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BACKGROUND/AIMS: Gastric acid secretion is suspected to be a pivotal contributor to the pathogenesis of functional dyspepsia. The present study investigates the potential association of the gastric acid secretion estimated by measuring serum pepsinogen with therapeutic responsiveness to the prokinetic drug acotiamide. METHODS: Dyspeptic patients consulting participating clinics from October 2017 to March 2019 were prospectively enrolled in the study. The dyspeptic symptoms were classified into postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS). Gastric acid secretion levels were estimated by the Helicobacter pylori infection status and serum pepsinogen using established criteria and classified into hypo-, normo-, and hyper-secretion. Each patient was then administered 100 mg acotiamide thrice daily for 4 weeks, and the response rate to the treatment was evaluated using the overall treatment efficacy scale. RESULTS: Of the 86 enrolled patients, 56 (65.1%) and 26 (30.2%) were classified into PDS and EPS, respectively. The estimated gastric acid secretion was not significantly different between PDS and EPS. The response rates were 66.0% for PDS and 73.1% for EPS, showing no significant difference. While the response rates were stable, ranging from 61.0% to 75.0% regardless of the estimated gastric acid secretion level among subjects with PDF, the rates were significantly lower in hyper-secretors than in non-hyper-secretors among subjects with EPS (42.0% vs 83.0%, P = 0.046). CONCLUSION: Although acotiamide is effective for treating EPS as well as PDS overall, the efficacy is somewhat limited in EPS with gastric acid hypersecretion, with gastric acid suppressants, such as proton pump inhibitors, being more suitable.

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Familial hemophagocytic lymphohistiocytosis (FHL) is a severe inborn error of immunity caused by a genetic defect that impairs the function of cytotoxic T and NK cells. There are only a few reported cases of FHL with diffuse swelling of the cerebellum and obstructive hydrocephalus. We report a case of FHL3 with neurological symptoms associated with cerebellar swelling and obstructive hydrocephalus. A male patient was hospitalized several times due to fever and decreased feeding, hepatosplenomegaly, and cytopenia since the first month of life. At 7 months of age, disturbance of consciousness was seen. Brain magnetic resonance imaging revealed signal intensity in the bilateral cerebellar hemispheres, diffusely increased periventricular white matter, and ventriculomegaly. Although he was treated with methylprednisolone pulse therapy, he was unresponsive to the treatment. He was then transferred to a local hospital after tracheotomy but died. Targeted clinical sequencing revealed a homozygous splice-site mutation in UNC13D. Pediatric hemophagocytic lymphohistiocytosis (HLH) includes some cases of central nervous symptom (CNS)-isolated HLH or CNS HLH preceding systemic lesions, which often do not initially meet the diagnostic criteria for FHL. Patients with FHL initiated by cerebellar symptoms may present with an atypical clinical course for HLH, leading to delayed diagnosis and poor outcomes. Despite the usefulness of a combination of a high percentage of lymphocytes in the peripheral leukocytes, a low lactate dehydrogenase level, and a high sIL-2R/ferritin ratio for identifying FHL, the diagnosis may be missed due to the absence of these results. Presymptomatic diagnosis of FHL by screening of newborns and subsequent early treatment of patients with a predicted poor prognosis may contribute to better outcomes.

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Spindle cell carcinoma of the breast is a rare tumor. This tumor can proliferate rapidly and cause cystic changes because of internal tissue necrosis. We evaluated a 54-year-old woman with right breast lump. Mammography showed a category four mass with a diameter of 2.5 cm. Ultrasonography (US) revealed a complex cystic lesion, and fine-needle aspiration (FNA) cytology demonstrated bloody fluid and malignant cells. Partial breast resection and sentinel lymph node biopsy were performed. Immunohistology revealed spindle cells with positive results for cytokeratin (AE1/AE3) and vimentin, partially positive results for s-100, and negative results for desmin and α-actin. The pathological stage was IIA, and biochemical characterization showed that the tumor was triple negative. Six courses of FEC-100 chemotherapy (5-fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2), and cyclophosphamide 500 mg/m(2)) were administered. Radiotherapy was performed. This case is discussed with reference to the literature.

