Suitability of the expanded indication criteria for the treatment of early gastric cancer by endoscopic submucosal dissection: Japanese multicenter large-scale retrospective analysis of short- and long-term outcomes.

OBJECTIVE: The criteria for endoscopic resection for early gastric cancer include absolute and expanded indications. Consensus already exists for the absolute indications. However, the suitability of the expanded indications must be validated by long-term outcome analyses since such lesions have only recently become resectable with the development of endoscopic submucosal dissection. The aim of this study is to clarify the suitability of the expanded indications for the treatment of early gastric cancer with endoscopic submucosal dissection. MATERIALS AND METHODS: The medical records of 1161 patients with early gastric cancers (1332 lesions) treated by endoscopic submucosal dissection and meeting the criteria for absolute or expanded indications without additional treatment with gastrectomy were divided into absolute indication group or expanded indication group. RESULTS: Complete resection rates were 96.4% and 93.4% in absolute and expanded indication groups, respectively, with no significant differences between the groups. Delayed bleeding rates were significantly higher in the expanded indication group, whereas all cases were successfully managed conservatively. The 5-year overall survival and recurrence-free rates were 93.7%/99.77% and 90.49%/98.90% in the absolute and the expanded indication groups, respectively, with no significant differences between the groups for either measure. Multivariate analyses revealed that affected horizontal margin and tumor location were independent predictive factors for recurrence. CONCLUSION: The expanded indication group showed excellent post-endoscopic submucosal dissection short-term and long-term outcomes compared with the absolute indications group, demonstrating that expanded indications are suitable for endoscopic submucosal dissection for early gastric cancer.

Mucosal-incision assisted biopsy for suspected gastric gastrointestinal stromal tumors.

To evaluate the diagnostic yield of the procedure, mucosal-incision assisted biopsy (MIAB), for the histological diagnosis of gastric gastrointestinal stromal tumor (GIST), we performed a retrospective review of the 27 patients with suspected gastric GIST who underwent MIAB in our hospitals. Tissue samples obtained by MIAB were sufficient to make a histological diagnosis (diagnostic MIAB) in 23 out of the 27 patients, where the lesions had intraluminal growth patterns. Alternatively, the samples were insufficient (non-diagnostic MIAB) in remaining 4 patients, three of whom had gastric submucosal tumor with extraluminal growth patterns. Although endoscopic ultrasound and fine needle aspiration is the gold standard for obtaining tissue specimens for histological and cytological analysis of suspected gastric GISTs, MIAB can be used as an alternative method for obtaining biopsy specimens of lesions with an intraluminal growth pattern.

Characteristics of hemorrhagic peptic ulcers in patients receiving antithrombotic/nonsteroidal antiinflammatory drug therapy.

BACKGROUND/AIMS: Antithrombotic/nonsteroidal antiinflammatory drug (NSAID) therapies increase the incidence of upper gastrointestinal bleeding. The features of hemorrhagic peptic ulcer disease in patients receiving antithrombotic/NSAID therapies were investigated. METHODS: We investigated the medical records of 485 consecutive patients who underwent esophagogastroduodenoscopy and were diagnosed with hemorrhagic gastroduodenal ulcers. The patients treated with antithrombotic agents/NSAIDs were categorized as the antithrombotic therapy (AT) group (n=213). The patients who were not treated with antithrombotics/NSAIDs were categorized as the control (C) group (n=263). The clinical characteristics were compared between the groups. RESULTS: The patients in the AT group were significantly older than those in the C group (p<0.0001). The hemoglobin levels before/without transfusion were significantly lower in the AT group (8.24±2.41 g/dL) than in the C group (9.44±2.95 g/dL) (p<0.0001). After adjusting for age, the difference in the hemoglobin levels between the two groups remained significant (p=0.0334). The transfusion rates were significantly higher in the AT group than in the C group (p=0.0002). However, the outcome of endoscopic hemostasis was similar in the AT and C groups. CONCLUSIONS: Patients with hemorrhagic peptic ulcers receiving antithrombotic/NSAID therapies were exposed to a greater risk of severe bleeding that required transfusion but were still treatable by endoscopy.

