Biomedical subjects

Takao Kawabe

Publications and source records attributed to Takao Kawabe.

At least 19 recordsLinked to original sources

PubMed2006

Dysregulated expression of stem cell factor Bmi1 in precancerous lesions of the gastrointestinal tract.

PURPOSE: It is important to identify the definitive molecular switches involved in the malignant transformation of premalignant tissues. Cellular senescence is a specific characteristic of precancerous tissues, but not of cancers, which might reflect tumorigenesis-protecting mechanisms in premalignant lesions. Polycomb protein Bmi1, which is a potent negative regulator of the p16INK4 gene, suppresses senescence in primary cells and is overexpressed in various cancers. We hypothesized that Bmi1 expression would also be dysregulated in precancerous lesions in human digestive precancerous tissues. EXPERIMENTAL DESIGN: Bmi1 expression was investigated in cancerous and precancerous tissues of the digestive tract. The expression of p16, beta-catenin, and Gli1 and the in vivo methylation status of the p16 gene were also analyzed in serial sections of colonic precancerous lesions. RESULTS: Bmi1 was clearly overexpressed across a broad spectrum of gastrointestinal cancers, and the expression of Bmi1 increased in a manner that reflected the pathologic malignant features of precancerous colonic tissues (low-grade dysplasia, 12.9 +/- 2.0%; high-grade dysplasia, 82.9 +/- 1.6%; cancer, 87.5 +/- 2.4%). p16 was also strongly expressed in high-grade dysplasia, but not in cancers. p16 promoter methylation was detected only in some Bmi1-positive neoplastic cells. CONCLUSIONS: Bmi1 overexpression was correlated with the malignant grades of human digestive precancerous tissues, which suggests that advanced Bmi1 dysregulation might predict malignant progression. The abnormal Bmi1 expression might link to malignant transformation via the disturbance of orderly histone modification.

Cell Line, Tumor↗

PubMed2006

A randomized controlled trial evaluating the usefulness of a transparent hood attached to the tip of the colonoscope.

OBJECTIVES: Considering the increasing demand for colonoscopy, auxiliary devices that could facilitate the examination would be useful. A hood attached to the tip of the colonoscope has been reported to be helpful in detecting and removing colorectal polyps. However, its usefulness in aiding scope intubation has not been fully evaluated. METHODS: Patients for colonoscopy between July 2004 and May 2005 in Tokyo University Hospital were enrolled to this randomized controlled trial, and assigned to colonoscopy with a transparent hood, a short hood, or no hood. Colonoscopies were conducted by trainees without sedation. The evaluated outcomes were cecal intubation rate, trainee intubation rate (cecal intubation within 15 min), cecal intubation time, and polyp detection rate. RESULTS: Enrolled 684 patients were randomly assigned to transparent hood (N = 221), short hood (N = 228), and no hood (N = 235) groups. The overall cecal intubation rate was 95.3% (652/684) and did not differ among the groups. The overall trainee intubation rate was 55.1% (377/684) and significantly higher in the transparent hood group than in the no hood group for female patients (60.7%vs 37.4%, P = 0.003). Cecal intubation time was 11.5, 13.5, and 14.0 min in the transparent, short, and no hood groups, respectively, and significantly shorter in the transparent hood group than in the no hood group among overall (P = 0.008), female (P = 0.001), and old (P = 0.04) patients. Polyp detection rate was higher in the transparent hood group than in the no hood group (49.3%vs 39.1%, P = 0.04). CONCLUSIONS: The transparent hood was useful in shortening the cecal intubation time especially in difficult cases.

Clinical Competence↗

PubMed2006

Pancreatic cancer in patients with pancreatic cystic lesions: a prospective study in 197 patients.

