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To investigate the risk factors for delayed bleeding following endoscopic submucosal dissection (ESD) treatment for colorectal neoplasms.We retrospectively reviewed the medical records of 317 consecutive patients with 325 lesions who underwent ESD for superficial colorectal neoplasms at our hospital from January 2009 to June 2013. Delayed post-ESD bleeding was defined as bleeding that resulted in overt hematochezia 6 h to 30 d after ESD and the observation of bleeding spots as confirmed by repeat colonoscopy or a required blood transfusion. We analyzed the relationship between risk factors for delayed bleeding following ESD and the following factors using univariate and multivariate analyses: age, gender, presence of comorbidities, use of antithrombotic drugs, use of intravenous heparin, resected specimen size, lesion size, lesion location, lesion morphology, lesion histology, the device used, procedure time, and the presence of significant bleeding during ESD.Delayed post-ESD bleeding was found in 14 lesions from 14 patients (4.3% of all specimens, 4.4% patients). Patients with episodes of delayed post-ESD bleeding had a mean hemoglobin decrease of 2.35 g/dL. All episodes were treated successfully using endoscopic hemostatic clips. Emergency surgery was not required in any of the cases. Blood transfusion was needed in 1 patient (0.3%). Univariate analysis revealed that lesions located in the cecum (P = 0.012) and the presence of significant bleeding during ESD (P = 0.024) were significantly associated with delayed post-ESD bleeding. The risk of delayed bleeding was higher for larger lesion sizes, but this trend was not statistically significant. Multivariate analysis revealed that lesions located in the cecum (OR = 7.26, 95%CI: 1.99-26.55, P = 0.003) and the presence of significant bleeding during ESD (OR = 16.41, 95%CI: 2.60-103.68, P = 0.003) were independent risk factors for delayed post-ESD bleeding.Location in the cecum and significant bleeding during ESD predispose patients to delayed post-procedural bleeding. Therefore, careful and additional management is recommended for these patients.

To evaluate the usefulness of real-time virtual sonography (RVS) in biliary and pancreatic diseases.This study included 15 patients with biliary and pancreatic diseases. RVS can be used to observe an ultrasound image in real time by merging the ultrasound image with a multiplanar reconstruction computed tomography (CT) image, using pre-scanned CT volume data. The ultrasound used was EUB-8500 with a convex probe EUP-C514. The RVS images were evaluated based on 3 levels, namely, excellent, good and poor, by the displacement in position.By combining the objectivity of CT with free scanning using RVS, it was possible to easily interpret the relationship between lesions and the surrounding organs as well as the position of vascular structures. The resulting evaluation levels of the RVS images were 12 excellent (pancreatic cancer, bile duct cancer, cholecystolithiasis and cholangiocellular carcinoma) and 3 good (pancreatic cancer and gallbladder cancer). Compared with conventional B-mode ultrasonography and CT, RVS images achieved a rate of 80% superior visualization and 20% better visualization.RVS has potential usefulness in objective visualization and diagnosis in the field of biliary and pancreatic diseases.

AIM: To determine the effective hospitalization period as the clinical pathway to prepare patients for endoscopic submucosal dissection (ESD). METHODS: This is a retrospective observational study which included 189 patients consecutively treated by ESD at the National Cancer Center Hospital from May 2007 to March 2009. Patients were divided into 2 groups; patients in group A were discharged in 5 d and patients in group B included those who stayed longer than 5 d. The following data were collected for both groups: mean hospitalization period, tumor site, median tumor size, post-ESD rectal bleeding requiring urgent endoscopy, perforation during or after ESD, abdominal pain, fever above 38 °C, and blood test results positive for inflammatory markers before and after ESD. Each parameter was compared after data collection. RESULTS: A total of 83% (156/189) of all patients could be discharged from the hospital on day 3 post-ESD. Complications were observed in 12.1% (23/189) of patients. Perforation occurred in 3.7% (7/189) of patients. All the perforations occurred during the ESD procedure and they were managed with endoscopic clipping. The incidence of post-operative bleeding was 2.6% (5/189); all the cases involved rectal bleeding. We divided the subjects into 2 groups: tumor diameter ≥ 4 cm and < 4 cm; there was no significant difference between the 2 groups (P = 0.93, χ2 test with Yates correction). The incidence of abdominal pain was 3.7% (7/189). All the cases occurred on the day of the procedure or the next day. The median white blood cell count was 6800 ± 2280 (cells/μL; ± SD) for group A, and 7700 ± 2775 (cells/μL; ± SD) for group B, showing a statistically significant difference (P = 0.023, t-test). The mean C-reactive protein values the day after ESD were 0.4 ± 1.3 mg/dL and 0.5 ± 1.3 mg/dL for groups A and B, respectively, with no significant difference between the 2 groups (P = 0.54, t-test). CONCLUSION: One-day admission is sufficient in the absence of complications during ESD or early post-operative bleeding.