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BACKGROUND AND AIM: We recently encountered patients with localized esophageal eosinophilia in a small area of the esophagus. However, this condition remains to be described in detail, and its clinical significance has not been established. We investigated the clinical, endoscopic and histological features of localized esophageal eosinophilia in comparison with diffuse esophageal eosinophilia. METHODS: We investigated 10 patients with localized esophageal eosinophilia, and compared them with 23 who had diffuse esophageal eosinophilia. Whether esophageal eosinophilia was localized or diffuse was determined on the basis of endoscopic findings. Localized esophageal eosinophilia was defined endoscopically as a focal area of esophageal eosinophilia, whereas diffuse esophageal eosinophilia was defined as a widespread area of esophageal eosinophilia involving more than one of three locations: the upper, middle and lower esophagus. Histological esophageal eosinophilia in the mucosa showing endoscopic abnormality was confirmed by biopsy with a peak of ≥ 15 eosinophils/high-power field. RESULTS: There were no significant differences in age, gender distribution, allergic conditions or peripheral eosinophilia between the two groups. In all cases but one, localized esophageal eosinophilia was observed in a small area above the esophagogastric junction. Esophageal symptoms such as dysphagia, heartburn or chest pain were present in 20% of the localized group and in 65% of the diffuse group, the difference being statistically significant (P<0.05). The maximum amounts of eosinophils infiltrating the esophageal mucosa did not differ between the groups. CONCLUSIONS: Esophageal eosinophilia can be localized in a small area, especially above the esophagogastric junction. Gastric acid reflux or contact may influence this condition in addition to its allergic pathogenesis.

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We report an extremely rare case of undifferentiated pleomorphic sarcoma of the stomach. A 74-year-old woman was admitted for abdominal discomfort. A 13-cm gastric submucosal tumor and multiple liver and bone metastases were detected by computed tomography. The tumor had not been detected 8 months earlier. We performed EUS-FNAB for a suspected mesenchymal tumor, but the immunohistochemical test (c-kit, CD34, desmin, SMA, S-100) findings were negative. The tumor was confirmed as wild type for c-kit and PDGFRα. It grew rapidly and the patient died 2 months after admission. Pathological analysis of the EUS-FNAB specimens and autopsy revealed an undifferentiated pleomorphic sarcoma.

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BACKGROUND: Several reports have described the usefulness of magnifying endoscopy in observing the surface structure in gastric neoplasia. The aim of the present study was to evaluate the characteristics of the surface structure of non-cancerous mucosa surrounding gastric cancer. METHODS: Sixty Japanese patients with early gastric cancer were enrolled in this study. We observed the non-cancerous gastric mucosa surrounding gastric carcinoma by magnifying endoscopy and classified the magnified view into four patterns: (A) dotted; (B) short-linear; (C) striped; and (D) granular, according to Sakaki's classification. RESULTS: All patients were diagnosed as having Helicobacter pylori infection, and histological evaluation revealed 46 types of differentiated and 14 types of undifferentiated-type gastric carcinomas. There were significant differences in the gender, age and endoscopic-atrophic-border scale between patients with these two types. In all, the surface structure at 240 points (4 points each in 60 patients) of non-cancerous mucosa was observed by magnifying endoscopy. The prevalences of the surface patterns of the mucosa surrounding differentiated carcinoma were: A, 1.1%; B, 8.1%; C, 28.3%; D, 62.5%, and those of the mucosa surrounding undifferentiated carcinoma were: A, 8.9%; B, 73.2%; C, 14.3%; D, 3.6%. There were significant differences in the surface structure of the non-cancerous mucosa surrounding differentiated and undifferentiated gastric carcinoma. CONCLUSION: The microsurface structure of the gastric mucosa surrounding gastric cancer lesions differed between patients with differentiated and undifferentiated gastric cancer. These findings are expected to be useful for the early detection of gastric carcinoma lesions or for the determination of extensions of carcinoma lesions.

