Autofluorescence imaging colonoscopy for the diagnosis of dysplasia in ulcerative colitis.
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Publications and source records attributed to Takashi Yao.
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PURPOSE: Phospholipase A2 Group IIa has been suggested to be a possible disease modifier gene in familial adenomatous polyposis. This investigation was designed to elucidate possible association between phospholipase A2 Group IIa polymorphism and phenotypes of patients with familial adenomatous polyposis. METHODS: Phospholipase A2 Group IIa was examined by polymerase chain reaction-based single strand conformation polymorphism and direct sequencing in 55 patients from 45 families with familial adenomatous polyposis. The patients were examined by gastroduodenoscopy plus biopsy with respect to fundic gland polyposis and gastroduodenal adenomas. Helicobacter pylori status was determined by rapid urease test. Contributions of genetic alteration and Helicobacter pylori infection to intestinal and extraintestinal lesions were investigated. RESULTS: Four types of single nucleotide polymorphism were found in exon 3 of phospholipase A2 Group IIa, among which single nucleotide polymorphism in codon 32 was the most frequent. The prevalence of fundic gland polyposis was higher in patients positive for single nucleotide polymorphism of phospholipase A2 Group IIa than those negative for single nucleotide polymorphism (61 vs. 33 percent; P < 0.05). In contrast, positive rate of Helicobacter pylori infection was lower in the former than in the latter (22 vs. 52 percent; P < 0.05). The prevalence of the other phenotypes was not different significantly. Logistic regression analysis revealed a possibility toward single nucleotide polymorphism of phospholipase A2 Group IIa as an independent risk factor for fundic gland polyposis (95 percent confidence interval, 00.9-14.3; P = 0.06). CONCLUSIONS: Phospholipase A2 Group IIa may be a modifier gene for fundic gland polyposis in patients with familial adenomatous polyposis.
BACKGROUND: The majority of gastric mucosa-associated lymphoid tissue (MALT) lymphoma develops in Helicobacter pylori-associated chronic gastritis. Little is still known regarding the clinicopathologic features of gastric MALT lymphoma not associated with H. pylori infection. METHODS: One hundred thirty-seven patients with gastric MALT lymphoma, in whom H. pylori status was evaluated using at least both serology and histology, were enrolled. Clinical, histopathologic, and molecular findings were compared between H. pylori-negative group (n = 12; 9%) and H. pylori-positive group (n = 125; 91%). t(11;18)(q21;q21) was investigated by reverse-transcription polymerase chain reaction and interphase fluorescence in situ hybridization. RESULTS: In cases without diffuse large B-cell lymphoma (DLBCL) component, H. pylori-negative lymphomas located more frequently in the proximal stomach (70%), less frequently appeared as superficial type (40%), and frequently invaded the submucosa or beyond (70%). Histologically, lymphoepithelial lesions (57%), lymphoid follicles (43%), and background mucosal atrophy (50%) in the H. pylori-negative group were less frequent than in the H. pylori-positive group (91%, 93%, and 100%, respectively). The frequencies of t(11;18)(q21;q21) (100%) and BCL10 nuclear expression (100%) in the H. pylori-negative group were significantly higher than in the H. pylori-positive group (2% and 27%, respectively). Response to antibiotic treatment was observed not only in the H. pylori-positive group (75%), but also in the H. pylori-negative group (2 of 7 patients, 29%). In cases with a DLBCL component, such differences were not observed between the 2 groups. CONCLUSIONS: H. pylori-negative gastric MALT lymphoma is characterized by frequent t(11;18)(q21;q21). Antibiotic treatment should be considered also for this disease, although cases with t(11;18)(q21;q21) may need additional strategies.
Although there are some case reports of combined aldosterone and cortisol producing adrenal tumor, overt diabetes mellitus has been rarely described. A 55-year-old hypertensive woman had hypokalemia and overt hyperglycemia without Cushingoid clinical features. The body mass index was 18.2 kg/m2, fasting blood glucose was 302 mg/dl and hemoglobin A1c was 11.6%. Endogenous insulin secretion was well preserved, whereas insulin sensitivity measured by short insulin tolerance test was markedly impaired. A solitary left aldosterone- and cortisol-producing adrenal tumor was diagnosed. We described a rare case of overt diabetes mellitus in a patient with combined primary aldosteronism and Cushing's syndrome.