To investigate the diagnosis of nonalcoholic steatohepatitis (NASH) using contrast ultrasonography in the NASH rat model.The liver in methionine choline-deficient diet (MCDD) rats, a NASH model constructed by feeding an MCDD, was examined by contrast ultrasonography at weeks 2, 4, 8, 12 and 16, with late phase images of contrast ultrasonography (Kupffer imaging) in which contrast enhancement was achieved by incorporation of a contrast agent by Kupffer cells (KCs), and images were compared to those in rats taking a regular chow.Decrease in contrast enhancement was observed first in MCDD rats at week 2. KCs were counted based on immunohistochemistry, but their numbers were not reduced and it was assumed that attenuation of contrast enhancement was attributable to reduced phagocytic activity of the KCs.It is suggested that clinical application of contrast ultrasonography may be valuable for non-invasive diagnosis of NASH.

To evaluate the relationship between the signal intensity of hepatobiliary phase images on gadoxetic acid-enhanced magnetic resonance imaging (MRI) and histological grade.Fifty-nine patients with 82 hepatocellular lesions were evaluated retrospectively. Hepatobiliary phase images on gadoxetic acid-enhanced MRI were classified into 3 groups: low, iso or high. Angiography-assisted computed tomography (CT) findings were also classified into 3 groups: CT during arterial portography, and CT hepatic arteriography: A: iso, iso or low; B: slightly low, iso or low; and C: low, high. We correlated angiography-assisted CT, hepatobiliary phase findings during gadoxetic acid-enhanced MRI and histological grades. Furthermore, correlations between MRI findings and histological grade for each hemodynamic pattern were performed. Correlations among radiological and pathological findings were statistically evaluated using the chi-square test and Fisher' s exact test.There was a significant correlation between histological grade and hemodynamic pattern (P0.05). There was a significant correlation between histological grade and signal intensity in the hepatobiliary phase (P0.05) in group A lesions. There was no significant correlation between histological grade and signal intensity in the hepatobiliary phase in group B or C lesions (P0.05).Signal intensity in the hepatobiliary phase correlated with histological grade in the lesions that maintained portal blood flow, but did not correlate in lesions that showed decreased or defective portal blood flow.

Endoscopic therapy of pancreatic duct (PD) strictures using balloon dilation and pancreatic duct stent (PS) placement has been reported to improve the severity of abdominal pain in selected patients with chronic pancreatitis (CP). However, some strictures are refractory and require frequent PS exchange to control symptoms. We describe two cases of successful endoscopic PD incision for difficult PD stricture using a wire-guided snare. The snare is partially opened within the strictured pancreatic duct while applying current, thus incising the duct. Although both cases were successful without complications we do not advocate that this method be used routinely because of the potential for severe complications, e.g. bleeding, ductal perforation or pancreatic parenchymal damage. In order to prevent these complications, we developed a wire-guided technique under fluoroscopic control. We think this procedure may be useful in patients with short, straight PD strictures. Although further study is required, this approach may have potential for selected patients with refractory PD strictures due to CP.

