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Background: Accurate diagnosis of the lateral extent of early gastric cancer during endoscopic submucosal dissection (ESD) is crucial to achieve negative resection margins. Similar to intraoperative consultation with a frozen section in surgery, rapid frozen section diagnosis with endoscopic forceps biopsy may be useful in assessing tumor margins during ESD. This study aimed to evaluate the diagnostic accuracy of frozen section biopsy. Methods: We prospectively enrolled 32 patients undergoing ESD for early gastric cancer. Biopsy samples for the frozen sections were randomly collected from fresh resected ESD specimens before formalin fixation. Two different pathologists independently diagnosed 130 frozen sections as "neoplasia," "negative for neoplasia," or "indefinite for neoplasia," and the frozen section diagnosis was compared with the final pathological results of the ESD specimens. Results: Among the 130 frozen sections, 35 were from cancerous areas, and 95 were from non-cancerous areas. The diagnostic accuracies of the frozen section biopsies by the two pathologists were 98.5 and 94.6%, respectively. Cohen's kappa coefficient of diagnoses by the two pathologists was 0.851 (95% confidence interval: 0.837–0.864). Incorrect diagnoses resulted from freezing artifacts, a small volume of tissue, inflammation, the presence of well-differentiated adenocarcinoma with mild nuclear atypia, and/or tissue damage during ESD. Conclusions: Pathological diagnosis of frozen section biopsy is reliable and can be applied as a rapid frozen section diagnosis for evaluating the lateral margins of early gastric cancer during ESD. [ABSTRACT FROM AUTHOR]

Patients with primary intestinal follicular lymphoma are often followed-up without a specific treatment, and this approach is called the "watch-and-wait approach." However, the long-term outcomes of this patient group have not been sufficiently investigated. We enrolled patients with primary intestinal follicular lymphoma who were diagnosed before 2016 and managed with the watch-and-wait approach in 20 institutions. We retrospectively investigated the overall, disease-specific, and event-free survival rates as well as the rate of spontaneous regression. Among the 248 patients with follicular lymphoma with gastrointestinal involvement, 124 had localized disease (stage I or II1). We analyzed the data of 73 patients who were managed using the watch-and-wait approach. During the mean follow-up period of 8.3 years, the follicular lymphoma had spontaneously resolved in 16.4% of the patients. The 5-year and 10-year overall survival rates were 92.9% and 87.1%, respectively. With disease progression (n = 7), initiation of therapy (n = 7), and histologic transformation to aggressive lymphoma (n = 0) defined as events, the 5-year and 10-year event-free survival rates were 91.1% and 86.9%, respectively. No patient died of progressive lymphoma. Thus, both 5-year and 10-year disease-specific survival rates were 100%. In conclusion, an indolent long-term clinical course was confirmed in the patients with primary intestinal follicular lymphoma. The watch-and-wait strategy is a reasonable approach for the initial management of these patients. [ABSTRACT FROM AUTHOR]

Background: The risk of bleeding after gastric endoscopic submucosal dissection (ESD) in antithrombotic agent users has increased, and its management remains a problem. Second-look endoscopy (SLE) following gastric ESD in antithrombotic agent users may be effective in preventing delayed bleeding, but this requires elucidation. Therefore, this study aimed to investigate the efficacy of SLE in reducing bleeding after gastric ESD in patients receiving antithrombotic agents. Methods: This retrospective cohort study was conducted at 19 referral hospitals in Japan. A total of 1,245 patients who were receiving antithrombotic agents underwent gastric ESD between January 2013 and July 2018. The incidence of delayed bleeding was compared between SLE and non-SLE groups using propensity score matching analysis. Results: Overall, 858 patients (SLE group, 657 patients; non-SLE group, 201 patients) were analyzed. After matching, 198 pairs were created. Delayed bleeding occurred in 10 patients (5.1%) in the SLE group and 16 patients (8.1%) in the non-SLE group [odds ratio (OR) 0.605, 95% confidence interval (CI) 0.23–1.46, p = 0.310]. In the subgroup analysis, SLE reduced the incidence of delayed bleeding in patients receiving heparin bridging therapy (6.3% and 40.0%, respectively; p = 0.004). In the SLE group, prophylactic coagulation did not significantly reduce delayed bleeding compared to the no treatment group (14.6% and 8.6%, respectively; p = 0.140). Conclusions: SLE was ineffective in reducing bleeding after gastric ESD in antithrombotic agent users, overall. A prospective comparative study is warranted to definitively evaluate the effectiveness of SLE in reducing bleeding in high-risk patients. [ABSTRACT FROM AUTHOR]