BACKGROUND & AIMS: K-ras mutation is frequently detected in pancreatic juice of patients with pancreatic small cystic lesions, as well as those with pancreatic cancer. Those cystic lesions are often found by chance with modern radiologic imaging modalities. In this study, we prospectively examined the prognosis of patients with pancreatic cystic lesions, focusing on pancreatic cancer development. METHODS: A total of 197 patients with pancreatic cystic lesions, 80 with intraductal papillary mucinous neoplasm (IPMN) and 117 with non-IPMN cysts, were followed up for 3.8 years on average. Blood tests and imaging diagnosis were performed twice a year. The observed incidence of pancreatic cancer was compared with the expected incidence calculated on the basis of age- and gender-matched mortality of pancreatic cancer in the general Japanese population. RESULTS: Pancreatic cancer developed in 7 patients during the observation period (0.95% per year), infiltrating ductal carcinoma in 5 and intraductal papillary mucinous carcinoma in 2. Three of the ductal cancer cases had pancreatic non-IPMN cyst as preexisting lesion. At least 2 of the carcinomas arose in regions remote from preexisting lesions. The observed incidence of pancreatic cancer was 22.5 times higher (95% confidence interval, 11.0-45.3) than expected mortality from this cancer among general population. CONCLUSIONS: Patients with pancreatic cystic lesions are at a considerably high risk for pancreatic cancer, with a standardized incidence rate of 22.5. Cancer might develop in regions remote from the preexisting cystic lesion, suggesting diffuse pathologic changes predisposing to malignant transformation in the entire pancreas harboring cystic lesions.

Adult↗

PubMed2006

Endoscopic management of biliary complications after adult living donor liver transplantation.

OBJECTIVES: Biliary complications are one of the important issues to be addressed after liver transplantation. Endoscopic management of biliary complications after deceased donor liver transplantation (DDLT) is widely accepted, but it remains to be established in patients after living donor liver transplantation (LDLT). Endoscopic management in LDLT patients is difficult mainly because of the complexity of duct-to-duct reconstruction. METHODS: A total of 174 adult LDLTs with duct-to-duct reconstruction were performed in our institution. Biliary complications developed in 53 patients (30%). Among these, 18 patients were referred for endoscopic management and were the subjects of the present study. Success rate, early morbidity, and outcome were evaluated in these 18 patients. RESULTS: The type of graft was the right liver in six, left liver in eight, and right lateral sector in four patients. Ten out of 18 patients had one biliary anastomosis and the remaining eight had multiple anastomoses. Six patients had a previous history of surgical or percutaneous intervention for biliary complications after LDLT. Seventeen patients had one or more biliary strictures. Biliary casts were found in nine patients, three of whom had concomitant bile leaks. Strictures were successfully treated with endoscopic balloon dilation in 12 (71%) of the 17 patients (nasobiliary catheter placement in eight and stent placement in four patients). Bile leak was successfully managed in two of three patients. Biliary casts were removed by endoscopic papillary balloon dilation in eight of nine patients. Five patients with failed endoscopic therapy were converted to percutaneous or surgical intervention. Endoscopic-procedure-related cholangitis developed in one patient. During follow-up with median periods of 10 months (range 2-20 months), four of nine patients without stent placement developed biliary strictures, and these were relieved by additional endoscopic management. CONCLUSIONS: Endoscopic approach has the potential to be a first-line therapy for the management of biliary complications after LDLT.

Adult↗

PubMed2006

MDM2 promoter SNP309 is associated with the risk of hepatocellular carcinoma in patients with chronic hepatitis C.

PURPOSE: A single nucleotide polymorphism (SNP) in the promoter region of MDM2 gene, SNP309, has recently been shown to be associated with accelerated tumor formation in both hereditary and sporadic cancers in humans. However, the association of SNP309 with hepatocellular carcinoma is unknown. We evaluated the association of SNP309 with the risk of hepatocellular carcinoma development among Japanese patients with chronic hepatitis C virus infection. EXPERIMENTAL DESIGN: We genotyped the SNP309 at the MDM2 promoter in 435 Japanese patients with chronic hepatitis C virus infection, including 187 patients with hepatocellular carcinoma and 48 healthy subjects, using a fluorogenic PCR. Presence of SNP was also confirmed by direct sequencing of the MDM2 promoter region. RESULTS: The proportion of G/G genotype of the SNP309 in patients with hepatocellular carcinoma (33%) was significantly higher than that in patients without hepatocellular carcinoma (23%), with an odds ratio (95% confidence interval) of 2.28 (1.30-3.98). A multivariate analysis revealed that MDM2 SNP309 (G/G versus T/T), age >60 years, male gender, presence of cirrhosis, serum alpha-fetoprotein >20 mug/L, and serum albumin <3.2 g/dL were independently associated with the hepatocellular carcinoma development at odds ratio of 2.27, 2.46, 3.08, 4.15, 4.87, and 6.33, respectively. CONCLUSIONS: The MDM2 promoter SNP309 is associated with the presence of hepatocellular carcinoma in Japanese patients with chronic hepatitis C.