AIM: To evaluate whether an endoscopy position detecting unit (UPD-3) can improve cecal intubation rates, cecal intubation times and visual analog scale (VAS) pain scores, regardless of the colonoscopist’s level of experience. METHODS: A total of 260 patients (170 men and 90 women) who underwent a colonoscopy were divided into the UPD-3-guided group or the conventional group (no UPD-3 guidance). Colonoscopies were performed by experts (experience of more than 1000 colonoscopies) or trainees (experience of less than 100 colonoscopies). Cecal intubation rates, cecal intubation times, insertion methods (straight insertion: shortening the colonic fold through the bending technique; roping insertion: right turn shortening technique) and patient discomfort were assessed. Patient discomfort during the endoscope insertion was scored by the VAS that was divided into 6 degrees of pain. RESULTS: The cecum intubation rates, cecal intubation times, number of cecal intubations that were performed in < 15 min and insertion methods were not significantly different between the conventional group and the UPD-3-guided group. The number of patients who experienced pain during the insertion was markedly less in the UPD-3-guided group than in the conventional group. Univariate and multivariate analysis showed that the following factors were associated with lower VAS pain scores during endoscope insertion: insertion method (straight insertion) and UPD-3 guidance in the trainee group. For the experts group, univariate analysis showed that only the insertion method (straight insertion) was associated with lower VAS pain scores. CONCLUSION: Although UPD-3 guidance did not shorten intubation times, it resulted in less patient pain during endoscope insertion compared with conventional endoscopy for the procedures performed by trainees.

AIM: To assess the diagnostic concordance between endoscopic and histological atrophy in the United Kingdom and Japan. METHODS: Using published data, a total of 252 patients, 126 in the United Kingdom and 126 in Japan, aged 20 to 80 years, were evaluated. The extent of endoscopic atrophy was classified into five subgroups according to a modified Kimura-Takemoto classification system and was compared with histological findings of atrophy at five biopsy sites according to the updated Sydney system. RESULTS: The strength of agreement of the extent of atrophy between histology and visual endoscopic inspection showed good reproducibility, with a weighted kappa value of 0.76 (P < 0.001). Multivariate analysis showed that three factors were associated with decreased concordance: Japanese ethnicity [odds ratio (OR) 0.22, 95% confidence interval (CI) 0.11-0.43], older age (OR = 0.32, 95%CI: 0.16-0.66) and endoscopic atrophy (OR = 0.10, 95%CI: 0.03-0.36). The strength of agreement between endoscopic and histological atrophy, assessed by cancer risk-oriented grading, was reproducible, with a kappa value of 0.81 (95%CI: 0.75-0.87). Only nine patients (3.6%) were endoscopically underdiagnosed with antral predominant rather than extensive atrophy and were considered false negatives. CONCLUSION: Endoscopic grading can predict histological atrophy with few false negatives, indicating that precancerous conditions can be identified during screening endoscopy, particularly in patients in western countries.

AIM: To evaluate the usefulness of three-dimensional (3D) shear-wave elastography (SWE) in assessing the liver ablation volume after radiofrequency (RF) ablation. METHODS: RF ablation was performed in vivo in 10 rat livers using a 15-gauge expandable RF needle. 3D SWE as well as B-mode ultrasound (US) were performed 15 min after ablation. The acquired 3D volume data were rendered as multislice images (interslice distance: 1.10 mm), and the estimated ablation volumes were calculated. The 3D SWE findings were compared against digitized photographs of gross pathological and histopathological specimens of the livers obtained in the same sectional planes as the 3D SWE multislice images. The ablation volumes were also estimated by gross pathological examination of the livers, and the results were then compared with those obtained by 3D SWE. RESULTS: In B-mode US images, the ablation zone appeared as a hypoechoic area with a peripheral hyperechoic rim; however, the findings were too indistinct to be useful for estimating the ablation area. 3D SWE depicted the ablation area and volume more clearly. In the images showing the largest ablation area, the mean kPa values of the peripheral rim, central zone, and non-ablated zone were 13.1 ± 1.5 kPa, 59.1 ± 21.9 kPa, and 4.3 ± 0.8 kPa, respectively. The ablation volumes depicted by 3D SWE correlated well with those estimated from gross pathological examination (r2 = 0.9305, P = 0.00001). The congestion and diapedesis of red blood cells observed in histopathological examination were greater in the peripheral rim of the ablation zone than in the central zone. CONCLUSION: 3D SWE outperforms B-mode US in delineating ablated areas in the liver and is therefore more reliable for spatially delineating thermal lesions created by RF ablation.