The aim of this study was to reveal the histological features of oxyntic gland adenomas and gastric adenocarcinoma of the fundic-gland type (GA-FG). We retrospectively examined the histological features of 126 lesions of oxyntic gland adenoma and/or GA-FG in 116 patients. The prevalence of oxyntic gland adenomas and GA-FG was approximately equal. The majority of the lesions were resected by endoscopic mucosal resection using a diathermic snare (EMR, n = 42) or endoscopic submucosal dissection (ESD, n = 72). Histologically, there were no lesions with invasion at the level of the muscularis propria or deeper, and lymphovascular invasion was present in 1.6%. Of the ESD and EMR specimens, there were no lesions that were positive for vertical margins. Among the eight GA-FG patients with deep (≥ 500 μm) submucosal invasion, six were treated with endoscopic resection alone, and no recurrence was documented. No patients died of the disease during the median follow-up period of 14.5 months. In conclusion, all lesions were confined to the mucosa or submucosa and were negative for vertical margins. Lymphovascular invasion was present in only 1.6% of the patients. Thus, we believe that endoscopic resection is a suitable initial treatment method for oxyntic gland adenoma and GA-FG. [ABSTRACT FROM AUTHOR]

Background: Esophageal squamous cell carcinoma (ESCC) confined to the muscularis mucosae (MM) or up to 200 µm of the submucosa (SM1) confers the risk for lymph node metastasis, and is defined as relative indication for endoscopic submucosal dissection (ESD) by the Japan Esophageal Society guidelines. Although additional surgical treatment after ESD is recommended, long-term outcomes of ESD compared with those of surgery have not been clarified. This study aimed to evaluate the long-term outcomes of ESD and surgery for cN0M0 relative indication lesions of ESCC. Methods: Between 2006 and 2016, patients with relative indication lesions of ESCC who underwent ESD or surgery at nine participating hospitals were examined retrospectively. Using propensity score matching, we evaluated survival curves for and hazard ratios associated with endoscopic submucosal dissection and surgery. Results: In total, 155 lesions in the ESD group and 106 lesions in the surgery group met the pathological criteria of relative indication for endoscopic resection. After matching, 50 matched pairs of patients who underwent ESD or surgery were selected. The 5-year overall survival rates were 84.5% [95% confidence interval (CI) 68–93] in the ESD group and 79% [95% CI 60–90] in the surgery group. The hazard ratio of mortality for ESD compared with that for surgery estimated by Cox regression analysis was 0.79 (95% CI 0.3–2.06, p = 0.63). Conclusions: Compared with surgery, ESD does not compromise long-term outcomes. ESD alone or ESD with chemotherapy and/or radiotherapy may be an option for the treatment of MM and SM1 ESCC. [ABSTRACT FROM AUTHOR]

Neuroendocrine carcinoma in Barrett's esophagus is rare and its developmental mechanisms remain unclear. Neuroendocrine carcinoma arising in Barrett's esophagus with adenocarcinoma was detected at an early stage and resected by endoscopic submucosal dissection. Detailed pathological examination revealed that the neuroendocrine carcinoma originated via differentiation of the preexisting adenocarcinoma. A 79-year-old man presented with a flat protruding lesion in the esophagogastric junction. Esophagogastroduodenoscopy revealed a red flat 10-mm protruding lesion in the Barrett's epithelium and a shallow depression at the distal end. Narrow band imaging with magnification showed that the blood vessels in the protrusion were dilated and meandered irregularly, while those in the depression were small and did not form a network; the blood vessels were missing in some parts of the depression. Well-differentiated adenocarcinoma was diagnosed after analysis of the biopsy specimen of the protrusion, and endoscopic submucosal dissection was performed. The pathological diagnosis was neuroendocrine carcinoma with an adenocarcinoma component. [ABSTRACT FROM AUTHOR]

Background: Small bowel adenocarcinoma (SBA) is a rare malignancy that accounts for 1-2% of gastrointestinal tumours. We investigated the clinical characteristics, outcomes, and prognostic factors of primary SBA.Methods: We retrospectively analysed the characteristics and clinical courses of 205 SBA patients from 11 institutions in Japan between June 2002 and August 2013.Results: The primary tumour was in the duodenum and jejunum/ileum in 149 (72.7%) and 56 (27.3%) patients, respectively. Sixty-four patients (43.0%) with duodenal adenocarcinoma were asymptomatic and most cases were detected by oesophagogastroduodenoscopy (EGD), which was not specifically performed for the detection or surveillance of duodenal tumours. In contrast, 47 patients (83.9%) with jejunoileal carcinoma were symptomatic. The 3-year survival rate for stage 0/I, II, III, and IV cancers was 93.4%, 73.1%, 50.9%, and 15.1%, respectively. Multivariate analysis revealed performance status 3-4, high carcinoembryonic antigen, high lactate dehydrogenase (LDH), low albumin, symptomatic at diagnosis, and stage III/IV disease were independent factors for overall survival (OS). Ten patients (18.5%) with stage IV disease were treated with a combination of resection of primary tumour, local treatment of metastasis, and chemotherapy; this group had a median OS of 36.9 months.Conclusions: Although most SBA patients were diagnosed with symptomatic, advanced stage disease, some patients with duodenal carcinoma were detected in early stage by EGD. High LDH and symptomatic at diagnosis were identified as novel independent prognostic factors for OS. The prognosis of advanced SBA was poor, but combined modality therapy with local treatment of metastasis might prolong patient survival. [ABSTRACT FROM AUTHOR]