Adult↗

PubMed2006

Cholecystitis after metallic stent placement in patients with malignant distal biliary obstruction.

BACKGROUND & AIMS: Cholecystitis after metallic stent (MS) placement is an issue requiring attention. From our experience, cholecystitis seemed to occur mainly in patients with tumor involvement to the cystic duct orifice. The aim of the present study was to identify risk factors for cholecystitis in patients treated with covered or uncovered MS. METHODS: We analyzed 246 patients who received MS placement (covered MS in 171 and uncovered in 75) between August 1997 and May 2005 for the treatment of unresectable distal malignant biliary obstruction. Causative diseases were as follows: pancreatic cancer in 162, papillary cancer in 10, bile duct cancer in 41, and metastatic nodes in 33 patients. Tumor involvement to orifice of the cystic duct (OCD) was diagnosed based on cholangiography and intraductal ultrasonography. RESULTS: Cholecystitis after MS placement was found in 13 patients (5.3%). There was no significant difference in the incidence of cholecystitis between covered (5.8%) and uncovered (4.0%) MS. By univariate analysis, tumor involvement of the OCD, MS placed above the papilla, and stricture located at midportion were associated significantly with cholecystitis. By multivariate analysis, only tumor involvement of the OCD was a risk factor, with an odds ratio of 47.206 (95% confidence interval, 5.84-381.60). CONCLUSIONS: Cholecystitis after MS placement is associated with tumor involvement to the orifice of the cystic duct, regardless of the type of stent.

Aged↗

PubMed2006

Modulation of luminescence intensity of lanthanide complexes by photoinduced electron transfer and its application to a long-lived protease probe.

Luminescent lanthanide complexes (Tb(3+), Eu(3+), etc.) have excellent properties for biological applications, including extraordinarily long lifetimes and large Stokes shifts. However, there have been few reports of lanthanide-based functional probes, because of the difficulty in designing suitable complexes with a luminescent on/off switch. Here, we have synthesized a series of complexes which consist of three moieties: a lanthanide chelate, an antenna, and a luminescence off/on switch. The antenna is an aromatic ring which absorbs light and transmits its energy to the metal, and the switch is a benzene derivative with a different HOMO level. If the HOMO level is higher than a certain threshold, the complex emits no luminescence at all, which indicates that the lanthanide luminescence can be modulated by photoinduced electron transfer (PeT) from the switch to the sensitizer. This approach to control lanthanide luminescence makes possible the rational design of functional lanthanide complexes, in which the luminescence property is altered by a biological reaction. To exemplify the utility of our approach to the design of lanthanide complexes with a switch, we have developed a novel protease probe, which undergoes a significant change in luminescence intensity upon enzymatic cleavage of the substrate peptide. This probe, combined with time-resolved measurements, was confirmed in model experiments to be useful for the screening of inhibitors, as well as for clinical diagnosis.

Chemistry, Clinical↗

PubMed2006

Endoscopic submucosal dissection of esophageal squamous cell neoplasms.

BACKGROUND & AIMS: Endoscopic submucosal dissection (ESD) has recently been developed for en bloc resection of stomach neoplasms, which results in high tumor eradication rates as well as a modality for the precise histologic assessment of the entire lesion. Application of the technique is desirable for esophageal squamous cell neoplasms (SCNs), but there have been no reports on the use of this procedure in the esophagus. METHODS: An ESD with methods similar to those used for resections of early gastric cancer was performed on 58 consecutive esophageal SCNs with preoperative diagnoses of intraepithelial neoplasm or intramucosal invasive carcinoma occurring in 43 enrolled patients. The therapeutic efficacy, complications, and follow-up results were assessed. RESULTS: The rate of en bloc resection was 100% (58/58), and en bloc resection with tumor-free lateral/basal margins (R0 resection) was 78% (45/58). There was no evidence of significant bleeding. Perforation occurred in 4 (6.9%) patients during the ESD, who were managed by conservative medical treatments after endoscopic closure of the perforation. Removal of 9 (16%) lesions resulted in esophageal stricture requiring balloon dilation after ESD. Of 40 lesions occurring in 31 patients fulfilling the criteria of node-negative tumors (mean follow-up, 17 months), 1 lesion resected by en bloc resection with nonevaluable tumor-free lateral margins (Rx [lateral] resection) recurred locally 6 months after ESD, which was treated successfully by a second ESD procedure. CONCLUSIONS: The ESD is applicable to the esophagus with promising results, but notification of risk is essential.