An inverse correlation of human peripheral blood regulatory T cell frequency with the disease activity of ulcerative colitis.

Evidence suggests that CD4+CD25+ regulatory T cells play a crucial role in the suppression of intestinal inflammation. However, their role in the suppression of inflammatory bowel disease has not yet been addressed. We examined the proportion of regulatory T cells in inflammatory bowel disease. First, we isolated CD4+CD45RO+CD25+ T cells from the peripheral blood of healthy persons and showed that these cells suppressed T cell proliferation profoundly and expressed FoxP3 abundantly, revealing that they are regulatory cells. Then the proportion of CD45RO+CD25+ in peripheral blood CD4+ T cells was analyzed in patients and healthy controls by flow cytometry. CD4+CD45RO+CD25+ T cell frequency was significantly lower in active ulcerative colitis than in the control and inactive ulcerative colitis. CD4+CD45RO+CD25+ T cell frequency was inversely correlated with the clinical and endoscopic severity of ulcerative colitis. These results suggest that a deficiency of regulatory T cells is associated with the progression of ulcerative colitis.

Somatic DNA recombination yielding circular DNA and deletion of a genomic region in embryonic brain.

In this study, a mouse genomic region is identified that undergoes DNA rearrangement and yields circular DNA in brain during embryogenesis. External region-directed inverse polymerase chain reaction on circular DNA extracted from late embryonic brain tissue repeatedly detected DNA of this region containing recombination joints. Wide-range genomic PCR and digestion-circularization PCR analysis showed this region underwent recombination accompanied with deletion of intervening sequences, including the circularized regions. This region was mapped by fluorescence in situ hybridization to C1 on mouse chromosome 16, where no gene and no physiological DNA rearrangement had been identified. DNA sequence in the region has segmental homology to an orthologous region on human chromosome 3q.13. These observations demonstrated somatic DNA recombination yielding genomic deletions in brain during embryogenesis.

Novel germline mutation of the PTEN gene in a Japanese family with Cowden disease.

We report a novel germline mutation of the PTEN gene in a Japanese family with Cowden disease. A 46-year-old Japanese man and his mother were diagnosed as having Cowden disease. Their physical examinations revealed multiple facial trichilemmoma, oral mucosal papillomatosis, palmoplantar keratosis, and gastrointestinal polyposis. The single-strand conformation polymorphism (SSCP) analysis showed an abnormal band on exon 7 of their PTEN gene. Direct sequence analysis of exon 7 detected a TAAA insertion to codon 221, producing a stop codon (c.663ins TAAA).

Gastric mucosa-associated lymphoid tissue lymphoma with adult T cell leukemia/lymphoma cell infiltration. case report.

This is the first case report of gastric mucosal-associated lymphoid tissue lymphoma with adult T cell leukemia/lymphoma (ATLL) cell infiltration. A 43-yr-old Japanese woman who was seropositive for antihuman T cell leukemia virus-I antibody complained of epigastric pain in April, 1996. Endoscopy showed gastric ulcers in the antrum. Biopsy specimens showed Helicobacter pylori infection. Her symptoms were relieved by treatment with ranitidine. In March, 1998, she complained of epigastric pain and abdominal fullness. Smears of peripheral blood revealed atypical lymphocytes with nuclear irregularity, consistent with ATLL cells. She was diagnosed to have ATLL. Endoscopy revealed multiple gastric ulcers in the antrum and the angle. Biopsy specimens demonstrated small centrocyte-like cells forming lymphoepithelial lesions, with infiltrations of large atypical lymphoid cells of ATLL. On immunohistochemical staining, the small centrocyte-like cells were positive for B cell markers (L26, CD20), whereas the large atypical lymphoid cells were positive for T cell marker (UCHL-1, CD45RO). Her findings were attributed to gastric mucosal-associated lymphoid tissue lymphoma with gastric involvement with ATLL.