Backgrounds: The present study sought to establish a standard third-line eradication regimen for Helicobacter pylori in Japan. Methods: Subjects were 204 patients with H. pylori infection in whom the standard Japanese first- and second-line eradication therapies had proven unsuccessful. Patients were randomly assigned to one of the following third-line eradication therapy groups: (1) LA group: lansoprazole (LPZ) 30 mg 4 times a day (qid) + amoxicillin (AMPC) 500 mg qid for two weeks; (2) LAL group: LPZ 30 mg twice a day (bid) + AMPC 750 mg bid + levofloxacin (LVFX) 300 mg bid for one week; (3) LAS group: LPZ 30 mg bid + AMPC 750 mg bid + sitafloxacin (STFX) 100 mg bid for one week. Patients for whom these therapies failed underwent a crossover fourth-line eradication regimen. Drug sensitivity was also tested for AMPC, clarithromycin (CAM), MNZ, LVFX, and STFX. Results: Drug resistance rates prior to third-line eradication therapy were 86.4 % for CAM, 71.3 % for MNZ, 57.0 % for LVFX, 8.2 % for AMPC, and 7.7 % for STFX. Intention-to-treat analysis of third-line eradication therapy eradication rates showed a significantly higher rate in the LAS group (70.0 %) compared with the LA group (54.3 %; p < 0.05) and the LAL group (43.1 %; p < 0.001). The significantly lower rate in the LAL group than the LAS group was caused by bacterial resistance to LVFX. Conclusions: The findings suggest that triple therapy with PPI, AMPC, and STFX for one week would be an effective standard third-line eradication regimen for H. pylori in Japan. [ABSTRACT FROM AUTHOR]

: ObjectivesGenetic polymorphism of interleukin (IL)–1β is associated with differences in gastric acid suppression in response to Helicobacter pylori (H. pylori) infection. Thus, the polymorphism might affect H. pylori eradication therapy, as antibiotics used in treatment regimens may be acid sensitive. In this study, we examined the impact of IL-1β genetic polymorphism on the cure rate of triple therapy for H. pylori in relation to cytochrome P (CYP) 2C19 genotype and antibiotic resistance.: MethodsA total 249 patients with peptic ulcer disease were randomized to receive one of the following regimens: amoxicillin and clarithromycin together with omeprazole, lansoprazole, or rabeprazole. CYP2C19 and IL-1β-511 genetic polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism.: ResultsThe intention-to-treat-based overall cure rate was 74.3% (95% CI = 68–79%). In the normal acid secretion IL-1β genotype group, the cure rate among CYP2C19 poor metabolizers (93.3%, 95% CI = 56–99%) was significantly higher than among subjects in the CYP2C19 homozygous (60.0%, 95% CI = 38–78%) and heterozygous (63.6%, 95% CI = 46–78%), i.e., extensive metabolizer, groups (p < 0.05). In the low acid secretion IL-1β genotype group, there was no difference in the cure rate among the CYP2C19 genotype groups. Multiple logistic regression analysis identified susceptibility to clarithromycin (p < 0.0001) and CYP2C19 genotype status (p = 0.03) as significant independent factors for treatment failure.: ConclusionIL-1β genetic polymorphism, although not an independent factor in treatment outcome, influences the impact of the CYP2C19 genotype on the cure rate of 1-wk triple therapy for H. pylori infection. [Copyright &y& Elsevier]

Epithelial cells of several types of hepatic cysts were examined by mucin histochemistry and immunohistochemically. There were some differences in mucus and antigenic expression among the hepatic cysts examined. Epithelial cells of non-parasitic simple cysts and adult-type polycystic liver showed similar mucin-histochemical and immunohistochemical features, and were characterized by little mucin and weak immunoreactivities to several antibodies examined. Epithelial cells of hepatic hilar cysts were characterized by much mucin and moderate immunoreactivities to carbohydrate antigen 19-9 (CA 19-9), carcinoembryonic antigen (CEA) and epithelial membrane antigen (EMA). Epithelial cells of ciliated hepatic foregut cysts were characterized by much mucin and immunoreactivities to actin and tubulin which were positive in cilia. Epithelial cells of biliary cystadenoma were characterized by much mucin and moderate to strong immunoreactivities to cytokeratins CAM5.2 and AE1 and 3 as well as to CA 19-9, CEA, EMA and DU-PAN-2. Epithelial cells of biliary cystadenocarcinoma were characterized by much mucin and moderate to strong immunoreactivities to cytokeratins CAM5.2 and AE1 and 3 as well as to CA 19-9, CEA, EMA and DU-PAN-2. These differences in epithelial mucus and antigenic expression among several types of hepatic cysts may reflect differences in their origin and biological characteristics. These differences may be helpful in the differential diagnosis of hepatic cysts in small biopsy specimens. [ABSTRACT FROM AUTHOR]