Influence of Helicobacter Pylori Infection on Hepcidin Expression in the Gastric Mucosa.

BACKGROUND: Hepcidin is an antimicrobial peptide and a key hormone involved in iron homeostasis. Hepcidin level is elevated in the serum during the course of Helicobacter pylori infection and hepcidin is considered to contribute to iron deficiency anemia. However, it is unclear whether H. pylori infection influences hepcidin expression in the gastric mucosa. METHOD: In this study, 15 patients with H. pylori-infected nodular gastritis, 43 patients with H. pylori-infected chronic gastritis, and 33 patients without H. pylori infection were enrolled. Endoscopic biopsy, and histological and immunohistochemical analysis were performed to evaluate the expression of hepcidin and its distribution in the gastric mucosa. RESULT: Hepcidin was strongly expressed in the lymph follicles of patients with nodular gastritis. The detection rates of gastric hepcidin-positive lymphocytes in patients with nodular gastritis and chronic gastritis were significantly higher than that without H. pylori infection. Moreover, regardless of the H. pylori infection status, hepcidin was expressed in the cytoplasm and intracellular canaliculi of gastric parietal cells. CONCLUSION: Hepcidin is expressed at a steady state in gastric parietal cells, and H. pylori infection may induce hepcidin expression in lymphocytes present in the gastric mucosal lymphoid follicles. This phenomenon may be associated with systemic hepcidin overexpression and iron deficiency anemia in patients with H. pylori-infected nodular gastritis.

Electrical stimulation-based evaluation for functional modification of renal autonomic nerve activities induced by catheter ablation.

BACKGROUND: Catheter ablation of the renal artery can be performed without apparent angiographic stenosis. This suggests that renal nerve function can be attenuated with minor structural damage to the renal artery. OBJECTIVE: To clarify this hypothesis, we examined the relationship between electrical nerve stimulation (ENS)-induced blood pressure (BP) response and severity of histological injury of the renal artery using an acute canine model of renal artery ablation. METHODS: An irrigation catheter was inserted into the renal arteries of 8 dogs, and radiofrequency current was delivered at 15, 20, or 25 W. ENS was applied to each artery before and after ablation. RESULTS: Before ablation, ENS increased the BP and heart rate from 145 ± 15/86 ± 13 to 189 ± 21/111 ± 19 mm Hg and from 116 ± 9 to 130 ± 6 beats/min, respectively. Heart rate variability indices and serum catecholamine levels were elevated concomitantly. After ablation, the ENS-induced increase in BP and heart rate were markedly attenuated after 15 W ablation and those were nearly completely inhibited after 20 or 25 W ablation. An increase in heart rate variability indices and serum catecholamine levels became insignificant regardless of the applied energy. Renal artery angiograms revealed stenotic lesions only after 25 W ablation procedures. Histological studies showed mild to moderate injury of the arterial wall and autonomic nerves caused by 20 and 25 W ablation procedures, whereas only minor changes caused by 15 W ablation. CONCLUSION: Functional renal autonomic nerve ablation is potentially performable with the guidance of ENS.

Digestive disease management in Japan: a report on the 6th diagnostic pathology summer fest in 2012.

The 6th Diagnostic Pathology Summer Fest, held in Tokyo on August 25-26, 2012, opened its gates for everyone in the medical profession. Basic pathology training can contribute to the improvement of algorithms for diagnosis and treatment. The 6th Summer Fest with the theme 'Pathology and Clinical Treatment of Gastrointestinal Diseases' was held at the Ito International Research Center, The University of Tokyo. On August 25, 'Treatment of Early Gastrointestinal Cancer and New Guidelines' was discussed in the first session, followed by 'Biopsy Diagnosis of Digestive Tract: Key Points of Pathological Diagnosis for Inflammation and Their Clinical Significance' in the second session. On August 26, cases were discussed in the third session, and issues on pathological diagnosis and classification of neuroendorcrine tumor in the fourth session. The summaries of speeches and discussions are introduced along with the statements of each speaker. This meeting was not a formal evidence-based consensus conference, and 20 experts gave talks on their areas of specialty. Discussion was focused on how the management strategy should be standardized on the algorithm of patient care.

Usefulness of endoscopic submucosal dissection for type I gastric carcinoid tumors compared with endoscopic mucosal resection.

BACKGROUND/AIMS: Gastric carcinoid tumors (GCTs) often extends into the submucosa, and are therefore difficult to resect completely by using conventional endoscopic mucosal resection (EMR). Endoscopic submucosal dissection (ESD) allows en bloc resection of submucosal gastrointestinal lesions. Therefore, ESD may be a feasible method for complete resection of GCT. Our purpose is to clarify the usefulness of ESD for treatment of type I GCT. METHODOLOGY: Between 1998 and 2011, EMR or ESD was performed for 13 lesions in 12 patients with type I GCTs. Among the 13 GCTs, 6 were resected using EMR, and 7 were removed using ESD. RESULTS: All lesions were histologically classified as Grade 1. The depth of invasion was the mucosa for 1 lesion and the submucosa for 12 lesions. The horizontal margins of excision were negative for all lesions; however, the vertical margins were positive in 4 lesions (66.7%) in the EMR group and no lesions (0%) in the ESD group. CONCLUSIONS: The results of this study suggest that ESD for small type I GCT is better to achieve complete resection than conventional EMR. ESD would be an effective technique for the treatment of small type I GCT.

