Vonoprazan versus lansoprazole in the treatment of artificial gastric ulcers after endoscopic submucossal dissection: a randomized, open-label trial.

BACKGROUND: Vonoprazan is more potent and longer acting than traditional proton pump inhibitor. Although vonoprazan is expected to be superior to proton pump inhibitor, its efficacy in the treatment of gastric ulcers following endoscopic submucosal dissection (ESD) is not fully understood. The aim of this study was to evaluate the effectiveness of vonoprazan in artificial ulcer healing following ESD. METHODS: Patients with gastric tumors were randomly assigned to the vonoprazan group (group V) or lansoprazole group (group L) after ESD. Patients received intravenous lansoprazole (30 mg) twice on the day of ESD. Thereafter, patients were treated with vonoprazan (20 mg/day) in group V or lansoprazole (30 mg/day) in group L. Esophagogastroduodenoscopy was performed 4 and 8 weeks after the ESD. RESULTS: A total of 168 patients were analyzed. The 4-week healing rate for artificial ulcer was not significantly higher in group V versus group L (17/85, 20.0% vs. 14/83, 16.9%, respectively). In addition, there were no significant differences between the 4-week shrinkage rates between the two groups. Postoperative bleeding occurred in none of the patients in group V and three in group L. One patient in group V presented delayed perforation 2 days after ESD. CONCLUSIONS: Vonoprazan might not be superior to lansoprazole in the healing of artificial gastric ulcer after ESD. TRIAL REGISTRATION: University hospital Medical Information Network (registration number: UMIN000016642), Registered 27 February 2015, https://www.umin.ac.jp/ctr/index-j.htm.

A Japanese Patient with Gastric Cancer and Dihydropyrimidine Dehydrogenase Deficiency Presenting with DPYD Variants.

A 63-year-old Japanese male with stomach adenocarcinoma received oral 5-fluorouracil derivative, cisplatin and trastuzumab chemotherapy. On day 8, severe diarrhea and mucositis developed; chemotherapy was stopped. On day 14, the patient developed renal dysfunction and febrile neutropenia. He also suffered from pneumonia due to Candida albicans. Systemic symptoms improved after intensive conservative treatment. Best supportive care was continued until the patient died from gastric cancer. The dihydropyrimidine dehydroge-nase protein level was low at 3.18 U/mg protein. The result of DPYD genotyping revealed three variants at posi-tions 1615 (G > A), 1627 (A > G), and 1896 (T > C) in exons 13, 13, and 14, respectively.

Preoperative Pulmonary Function Tests Predict Aspiration Pneumonia After Gastric Endoscopic Submucosal Dissection.

BACKGROUND: ESD allows higher rates of en-bloc and R0 resections, but has occasionally complications such as aspiration pneumonia. Factors associated with aspiration pneumonia are not completely understood. AIMS: To analyze the relationship between aspiration pneumonia and preoperative factors including pulmonary function tests. METHODS: A total of 978 patients with gastric tumors who had received pulmonary function tests were treated by ESD between June 2006 and May 2014. Pulmonary function tests were assessed using a spirometer. The patients were categorized into four groups according to the predicted vital capacity (%VC) and forced expiratory volume in 1 s as a percentage of forced vital capacity (FEV1.0%): normal; restrictive pulmonary dysfunction; obstructive; and mixed. The factors associated with aspiration pneumonia were retrospectively analyzed. RESULTS: Among the 268 cases with abnormal pulmonary function, 10 cases (3.7%) developed aspiration pneumonia. On the other hand, 7 cases (1.0%) with normal pulmonary function developed pneumonia. There was a significant correlation between pulmonary function and aspiration pneumonia (p = 0.010). When the pulmonary function cases were stratified into subgroups, 2.5% of cases with obstructive pulmonary dysfunction developed pneumonia, 5.5% with restrictive and 5.3% with mixed. By logistic regression analysis, pulmonary function, the presence of cerebral vascular disease, and procedure time were identified as significant independent risk factors associated with aspiration pneumonia. The odds ratios for pulmonary function, cerebral vascular disease, and procedure time were 3.6, 5.1, and 5.2, respectively. CONCLUSIONS: Preoperative pulmonary function tests may be useful markers to evaluate the risk for aspiration pneumonia after gastric ESD.

