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OBJECTIVES There are few reports on the long-term prognosis of papillary tumors after endoscopic papillectomy. Here, we report a retrospective study of the therapeutic effects, long-term prognosis, and affecting factors. METHODS The inclusion criteria were papillary adenoma with/without an adenocarcinoma component on biopsy results and ≤10 mm intraductal extension, and the exclusion criteria were moderate to poorly differentiated adenocarcinoma on biopsy results. If no residual lesion was confirmed ≥6 months after the last endoscopic treatment, remission was defined. Subsequently, follow-up endoscopy was scheduled once a year. Surgery was required in the case of adenocarcinoma recurrence or intraductal lesions >10 mm. The rates of adverse events, remission, recurrence, and need for surgery were examined. The affecting factors were calculated. RESULTS There were a total of 253 subjects, including 65 with adenocarcinoma. Pancreatitis (7.5%), bleeding (9.1%) and perforation (2.8%) were observed as adverse events. Among 221 subjects with ≥6 months of follow-up, 212 (95.9%) were in remission. The cumulative recurrence rate using the Kaplan-Meier analysis at 5 years was 16.9% (22 cases), with the need for surgery in 5.9% (5 cases). Intraductal extension on preoperative diagnosis was the only significant risk factor for both recurrence (P

Large amounts of radioactive cesium (CsA) have been introduced into the underground environments, through a natural process, as a result of nuclear power plant accidents. It is known that the active Cs sorption onto colloidal-size clay minerals in groundwater is observed and the active Cs can be transported with the colloidal fraction of groundwater by water flows. However, the longtime behavior of radioactive Cs, contained in the flowing groundwater in the aquifers of groundwater source areas, is unknown in terms of the natural water cycle. Herein, we investigate the Cs concentration in natural spring drinking water with the residence time in a groundwater source area of a mountainside composed of volcanic rock, compared with those of other trace elements. This investigation demonstrates that the observed Cs concentration in natural spring drinking water exponentially decreases slowly with the groundwater residence time (∼45 yr), while several trace elements, namely, P, V, Ga, and Ge, increase in concentration with the groundwater residence time through chemical weathering. The findings suggest that CsA, contained in flowing groundwater in mountain water source areas, may decrease exponentially at the rate of one-tenth in twenty-two years, by sorption onto the aquifer through rock–water interaction excluding radioactive decay. For the sustainable management of water sources and ecosystems, the long-term (∼50 yr) monitoring of the active Cs in groundwater is needed in mountain water source areas where radioactive cesium has been dispersed at times of nuclear power plant accidents.

Background and Aims The population of patients chronically infected with hepatitis C virus (HCV) is aging, and the number of older patients with HCV-related hepatocellular carcinoma (HCC) is increasing. The purpose of this study was to elucidate the effects of peginterferon and ribavirin combination therapy on prevention of HCC in older patients with chronic hepatitis C (CH-C). Methods We compared the sustained virological response (SVR) and treatment discontinuation rates between older (≥ 65 years) and younger patients (

Obtaining a better understanding of the mechanisms associated with hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) loss in patients with hepatitis B virus (HBV) is important for treating patients with chronic hepatitis B. We herein describe the case of a patient with HBV and human immunodeficiency virus whose chronic hepatitis was stabilized due to HBe and HBs seroconversion with the emergence of lamivudine-associated and core mutations after CD4 elevation. A full-length HBV DNA analysis indicated that HBsAg had been lost after the development of the rtS143T mutation, which corresponded to the emergence of the sF134L and core mutations. The details of this case shed some light on the mechanisms associated with HBsAg and HBeAg clearance.