Blood pressure and autonomic responses to electrical stimulation of the renal arterial nerves before and after ablation of the renal artery.

Radiofrequency (RF) catheter ablation of the renal artery is therapeutic in patients with drug-refractory essential hypertension. This study was designed to examine the role of the renal autonomic nerves and of RF application from inside the renal artery in the regulation of blood pressure (BP). An open irrigation catheter was inserted into either the left or right renal artery in 8 dogs. RF current (17 ± 2 watts) was delivered to one renal artery. Electrical autonomic nerve stimulation was applied to each renal artery before and after RF ablation. BP, heart rate, indices of heart rate variability, and serum catecholamines were analyzed. Before RF ablation, electrical autonomic nerve stimulation of either renal artery increased BP from 150 ± 16/92 ± 15 to 173 ± 21/105 ± 16 mm Hg. After RF ablation, BP increased similarly when the nonablated renal artery was electrically stimulated, although the rise in BP was attenuated when the ablated renal artery was stimulated. Serum catecholamines and sympathetic nerve indices of heart rate variability increased when electrical autonomic nerve stimulation was applied before RF ablation and to the nonablated renal artery after RF ablation, although it changed minimally when the ablated renal artery was stimulated, suggesting interconnectivity between afferent renal nerve stimulation and systemic sympathetic activity. Renal artery angiogram showed no apparent injury after RF ablation. In conclusion, electrical stimulation of the renal arterial autonomic nerves increases BP via an increase in central sympathetic nervous activity. This response might be used to determine the target ablation site and end point of renal artery RF ablation.

[Investigation on the affinity between questions in the national examination for medical technologists and student level of education in the course of laboratory medicine--nine years history of the committee evaluating appropriate questions].

In order to evaluate the each question in the National Examination for Medical Technologist by comparison with the educated level in the course of laboratory medicine and the practical level of medical technologists, the investigation has been carried out by our committee established in the National University Association for Education of Laboratory Medicine during 9 years since 1997. The committee has asked each school of the 20 members of the Association to pick up good and/or inappropriate questions with the reasons why they are classified as good or improper ones. Some questions were considered as good ones by a large number of schools, while the others were considered improper. The reasons for the judgment have been sometimes very controversial and opinions uncommonly run counter to each other. It is suggested that a good question may become to be improper when the questionnaire is carelessly arranged even if the concept of the question is initially well considered. It is presumed that the annual reports of our committee may have played a role to gain common recognition that the numbers of the inappropriate questions have been decreasing in the recent National Examination for Medical Technologist.

Severe gastrointestinal involvement in paraneoplastic pemphigus.

Paraneoplastic pemphigus (PNP) is an autoimmune mucocutaneous disease, associated with neoplasia, which has characteristic clinical, histological and immunological features. While respiratory epithelial involvement has been described in several cases, lesions in the colon epithelium have never been reported. We describe a 57-year-old Japanese woman with PNP who had many aphthae-like erosions on the colon epithelium, in addition to typical mucocutaneous PNP lesions. The intestinal erosions had histological features similar to those of PNP and linear deposition of complement, but not IgG, was observed along the colon epithelial basement membrane.

[Diagnosis and treatment of carcinoid tumors in the gastrointestinal tract].

Histopathologically and biologically, endocrine cell tumors in the gastrointestinal tract are divided into two groups: 1) carcinoid, a low-grade malignancy, and 2) endocrine cell carcinoma (synonymous with small cell carcinoma), a high-grade malignancy. Atypical carcinoid, which has increased histological atypia and proliferative activity, shows more aggressive biological behavior than classical carcinoid. As a rule, endocrine cell carcinoma should be resected surgically with dissection of lymph nodes and adjuvant therapy if needed, while carcinoid should be treated by endoscopic resection or localized resection without lymph node dissection. Classical carcinoid of more than 2.0 cm in size and atypical carcinoid should be treated more carefully because of the increased risk of vascular permeation or distant metastasis.

Carcinogenesis of gastric endocrine cell carcinoma: analysis of histopathology and p53 gene alteration.