The aim of this investigation was to clarify the histological characteristics of gastric cancer in the young. Twenty-three surgically resected specimens of young patients (under 30 years of age; young group) with intramucosal cancer of poorly differentiated type and 42 surgically resected specimens of elderly patients (more than 40 years of age; elderly group) with tumors of the identical depth and histological type were examined. The degree of gastritis and Helicobacter pylori (H. pylori) infection was evaluated according to the updated Sydney system. The incidence of H. pylori infection was significantly higher in the young group than in the elderly group (96 vs 36%, P<0.05). Within the background mucosa, antral chronic inflammatory infiltrates with lymphoid-follicle hyperplasia were more severe, and intestinal metaplasia was less frequent in the young group than in the elderly group. Glandular atrophy was not different between the two groups. Intramucosal gastric adenocarcinomas of poorly differentiated type in the young may be associated with H. pylori infection with antral chronic inflammation with lymphoid-follicle hyperplasia, regardless of the existence of intestinal metaplasia within the background gastric mucosa.
Chronic nonspecific multiple ulcers of the small intestine (CNSU) and nonsteroidal anti-inflammatory drug-induced enteropathy (NSAID-enteropathy) share common clinicopathologic features characterized by histologically nonspecific ulcers and persistent blood loss. The aim was to compare enteroscopic findings between CNSU and NSAID-enteropathy. Four patients with CNSU and five patients with NSAID-enteropathy were examined by enteroscopies. The site of involvement was heterogeneous in NSAID-enteropathy, while the ileum was the predominant site in CNSU. Three patients with NSAID-enteropathy and all four patients with CNSU had concentric stenosis. Circular ulcers were found in all five patients with NSAID-enteropathy and in three patients with CNSU. Active ulcer was seen in only two patients with NSAID-enteropathy. In contrast, all four patients with CNSU had active ulcer. These findings suggest that in patients with persistent GI bleeding and enteroscopically active small intestinal ulcers, CNSU, as well as NSAID-enteropathy, should be considered.
AIM: Minimal deviation carcinoma of the uterine cervix, otherwise known as extremely well-differentiated adenocarcinoma (EWDA), is characterized by its benign microscopic appearance in contrast to its aggressive behavior. In order to elucidate the clinicopathological features and biological behavior of the gastric counterpart of EWDA, we, using immunohistochemistry, analyzed nine lesions for the phenotypic expression, proliferative activity, and the expression of oncogene-associated products. METHODS: Clinicopathological features, including pre-operative biopsy diagnosis, were reviewed. Using immunohistochemistry, Ki-67 labeling index and expression of p53 and c-erbB-2 protein in the gastric lesions were detected. RESULT: Locations in the middle or upper third of the stomach and polypoid macroscopic features are characteristic of EWDA of the stomach. Although 4 of the 9 lesions showed only focal lymphatic or venous invasion, lymph node metastasis was not present and none of the patients died of the lesions (mean follow-up period, 56 mo). All 9 cases of EWDA could be classified into gastric phenotype (5 lesions) and intestinal phenotype (4 lesions). The former resembled gastric foveolar epithelium, mucous neck cells or pyloric glands, but their papillary structures were frequently elongated and the tumor cells and their nuclei were slightly larger and more hyperchromatic compared to normal epithelium. The latter resembled intestinal metaplasia with minimal nuclear atypia and irregular glands; two of these lesions demonstrated complete intestinal phenotype, while two demonstrated incomplete intestinal phenotype. Ki-67 labeling index was low and none of the cases revealed over-expression of p53 and c-erbB-2 protein. CONCLUSION: Unlike minimal deviation carcinoma of the cervix, these findings suggest that EWDA of the stomach is a lesion of low-grade malignancy. This favorable biological behavior is supported by the data of a low Ki-67 labeling index and a lack of p53 or c-erbB-2 protein over-expression. Because of its resemblance to normal gastric mucosa or mucosa with intestinal metaplasia, EWDA is often misdiagnosed. To prevent the misdiagnosis of such lesions, the clinical and pathologic characteristics should be taken into consideration.