Reactivation of hepatitis B virus during interferon-free therapy with daclatasvir and asunaprevir in patient with hepatitis B virus/hepatitis C virus co-infection.

Direct-acting antiviral agents (DAA) for hepatitis C virus (HCV) are not effective for hepatitis B virus (HBV), which may be suggestive of reactivation of anti-HBe hepatitis during interferon (IFN)-free DAA therapy in HBV/HCV co-infected patients with inactive HBV. A 69-year-old male patient was diagnosed with chronic hepatitis due to HBV/HCV co-infection with serum levels of alanine aminotransferase (ALT) of 94 U/L, HCV RNA of 4.2 log IU/mL and HBV DNA of 2.5 log copies/mL. HCV was thought to be responsible for the hepatitis activity because of low level of HBV core-related antigen (3.1 log U/mL). He was treated with combination therapy of daclatasvir and asunaprevir. Serum ALT gradually increased, and reached 237 U/L on day 43 in spite of undetectable HCV RNA. Serum HBV DNA was increasing to 7.0 log copies/mL at that time. The treatment was stopped due to suspicion of drug-induced liver injury and/or HBV reactivation. Administration of entecavir reduced HBV DNA levels, followed by improvement in ALT levels. This report proposes that close monitoring of HBV DNA during the anti-HCV DAA therapy and the commencement of anti-HBV therapy with nucleoside analogs after the increase of HBV DNA should be considered in patients with HBV/HCV co-infection.

Clinical Outcomes of Endoscopic Hemostasis in Marginal Ulcer Bleeding.

The usefulness of endoscopy in marginal ulcer bleeding has rarely been studied, and the optimal method for preventing rebleeding is unclear. Here we assessed the efficacy of endoscopy in marginal ulcer bleeding and examined the efficacy of proton pump inhibitors (PPIs) in the prevention of rebleeding. A total of 28 patients with marginal ulcer bleeding (21 men, 7 women; median age 58.5 years) were treated by endoscopy. We analyzed the clinical characteristics, results of endoscopic therapy, characteristics of rebleeding patients, and relation between the use of PPIs and the duration of rebleeding. Sixteen patients had active bleeding. Initial hemostasis was achieved in all patients. There were no procedure-related adverse events. Rebleeding occurred in one patient within the first month and in 7 patients thereafter. There was a significant difference in the rebleeding rate between the patients who received a PPI and those who did not. In a multivariate analysis, the non-use of PPIs was a risk factor for rebleeding (hazard ratio, 6.22). Therapeutic endoscopy is effective in achieving hemostasis from marginal ulcer bleeding. PPIs may prevent rebleeding from marginal ulcers.

A Randomized Trial of Monopolar Soft-mode Coagulation Versus Heater Probe Thermocoagulation for Peptic Ulcer Bleeding.

