are produced by the fermentation of dietary fiber by intestinal microbiota, may positively influence immune responses and protect against gut inflammation. SCFAs bind to G protein-coupled receptor 43 (GPR43). Here, we show that SCFA-GPR43 interactions profoundly affect the gut inflammatory response. METHODS: Colitis was induced by adding dextran sulfate sodium to the drinking water of GPR43 knockout (-/-) and wild-type mice. RESULTS: Dextran sulfate sodium-treated GPR43 mice exhibited weight loss, increased disease activity index (a combined measure of weight loss, rectal bleeding, and stool consistency), decreased hematocrit, and colon shortening, resulting in significantly worse colonic inflammation than in wild-type mice. Tumor necrosis factor alpha and interleukin 17 protein levels in the colonic mucosa of GPR43 mice were significantly higher than in wild-type mice. Treatment of wild-type mice with 150 mM acetate in their drinking water markedly improved these disease indices, with an increase in colon length and decrease in the disease activity index; however, it had no effect on GPR43 mice. Mononuclear cell production of tumor necrosis factor alpha after lipopolysaccharide stimulation was suppressed by acetate. This effect was inhibited by anti-GPR43 antibody. CONCLUSIONS: SCFA-GPR43 interactions modulate colitis by regulating inflammatory cytokine production in mononuclear cells.

Nonsteroidal anti-inflammatory drug-induced visible and invisible small intestinal injury.

Permeation of the small intestinal mucosa is a key mechanism in the induction of enteropathy. We investigated the effect of rebamipide in healthy subjects with diclofenac-induced small intestinal damage and permeability. In this crossover study, each treatment period was 1 week with a 4-week washout period. Diclofenac (75 mg/day) and omeprazole (20 mg/day) plus rebamipide (300 mg/day) or placebo were administered. Capsule endoscopy and a sugar permeability test were performed on days 1 and 7 in each period. Ten healthy subjects were enrolled. Small intestinal injuries were observed on day 7 in 6 of 10 subjects in both groups. Urinary excretion of administered lactulose increased from 0.30% to 0.50% of the initial dose during the first treatment period in the placebo group, and from 0.13% to 0.33% in the rebamipide group. Despite recovery from small-intestinal mucosal damage, the increased permeability in both groups resulted in sustained high levels of lactulose (0.50% to 1.06% in the placebo group and 0.33% to 1.12% in the rebamipide group) through the 4-week washout period. Diclofenac administration induced enteropathy and hyperpermeability of the small intestine. The sustained hyperpermeability during the washout period may indicate the presence of invisible fragility.

Effect of aspirin cessation before endoscopy in Japanese patients with low-dose-aspirin-associated gastroduodenal mucosal injury.

BACKGROUND: The incidence of upper gastrointestinal injury by low-dose aspirin (LDA) has increased. OBJECTIVE: We aimed to clarify the risk factors and prevention strategies associated with LDA-induced gastroduodenal ulcer in Japanese patients. METHODS: A retrospective study involving 284 LDA users who underwent oesophagogastroduodenoscopy between January and December 2010 were included. We investigated the patients' clinical characteristics and endoscopic findings. RESULTS: Of 284 patients, 29 (10.2%) had gastro and/or duodenal ulcers. Male gender, peptic ulcer history, abdominal symptoms, half-dose proton pump inhibitors (PPIs), complete-dose PPIs, and nonsteroidal anti-inflammatory drugs were significantly associated with LDA-induced gastro and/or duodenal ulcers: odds ratio (95% confidence interval) 3.62 (1.06-12.27), 6.60 (1.84-23.62), 3.06 (1.12-8.40), 0.16 (0.03-0.94), 0.07 (0.01-0.61), and 9.68 (1.64-57.18), respectively. PPI significantly reduced gastric ulcers and/or duodenal ulcers (p = 0.03). The modified Lanza score for gastric mucosal lesion in the LDA cessation group was significantly lower than in the LDA noncessation group (0.53 vs. 1.02; p = 0.008). CONCLUSIONS: Half-dose PPIs as well as complete-dose PPIs were effective for preventing LDA-induced gastric and/or duodenal ulcers. The cessation of LDA before endoscopy may lead to an underestimation of LDA-induced gastric injury.

