Evidence-based clinical practice guidelines for gastroesophageal reflux disease 2021.

In Japan, with the increasing prevalence of gastroesophageal reflux disease (GERD) and growing public interest, the Japanese Society of Gastroenterology issued Evidence-based Clinical Practice Guidelines for GERD (1st edition) in 2009 and a revised 2nd edition in 2015. A number of studies on GERD were subsequently conducted in Japan and abroad, and vonoprazan, a potassium-competitive acid blocker (P-CAB), became available for the first time in Japan in February 2015. The revised 3rd edition (Japanese edition), which incorporates new findings and information, was published in April 2021. These guidelines are summarized herein, particularly sections related to the treatment of GERD. The important clinical issues addressed in the present revision are (i) the introduction of treatment algorithms that classify GERD into reflux esophagitis and non-erosive reflux disease, (ii) the clarification of treatment algorithms based on to the severity of reflux esophagitis, and (iii) the positioning of vonoprazan in the treatment for GERD. The present guidelines propose vonoprazan as the initial/maintenance treatment for severe reflux esophagitis. They also recommend vonoprazan or PPI as an initial treatment for mild reflux esophagitis and recommended PPI and proposed vonoprazan as maintenance treatment. These updated guidelines offer the best clinical strategies for GERD patients in Japan and hope that they will be of global use for the diagnosis and treatment for GERD.

Impact of discontinuing non-steroidal antiinflammatory drugs on long-term recurrence in colonic diverticular bleeding.

AIM: To determine the effect of discontinuing non-steroidal antiinflammatory drugs (NSAIDs) on recurrence in long-term follow-up patients with colonic diverticular bleeding (CDB). METHODS: A cohort of 132 patients hospitalized for CDB examined by colonoscopy was prospectively enrolled. Comorbidities, lifestyle, and medications (NSAIDs, low-dose aspirin, antiplatelet agents, anticoagulants, acetaminophen, and corticosteroids) were assessed. After discharge, patients were requested to visit the hospital on scheduled days during the follow-up period. The Kaplan-Meier method was used to estimate recurrence. RESULTS: Median follow-up was 15 mo. The probability of recurrence at 1, 6, 12, and 24 mo was 3.1%, 19%, 27%, and 38%, respectively. Of the 41 NSAID users on admission, 26 (63%) discontinued NSAID use at discharge. Many of the patients who could discontinue NSAIDs were intermittent users, and could be switched to alternative therapies, such as acetaminophen or an antiinflammatory analgesic plaster. The probability of recurrence at 12 mo was 9.4% in discontinuing NSAID users compared with 77% in continuing users (P<0.01, log-rank test). The hazard ratio for recurrence in the discontinuing NSAIDs users was 0.06 after adjusting for age>70 years, right-sided diverticula, history of hypertension, and hemodialysis. No patients developed cerebrocardiovascular events during follow-up. CONCLUSION: There is a substantial recurrence rate after discharge among patients hospitalized for diverticular bleeding. Discontinuation of NSAIDs is an effective preventive measure against recurrence. This study provides new information on risk reduction strategies for diverticular bleeding.

High-dose barium impaction therapy for the recurrence of colonic diverticular bleeding: a randomized controlled trial.

OBJECTIVE: We compared the clinical efficacy of barium therapy and conservative therapy in preventing recurrence in patients with diverticular bleeding. BACKGROUND: Previous case reports have indicated that barium impaction therapy provides initial hemostasis for diverticular bleeding and prevention against rebleeding. METHODS: After spontaneous cessation of bleeding, patients were randomly assigned to conservative treatment (n = 27) or high-dose barium impaction therapy (n = 27). Patients were followed up for 1 year after enrollment of the last patient. The main outcome measure was rebleeding. RESULTS: Median follow-up period was 584.5 days. The probability of rebleeding at 30-day, 180-day, 1-year, and 2-year follow-up in all patients was 3.7%, 14.8%, 28.4%, and 32.7%, respectively. By group, probability at 1 year was 42.5% in the conservative group and 14.8% in the barium group (log-rank test, P = 0.04). After adjustment for a history of hypertension, the hazard ratio of rebleeding in the barium group was 0.34 (95% confidence interval, 0.12-0.98). No complications or laboratory abnormalities due to barium therapy were observed. Compared with the conservative group, the barium group had significantly (P < 0.05) fewer hospitalizations per patient (1.7 vs 1.2), units of blood transfused (1.9 vs 0.7), colonoscopies (1.4 times vs 1.1 times), and hospital stay days (15 days vs 11 days) during the follow-up period. No patients died and none required angiographic or surgical procedures in either group. CONCLUSIONS: High-dose barium impaction therapy was effective in the long-term prevention of recurrent bleeding, and reduced the frequency of rehospitalization and need for blood transfusion and colonoscopic examination. ClinicalTrials.gov Identifier, UMIN 000002832.

Colonoscopy can miss diverticula of the left colon identified by barium enema.

