Junichirou Nasu

A prospective, multicenter study of 1111 colorectal endoscopic submucosal dissections (with video)

BACKGROUND Endoscopic submucosal dissection (ESD) is accepted as a minimally invasive treatment for early gastric cancer, although it is not widely used in the colorectum because of technical difficulty. OBJECTIVE To examine the current status of colorectal ESDs at specialized endoscopic treatment centers. DESIGN AND SETTING Multicenter cohort study using a prospectively completed database at 10 specialized institutions. PATIENTS AND INTERVENTIONS From June 1998 to February 2008, 1111 colorectal tumors in 1090 patients were treated by ESD. MAIN OUTCOME MEASUREMENTS Tumor size, macroscopic type, histology, procedure time, en bloc and curative resection rates and complications. RESULTS Included in the 1111 tumors were 356 tubular adenomas, 519 intramucosal cancers, 112 superficial submucosal (SM) cancers, 101 SM deep cancers, 18 carcinoid tumors, 1 mucosa-associated lymphoid tissue lymphoma, and 4 serrated lesions. Macroscopic types included 956 laterally spreading tumors, 30 depressed, 62 protruded, 44 recurrent, and 19 SM tumors. The en bloc and curative resection rates were 88% and 89%, respectively. The mean procedure time ± standard deviation was 116 ± 88 minutes with a mean tumor size of 35 ± 18 mm. Perforations occurred in 54 cases (4.9%) with 4 cases of delayed perforation (0.4%) and 17 cases of postoperative bleeding (1.5%). Two immediate perforations with ineffective endoscopic clipping and 3 delayed perforations required emergency surgery. Tumor size of 50 mm or larger was an independent risk factor for complications, whereas a large number of ESDs performed at an institution decreased the risk of complications. LIMITATIONS No long-term outcome data. CONCLUSIONS ESD performed by experienced endoscopists is an effective alternative treatment to surgery, providing high en bloc and curative resection rates for large superficial colorectal tumors.

Utility of Contrast-Enhanced FDG-PET/CT in the Clinical Management of Pancreatic Cancer: Impact on Diagnosis, Staging, Evaluation of Treatment Response, and Detection of Recurrence

Objectives Fluorodeoxyglucose (FDG)–positron emission tomography/contrast-enhanced computed tomography (PET/CE-CT) involving whole-body scanning first by non–CE-CT and FDG-PET followed by CE-CT has been used for detailed examination of pancreatic lesions. We evaluated PET/CE-CT images with regard to differential diagnosis, staging, treatment response, and postoperative recurrence in pancreatic cancer. Methods Positron emission tomography/CE-CT was conducted in 108 patients with pancreatic cancer and in 41 patients with other pancreatic tumor diseases. Results The maximum standardized uptake value (SUVmax) overlapped in benign and malignant cases, suggesting that differential diagnosis of pancreatic tumors based on the SUVmax is difficult. In the evaluation of staging in 31 resectable pancreatic cancer by PET/CE-CT, the diagnostic accuracy rate was more than 80% for most factors concerning local invasion and 94% for distant metastasis but only 42% for lymph node metastasis. Significant positive correlations were found between the SUVmax and tumor size/markers, suggesting that SUVmax may be a useful indicator for the treatment response. Regarding the diagnosis of the postoperative recurrence, PET/CE-CT correctly detected local recurrence in all the 11 cases of recurrence, whereas abdominal CE-CT detected only 7 of 11 cases, suggesting that PET/CE-CT is superior in this context. Conclusions Positron emission tomography/CE-CT is useful for the clinical management of pancreatic cancer.

A randomized open trial for comparison of proton pump inhibitors, omeprazole versus rabeprazole, in dual therapy for Helicobacter pylori infection in relation to CYP2C19 genetic polymorphism

Background and Aim: The genetic polymorphism of cytochrome P450 (CYP) 2C19 has been shown to influence the efficacy of Helicobacter pylori eradication therapy with a proton pump inhibitor (PPI) and amoxicillin (so‐called dual therapy). Omeprazole, a widely used PPI, and rabeprazole, a new PPI, are metabolized in different pathways in terms of CYP2C19 genetic polymorphisms. In this study, we compared the efficacy of omeprazole and rabeprazole in a 2‐week dual therapy in relation to CYP2C19 polymorphism.