Endoscopic submucosal dissection with sheath-assisted counter traction using a novel sheath for early gastric cancers.

BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) is technically demanding and requires considerable skill. We previously described sheath-assisted counter traction ESD that uses simple materials and methods to improve cutting line visualization. We recently improved counter-traction of the submucosal layer using a novel chemically treated sheath that reduces slippage and maintains traction, and investigated the utility of the novel sheath for ESD. METHODOLOGY: Forty-three and 25 consecutive patients with early gastric carcinomas were treated by standard ESD and traction ESD assisted with novel sheaths, respectively. The mean duration of procedures relative to tumor size and location, as well as complications after ESD between the two groups were compared. RESULTS: The mean duration of ESD procedures for lesions =20mm in diameter was significantly reduced using the novel sheath. The mean duration of procedures for all locations of resected tumors in the stomach was significantly reduced using the novel sheath. However, no perforation and delayed bleeding developed after treatment with the novel sheath. CONCLUSIONS: Sheath-assisted counter traction ESD by the novel sheath was technically simpler and thus less time-consuming regardless of the location of lesions, especially when =20mm in diameter. The traction ESD with the novel sheath is safe and not invasive, and it can be universally applied to standard ESD.

Long-term survival and improved quality of life after chemoradiotherapy to treat esophageal small cell carcinoma: a report of two cases.

In case 1, endoscopy revealed a submucosal tumor with central ulceration in the esophagus of a 54- year-old man. A biopsy specimen revealed small cell carcinoma without metastasis and the stage of the cancer was stage I (T2N0M0). Two cycles of concurrent cisplatin, etoposide and radiotherapy resulted in an incomplete response/stable disease. The tumor recurred and had metastasized to the brain, lung, liver, lymph nodes of the mediastinum, abdomen and bones after six cycles. Two cycles of irinotecan and cisplatin then elicited a complete response in the primary esophageal lesion. However, progressive disease was identified in the metastatic bone tumors. Despite two further cycles of therapy, he died 447 days after the initial course. In case 2, a biopsy specimen of a tumor with central ulceration in the esophagus of a 77-year old man with swallowing difficulty indicated small cell carcinoma. The stage of the cancer was diagnosed as stage II (T3N0M0). Two cycles of irinotecan, cisplatin and concurrent radiotherapy elicited a complete response. However, the tumor metastasized to the brain and the liver 644 days after starting treatment. Two cycles of carboplastin plus irinotecan elicited a partial response in the metastatic tumors, but he died 988 days after starting chemotherapy.

Usefulness of a slow nutrient drinking test for evaluating gastric perception and accommodation.

BACKGROUND/AIM: An implication of the drinking test for gastric function is controversial. We evaluated the usefulness of a nutrient drinking test for examining gastric function by comparing it with a gastric barostat study. METHODS: We investigated perceived pressure of an intragastric bag with stepwise distension and postprandial peak gastric volume (accommodation volume) with a consistent pressure after drinking a liquid meal (200 ml, 300 kcal) in 18 volunteers. Drinking a similar liquid meal on a different day at a continual rate of 15 ml/min was performed to score satiety and bloated sensations at 5-min intervals. An additional 10 volunteers performed the drinking test before and after administration of mosapride citrate or a placebo in a double-blind crossover study. RESULTS: Pressure to induce severe discomfort correlated positively with maximum satiety volume in the drinking test (r = 0.60, p = 0.02). Accommodation volume in the barostat study showed a significant correlation (r = 0.59, p = 0.03) with threshold volume to induce bloating in the drinking test. Mosapride tended to increase the volume inducing the first bloated sensation as compared to the placebo. CONCLUSION: The present drinking test may be useful for evaluating the threshold to induce severe discomfort and accommodation volume.

