Kenji Matsuzawa

Helicobacter pylori and two ultrastructurally distinct layers of gastric mucous cell mucins in the surface mucous gel layer

BACKGROUND AND AIMS Helicobacter pylori locate not only on the apical surface of surface mucous cells but also in the mucous gel layer covering the gastric mucosa. The present study was undertaken to observe the mucous gel layer itself and any H pylori in this layer at the electron microscopic level, and to determine whether H pylori proliferate in this layer. METHODS We examined resected human stomachs (five cases, fixed in Carnoys solution, paraffin embedded) under the light microscope, and gastric biopsy specimens (10 cases, fixed in glutaraldehyde with or without osmium, epoxy embedded) under the electron microscope. We performed histochemical staining for gastric mucins and immunostaining forH pylori, gastric gland mucous type mucins, and intestinal mucins. RESULTS Under the electron microscope, surface mucous cell type mucins and gland mucous cell type mucins in the mucous gel layer covering gastric mucosa without intestinal metaplasia showed reticular and band like structures, respectively. H pylori were frequently found as small aggregates within the mucous gel layer of surface mucous cell type mucins, and H pyloriwithin these aggregates were seen dividing.H pylori were frequently found in the mucous gel layer of the surface mucous cell type mucins along the border with the layer of gland mucous cell mucins. Occasionally, H pylori were trapped by frayed thin threads of the gland mucous cell type mucins. CONCLUSIONS The two types of gastric mucins in the mucous gel layer differ in ultrastructure. H pylori preferentially colonise and form microcolonies within the mucous gel layer of surface mucous cell type mucins. Mucins from gland mucous cells may disturb the movement of H pylori within the mucous gel layer.

Helicobacter heilmannii infection: Clinical, endoscopic and histopathological features in Japanese patients

Gastric biopsy materials of 4074 consecutive Japanese patients undergoing esophagogastroduodenoscopy were reviewed, along with those of 15 patients with Helicobacter heilmannii infection (11, chronic gastritis; four, mucosa‐associated lymphoid tissue (MALT) lymphoma). In four patients with H. heilmannii infection, the materials were examined by transmission electronmicroscopy. Urea breath test (three patients) and antibody test (five patients) were performed in patients with H. heilmannii infection. In two patients with MALT lymphoma, H. heilmannii was eradicated. The prevalence of H. heilmannii was 0.1% in the consecutive series. In chronic gastritis, the gastric mucosa was endoscopically normal (13.3%), had erythema (33.3%), or had erosions (53.3%); histologically, it showed no epithelial change, mild mononuclear cell infiltration, and slight and focal neutrophil infiltration; Helicobacter heilmannii was positive with anti‐H. pylori antibody, and was detected in the mucous gel layer and in foveolae. In MALT lymphoma, the gastric mucosa was coarsely granular with enlarged mucosal folds without ulcers (two cases), with small ulcers (one case), or with multiple erosions (one case). Urea breath test and antibody test were both negative. Eradication of H. heilmannii resulted in remission of MALT lymphoma. Helicobacter heilmannii infection is therefore uncommon in Japanese adults, but is associated with chronic gastritis and gastric MALT lymphoma.

Churg-Strauss syndrome (allergic granulomatous angitis) presenting with ileus caused by ischemic ileal ulcer

Abstract: We report a rare case of Churg-Strauss syndrome (CSS) in a 41-year-old Japanese man with a history of middle-age onset of bronchial asthma who had severe abdominal pain. He presented with ileus caused by an annular ulcer of the ileum, attributable to mucosal ischemia resulting from necrotizing vasculitis of the mesenteric artery. He also had marked hypereosinophilia (51.5%), elevated serum IgE levels (34040 IU/ml), and generalized enlargement of the superficial cervical lymph nodes, containing eosinophilic granulomas. A stenotic lesion caused by an annular ulcer in the ileum was found and resected by laparotomy. Microscopic examination of the resected specimen revealed luminal narrowing or occlusion of small arteries in the ulcer base, subserosa, and mesenterium resulting from marked fibrotic intimal thickening with fragmentation or lack of the internal elastic lamina. These findings were diagnosed as vasculitis, scar stage. The postoperative course was uneventful, with the patient receiving a maintenance dose of prednisolone (10–15 mg/day) for 7 years subsequently. We must carefully diagnose and treat patients with middle-age onset asthma, because the symptom may be a lung manifestation of CSS, in which various organs including gastrointestinal tract are involved as a result of systemic necrotizing vasculitis.