Histone H3 lysine 9 (H3K9) methylation is a hallmark of heterochromatin. H3K9 demethylation is crucial in mouse sex determination; The H3K9 demethylase Jmjd1a deficiency leads to increased H3K9 methylation at the Sry locus in embryonic gonads, thereby compromising Sry expression and causing male-to-female sex reversal. We hypothesized that the H3K9 methylation level at the Sry locus is finely tuned by the balance in activities between the H3K9 demethylase Jmjd1a and an unidentified H3K9 methyltransferase to ensure correct Sry expression. Here we identified the GLP/G9a H3K9 methyltransferase complex as the enzyme catalyzing H3K9 methylation at the Sry locus. Based on this finding, we tried to rescue the sex-reversal phenotype of Jmjd1a-deficient mice by modulating GLP/G9a complex activity. A heterozygous GLP mutation rescued the sex-reversal phenotype of Jmjd1a-deficient mice by restoring Sry expression. The administration of a chemical inhibitor of GLP/G9a enzyme into Jmjd1a-deficient embryos also successfully rescued sex reversal. Our study not only reveals the molecular mechanism underlying the tuning of Sry expression but also provides proof on the principle of therapeutic strategies based on the pharmacological modulation of epigenetic balance., Author summary In eukaryotes, DNA wraps an octamer of the core histones. Covalent modifications on the histones have diverse biological functions including transcriptional regulation. Histone H3 lysine 9 (H3K9) methylation is a hallmark of transcriptionally silenced chromatin. In mammals, the sex-determining gene Sry initiates testis differentiation in embryonic gonads. Sry expression in gonads is fine-tuned in both space and time. Here, we demonstrated that fine-tuning of Sry expression is achieved by the balance in activities between H3K9 demethylase and H3K9 methyltransferase. We found that the GLP/G9a complex is the enzyme catalyzing H3K9 methylation of Sry. Based on this finding, we tried to rescue the sex-reversal phenotype of the mutant mice by modulating the H3K9 methylation balance of Sry. We succeeded by modulating the H3K9 methylation balance not only with a genetic approach but also with a chemical approach using an inhibitor of GLP/G9a enzyme. Aberrant histone methylation levels are associated with diseases, including cancer, and intellectual disability. Our study provides proof for the principle of therapeutic strategies based on the pharmacological modulation of histone methylation balance.

Background and Aim The single nucleotide polymorphism (SNP) of interleukin 28B (IL28B) and the mutations in the NS5A region of hepatitis C virus (HCV) genotype 1 have been associated with response to interferon (IFN) therapy. However, these relationships in patients with HCV genotype 2 are not well understood. The aim of this study was to investigate whether the SNP of IL28B (rs8099917) and amino acid substitutions in the NS5A region in patients with HCV genotype 2 affect the response to IFN and ribavirin combination therapy. Methods The study enrolled 286 patients with chronic hepatitis C genotype 2. Patients received pegylated-IFN-alpha 2b once each week plus oral ribavirin daily for 24 weeks. Results Of the 286 patients, 215 (75.2%) achieved sustained virologic response (SVR). Rate of SVR was similar in patients with IL28B TT allele (76%) and those with TG or GG alleles (72%). Patients with SVR were younger than those without SVR (P

An accurate diagnosis of pancreatic fibrosis is clinically important and may have potential for staging chronic pancreatitis. The aim of this study was to diagnose the grade of pancreatic fibrosis through a quantitative analysis of endoscopic ultrasound elastography (EUS-EG). From September 2004 to October 2010, 58 consecutive patients examined by EUS-EG for both pancreatic tumors and their upstream pancreas before pancreatectomy were enrolled. Preoperative EUS-EG images in the upstream pancreas were statistically quantified, and the results were retrospectively compared with postoperative histological fibrosis in the same area. For the quantification of EUS-EG images, 4 parameters (mean, standard deviation, skewness, and kurtosis) were calculated using novel software. Histological fibrosis was graded into 4 categories (normal, mild fibrosis, marked fibrosis, and severe fibrosis) according to a previously reported scoring system. The fibrosis grade in the upstream pancreas was normal in 24 patients, mild fibrosis in 19, marked fibrosis in 6, and severe fibrosis in 9. Fibrosis grade was significantly correlated with all 4 quantification parameters (mean r = −0.75, standard deviation r = −0.54, skewness r = 0.69, kurtosis r = 0.67). According to the receiver operating characteristic analysis, the mean was the most useful parameter for diagnosing pancreatic fibrosis. Using the mean, the area under the ROC curves for the diagnosis of mild or higher-grade fibrosis, marked or higher-grade fibrosis and severe fibrosis were 0.90, 0.90, and 0.90, respectively. An accurate diagnosis of pancreatic fibrosis may be possible by analyzing EUS-EG images.