Endoscopic submucosal dissection with sheath-assisted counter traction for early gastric cancers.

AIM: Endoscopic submucosal dissection (ESD) is associated with frequent complications, such as bleeding and perforation. The procedure is technically difficult, requires considerable skill and is longer than conventional endoscopic mucosal resection (EMR). Thus, non-invasive tools and methods are needed to facilitate direct visualization of the submucosal layer during ESD. METHODS: An insulation-tipped (IT) knife was inserted into one channel, and a conventional injection sheath was inserted to the other channel of a double-channel fiberscope. The submucosal layer was lifted via a circumferential incision using the conventional injection sheath for visualizing cutting lines, and the submucosal layer under the lesion was directly dissected from the underlying muscularis propria. RESULTS: Sheath-assisted traction resulted in successful ESD with en bloc resection in all 25 patients. Hemostasis and manipulation of blood vessels were uncomplicated and dissection was completed safely, without either bleeding or perforation. The movement of the sheath was not suppressed while lifting the submucosal layer and the IT knife could be moved freely, which allowed submucosal dissection independently of the sheath movement. CONCLUSION: Sheath-assisted traction ESD, using simple materials and methods, has several advantages over other standard traction methods. Our procedure is straightforward, safe, non-invasive, cost-effective and uses readily available instruments to enhance visualization of cutting lines.

Intussusception in a child caused by capillary hemangioma of the colon.

Intussusception is one of the most common abdominal emergencies in children, but identifying the cause is very difficult. Hemangioma is a common tumor of the head and neck area in children, but it rarely arises in the gastrointestinal tract. This report describes a rare occurrence of intussusception caused by capillary hemangioma of the colon that was identified by ultrasonography (US), computed tomography (CT), and colonoscopy. A male child aged 2 years and 10 months developed painful abdominal cramps and hematochezia. Abdominal US and CT revealed both target and pseudo-kidney signs in the colon, indicating colonic intussusception. An initial diagnostic and therapeutic laparotomy did not reveal any abnormalities. Seven days later, severe abdominal pain recurred. A barium enema revealed the shadow of a 25-mm mass at the hepatic flexure of the colon. Colonoscopic findings revealed a submucosal tumor in the descending colon that was moved to the cecum by compressed air introduced through the colonoscope. We considered that the mass in the cecum had caused the intussusception. The tumor was removed at a second laparotomy, and microscopic pathological examination revealed that it was a capillary hemangioma.

Successful treatment for pouchitis with rebamipide refractory to a combination of metronidazole (MNZ) and ciprofloxacin (CFX).

A 35-year-old male who had undergone proctocolectomy and ileo-anal pouch surgery (IPAA) because of ulcerative colitis presented with worsening diarrhea and hematochezia. Pouchitis was diagnosed, and he was prescribed with metronidazole (MNZ) and a betamethasone enema. However, his condition did not remarkably improve despite these strategies. Endoscopy revealed ulceration and inflammation in the ileal pouch together with contact bleeding and mucous discharge. He underwent granulocytapheresis (G-CAP) and was prescribed anal 5-aminosalicylic acid (5-ASA) and oral prednisolone. Oral azathioprine (AZA) and a combination of MNZ and ciprofloxacin (CFX) did not result in any improvement. He was then treated with rebamipide enemas twice daily for 8 weeks without additional drug therapy. Two weeks thereafter, stool frequency started to decrease, fecal hemoglobin became negative, and his symptoms gradually improved. Endoscopic findings after the rebamipide therapy showed that the ulcers in the ileal pouch had mostly healed without obvious inflammation and bleeding. Rebamipide was thus maintained throughout the therapeutic period and for 13 months of follow-up. Rebamipide effectively treated severe pouchitis that was refractory to intensive conventional medication including antibiotics and corticosteroids.