Predictive factors of lymph node metastasis in patients with undifferentiated early gastric cancers.

Background For intramucosal differentiated early gastric cancer that has little risk of lymph node metastasis, local treatment such as endoscopic mucosal resection has been generally accepted as an adequate treatment. We studied clinicopathological characteristics of undifferentiated early gastric cancer at our institution to identify the predictive factors for lymph node metastasis and qualify lesions that should be referred for gastrectomy and not endoscopic mucosal resection. Methods We retrospectively analyzed the clinicopathological features (patient age and gender, tumor size, location, macroscopic type and histological type, presence of ulceration, depth of tumor invasion, and lymphatic-vascular involvement) in 332 patients with undifferentiated early gastric cancer who underwent gastrectomy with regional lymph node dissection. Results Lymph node metastasis was observed in 45 patients (14%). Univariate analysis revealed that depth of tumor invasion (submucosa), tumor size (>30 mm), and lymphatic-vascular involvement (positive) were associated with lymph node metastasis. Only lymphatic-vascular involvement (positive) was found to have a significant association (odds ratio, 7.4; 95% confidence interval, 2.9–19.0) by multivariate analysis. Conclusions Lymphatic-vascular involvement was the only independent predictive risk factor for lymph node metastasis. This pathologic factor was not useful for identifying patients at high risk of lymph node metastasis who should be offered gastrectomy rather than endoscopic mucosal resection.

Distribution of activated complement, C3b, and its degraded fragments, iC3b/C3dg, in the colonic mucosa of ulcerative colitis (UC)

The third component of complement (C3) is central to both the classical and alternative pathways in complement activation. In this study, involvement of C3 activation in the mucosal injury of UC was investigated. We examined the distribution of activated (C3b) and degraded fragments (iC3b/C3dg) of C3, terminal complement complex (TCC), and complement regulatory proteins in normal and diseased colonic mucosa including UC and other types of colitis using immunohistochemical techniques at the level of light and electron microscopy. While C3b and iC3b/C3dg staining was negligible in the normal mucosa, iC3b/C3dg and, to a lesser extent, C3b were deposited in UC mucosa along the epithelial basement membrane. The deposition was enhanced in relation to the severity of mucosal inflammation (C3b, P < 0.05; iC3b/C3dg, P < 0.01). Epithelial deposition of TCC was not observed in most UC mucosa. Immunoelectron microscopy showed that C3b and iC3b/C3dg were distributed mainly along the epithelial basement membrane and the underlying connective tissue in a granular, studded manner, and weakly present along the basolateral surface of epithelial cells. These C3 fragments were also deposited in inflammatory control mucosa such as ischaemic and infectious colitis. Our findings suggest that deposition of the C3 fragments occurs in inflamed colonic mucosa of diverse etiologies, including UC, but to define a role of the deposition in the development of mucosal injury in UC awaits direct study.

Cytokine-stimulated release of decay-accelerating factor (DAF; CD55) from HT-29 human intestinal epithelial cells

Expression of DAF (CD55) is enhanced on colonic epithelial cells of patients with ulcerative colitis (UC), and stool DAF concentrations are increased in patients with active disease. Cytokines are known to modulate DAF expression in various human cells, and lesions of UC reveal altered profiles of cytokine production. In this study, we evaluate the effects of various cytokines, IL‐1β, IL‐2, IL‐4, IL‐6, IL‐8, IL‐10, and interferon‐gamma (IFN‐γ), on the synthesis and kinetics of DAF protein in HT‐29 human intestinal epithelial cells. Using flow cytometry and an ELISA, we found that HT‐29 cells constitutively express DAF on the cell surface and spontaneously release DAF into the culture supernatant under standard culture conditions. When the culture supernatant was centrifuged at 100 000 g, nearly a half of DAF was precipitated, indicating that one half of the released DAF was present as a membrane‐bound form and the other half as a soluble form. Analysis of the culture supernatant of biotin surface‐labelled HT‐29 cells suggested that the soluble form DAF was derived by secretion from within the cell or by cleavage from the cell surface. Among the cytokines, IL‐4 markedly, and IL‐1β moderately, enhanced the expression and the release of DAF. Actinomycin D, cycloheximide, and brefeldin A inhibited the increase in DAF release induced by IL‐4 and IL‐1β stimulation. These results suggest that DAF is released from intestinal epithelial cells in response to cytokine stimulation and that IL‐4 and IL‐1β are possible cytokines involved in DAF release into the colonic lumen of patients with UC.