Coloring Agents↗

PubMed2006

TRAIL-induced cell death cooperates with IFN-gamma activation in the graft-versus-tumor effect against colon tumors.

The graft-versus-tumor (GVT) effect that occurs following allogeneic bone marrow transplantation (BMT) and donor lymphocyte infusion (DLI) is currently being subjected to intensive investigation because of clinical evidence for GVT efficacy against leukemia. In this report, we investigate the efficacy and molecular mechanisms of GVT against solid tumors, using a modification of the mouse parent-to-F1 BMT model. Mouse Colon26 cells in which tumor necrosis factor related apoptosis-inducing ligand (TRAIL) receptor expression was stably knocked down were transplanted to investigate the role of the TRAIL-TRAIL receptor system in the GVT effect. In addition, Fas ligand-(FasL) deficient mice on a C57BL6 (B6) background were used as donors, to determine the significance of the Fas-FasL system for the antitumor effect. The group that received B6 DLI followed by preconditioning with 950 rad irradiation underwent tumor reduction associated with the induction of IFN-gamma, TRAIL and tumor-cell apoptosis. In vitro cultured Colon26 cells were resistant to TRAIL but susceptible to the combination of IFN-gamma and TRAIL in a TRAIL-dose-dependent manner. The infusion of lymphocytes from FasL-defective donors reduced the tumor progression, although efficacy was decreased in the TRAIL receptor knockdown tumors but not in wild-type ones, compared with infusion of B6-derived lymphocytes. The findings indicate that GVT activity against subcutaneous colon tumors is efficiently induced by preconditioning with irradiation and allogeneic DLI, and that TRAIL and IFN-gamma act cooperatively in the antitumor effect.

Animals↗

PubMed2006

MyD88 and TNF receptor-associated factor 6 are critical signal transducers in Helicobacter pylori-infected human epithelial cells.

Helicobacter pylori induces NF-kappaB activation, leading to mucosal inflammation via cag pathogenicity island. Although recent studies have implicated several candidate proteins of both H. pylori and host, the molecular mechanism by which H. pylori activates NF-kappaB remains unclear. The aim of this study was to analyze the mechanism of cag pathogenicity island-mediated NF-kappaB activation in epithelial cells. The responses of human cell lines and mouse embryonic fibroblasts to infection with wild-type H. pylori or cagE mutant were investigated. The effect of small interfering RNAs (siRNAs) for several NF-kappaB signaling intermediate molecules was evaluated in H. pylori-induced IkappaBalpha phosphorylation and IL-8 production. Protein interactions of exogenously expressed TNFR-associated factor 6 (TRAF6) and MyD88 or receptor-interacting protein 2 and nucleotide-binding oligomerization domain 1 or those of endogenous IkappaB kinase, TGF-beta-activated kinase 1 (TAK1), and TRAF6 were assessed by immunoprecipitation. Cag pathogenicity island-dependent NF-kappaB activation was observed in human cell lines, but not in mouse fibroblasts. In human epithelial cells, H. pylori-induced IkappaBalpha phosphorylation and IL-8 production were severely inhibited by siRNAs directed against TAK1, TRAF6, and MyD88. In contrast, siRNAs for TRAF2, IL-1R-associated kinases 1 and 4, and cell surface receptor proteins did not affect these responses. H. pylori infection greatly enhanced MyD88 and TRAF6 complex formation in a cag-dependent manner, but did not enhance Nod1 and receptor-interacting protein 2 complex formation. H. pylori also induced TAK1 and TRAF6 complexes. These results suggest that the cag pathogenicity island of H. pylori is a cell type-specific NF-kappaB activator. TAK1, TRAF6, and MyD88 are important signal transducers in H. pylori-infected human epithelial cells.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Serum IgG4 concentrations in pancreatic and biliary diseases.