Malignant granular cell tumor of the esophagus

Sir, We have recently encountered an interesting case of a malignant granular cell tumor of the esophagus. The patient was a 71-year-old man who died of malignant granular cell tumor of the esophagus with pleural effusion and multiple liver metastases. The patient presented complaining of dysphagia for the past 10 months. A barium swallow showed a filling defect in the lower part of esophagus. Esophagogastroendoscopy showed a submucosal tumor with central ulceration located 35 cm distal from the incisor teeth. The computed tomography scan (CT) of his chest revealed a solid tumor mass measuring 6 4 cm in diameter with obstruction in the mid-esophagus. Biopsies of this area demonstrated a granular cell tumor. The patient subsequently underwent an esophagogastrectomy. The resected esophagus revealed a submucosal tumor in the mid-esophagus. It was a poorly defined mass, measuring 10 5 cm in length, with circumferential involvement. At the cut surface, the tumor was white, firm and involved beyond the proper muscle layer into the adventitia. Microscopically, tumor cells mainly grew in the submucosa and infiltrated beyond the proper muscle layer into the adventitia. The surgical margin was free of tumor cells. Pseudoepitheliomatous hyperplasia of the squamous epithelium overlying esophageal tumor was present. The tumor cells were arranged in small clusters divided by thin fibrous connective tissue septa (Fig. 1). The tumor cells showed oval, polygonal or spindle-shaped cytoplasm with abundant eosinophilic cytoplasmic granules (Fig. 1). Occasional mitotic figures were seen (mitotic index: 0.3%) (Fig. 1). In some areas, the tumor cells showed nuclear pleomorphism with prominent nuclear atypia. Small necrotic foci were present. Ovalshaped tumor cells with small blunt nuclei were noted to proliferate in the lamina propria, just beneath the esophageal epithelium. Lymph-node metastasis was not observed. Immunohistochemically, most tumor cells were positive for S-100 protein (Dako, CA, USA), keratan sulfate (Seikagaku Kogyo, Japan), neuron specific enolase (Dako), CD68 (Dako), and vimentin (Dako), and about one-third of tumor cells were positive for CD57 (Beckton Dickinson, CA, USA). Collagen type IV (Dako) was demonstrated around nests of tumor cells. The tumor cells showed no reactivity for carcinoembryonic antigen (Dako), myelin basic protein (Dako), CD34 (Dako), c-kit (Dako), chromogranin A (Dako), synaptophysin (Dako) and p53 (Dako). The tumor cells showed a higher Ki67 value (8.3%€2.1) than five cases of benign granular cell tumors used as controls (3.3%€2.9). In addition, the tumor cells with small blunt nuclei in the lamina propria, just beneath the esophageal epithelium, showed lower proliferative activity than the tumor cells showing pleoA. Yoshizawa · S. Kanai Department of Laboratory Medicine, Shinshu University Hospital, Matsumoto, Japan

Adenocarcinoma of the cervical oesophagus arising from ectopic gastric mucosa : the histochemical determination of its origin

A case of adenocarcinoma of the cervical oesophagus was examined by employing a battery of histochemical techniques and was demonstrated to arise from ectopic gastric mucosa. The patient was a 66-year-old Japanese male. Endoscopy revealed an ulcerated tumour on the right anterior wall of the cervical oesophagus, approximately 16 cm from the incisor teeth. Pathological examination of surgically removed specimens showed well-differentiated tubular adenocarcinoma. Ectopic gastric mucosa was found in the oesophageal mucosa adjoining the carcinoma. Histochemical stains for characterizing mucosubstances and immunostains for various antigens were used. In addition to this carcinoma, ectopic gastric mucosa in the oesophagus and normal oesophageal, cardiac, tracheal and bronchial mucosa were also examined. The results showed that the carcinoma contained mucins, which showed reactivities characteristic of the gastric surface mucous cell (galactose oxidase-cold thionin Schiff reactive) and gland mucous cell (paradoxical concanavalin A staining reactive). Ectopic gastric mucosa consistently contained these mucins, but other tissue sites lacked them.