AIM: To identify the diagnostic value of colonoscopy for diverticulosis as determined by barium enema. METHODS: A total of 65 patients with hematochezia who underwent colonoscopy and barium enema were analyzed, and the diagnostic value of colonoscopy for diverticula was assessed. The receiver operating characteristic area under the curve was compared in relation to age (< 70 or ≥ 70 years), sex, and colon location. The number of diverticula was counted, and the detection ratio was calculated. RESULTS: Colonic diverticula were observed in 46 patients with barium enema. Colonoscopy had a sensitivity of 91% and specificity of 90%. No significant differences were found in the receiver operating characteristic area under the curve (ROC-AUC) for age group or sex. The ROC-AUC of the left colon was significantly lower than that of the right colon (0.81 vs 0.96, P = 0.02). Colonoscopy identified 486 colonic diverticula, while barium enema identified 1186. The detection ratio for the entire colon was therefore 0.41 (486/1186). The detection ratio in the left colon (0.32, 189/588) was significantly lower than that of the right colon (0.50, 297/598) (P < 0.01). CONCLUSION: Compared with barium enema, only half the number of colonic diverticula can be detected by colonoscopy in the entire colon and even less in the left colon.

Inhibitory effect of 1α-hydroxyvitamin D3 on N-nitrosobis(2-oxopropyl)amine-induced cholangiocarcinogenesis in Syrian hamsters.

Sixty-three male 5-week-old Syrian hamsters received the carcinogen N-nitrosobis(2-oxopropyl)amine (BOP) s.c. in 5 weekly injections (the first, 70 mg/kg body, and the remaining, 20mg/kg each). The hamsters that received BOP were given intragastric administration of 0.2 ml of medium chain triglyceride (MCT) with or without 0.04 µg of 1α-hydroxyvitamin D3 [1α(OH)D3] through a feeding tube for 12 weeks. Thus, 3 groups were assigned:Group 1;BOP alone (n＝20), Group 2;BOP＋MCT (n＝18) and Group 3;BOP＋1α(OH)D3 (n＝25). The mean body weight of Group 3 was lower than those of Groups 1 and 2 at the end of the experiment (p＜0.001,Tukey-Kramer HSD test). At the end of week 12, all surviving hamsters were put to sleep. The incidences of liver tumors were 80%, 72% and 32% in Groups 1, 2 and 3, respectively. The incidence of tumors in Group 3 was significantly lower than in Group 1 and Group 2 (p＜0.05, χ2-test). All tumors were cholangiocarcinoma. These results indicated that BOP-induced cholangiocarcinogenesis was suppressed by the supplemental administration of 1α(OH)D3.

The effect of leg hyperthermia using far infrared rays in bedridden subjects with type 2 diabetes mellitus.

We examined the effect of leg hyperthermia on oxidative stress in bedridden subjects with type 2 diabetes mellitus using 15-min sessions of far infrared rays over a two-week period. Four subjects (male 1, female 3) incapacitated by a stroke were recruited for this study. All patients were admitted to Takahashi Central Hospital and ate the same hospital meals. Fasting plasma glucose, HbA1c, tumor necrosis factor (TNF)alpha, free fatty acid, leptin, adiponectin and plasma 8-epi-prostaglandin F2alpha (8-epi-PGF2alpha) levels as a marker of oxidative stress were measured on admission, just before and 2 weeks after local heating of the leg. Results showed that plasma total 8-epi-PGF2alpha levels were decreased significantly while TNFalpha levels were increased significantly. On the other hand, glucose, HbA1c, free fatty acid, leptin and adiponectin levels were not changed during the study period. These results suggest that repeated leg hyperthermia may protect against oxidative stress.

Heat-shock-induced three-dimensional-like proliferation of mouse fibroblasts mediated by hydroxyapatite.

The aim of the present study was to determine both the minimal and the optimal conditions under which heat treatment is effective for enhancing 3D (three-dimensional)-like cell proliferation. C3H10T1/2 mouse fibroblasts were cultured with hydroxyapatite granules for 10 weeks after heat treatment at 40, 41.5, 43, 44 or 45 degrees C for 2, 10, 15, 20, 30, 45, 60, 90, 180 and 360 min. Then minimal and optimal conditions of temperature and duration of heat treatment for induction of 3D-like proliferation of cells were determined. The minimal conditions of heat treatment to induce 3D-like proliferation were 43 degrees C for 2 min and the optimal conditions were 43 degrees C for 10 min. The mean rates of formation of 3D-like proliferation patterns by cells heat-treated at 43 degrees C for 2 and 10 min were significantly higher (1.7- and 3.7-fold respectively) than that by untreated cells (P<0.05). We also observed significantly greater effects of heat treatment on 3D-like proliferation at 40 degrees C for 90 or 180 min and at 41.5 degrees C for 15 min and 44 degrees C for 10 min. We found that apoptosis had occurred in 7.5 and 87.0% of the cells at 1 week after heat treatment at 43 degrees C for 10 min and 30 min respectively. Western-blot analysis demonstrated that phosphorylation of p38 MAPK (mitogen-activated protein kinase) was markedly increased by heat treatment at 43 degrees C for 10 min. These findings suggest that activation of p38 MAPK by heat shock is associated with 3D-like cell proliferation. The results of the present study should be useful for further studies aimed at elucidation of the physiological mechanisms underlying thermotherapy and hyperthermia.