BACKGROUND: Recently, it has been reported that the serum concentration of IgG4, a minor component of IgG subclasses, is increased in autoimmune pancreatitis. However, data regarding IgG4 concentrations in other pancreatic or biliary diseases have been insufficient. METHODS: Serum IgG4 was measured in 116 patients with pancreatic or biliary diseases (35 autoimmune pancreatitis, 24 chronic pancreatitis except autoimmune pancreatitis, 11 primary sclerosing cholangitis, 23 pancreatic cancer, 3 islet cell tumor, 2 papilla cancer, 15 bile duct cancer, and 3 gallbladder cancer patients). The cut-off concentration of IgG4 was 135 mg/dl. RESULTS: Increased serum IgG4 was observed in 33 of 35 patients with autoimmune pancreatitis, 0 of 24 with chronic pancreatitis, 4 of 11 with primary sclerosing cholangitis, 0 of 23 with pancreatic cancer, 0 of 3 with islet cell tumor, 0 of 2 with duodenal papilla cancer, 0 of 15 with bile duct cancer and 0 of 3 with gallbladder cancer patients. CONCLUSIONS: Serum IgG4 was increased in autoimmune pancreatitis and was within normal limits for other pancreatic or biliary diseases except primary sclerosing cholangitis.

Adolescent↗

PubMed2006

Radiofrequency ablation for hepatocellular carcinoma in so-called high-risk locations.

We evaluated the efficacy and safety of radiofrequency (RF) ablation for hepatocellular carcinoma (HCC) in presumably high-risk locations. Between February 1999 and December 2001, we performed RF ablation on 1419 nodules in 636 consecutive HCC patients, of which 231 nodules in 207 patients were in high-risk locations, defined as less than 5 mm from a large vessel or an extrahepatic organ. Eighty-one patients had a nodule adjacent to a large vessel, 145 patients had a nodule adjacent to an extrahepatic organ, of whom 19 also had one adjacent to a large vessel. Early complications and local tumor progression were analyzed with regard to the location of each nodule. The mean nodule diameter and average number per patient were 27 mm and 2.3, respectively. Early complications, within 30 days after ablation, occurred in 12 of 207 patients (5.8%) with a nodule in a high-risk location and in 15 of 429 patients (3.5%) without (P = .1776). There was no significant difference in local tumor progression rate between nodules in high-risk locations (1 year: 2.1%, 2 years: 3.1%, 3 years: 3.1%) and those elsewhere (1 year: 0.6%, 2 years: 1.7%, 3 years: 2.5%) (P = .2745). In conclusion, HCC nodules adjacent to a large vessel or extrahepatic organ were treated with RF ablation without compromising the efficacy of the procedure. However, even though without significant difference, some complications occurred at risky locations and need to be carefully considered.

Aged↗

PubMed2006

Prediction of recurrence of hepatocellular carcinoma after curative ablation using three tumor markers.

Three tumor markers for hepatocellular carcinoma (HCC) are available in daily practice in Japan: alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin (DCP), and lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3). To elucidate the predictability of these tumor markers on HCC recurrence after curative ablation, we enrolled 416 consecutive patients with naïve HCC who had been treated by percutaneous ablation at our department from July 1997 to December 2002. Tumor marker levels were determined immediately before and 2 months after the treatment. Complete ablation was defined on CT findings as nonenhancement in the entire lesion with a safety margin. Tumor recurrence was also defined as newly developed lesions on CT that showed hyperattenuation in the arterial phase with washout in the late phase. We assessed the predictability of recurrence via tumor markers in multivariate analysis, using proportional hazard regression after adjusting for other significant factors in univariate analysis. Until the end of follow-up, tumor recurrence was identified in 277 patients. Univariate analysis revealed the following factors to be significant for recurrence: platelet count; size and number of tumors; AFP, AFP-L3, and DCP preablation; and AFP and AFP-L3 postablation. Multivariate analysis indicated that AFP >100 ng/mL and AFP-L3 >15%, both pre- and postablation, were significant predictors. The positivity of AFP and AFP-L3 preablation that turned negative postablation was not significant. In conclusion, tumor markers pre- and post-ablation were significant predictors for HCC recurrence and can complement imaging modalities in the evaluation of treatment efficacy.

Aged↗

PubMed2006

Successful outcomes of a novel endoscopic treatment for GI tumors: endoscopic submucosal dissection with a mixture of high-molecular-weight hyaluronic acid, glycerin, and sugar.