BACKGROUND AND AIM: Endoscopic therapy has been demonstrated to be effective in achieving hemostasis for bleeding peptic ulcers. Thermal coagulation is one of the most commonly used methods, with a high success rate. Recently, endoscopic submucosal dissection for early gastric carcinoma was developed and hemostasis with soft coagulation using hemostatic forceps was introduced. The aim of this study was to compare the hemostatic efficacy of soft coagulation with heater probe thermocoagulation for peptic ulcer bleeding. METHODS: Patients who visited our hospital with hematemesis or melena underwent emergency endoscopy. Inclusion criteria were presentation with an actively bleeding ulcer, a nonbleeding visible vessel, or an adherent clot. Patients were excluded if they were unwilling to give written informed consent or had a bleeding gastric malignancy. Patients were randomized to receive endoscopic hemostasis with soft coagulation (Group S) or heater probe thermocoagulation (Group H). The primary endpoint was the primary hemostasis rate and secondary endpoints were rebleeding rate, complications, and the procedure time. RESULTS: Between May 2010 and February 2012, a total of 111 patients (89 gastric ulcers and 22 duodenal ulcers) were enrolled. Primary hemostasis was achieved in 54 patients (96%) in Group S and 37 (67%) in Group H (P<0.0001). Rebleeding occurred in 7 patients in Group H and none in Group S. Of these 7 patients, urgent surgery was performed in 1. Perforation occurred in 2 patients in Group H, which was managed conservatively. CONCLUSIONS: For patients with gastroduodenal ulcer bleeding, soft coagulation using monopolar hemostatic forceps is more effective than heater probe thermocoagulation for achieving hemostasis.

Monopolar soft-mode coagulation using hemostatic forceps for peptic ulcer bleeding.

BACKGROUND/AIMS: Upper gastrointestinal hemorrhage from bleeding peptic ulcer is sometimes difficult to treat by conventional endoscopic methods. Recently, monopolar electrocoagulation using a soft-coagulation system and hemostatic forceps (soft coagulation) has been used to prevent bleeding during endoscopic submucosal dissection. The aim of this study was to assess the safety and efficacy of soft coagulation in the treatment of bleeding peptic ulcer. METHODOLOGY: A total of 39 patients with peptic ulcers were treated using soft coagulation at our hospital between January 2005 and March 2010. Emergency treatment employed an ERBE soft-mode coagulation system using hemostatic forceps. Second-look endoscopy was performed to evaluate the efficacy of prior therapy. Initial hemostasis was defined as accomplished by soft coagulation, with or without other endoscopic therapy prior to soft coagulation. The rate of initial hemostasis, rebleeding, and ultimate hemostasis were retrospectively analyzed. RESULTS: The study subjects were 31 men and 8 women with a mean age of 68.3±13.7 years, with 29 gastric ulcers and 10 duodenal ulcers. Initial hemostasis was achieved in 37 patients (95%). During follow-up, bleeding recurred in two patients, who were retreated with soft coagulation. CONCLUSIONS: The monopolar soft coagulation is feasible and safe for treating bleeding peptic ulcers.

A Prospective Observational Study on Gastric Endoscopic Submucosal Dissection under Continuous Administration of Antithrombotic Agents.

Background: This study aimed to assess the completion rate and postoperative bleeding incidence of endoscopic submucosal dissection (ESD) for gastric tumors under continuous antithrombotic therapy. Methods: A prospective observational study was conducted including 88 patients with 100 gastric lesions who underwent gastric endoscopic submucosal dissection (ESD) and received continuous antithrombotic therapy. Additionally, retrospective data on gastric ESD in 479 patients with 534 lesions who did not receive antithrombotic therapy were collected for comparison. Results: The en bloc resection rates (100% in the continuous antithrombotic therapy group vs. 100% in the non-antithrombotic therapy group) and complete resection rates (97.0% vs. 96.3%, respectively) were high and comparable between the groups. No significant differences were found in the specimen size or procedure time. Perforation rates were low (0% vs. 2.3%, respectively) and were not significantly different between the groups. However, postoperative bleeding occurred significantly more frequently in the continuous antithrombotic therapy group (10.2% vs. 4.2%, respectively) than in the non-antithrombotic therapy group. The subgroup analysis revealed a higher incidence of postoperative bleeding in patients receiving thienopyridine derivatives. Conclusions: Continuous administration of antithrombotic agents, especially thienopyridines, increased the risk of postprocedural hemorrhage following gastric ESD. These findings support the need for careful consideration of pharamcological management before ESD, aligning with the current guidelines.