Phylogeny of a novel "Helicobacter heilmannii" organism from a Japanese patient with chronic gastritis based on DNA sequence analysis of 16S rRNA and urease genes.

Abstract“Helicobacter heilmannii” is an uncultivable spiral-shaped bacterium inhabiting the human gastric mucosa. It is larger and more tightly-coiled than H. pylori. We encountered a patient with chronic gastritis infected a “H. heilmannii”-like organism (HHLO), designated as SH6. Gastric mucosa derived from the patient was orally ingested by specific pathogen free mice. Colonization of the mice by SH6 was confirmed by electron microscopy of gastric tissue specimens. In an attempt to characterize SH6, 16S rRNA and urease genes were sequenced. The 16S rRNA gene sequence was most similar (99.4%; 1,437/1,445 bp) to HHLO C4E from a cheetah. However, the urease gene sequence displayed low similarity (81.7%; 1,240/1,516 bp) with HHLO C4E. Taxonomic analysis disclosed that SH6 represents a novel strain and should constitute a novel taxon in the phylogenetic trees, being discriminated from any other taxon, with the ability of infecting human gastric mucosa.

Relation between bile acid reflux into the stomach and the risk of atrophic gastritis and intestinal metaplasia: A multicenter study of 2283 cases

The relationship between bile acid reflux into the stomach and the risk of atrophic gastritis and intestinal metaplasia is still not well understood. Towards obtaining a better understanding, concentrations of bile acids were measured.

A case of multiple cavernous hemangioma of the small intestine and clinical review of the Japanese literature

SummaryWe report a case of multiple cavernous hemangioma of the small intestine which was diagnosed definitively before operation. A 33-yr-old male was found to have multiple polypoid lesions in the small intestine during examination for recurrent iron deficiency anemia. Plain X-ray film of the abdomen revealed multiple calcifications in the middle to lower region, suggestive of cavernous hemangioma, which was further confirmed by angiography and scintigraphy with Tc 99m-labeled red blood cells. Endoscopy during surgery was used to determine the extent of surgical resection. Seventy-three cases of hemangioma of the small intestine were reported in Japan between 1953 and 1988 and their clinical features were reviewed.

Histone H3 mRNA in situ hybridization for identifying proliferating cells in human pancreas, with special reference to the ductal system.

In general, the incidence of proliferating cells parallels that of carcinogenesis. We have investigated proliferating activity and phenotype expression in epithelial cells in normal tissue, mucinous metaplasia and ductal adenocarcinoma of the pancreas. Twenty-eight resected pancreases (15 cases of pancreatic ductal adenocarcinoma and 13 cases of other diseases) were examined. Formalin-fixed, paraffin-embedded tissue sections were examined for proliferating cell activity using histone H3 mRNA in situ hybridization and immunostaining for Ki-67. In the normal pancreas, the labelling indices for proliferating cells were low and no generating zone was found. The following progressive increase was found in the labelling indices: normal ductal epithelium < mucinous metaplasia without papillary hyperplasia < mucinous metaplasia with papillary hyperplasia < ductal carcinoma. In the pancreatic ductal adenocarcinomas, the S-phase fraction, as defined by the ratio H3-mRNA-labelling index/Ki-67-labelling index, increased as the degree of differentiation decreased. Mucinous metaplasia with papillary hyperplasia showed organoid differentiation toward pyloric mucosa. If used in combination with other proliferative markers on paraffin-embedded tissue sections, histone H3 mRNA in situ hybridization could open broader perspectives on the biology of cell proliferation in the pancreatic ductal system.

CASE REPORT: Rapid Four-Month Growth of an Early-Stage Adenocarcinoma of the Colon with Neuroendocrine Characteristics

Since neuroendocrine cells of the endocrine tissues (1) and gastrointestinal tract (2) were identified immunohistochemically with the aid of chromogranin, a protein secreted from adrenal medulla cells, chromogranin A (CGA) antibodies have been widely used to detect neuroendocrine cells in adenocarcinomas of the gastrointestinal tract. In addition, these antibodies have been used to determine the incidence and clinicopathological features of advanced adenocarcinomas of the colon with neuroendocrine characteristics (3–11). We report here a rare case of an earlystage colonic adenocarcinoma with neuroendocrine cells and with an endoscopically observed change in shape from superficial depressed-type to superficial elevated-type during the four-month follow-up period.