Detection of decay-accelerating factor in stool specimens of patients with colorectal cancer

BACKGROUND & AIMS Colorectal cancers have an increased expression of decay-accelerating factor (DAF). The aim of this study was to determine whether stool specimens of patients with colorectal cancer contain increased amounts of DAF. METHODS DAF was measured using an immunoassay in the stool specimens of 40 persons with colorectal cancer, 18 with colorectal adenomatous polyps, 13 with upper gastrointestinal cancer, and 41 without gastrointestinal disease. RESULTS Stool DAF concentrations in patients with colorectal cancer (0-9.8 ng/g stool; median, 1.6 ng/g) were significantly higher than those in patients with adenoma (0-6.4 ng/g; median, 0 ng/g) (P < 0.05), patients with upper gastrointestinal cancer (0-3.1 ng/g; median, 0 ng/g) (P < 0.05), and subjects without gastrointestinal disease (0-3.4 ng/g; median, 0 ng/g) (P < 0.01). Resection of colorectal cancers caused a marked decrease in stool DAF concentrations. The stool DAF test was positive in a substantial portion of patients with colorectal cancer whose tumors were small ( < 2 cm), at an early TNM stage, or unassociated with fecal occult blood positivity. The sensitivity of the test for colorectal cancer was 55%, and the specificity was 85%. CONCLUSIONS The measurement of stood DAF deserves evaluation as a test for detection of colorectal cancer.

Risk Factors and Indications for Colectomy in Ulcerative Colitis Patients are Different According to Patient’s Clinical Background

PurposeDespite progress in medical treatment for ulcerative colitis, a considerable fraction of ulcerative colitis patients undergo colectomy. We analyzed the clinical variables of ulcerative colitis patients and determined the risk factors and indications for colectomy.MethodsThe clinical records of 981 consecutive Japanese patients with ulcerative colitis were reviewed both retrospectively and prospectively.ResultsOf 981 patients with ulcerative colitis, 85 patients underwent colectomy. Multivariate analysis indicated that male gender (risk ratio, 2.16; 95 percent confidence interval, 1.37–3.42), onset year during and after 2000 (risk ratio, 2.85; 95 percent confidence interval, 1.31–6.22), severe disease activity (risk ratio, 2; 95 percent confidence interval, 1.15–3.48), corticosteroid resistance (risk ratio, 7.05; 95 percent confidence interval, 4.29–11.59), and complications because of corticosteroid administration (risk ratio, 3.55; 95 percent confidence interval, 2.08–6.06) were significant risk factors for colectomy. In patients with disease duration of more than five years, only corticosteroid resistance and complications because of corticosteroid were significant risk factors for colectomy. When we stratified indications for colectomy for the 85 cases via patient disease duration, massive hemorrhage was a relatively frequent cause of colectomy in patients with a disease duration of less than five years (P = 0.091). On the other hand, colon dysplasia or cancer was a major cause for colectomy in patients with a disease duration of more than ten years (P = 0.0001).ConclusionsIn ulcerative colitis patients, the risk factors and indications for colectomy were different according to the patients clinical background. Our findings may help to predict patients with ulcerative colitis who have a high risk for colectomy.

Polymorphic expression of decay-accelerating factor in human colorectal cancer

Background: We have previously shown that expression of decay‐accelerating factor (DAF), a complement regulatory protein, is enhanced immunohistochemically on the luminal surface of cancer glands in human colorectal cancer and is detected in stool specimens of patients with colorectal cancer. The amount of DAF present in the stools might be influenced by the stability of DAF on the cell surface which is regulated by biochemical properties such as glycosylation of the protein. In the present study, to help elucidate the mechanism for the release of DAF from human colorectal cancers, we biochemically analyzed DAF expression by western and northern blotting by using surgically resected specimens of colorectal cancers.

Enhanced expression of decay-accelerating factor and CD59/homologous restriction factor 20 in intestinal metaplasia, gastric adenomas and intestinal-type gastric carcinomas but not in diffuse-type carcinomas.

Enhanced expression of decay‐accelerating factor and CD59/homologous restriction factor 20 in intestinal metaplasia, gastric adenomas and intestinal‐type gastric carcinomas but not in diffuse‐type carcinomas