Background/Aims To confirm the feasibility of using newly developed endoscopic ultrasound (EUS) with Zone sonography™ technology (ZST; Fujifilm Corp.). Methods Seventy-five patients with pancreatic disorders were enrolled: 45 with intraductal papillary mucinous neoplasm; 15 with ductal carcinoma; five with neuroendocrine tumors; three with serous cystic neoplasms; and seven with simple cysts. The endoscopes used were EG-530UR2 and EG-530UT2 (Fujifilm Corp.). Two items were evaluated: visualization depth among four frequencies and image quality after automatic adjustment of sound speed (AASS), assessed using a 5-scale Likert scale by two endosonographers blinded to disease status. Because sound speed could be manually controlled, besides AASS, image quality at sound speeds of 1,440 and 1,600 m/sec were also assessed. Results In all cases, sufficient images were obtained in the range of 3 cm from the EUS probe. Judgments of image quality before AASS were 3.49±0.50, 3.65±0.48, respectively. After AASS, A and B scored 4.36±0.48 and 4.40±0.49 (p

Background: A close association between patterns identified by magnifying narrow-band imaging (M-NBI) and histological type has been described. M-NBI patterns were also recently reported to be related to the mucin phenotype; however, detials remain unclear. Materials and Methods: We investigated the cellular differentiation of gastric cancer lesions, along with their mucosal distribution observed by M-NBI. Ninety-seven depressed-type early gastric cancer lesions (74 differentiated and 23 undifferentiated adenocarcinomas) were visualized by M-NBI. Findings were divided into 4 patterns based on abnormal microvascular architecture: a chain loop pattern (CLP), a fine network pattern (FNP), a corkscrew pattern (CSP), and an unclassified pattern. Mucin phenotypes were judged as gastric (G-type), intestinal (I-type), mixed gastric and intestinal (M-type), and null (N-type) based on 4 markers (MAC5AC, MUC6, MUC2, and CD10). The relationship of each pattern of microvascular architecture with organoid differentiation indicated by cancer cell differentiation and its distribution in each histological type of early gastric cancer was investigated. Results: All CLP and FNP lesions were differentiated. The cancer cell distribution showed organoid differentiation in 84.2% (16/19) and 61.1% (22/36) of the two types of lesions, respectively, and there was a significant difference from the unclassified pattern with organoid differentiation (p

Clinical guidelines of the European Society of Gastrointestinal Endoscopy recommend the insertion of self-expandable metallic stents (SEMS) as opposed to plastic stents (PS) in patients with unresectable malignant perihilar stricture (MHS). However, PS are cheaper and easier to insert into the biliary duct compared to SEMS. Furthermore, PS are removable and easy to move into subsequent drainage procedures. We conducted the present retrospective single-center study to elucidate the predictive factors associated with stent patency period duration in patients with unresectable MHS who would benefit from a long patency period after PS placement. This study included 56 consecutive patients with unresectable MHS who were drained using PS. PS failure occurred in 26 (46.4%) patients. The median patency period was 72 days (95% confidence interval: 29.8-114). The only significant predictive factor associated with the length of the stent patency period was history of previous endoscopic sphincterotomy (EST). Median patency periods with and without previous EST were 28 and 109 days, respectively (P = 0.016). In conclusion, we suggest that conventional biliary drainage with PS is still a suitable option for the treatment of unresectable MHS in patients without previous EST.