BACKGROUND: Endoscopic submucosal dissection (ESD) has recently been developed for endoscopic treatment of GI tumors, which enables us to resect even large tumors en bloc. However, a considerable frequency of perforation has become another problem. The best way to prevent perforation is to create a sufficient submucosal fluid cushion (SFC). The aim of this study is to find out the feasibility of ESD by using a mixture of 1900 KDa hyaluronic acid (Suvenyl) and a 10% glycerin plus 5% fructose solution (Glyceol). METHODS: Sixty-seven consecutive GI tumors in 54 patients who met indication criteria of ESD were enrolled. The mixing ratios of Suvenyl and Glyceol were 1:3 for esophageal/colorectal tumors and stomach tumors with scar, and 1:7 for stomach tumors without scar. After creation of SFCs, mucosal incision around the tumors and submucosal dissection under the tumors were made by cutting devices. The clinical outcomes were investigated. RESULTS: Mean resected and tumor sizes were 38.6 and 25.6 mm, respectively. Perforation occurred in one colon tumor with severe fibrosis (1.5%), which was managed by endoscopic clipping without salvage surgery. No blood transfusion was performed. In one stomach and in one rectal tumor (3%), endoscopic hemostasis was necessary because of postoperative bleeding. Overall endoscopic and histologic en bloc resection rates were 94% (63/67) and 78% (52/67), respectively, and there was no recurrence after follow-up of 1 year. CONCLUSIONS: ESD when using a mixture of Suvenyl and Glyceol results in excellent outcomes, and this injection solution should be used for ESD.

Adjuvants, Immunologic↗

PubMed2006

Right-side shift of colorectal adenomas with aging.

BACKGROUND: Although it is known that right-side colon cancers increase with aging, the location of adenomas according to age has been controversial. Adenomas found at initial colonoscopies may be a mixture of polyps that arose at various earlier ages. OBJECTIVES: To elucidate the relationship between location and age at which adenomas actually developed. DESIGN: Prospective cohort study. SETTING: A large-scale health appraisal institution in Japan. PATIENTS: A total of 23,444 consecutive, asymptomatic Japanese who underwent total colonoscopy at their annual medical health check-up. INTERVENTIONS: We analyzed newly developed adenomas after confirmation of the absence of colorectal neoplasms by two serial total colonoscopies. MAIN OUTCOME MEASUREMENTS: The results of follow-up colonoscopies in 6304 subjects with no colorectal neoplasms at 2 initial colonoscopies were analyzed. The locations were separated into right-side colon and left-side colon from the splenic flexure. The locations of new adenomas found for the first time during the follow-up term were analyzed. RESULTS: A total of 1472 subjects developed new colorectal adenomas. In 1255 cases with single adenomas, the ratios of number of cases with right-side lesions to that with left-side lesions at the ages of <40 years, 40 to 49 years, 50 to 59 years, 60 to 69 years, and > or =70 years were 1.18, 1.00, 1.29, 1.31, and 1.89, respectively. In 217 cases with multiple adenomas found concurrently, the percentage of cases with adenomas only on the right side at the ages of <40 years, 40 to 49 years, 50 to 59 years, 60 to 69 years, and > or =70 years were 0%, 25%, 34%, 37%, and 63%, respectively. LIMITATIONS: Small lesions might have been missed even by 2 serial colonoscopies. CONCLUSIONS: Adenomas on the right-side colon increased with aging.

Adenoma↗

PubMed2006

Risk assessment for delayed hemorrhagic complication of colonic polypectomy: polyp-related factors and patient-related factors.