BACKGROUND: Endocrine cell carcinoma of the stomach is characterized by endocrine differentiation and aggressive biological behavior, and is frequently accompanied by an adenocarcinoma component. Because the carcinogenic parthway and genetic alterations remain unclear, we investigated the histogenesis of the tumor by histopathological and p53 gene analysis. METHODS: The materials were 68 gastric endocrine cell carcinomas and 30 carcinoid tumors, which were resected from 93 Japanese patients for histopathological and immunohistochemical investigation. We also analyzed the concordance of p53 mutational status between the associated adenocarcinoma and endocrine cell carcinoma components, using microdissection and direct sequencing techniques. RESULTS: An adenocarcinoma component was associated with 70.6% (48/68) of endocrine cell carcinomas, of which 42 (87.5%) were of well- to moderately differentiated type, while 36 of these 42 (85.7%) demonstrated histological continuity with the endocrine cell carcinoma components. Overexpression of p53 protein was observed in 58.8% (20/34) of cases. Common p53 mutational status between the two components was revealed in 73.3% (11/15) of cases analyzed. In contrast, carcinoid tumors did not exhibit p53 protein overexpression (0/15) or gene mutation (0/5). CONCLUSIONS: These data suggest that gastric endocrine cell carcinomas predominantly arise from endocrine precursor cell clones occurring in preceding adenocarcinoma components (particularly the differentiated type), transforming into endocrine cell carcinoma during rapid clonal expansion under the influence of p53 gene alteration. Endocrine cell carcinoma of the stomach is characterized by endocrine differentiation and aggressive biological behavior, and is frequently accompanied by an adenocarcinoma component. Because the carcinogenic pathway and genetic alterations remain unclear, we investigated the histogenesis of this tumor by histopathological and p53 gene analysis.

Pancreatic T-cell lymphoma with high level of soluble interleukin-2 receptor.

An 82-year-old man was admitted to hospital with symptoms of abdominal fullness and loss of appetite. Abdominal computed tomography (CT) scan and ultrasonography showed enlargement of the whole pancreas with para-aortic lymphadenopathy. Endoscopic retrograde pancreatography (ERP) showed diffuse narrowing of the main pancreatic duct (MPD), and brushing cytology from the MPD was non-neoplastic. Differential diagnosis between lymphoma and other exocrine and endocrine pancreatic malignancies was needed, and the level of serum soluble interleukin-2 receptor (17 751 U/ml) was revealed to be significantly high, which was strongly suggestive of pancreatic lymphoma. Chemotherapy was refused by the patient's family and the patient succumbed after 2 months of conservative follow-up. Autopsy revealed diffuse, mixed cell-type, non-Hodgkin's lymphoma of T-cell subtype.

Gastric carcinoid tumors without autoimmune gastritis in Japan: a relationship with Helicobacter pylori infection.

In Japan, most cases of gastric carcinoid tumor (GCT) are unassociated with either autoimmune gastritis (AIG) showing type-A chronic atrophic gastritis (CAG-A) or Zollinger-Ellison syndrome (ZES). However, the pathogenesis of this tumor remains unknown. Recent studies have determined that Helicobacter pylori infection induces gastric carcinoid in Mongolian gerbils and that H. pylori lipopolysaccharide exerts a mitogenic effect on ECL cells. We examined five patients with histologically diagnosed GCT, 40 patients with H. pylori-positive gastric ulcer (Hp+GU), 24 patients with H. pylori-positive duodenal ulcer (Hp+DU), and 12 patients with AIG showing CAG-A topographically. We compared the prevalence of H. pylori infection, and the levels of gastrin and pepsinogen (PG) in the serum of patients with GCT with those of patients with Hp+GU, or Hp+DU, and AIG. We also investigated the histological characteristics of the tumor and the gastric corpus mucosa in the GCT patients. The levels of serum gastrin and PG I and II were measured using an RIA kit. In all five (100%) patients with GCT, H. pylori infection was present, without any evidence of AIG or ZES. The serum levels of gastrin in the GCT patients were higher than those in either Hp+GU or Hp+DU patients and lower than those in the AIG patients. In contrast, serum PG I levels and the PG I/II ratio were lower in the GCT group than in the Hp+GU or Hp+DU groups. Histologically, all GCTs were ECL cell tumors and peritumoral corporal mucosal atrophy was observed in four of the five patients with GCT. In conclusions, H. pylori infection and hypergastrinemia were found in the patients with GCT without AIG. This finding suggests that H. pylori infection may induce corporal mucosal atrophy and hypergastrinemia that can produce a GCT with time.

Advanced gastric glandular-endocrine cell carcinoma with 1-year survival after gastrectomy.

Primary gastric endocrine cell carcinoma (ECC) is extremely rare. In general, when it is advanced, gastric ECC causes extensive ulceration (type 2) and invades or metastasizes to other organs, frequently to the liver and sometimes to the lungs or bones, and carries a poor prognosis. We herein report a 67-year-old man with advanced gastric ECC of extensive-polypoid shape (type 1) but without distant metastasis, who underwent total gastrectomy and treatment with oral tegafur-uracil (UFT), and showed no sign of recurrence 1 year later.