To evaluate the surface microvascular patterns of early colorectal cancer (ECC) using narrow-band imaging (NBI) with magnification and its effectiveness for invasion depth diagnosis.We studied 112 ECC lesions [mucosal/submucosal superficial (m/sm-s), 69; sm-deep (sm-d), 43]or = 10 mm that subsequently underwent endoscopic or surgical treatment at our hospital. We compared microvascular architecture revealed by NBI with magnification to histological findings and then to magnification colonoscopy pit pattern diagnosis.Univariate analysis indicated vessel density: non-dense (P0.0001); vessel regularity: negative (P0.0001); caliber regularity: negative (P0.0001); vessel length: short (P0.0001); and vessel meandering: positive (P = 0.002) occurred significantly more often with sm-d invasion than m/sm-s invasion. Multivariate analysis showed sm-d invasion was independently associated with vessel density: non-dense [odds ratio (OR) = 402.5, 95% confidence interval (CI): 12.4-13 133.1] and vessel regularity: negative (OR = 15.9, 95% CI: 1.2-219.1). Both of these findings when combined were an indicator of sm-d invasion with sensitivity, specificity and accuracy of 81.4%, 100% and 92.9%, respectively. Pit pattern diagnosis sensitivity, specificity and accuracy, meanwhile, were 86.0%, 98.6% and 93.8%, respectively, thus, the NBI with magnification findings of non-dense vessel density and negative vessel regularity when combined together were comparable to pit pattern diagnosis.Non-dense vessel density and/or negative vessel regularity observed by NBI with magnification could be indicators of ECC sm-d invasion.

AIM: To examine the coexistence of metachronous and synchronous cancer in branch duct intraductal papillary mucinous neoplasms of the pancreas (IPMN). METHODS: We reviewed the records of 145 patients with branch duct IPMN between January 1991 and April 2008 and assessed the relationship between IPMN and intra- or extra-pancreatic carcinoma and the outcome of IPMN. RESULTS: The mean observation period was 55.9 ± 45.3 mo. Among the 145 patients, the frequency of extra-pancreatic cancer was 29.0%. The frequency of gastric cancer, colon cancer, breast cancer, and pancreatic cancer were 25.5%, 15.7%, 13.7%, and 9.8%, respectively. Twenty (13.8%) of the patients died. The cause of death was extra-pancreatic carcinoma in 40%, pancreatic cancer in 25%, IPMN per se in 20%, and benign disease in 15% of the patients. CONCLUSION: The prognosis for IPMN depends not on the IPMN per se, but on the presence of intra- or extra-pancreatic cancer.

Endoscopic ultrasonography (EUS)-guided biliary drainage was performed for treatment of patients who have obstructive jaundice in cases of failed endoscopic retrograde cholangiopancreatography (ERCP). In the present study, we introduced the feasibility and outcome of EUS-guided choledochoduodenostomy in four patients who failed in ERCP. We performed the procedure in 2 papilla of Vater, including one resectable case, and 2 cases of cancer of the head of pancreas. Using a curved linear array echoendoscope, a 19 G needle or a needle knife was punctured transduodenally into the bile duct under EUS visualization. Using a biliary catheter for dilation, or papillary balloon dilator, a 7-Fr plastic stent was inserted through the choledochoduodenostomy site into the extrahepatic bile duct. In 3 (75%) of 4 cases, an indwelling plastic stent was placed, and in one case in which the stent could not be advanced into the bile duct, a naso-biliary drainage tube was placed instead. In all cases, the obstructive jaundice rapidly improved after the procedure. Focal peritonitis and bleeding not requiring blood transfusion was seen in one case. In this case, pancreatoduodenectomy was performed and the surgical findings revealed severe adhesion around the choledochoduodenostomy site. Although further studies and development of devices are mandatory, EUS-guided choledochoduodenostomy appears to be an effective alternative to ERCP in selected cases.