[The impact of guidelines for the management of acute cholecystitis in a rural area of Japan].

We monitored the management of acute cholecystitis in a rural area of Japan to determine the effectiveness of new guidelines for the management of acute cholecystitis and cholangitis. Between January 2000 and September 2011, 366 patients were treated for acute cholecystitis. Of these, 59 had common bile duct stones (CBDS) and 307 did not. Patients in both groups were further subdivided into two groups: a before guidelines group (BGG; n=153) and an after guideline group (AGG; n=154). Among the patients without CBDS, early cholecystectomy was more common in the AGG group (n=53) than in the BGG group. Furthermore, the length of hospital stay was four days shorter in the AGG group than in the BGG group (n=23). Among the patients with CBDS, the timing of cholecystectomy after endoscopic retrograde cholangiography was seven days earlier in the AGG group than in the BGG group. Even in a rural area of Japan, early cholecystectomy appears safe and can decrease the length of hospital stay.

Lymphoid Hyperplasia of the Gallbladder Extending to the Bile Duct.

A 72-year-old woman was referred for the examination of wall thickening of the bile duct and a polyp-like lesion on the gallbladder. The bile duct and gallbladder lesions were observed to be continuous on abdominal ultrasonography. We performed a bile duct biopsy, and pathological findings showed hyperplasia of the lymphoid follicles without malignancy. We considered these two lesions to be the same lesion, and laparoscopic cholecystectomy was performed to make a definite diagnosis. The pathological examination of the resected gallbladder also showed hyperplasia of the lymphoid follicles. We diagnosed the patient with lymphoid hyperplasia of the gallbladder extending to the bile duct.

Peppermint oil solution is useful as an antispasmodic drug for esophagogastroduodenoscopy, especially for elderly patients.

BACKGROUND: Although hyoscine butyl bromide (HB) and glucagon (GL) are often used as antispasmodic drugs during esophagogastroduodenoscopy (EGD), these agents may cause adverse effects. Recently, it was reported that peppermint oil solution (PO) was very effective and had few side effects. AIM: We clarified the efficacy and usefulness of PO as an antispasmodic during upper endoscopy, especially for elderly patients. METHODS: This study was a non-randomized prospective study. The antispasmodic score (1-5, where 5 represents no spasm) was defined according to the degree of spasms of the antrum and difficulty of biopsy. We compared the antispasmodic scores between non-elderly patients (younger than 70) and elderly patients (70 years old or older) according to the antispasmodic agent. RESULTS: A total of 8,269 (Group PO: HB: GL: NO (no antispasmodic) = 1,893: 6,063: 157: 156) EGD procedures were performed. There was no significant difference in the antispasmodic score between Group PO (mean score ± standard deviation: 4.025 ± 0.925) and Group HB (4.063 ± 0.887). Among the non-elderly patients, those in Group PO (n = 599, 3.923 ± 0.935) had a worse antispasmodic score than those in Group HB (n = 4,583, 4.062 ± 0.876, P < 0.001). However, among the elderly patients, those in Group PO (n = 1,294, 4.073 ± 0.917) had similar scores to those in Group HB (n = 1,480, 4.064 ± 0.921, P = 0.83), and significantly better scores than those in Group GL (n = 69, 3.797 ± 0.933, P < 0.05). CONCLUSION: Peppermint oil was useful as an antispasmodic during EGD, especially for elderly patients.

The presence of large serrated polyps increases risk for colorectal cancer.