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BACKGROUND AND AIM: The distributions and grades of Helicobacter pylori induced gastritis are known to vary among H. pylori-associated diseases. The aim of this study was to investigate the differences in distributions of gastric micromucosal structures observed by magnifying narrow band imaging (NBI) endoscopy among patients with different H. pylori-associated diseases. METHODS: Ninety-five patients with active duodenal ulcers (n = 24) and diffuse-type (n = 24) and intestinal-type (n = 47) early gastric cancers were enrolled. The magnified NBI findings were evaluated at the lesser and greater curvatures in the upper gastric corpus and were classified according to the modified A-B classification system. Biopsy specimens were also evaluated. RESULTS: In a total of 190 areas observed with magnifying NBI, histological grading (inflammation, activity, atrophy and intestinal metaplasia) showed significant differences among the classified micromucosal patterns (P < 0.001). Types B-1 and B-2, with mild atrophic changes and few areas of intestinal metaplasia, were seen mostly in the duodenal ulcers group. Types B-3 and A-1, with moderate atrophic changes, were seen in the diffuse-type early gastric cancers at the lesser curvature. Types A-1 and A-2, with severe atrophic change and a high frequency of intestinal metaplasia, were seen in the intestinal-type early gastric cancers at the lesser curvature. The prevalence of micromucosal structures differed significantly among the three groups both at the lesser and greater curvatures (P < 0.001). CONCLUSIONS: Magnifying NBI endoscopy clearly revealed detailed micromorphological differences corresponding to the histology and endoscopic findings among patients with different H. pylori-associated diseases.

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AIMS: The efficacy and the toxicity of oral fluorouracil derivative S-1 plus low-dose cisplatin in unresectable or recurrent gastric cancer were evaluated by a phase II study. METHODS: S-1 was administered orally for 28 days following 14 days' rest at 80-120 mg/body/day, depending on body surface area. During administration of S-1, cisplatin was given twice a week at the recommended dose (10 mg/m(2)), which was determined by a phase I study. Data from 34 patients in phase II and 8 patients treated with the recommended dose of cisplatin in phase I were analyzed. The primary endpoint was objective response. RESULTS: The response rate was 47.1%. The median survival time was 11.0 months and the median progression-free survival was 6.9 months. The grade 3/4 toxicities observed in 10% or more of the treated patients were neutropenia (16.7%), anemia (16.7%) and anorexia (11.9%). The serum concentration of cisplatin was 794 ± 341 ng/ml at day 25 of the first course. CONCLUSIONS: S-1 plus low-dose cisplatin may be a clinically useful regimen for unresectable or recurrent gastric cancer because of its infrequent adverse events in spite of considerable efficacy and its convenience of no hydration and no hospitalization.

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Follicular lymphoma of the small intestine remains relatively rare, especially in its early stage. Recently, double-balloon endoscopy has enabled observation of the entire small intestine. We describe a case of follicular lymphoma with multiple lesions in the small intestine detected by double-balloon endoscopy. The patient showed multiple whitish granules in descending portion of the duodenum on screening esophagogastroduodenoscopy, which were subsequently diagnosed as follicular lymphoma by immunohistochemistry. Endoscopic examination of the entire small intestine revealed multiple follicular lymphoma tumors in inferior portion of the duodenum and in the proximal jejunum. Double-balloon endoscopy is useful for evaluating tumor distribution of follicular lymphoma.

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From April 1989 to December 2004, we performed liver biopsy on 475 patients and obtained biopsy proven 35 cases of non-alcoholic fatty liver. Among them, 18 cases were diagnosed as non-alcoholic steatohepatitis (NASH). During the last three years, we have tried to detect NASH using ultrasonography and elevated value of serum ferritin (> 300 ng/ml). All of the eligible 7 cases biopsied during the course were diagnosed as NASH. In these 7 cases, ALT levels improved after the body weight loss accompanied by the parallel decrease of serum ferritin levels. Measurement of serum ferritin is useful in the detection of NASH but the normal value of ferritin cannot rule out the possibility of NASH.

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