We encountered a 65-year-old man with a carcinoid tumor of the minor duodenal papilla. Since he had liver cirrhosis and completely refused surgery, we performed an endoscopic snare papillectomy. The papillectomy was performed successfully without procedure-related complication. The specimens revealed a carcinoid tumor showing that the margin of the tumor was positive. One week later, upper GI endoscopy was performed and the biopsy specimens obtained from base of ulcer showed no neoplastic cells. We performed a duodenoscopy and CT 3, 6 and 18 mo later, and there was no macroscopic or microscopic evidence of tumor recurrence after more than 4 years.

To determine the utility of interferon (IFN)-alpha production capacity in patients with hepatitis C virus (HCV) infection for the measurement of immuno-surveillance potential and for the early detection of hepatocellular carcinoma (HCC) by investigating the Sendai virus (HVJ) stimulated IFN-alpha production capacity of patients with HCV infection.HVJ stimulated IFN-alpha production was determined in a large number of patients with HCV infection and the development of HCC was monitored for 3 years in patients with liver cirrhosis (LC).IFN-alpha production capacity decreases gradually with the progression of liver disease from chronic hepatitis (CH) to HCC. A significant correlation between the duration of HCV infection and impaired IFN-alpha production capacity was observed. IFN-alpha production in patients who developed HCC within 3 years was significantly lower than that of patients who remained in LC without developing HCC.Measurement of IFN-alpha production in LC patients may be useful for the early detection of HCC.

Persistent hepatitis B virus (HBV) infection is characterized by a weak CD8(+) T cell response to HBV. Immunotherapeutic strategies that overcome tolerance and boost these suboptimal responses may facilitate viral clearance in chronically infected individuals. Therefore, we examined whether CD25(+)CD4(+) regulatory T (Treg) cells might be involved in a inhibition of CD8(+) T cell priming or in the modulation of the magnitude of the 'peak' antiviral CD8(+) T cell response primed by DNA immunization.B10.D2 mice were immunized once with plasmid pCMV-S. Mice received 500 microg of anti-CD25 mAb injected intraperitoneally 3 d before DNA immunization to deplete CD25(+) cells. Induction of HBV-specific CD8(+) T cells in peripheral blood mononuclear cells (PBMCs) was measured by S28-39 peptide loaded DimerX staining and their function was analyzed by intracellular IFN-gamma staining.DNA immunization induced HBV-specific CD8(+) T cells. At the peak T cell response (d 10), 7.1+/-2.0% of CD8(+) T cells were HBV-specific after DNA immunization, whereas 12.7+/-3.2% of CD8(+) T cells were HBV-specific in Treg-depleted mice, suggesting that DNA immunization induced more antigen-specific CD8(+) T cells in the absence of CD25(+) Treg cells (n = 6, P0.05). Similarly, fewer HBV-specific memory T cells were detected in the presence of these cells (1.3+/-0.4%) in comparison to Treg-depleted mice (2.6+/-0.9%) on d 30 after DNA immunization (n = 6, P0.01). Both IFN-gamma production and the avidity of the HBV-specific CD8(+) T cell response to antigen were higher in HBV-specific CD8(+) T cells induced in the absence of Treg cells.CD25(+) Treg cells suppress priming and/or expansion of antigen-specific CD8(+) T cells during DNA immunization and the peak CD8(+) T cell response is enhanced by depleting this cell population. Furthermore, Treg cells appear to be involved in the contraction phase of the CD8(+) T cell response and may affect the quality of memory T cell pools. The elimination of Treg cells or their inhibition may be important in immunotherapeutic strategies to control HBV infection by inducing virus-specific cytotoxic T lymphocyte responses in chronically infected subjects.