BACKGROUND & AIMS: There is evidence that serrated polyps (serrated adenomas and hyperplastic polyps) have different malignant potential than traditional adenomas. We used a colonoscopy database to determine the association between the presence of serrated colorectal polyps and colorectal neoplasia. METHODS: We performed a multicenter observational study of 10,199 subjects who underwent first-time colonoscopies. Data collected on study subjects included age and sex and the location, size, and histology of polyps or tumors found at colonoscopy. Serrated polyps were defined as those diagnosed by the pathologists in the participating hospitals as a serrated lesion (a lesion given the term of "classical hyperplastic polyp," "traditional serrated adenoma," "sessile serrated adenoma," or "mixed serrated polyp"). Large serrated polyps (LSPs) were defined as those ≥ 10 mm. RESULTS: There were 1573 patients (15.4%) with advanced neoplasia, 708 patients (6.9%) with colorectal cancer (CRC), and 140 patients (1.4%) with LSPs in our cohort. Multivariate analysis associated the presence of LSPs with advanced neoplasia (odds ratio [OR], 4.01; 95% confidence interval [CI], 2.83-5.69) and CRC (OR, 3.34; 95% CI, 2.16-5.03). The presence of LSPs was the greatest risk factor for CRC, particularly for proximal CRC (OR, 4.79; 95% CI, 2.54-8.42). Proximal and protruded LSPs were the highest risk factors for proximal CRC (OR, 5.36; 95% CI, 2.40-10.8 and OR, 9.00; 95% CI, 2.75-19.2, respectively). CONCLUSIONS: The presence of LSPs is a risk factor for CRC, particularly CRC of the proximal colon.

Pancreatic actinomycosis treated by antibiotics after diagnosis using endoscopic ultrasound-guided fine-needle biopsy.

A 71-year-old man who had undergone total gastrectomy, partial pancreatectomy, and splenectomy with Roux-en-Y reconstruction for gastric cancer was referred for a possible pancreatic tail tumor. Contrast-enhanced computed tomography showed mold-like, poor contrast lesion in the dilated main pancreatic duct in the pancreatic tail. Endoscopic ultrasonography revealed a slightly hyperechoic solid lesion that occupied the lumen of the main pancreatic duct. Linear calcification was observed in the lesions on both computed tomography and endoscopic ultrasonography, and endoscopic ultrasound-guided fine-needle biopsy was performed. Histopathology revealed sulfur grains and inflammatory infiltrates with no malignant findings. We also performed an anaerobic culture using fine-needle biopsy specimens, and Actinomyces meyeri was detected in the culture results. After confirming susceptibility, oral administration of amoxicillin was initiated. After 8 months of treatment, the size of the lesion slightly decreased, and the antibiotics treatment is still ongoing. This shows that such cases could be diagnosed based on histological findings and anaerobic culture using a fine-needle biopsy specimen, and unnecessary surgery may be avoided. In the case of tumors developed in the residual pancreas without typical malignant imaging findings, pancreatic actinomycosis should be considered as a differential diagnosis.

Risk factors associated with local recurrence of early gastric cancers after endoscopic submucosal dissection.

BACKGROUND: Although endoscopic submucosal dissection (ESD) is expected to reduce the local recurrence of gastric cancers, we still experience cases of recurrence after an ESD. OBJECTIVE: To characterize clinical and pathologic features of cases with local recurrence of early gastric cancer after an ESD. DESIGN: A prospective cohort study. SETTING AND PATIENTS: A total of 306 patients with gastric cancers removed by ESD at Okayama University Hospital and Tsuyama Central Hospital between March 2001 and December 2005 were enrolled. INTERVENTION: ESD. MAIN OUTCOME MEASUREMENT: Local recurrence. RESULTS: The incidence of a complete en bloc resection was 80.4% when pathologically evaluated. Within a median follow-up period of 26 months (12-64 months), a local recurrence was found in 7 cases, all of which had been declared incomplete resections. One patient underwent a second ESD, and the remaining 6 underwent a surgical resection. All removed lesions were mucosal cancers. No lymph-node metastases were found in patients with a surgical resection. There was a significant correlation between the incidence of an incomplete resection and that of a local recurrence (P < .0001). Among the clinical characteristics, tumor size (>30 mm vs <20 mm; odds ratio [OR] 16 mm [95% CI, 2.0-130 mm]) and tumor location (upper vs middle or lower; OR 7.6 [95% CI, 1.3-45]) were identified as factors that were significantly associated with the incidence of a local recurrence. LIMITATION: Short follow-up duration. CONCLUSIONS: The incidence of a local recurrence was strongly associated with that of an incomplete resection. The frequency of a local recurrence also showed significant correlations with the tumor size and location within the stomach.