BACKGROUND: Hemorrhage is among the most serious complications of colorectal polypectomy and may occur after a longer postprocedure interval. OBJECTIVE: We aimed to elucidate the risk factors for delayed postpolypectomy hemorrhage, including both polyp characteristics and the general condition of the patients. DESIGN: Retrospective cohort study. PATIENTS: A total of 6617 cases of colorectal polypectomy was performed in 3138 consecutive patients in Japan. MAIN OUTCOME MEASUREMENTS: The risk factors for delayed postpolypectomy hemorrhage were assessed among polyp characteristics (form, size, histologic features) and the method of resection by unconditional logistic regression. Patient conditions (smoking, alcohol, hypertension, diabetes mellitus, hyperlipidemia) were compared between case-control pairs matched on polyp-related characteristics by conditional logistic regression. RESULTS: Hemorrhage occurred in 38 lesions (0.57%) of 37 patients (1.2%): 22 required endoscopic hemostasis and 1 required blood transfusion. Although polyp size was associated with the occurrence of delayed hemorrhage (10.0 +/- 6.9 mm in hemorrhage cases vs 5.6 +/- 3.8 mm in others, P < .0001), other polyp-related factors were not significant. Hypertension was a complication in 25 of 37 (68%) cases and in 21 of 74 (28%) matched controls, showing an adjusted odds ratio of 5.6 (95% CI 1.8-17.2, P = .001). Other patient characteristics were not significant. The interval between polypectomy and hemorrhage was significantly longer in patients with hypertension (median 6 days, range 2-14 days) than in those without hypertension (2.5 days, 1-9 days; P = .019). LIMITATIONS: This study does not provide information regarding prevention of hemorrhage. CONCLUSIONS: Hypertension is a significant risk factor for delayed colorectal postpolypectomy hemorrhage. The interval between polypectomy and hemorrhage can be as long as 14 days in the presence of hypertension.

Aged↗

PubMed2006

Hepatitis C virus core protein is a potent inhibitor of RNA silencing-based antiviral response.

BACKGROUND & AIMS: Persistent infection with hepatitis C virus (HCV) leads to chronic hepatitis and hepatocellular carcinoma (HCC). RNA interference (RNAi) may act as a host antiviral response against viral RNA. METHODS: The effects of RNAi on both the replicative intermediates and the internal ribosome entry site (IRES) of HCV were studied by using HCV-related short interfering RNA (siRNA) detection assay. The mechanism that permits HCV to escape RNAi was studied by using RNAi assay materials. RESULTS: These studies demonstrate that the Dicer, an RNase enzyme that generates short siRNA, can target and digest both the IRES and the replicative intermediate of HCV into siRNA of approximately 22 nucleotides. Further studies also show that Dicer can inhibit the replication of the HCV subgenomic replicon. However, the HCV core protein inhibits this RNAi and rescues the replication of the HCV subgenomic replicon through a direct interaction with Dicer. CONCLUSIONS: RNAi is a limiting factor for HCV infection, and the core protein suppresses the RNA silencing-based antiviral response. This ability of the core protein to counteract the host defense may lead to a persistent viral infection and may contribute to the pathogenesis of HCV.

Cell Line↗

PubMed2006

Efficacy of peppermint oil as an antispasmodic during endoscopic retrograde cholangiopancreatography.

BACKGROUND: During endoscopic retrograde cholangiopancreatography (ERCP), hyoscine-N-butylbromide (Buscopan) or glucagon is used to inhibit duodenal motility. However, they may cause adverse effects. Peppermint oil has an antispasmodic effect and is used as a less hazardous antispasmodic during colonoscopy and upper gastrointestinal endoscopy. The purpose of the present paper was therefore to investigate peppermint as an antispasmodic for ERCP. METHODS: Forty patients were enrolled prospectively. They were assigned to four groups according to the peppermint oil concentration and site of administration: group 1, 20 mL of 1.6% solution around duodenal papilla; group 2, 20 mL of 1.6% solution both to the antrum of the stomach and around the duodenal papilla; group 3, 20 mL of 3.2% solution around the duodenal papilla; and group 4, 3.2% solution both to the antrum and around the duodenal papilla. Glucagon or hyoscine-N-butylbromide was added when duodenal peristalsis was not adequately diminished. Sixteen patients undergoing ERCP with glucagon were employed as historical controls. RESULTS: The ERCP was attempted in all except one patient in group 2 who had bleeding from invaded tumor to the duodenum. Peppermint administration equally reduced duodenal motility in the groups. Duodenal movement was none or mild in 69.2% of patients. The ERCP was successfully performed with peppermint alone in 91.4% of patients (37/39). Glucagon or hyoscine-N-butylbromide was needed in one patient each in groups 1 and 4. Serious complications related to peppermint oil did not occur. Inhibitory effect of peppermint appears to be identical to that of glucagon. CONCLUSION: Duodenal relaxation was obtained with 20 mL of 1.6% peppermint oil solution in the duodenum, but additional administration may be required. Peppermint oil is useful as an antispasmodic agent for ERCP.

Adult↗