This report describes an extremely rare adult case of an omphalomesenteric cyst resected by laparoscopic-assisted surgery. A 29-years-old Japanese man was referred and admitted to Kyushu University Hospital because of an abdominal mass and an elevated serum CEA (carcinoembryonic antigen) level (21.3 ng/mL) in August 2001. Abdominal CT and US demonstrated a cystic mass with septum and calcification. Laparoscopy showed a large mass to be attached to his abdominal wall, measuring 110 mm x 70 mm x 50 mm and filled with mucus. The mass was resected by laparoscopic-assisted surgery. The histological findings of its wall showed fibromuscular tissue, adipose tissue, calcification, and an intestinal structure. It was finally diagnosed to be an omphalomesenteric cyst.
BACKGROUND AND OBJECTIVE: Diagnostic accuracy of probe EUS depends on the constant maintenance of luminal medium for acoustic coupling. This study compared the accuracy of probe EUS by a jelly-filled method (EUS-J) and by a water-filled balloon method (EUS-W) for the assessment of invasion depth in superficial esophageal cancer. DESIGN AND SETTING: A prospective, single-center study. PATIENTS: Forty superficial esophageal cancers in 38 patients. INTERVENTIONS: Patients were alternately assigned to EUS-J or EUS-W. The depth of invasion was classified into epithelium or lamina propria mucosae (D1), muscularis mucosae or superficial layer of the submucosa (D2), and deep portion of the submucosa (D3). Depiction rate, interobserver variation between 2 observers, and accuracy for the determination of invasion depth were compared between EUS-J and EUS-W. MAIN OUTCOME MEASUREMENTS AND RESULTS: Eighteen cancers were examined by EUS-J, and 22 cancers were examined by EUS-W. The actual depth of invasion was D1 in 21 cancers, D2 in 9 cancers, and D3 in 10 cancers. Depiction rate (94.4% vs 77.2%, P = .14) and interobserver agreement of EUS determination (82.3% vs 58.8%, P = .13) was higher in EUS-J than in EUS-W. The overall accuracy for the diagnosis of invasion depth was 77.8% in EUS-J and 59.1% in EUS-W (P = .18). The sensitivity for the diagnosis of D1 cancer was significantly higher in EUS-J than in EUS-W (100% vs 50%, P = .03), while the specificity was not different between the 2 procedures (81.8% vs 87.5%). CONCLUSIONS: EUS-J is superior to EUS-W for the assessment of invasion depth in superficial esophageal cancer, especially for intramucosal cancer.
BACKGROUND: The aim of the present study was to elucidate the effect of sulindac on uncolectomized familial adenomatous polyposis (FAP). METHODS: Seven FAP patients (SU group) without proctocolectomy were given sulindac 300 mg/day orally for 12 months. Six FAP patients without sulindac (non-SU group) served as controls. Colorectal lesions were assessed by protrusion index (no. radiolucent areas/cm(2); PI) under barium enema examination and non-polypoid lesion were assessed under chromoscopy prior to and at the end of the observation period. In the SU group, germline adenomatous polyposis coli (APC) mutation was determined by protein truncation test. RESULTS: In the SU group, PI decreased significantly in the distal colon (from 3.0 +/- 1.1 to 1.1 +/- 0.8/cm(2), P < 0.02) and in the proximal colon (from 3.4 +/- 2.4 to 0.9 +/- 1.3/cm(2), P < 0.02). The PI in the non-SU group slightly but significantly increased in the distal colon (from 1.0 +/- 0.8 to 1.2 +/- 0.9/cm(2); P < 0.05) and it remained unchanged in the proximal colon (from 0.6 +/- 0.3 to 0.7 +/- 0.3/cm(2); P > 0.05). Chromoscopy at the end of observation identified non-polypoid lesions in five patients in the SU group, whereas such lesions were not found in the non-SU group (71% vs 0%, P = 0.016). Decrease in PI was not different among distal APC mutation (exons 1-9), proximal APC mutation (exons 10-15) and negative mutation. CONCLUSION: Sulindac reduces colorectal adenomas of protruding type in uncolectomized FAP. The effect of sulindac may be unrelated to genotype of FAP.
Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal neoplasm, and malignant cases are extremely rare. A case of malignant PEComa arising in the colon is described herein. The patient was a 43-year-old Japanese woman without a history of tuberous sclerosis complex. The tumor occurred in the abdominal cavity attached to the serosal side of the descending colon. Histologically, the tumor consisted of sheets or closely packed nests of epithelioid cells with clear or eosinophilic cytoplasms. The tumor cells were positive for HMB-45 but negative for S-100 protein and cytokeratins by immunohistochemical staining. Ki-67 labeling index was 2.9%. Peritoneal dissemination of tumor occurred at 20 months and the patient died of tumor at 38 months after the initial operation. This was considered to be a case of malignant PEComa, based on the histological and clinical features. Tumor cells showed overexpression of cyclin D1 but lacked the loss of heterozygosity of the TSC1 and TSC2 genes. The result suggests that the overexpression of cyclin D1 may play an important role in the tumorigenesis of PEComa. Because PEComas can behave in an aggressive manner, careful follow up is warranted.
A 77-year-old man was admitted to our hospital with complaints of abdominal pain and body weight loss. Esophagogastroduodenoscopy on admission revealed large ulcerative tumor in the entire region from upper to lower body of the stomach. We diagnosed gastric malignant lymphoma, diffuse large B-cell type and determined stage IV according to the Lugano International Conference classification. Due to gastric perforation occurred on day 4 of chemotherapy, total gastrectomy and partial resection of the transverse colon were performed. Complete remission was achieved by 2 cycles of postoperative chemotherapy together with rituximab.
Reactive oxygen species (ROS) are thought to be involved in the gastric ulcer formation induced by indomethacin, a typical nonsteroidal anti-inflammatory drug. However, the location and the time course of ROS generation remain unknown. To assess the sites of ROS generation, we applied the noninvasive measurement of ROS to indomethacin-treated rats. By giving orally a membrane-permeable or impermeable probe, the spectra were collected as a function of time by in vivo 300-MHz electron spin resonance (ESR) spectroscopy. The ESR signal-decay rates of membrane-permeable probes, hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) and 3-methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine-1-oxyl, in the gastric mucosal region were significantly enhanced 1 h after indomethacin treatment, and they both caused the protection of ulcer formation; however, membrane-impermeable probes, carboxy- and trimethylammonium-TEMPO, which did not exhibit the enhanced signal decay, had no effect on ulcer formation. The enhanced signal decay in the gastric mucosa was suppressed by coadministration of the antioxidants tiron or dimethylthiourea with the nitroxyl probe. The results suggest that the enhanced signal-decay rates in the gastric ulcers observed by in vivo ESR are associated with protective effects. The enhanced signal decay caused by ROS generation in stomach, contributing to the ulcer formation induced by indomethacin, is also suggested to occur at the gastric mucus layer or the interface or the intracellular compartment of epithelial cells. Overall, these results show the potentials of noninvasive assessment of ROS production and the sites of damage by in vivo ESR using nitroxyl probes directed to specific subcellular regions.
BACKGROUND: Although caspase recruitment domain (CARD) membrane-associated guanylate kinase (MAGUK) protein 1 (CARMA1) and CARD9 play important roles in lymphocyte activation, the significance of CARMA1 and CARD9 in the pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma remains to be elucidated. METHODS: By using reverse transcription-polymerase chain reaction analysis, the expression levels of mRNA of CARMA1, CARD9, Bcl10, and the apoptosis inhibitor 2 (API2)-MALT1 chimeric transcript were determined in tissue specimens from 65 patients with primary gastric B-cell lymphoma (43 patients with low-grade MALT lymphoma, 16 patients with MALT lymphoma plus diffuse large B-cell lymphoma [DLBL], and 6 patients with DLBL without MALT lymphoma) and in tissue specimens from 18 patients with chronic gastritis. The expression levels of CARMA1 and BCL10 were examined immunohistochemically in 30 patients with lymphoma. RESULTS: CARMA1 mRNA was detected in 55% of lymphoma patients but in only 17% of chronic gastritis patients. The positive rates for CARD9, Bcl10, and API2-MALT1 chimeric transcript in the lymphoma patients were 48%, 98%, and 8%, respectively, whereas the 3 molecules were not detected in any specimens from patients with chronic gastritis. The expression of CARMA1 and CARD9 was frequent in the Helicobacter pylori-negative patients (100% and 86%, respectively), in the API2-MALT1 chimeric transcript-positive patients (100% and 100%, respectively), and in the specimens from patients who did not respond to H. pylori eradication (76% and 71%, respectively). In addition, CARMA1 expression was positive more frequently in patients of DLBL without MALT lymphoma (100%) than in patients of MALT lymphoma (51%). CARMA1 protein expression was correlated significantly with the expression of CARMA1 mRNA and also with the expression of nuclear BCL10. CONCLUSIONS: The overexpression of CARMA1 and CARD9 presumably is associated with the development or progression of gastric B-cell lymphoma, especially among patients who have disease in which the pathogenesis is not related to H. pylori.