A Japanese Case of Esophageal Lichen Planus that Was Successfully Treated with Systemic Corticosteroids.

Esophageal lichen planus (ELP) is rare and only about 80 cases have been reported in the literature. An 85-year-old woman presented with dysphagia and odynophagia. Endoscopy revealed a severe stricture in the proximal esophagus. Oral examinations at two years after the first endoscopy revealed erosions around the gingiva, and an examination of biopsy specimens taken from the site of erosion led to a diagnosis of oral lichen planus. Esophageal endoscopy was performed again, and biopsy specimens showed spongiosis and necrotic keratinocytes in the epithelium (civatte bodies). The patient was diagnosed with ELP and was treated with systemic corticosteroids, which resulted in clinical relief.

Comparing reduced-dose sodium phosphate tablets to 2 L of polyethylene glycol: A randomized study.

AIM: To compare the tolerability and quality of bowel cleansing between 2 L polyethylene glycol (PEG) and reduced-dose sodium phosphate (NaP) tablets as a preparation for colonoscopy. METHODS: Two hundred patients were randomly assigned to the PEG or NaP groups at the same ratio. The NaP group patients took 30 tablets with 2 L of clear liquid, while the PEG group patients took 2L of PEG. Tolerability was assessed by a questionnaire about taste, volume, and the overall impression. The bowel cleansing quality was evaluated by colonoscopists. RESULTS: Although NaP showed better tolerability in terms of taste, volume and overall impression (P < 0.01, P < 0.01 and P = 0.02, respectively), the overall cleansing quality was better in the PEG group (P < 0.01). A subgroup analysis, stratified by sex and age, indicated that NaP was associated with better tolerability and equivalent bowel cleansing quality in females of < 50 years of age. CONCLUSION: Despite the better tolerability, the use of 30 NaP tablets with 2 L of clear liquid should be limited due to its lower cleansing quality; however, in certain cases the regimen may deserve consideration, particularly in cases involving young women.

Tolerability of magnifying narrow band imaging endoscopy for esophageal cancer screening.

AIM: To compare the tolerability of magnifying narrow band imaging endoscopy for esophageal cancer screening with that of lugol chromoendoscopy. METHODS: We prospectively enrolled and analyzed 51 patients who were at high risk for esophageal cancer. All patients were divided into two groups: a magnifying narrow band imaging group, and a lugol chromoendoscopy group, for comparison of adverse symptoms. Esophageal cancer screening was performed on withdrawal of the endoscope. The primary endpoint was a score on a visual analogue scale for heartburn after the examination. The secondary endpoints were scale scores for retrosternal pain and dyspnea after the examinations, change in vital signs, total procedure time, and esophageal observation time. RESULTS: The scores for heartburn and retrosternal pain in the magnifying narrow band imaging group were significantly better than those in the lugol chromoendoscopy group (P = 0.004, 0.024, respectively, ANOVA for repeated measures). The increase in heart rate after the procedure was significantly greater in the lugol chromoendoscopy group. There was no significant difference between the two groups with respect to other vital sign. The total procedure time and esophageal observation time in the magnifying narrow band imaging group were significantly shorter than those in the lugol chromoendoscopy group (450 ± 116 vs 565 ± 174, P = 0.004, 44 ± 26 vs 151 ± 72, P < 0.001, respectively). CONCLUSION: Magnifying narrow band imaging endoscopy reduced the adverse symptoms compared with lugol chromoendoscopy. Narrow band imaging endoscopy is useful and suitable for esophageal cancer screening periodically.