Aim Previous studies have suggested that patients with chronic hepatitis C with a low pretreatment hepatitis C virus (HCV) level have a high sustained virological response (SVR) rate, and that there would be a subpopulation of patients in which HCV can be eradicated with pegylated interferon (PEG IFN) alone without a decrease in SVR. However, the efficacy of PEG IFN monotherapy in patients with low HCV RNA levels is unclear. Several studies have reported that interferon sensitivity-determining region (ISDR) and the single-nucleotide polymorphism (SNP) of interleukin-28B (IL-28B) contribute to IFN response, but these relationships are controversial. The aim of this study was to determine whether the SNP of IL-28B (rs8099917) and amino acid substitutions in the ISDR among patients with low HCV levels affect the response to PEG IFN monotherapy. Methods One hundred and four patients with low-level HCV infection were studied. Low HCV level was defined as 100 KIU/mL or less. Results SVR was achieved in 94 patients (92.2%). HCV levels (≤50 KIU/mL) and ISDR (≥2 mutations) were associated with SVR on univariate analysis. The rates of SVR in the patients with IL-28B genotypes TT, TG and GG were 94.5%, 77.8% and 100%, respectively. The G allele tended to be associated with poor response to IFN therapy (P = 0.0623). On multivariate analysis, the ISDR was the factor predictive of SVR (P = 0.004). Conclusion The ISDR is significantly associated with a good response to PEG IFN monotherapy in patients with low HCV levels.

In a decision-making process, one finds that there are alternatives which can be categorized into several groups, based on his or her perspectives, and/or on expected outcome, such as whether his or her choice brings about gains or losses, or that such a choice is right or wrong. Besides, there are many cases with a dilemma where it is hard to select the best choice through transitive relations. This paper presents a new method to dissolve this dilemma by using ANP (Analytic Network Process) with a newly defined criteria matrix. The case of the super-matrix of ANP is examined in an alternative matrix with a dilemma. The paper shows mathematically that the eigenvector of the super-matrix serves as a solution to this simple dilemma, describes the proposed method, and attempts to apply this method to other dilemmas. The proposed method is limited to up to three alternatives.

A 780 nm-range 40 channels vertical-cavity surface-emitting laser (VCSEL) array was developed as a writing light source for printers. A 15° off missoriented GaAs substrate, an aluminum-free GaInAsP/GaInP compressively-strained multiple quantum well and an anisotropic-shape transverse-mode filter were employed to control polarization characteristics. The anisotropic-shape transverse-mode filter also suppressed higher transverse-mode and enabled high-power single-mode operation. Thus, orthogonal-polarization suppression-ratio (OPSR) of over 22 dB and side-mode suppression-ratio (SMSR) of 30 dB were obtained at operation power of 3mW at same time for wide oxide-aperture range below 50 μm2. Moreover, a thermal resistance was reduced for 38% by increasing a thickness of high thermal conductivity layer (3λ/4-AlAs layer) near a cavity. By this structure, a peak-power increased to 1.3 times. Moreover, a power-fall caused by self-heating at pulse-rise was decreased to 10% and the one caused by a thermal-crosstalk between channels was decreased to 46%. The VCSEL array was mounted in a ceramic package with a tilted seal glass to prevent optical-crosstalk caused by other channels. Thus, we achieved stable-output and high-quality beam characteristics for long-duration pulse drive.

Background and Aim Although peripancreatic vascular lesions are occasionally encountered in autoimmune pancreatitis (AIP), there are few reports focusing on these involvements. We aimed to investigate the peripancreatic vascular involvements associated with AIP. Methods We retrospectively analyzed 54 AIP patients who met the International Consensus Diagnostic Criteria for AIP between July 2003 and October 2010. All of the 54 patients were subjected to multiphasic multidetector computed tomography, and the prevalence, location and prognosis of peripancreatic vascular involvements were investigated. Results Of the 54 AIP patients, 24 (44.4%) exhibited involvements in the form of peripancreatic vascular lesions (stenoses of the splenic vein in 22 and of the superior mesenteric-portal vein in 13, development of perigastric collateral circulation in 18, gastric varices with a red color sign in one and thrombosis inside the portal vein in one). Diffuse-type AIP was associated with a significantly higher prevalence of vascular involvements compared with focal-type AIP (P = 0.033). A total of 14 out of 16 patients who underwent corticosteroid treatment showed improvement in vascular lesions. One case followed up without corticosteroid treatment and presenting an obstruction of the splenic vein exhibited involvements in the form of an infarction and hemorrhagic cysts of the spleen and ultimately underwent distal pancreatectomy and splenectomy. Conclusions Autoimmune pancreatitis patients show a high prevalence of peripancreatic vascular involvements. Thus, patients with vascular involvements are suitable candidates for steroid therapy with evaluation of its potential merits and demerits, even if they are asymptomatic.