BACKGROUND: The goals of the current study were to elucidate the long-term outcome of Helicobacter pylori eradication therapy for gastric mucosa-associated lymphoid tissue (MALT) lymphoma and to clarify the therapeutic efficacy of stomach-conserving treatments for patients not responding to eradication therapy. METHODS: Ninety-six patients with gastric MALT lymphoma, including 17 patients with areas of diffuse large B-cell lymphoma, were treated by H. pylori eradication. Patients not responding to eradication therapy underwent either a gastrectomy, multiagent chemotherapy, oral monochemotherapy (OMC), or radiotherapy (RT). Predictive factors for the response to eradication therapy, overall survival (OS), and event-free survival (EFS) were determined by the Kaplan-Meier analysis with the log-rank test. The efficacy of second-line treatment was compared between OMC and RT. RESULTS: After eradication therapy, 62 (65%) patients achieved complete disease remission (CR). Transient histologic disease recurrence was confirmed in 4 (6.5%) of 62 patients with CR during the follow-up (median, 37.5 months). The OS and EFS probabilities after 5 years were 0.96 and 0.80, respectively. Second-line treatment was performed in 31 patients; gastrectomy in 4 patients, multiagent chemotherapy in 5 patients, OMC in 12 patients, and RT in 10 patients. There were no differences in the CR rate, OS, EFS, or toxicity between the OMC and RT groups. CONCLUSIONS: H. pylori eradication therapy was an effective first-line treatment for patients with gastric MALT lymphoma, which led to a favorable long-term outcome. OMC and RT had an equivalent efficacy as a second-line treatment in nonresponding patients to eradication therapy.
We treated a 39-year-old woman with hypoproteinemia and anemia who had profuse gastric polyposis. Radiographic and endoscopic examination showed numerous polyps restricted to the stomach. The patient had pulmonary arteriovenous malformations in the left lung. Histological examination of the resected stomach revealed the gastric polyposis to be composed of cystic dilatation of the glands with small areas of adenocarcinoma. These findings were compatible with gastric juvenile polyposis (GJP) accompanied by gastric cancer. Analysis of genomic DNA revealed that the patient had truncating mutation of SMAD4, a responsible gene for juvenile polyposis (JP). Our case suggests that SMAD4 is possibly a responsible gene for GJP.
A 32-year-old Japanese woman with a 14-month history of ulcerative colitis (UC), pancolitis type, was referred to our institution, because of abdominal distention. Plain abdominal X-ray and computed tomography (CT) showed marked dilatation of the right side of the colon. The patient was treated by immediate total colectomy, with the diagnosis of toxic megacolon. Macroscopically, there was a constricting lesion with giant polyposis in the middle part of the transverse colon. Histologically, there was transmural inflammation with a thickened proper muscular layer overlaid by inflammatory polyposis. This case suggests that giant polyposis in UC patients may result in severe stenosis and that such a condition should not be misinterpreted as toxic megacolon or as colitic cancer.
Extremely well differentiated primary gastric adenocarcinoma, which accounts for less than 0.2% of all gastric cancers, is associated with a better prognosis than other types of differentiated adenocarcinoma. Among 2070 gastric carcinomas, diagnosed between 1983 and 2002 at Fukuoka University Hospital and Hamanomachi Hospital, there were three cases of primary extremely well differentiated adenocarcinoma. We report the clinicopathological details of one case of primary gastric extremely well differentiated adenocarcinoma. A 57-year-old man was reffered to our hospital for investigation and treatment of a gastric tumor. Physical and laboratory examinations revealed no abnormalities except for diabetes mellitus. Radiological, endoscopic, and imaging examinations showed an esophageal achalasia-like stenotic lesion. The surface mucosa consisted of almost normal epithelium without any signs of malignancy. Macroscopically, the surgical specimen contained a submucosal tumor, and histological examination revealed extremely well differentiated adenocarcinoma. Although this type of carcinoma is very rare, it should be considered in the differential diagnosis of esophageal and gastric mucosal lesions.