Contrast-enhanced endoscopic ultrasonography (CE-EUS) was introduced in the early 1990s. The concept of the injection of carbon dioxide microbubbles into the hepatic artery as a contrast material (enhanced ultrasonography) led to "endoscopic ultrasonographic angiography". After the arrival of the first-generation contrast agent, high-frequency (12 MHz) EUS brought about the enhancement of EUS images in the diagnosis of pancreatico-biliary diseases, upper gastrointestinal (GI) cancer, and submucosal tumors. The electronic scanning endosonoscope with both radial and linear probes enabled the use of high-end ultrasound machines and depicted the enhancement of both color/power Doppler flow-based imaging and harmonic-based imaging using second-generation contrast agents. Many reports have described the usefulness of the differential diagnosis of pancreatic diseases and other abdominal lesions. Quantitative evaluation of CE-EUS images was an objective method of diagnosis using the time-intensity curve (TIC), but it was limited to the region of interest. Recently developed Inflow Time Mapping™ can be generated from stored clips and used to display the pattern of signal enhancement with time after injection, offering temporal difference of contrast agents and improved tumor characterization. On the other hand, three-dimensional CE-EUS images added new information to the literature, but lacked positional information. Three-dimensional CE-EUS with accurate positional information is awaited. To date, most reports have been related to pancreatic lesions or lymph nodes. Hemodynamic analysis might be of use for diseases in other organs: upper GI cancer diagnosis, submucosal tumors, and biliary disorders, and it might also provide functional information. Studies of CE-EUS in diseases in many other organs will increase in the near future.

Background Small-bowel tumors (SBTs) represent a diagnostic challenge. Objective To evaluate the usefulness of contrast-enhanced CT (CECT), fluoroscopic enteroclysis (FE), videocapsule endoscopy (VCE), and double-balloon endoscopy (DBE) and the outcome after treatment. Design Single-center, retrospective study. Setting Tertiary-care referral hospital. Patients Between June 2003 and May 2011, 159 consecutive patients with SBTs (93 malignant and 66 benign) were enrolled. Main Outcome Measurements Comparison of diagnostic yields among CECT, FE, VCE, and DBE and the prognosis. Results CECT and FE had significantly lower diagnostic yields of SBTs ≤10 mm, but VCE and DBE had high yields of SBTs regardless of size. CECT had a significantly lower diagnostic yield of epithelial tumors compared with subepithelial tumors. When stratified by the site, the diagnostic yield of VCE for SBTs located only in the distal duodenum/the proximal jejunum (73%) was significantly lower than that for SBTs located in other areas (90%). Comparisons among the 4 methods revealed that VCE and DBE had significantly higher diagnostic yields than CECT, and DBE had significantly higher diagnostic yields than VCE, but a combination of CECT and VCE had a diagnostic yield similar to that of DBE. The histologic diagnostic yield of SBTs by DBE was 92%, and 25% of SBTs were enteroscopically treated. Metastatic tumors had the poorest overall survival, followed by adenocarcinomas and malignant lymphomas. Limitations Retrospective comparative study. Conclusion For the detection of SBTs, a combination screening method by using VCE and CECT is recommended. DBE is useful for histologic diagnosis and endoscopic treatment.

Background and Aim: HFE mutations, a common cause of hereditary hemochromatosis (HH), are reportedly associated with hepatic iron overload, severe liver fibrosis, and good response to interferon treatment in European patients with chronic hepatitis C (CHC). HH shows ethnicity-based differences and little is known about the effects of HH mutations on CHC in the Japanese. Thus, the aim of this study was to clarify the clinical influence of HFE mutations in Japanese CHC patients. Methods: In a total of 251 patients with CHC, we analyzed the frequencies of H63D and S65C mutations in the HFE gene, and the influence of these mutations on clinical parameters and response to pegylated-interferon-alpha 2b (PEG-IFN) plus ribavirin therapy. Results: Fourteen patients (5.6%) carried the H63D mutation; all were heterozygotes. No S65C mutations were found. Only hemoglobin levels in the H63D heterozygotes were higher than in wild-type patients. Eleven of 14 H63D heterozygotes achieved sustained virological response (SVR). On univariate analysis, factors associated with SVR were interleukin 28B (IL28B) polymorphism, age, hepatitis C virus (HCV) genotype, HCV viral load, white blood cell count, stage of fibrosis and H63D mutation. All patients with both TT genotype in IL28B (rs8099917) and H63D mutation in HFE (n = 10) achieved SVR. Conclusions: The H63D mutation has little impact on the clinical characteristics of CHC, but is related to favorable response to PEG-IFN plus ribavirin therapy, particularly in patients with the TT allele in IL28B.

Background: The sensitivity of transpapillary biliary forceps biopsy for malignancy has been reported as varying from 43–81%. Therefore, there are false negatives in more than 20% of patients, which makes it difficult to diagnose benign biliary stricture as benignancy in a clinical setting. Methods: To clarify the number of tissue samples that should be obtained during transpapillary forceps biopsy to distinguish benign biliary stricture from malignancy, patients undergoing transpapillary biliary forceps biopsy at our institute were examined retrospectively in this study. Results: Seventy-two biliary forceps biopsy procedures were performed on 61 patients. The final diagnoses were malignant biliary stricture in 34 patients and benign stricture in 27 patients. The overall sensitivity and specificity for malignancy in this study were 76.5% and 100%, respectively. There were zero out of 10 (0%) false-negative patients when three or more tissue samples were obtained. In contrast, when four or more tissue samples were obtained, eight out of eight (100%) patients had negative diagnoses for malignancy and were finally diagnosed with benignancy. Conclusion: We suggest that three or more tissue samples are recommended for the diagnosis of biliary malignant stricture.

Hepatitis C virus (HCV) genotype 1a is rare in Japanese patients and the clinical characteristics of this genotype remain unclear. The interferon (IFN) sensitivity-determining region (ISDR) and single-nucleotide polymorphisms (SNPs) of interleukin-28B (IL28B) among patients with HCV genotype 1b are associated with IFN response, but associations among patients with genotype 1a are largely unknown. This study investigated the clinical characteristics of genotype 1a and examined whether genomic heterogeneity of the ISDR and SNPs of IL28B among patients with HCV genotype 1a affects response to combination therapy with pegylated-IFN-α2b and ribavirin. Subjects comprised 977 patients infected with HCV genotype 1, including 574 men and 412 women (mean age, 55.2 ± 10.6 years). HCV was genotyped by direct sequencing of the 5′-untranslated region and/or core regions and confirmed by direct sequencing of the NS5A region. HCV genotypes 1a (n = 32) and 1b (n = 945) were detected. Twenty-three (71.9%) of the 32 patients with genotype 1a were patients with hemophilia who had received imported clotting factors. Prevalence of genotype 1a after excluding patients with hemophilia was thus 0.9%. Of the 23 patients with genotype 1a who completed IFN therapy, 11 (47.8%) were defined as achieving sustained virological response. Factors related to sustained virological response by univariate analysis were IL28B and ISDR. In conclusion, HCV genotype 1a is rare in Japan. The presence of IL28B genotype TT, and more than two mutations, in the ISDR are associated with a good response to IFN therapy in patients with HCV genotype 1a. J. Med. Virol. 84:438–444, 2012. © 2011 Wiley Periodicals, Inc.

A 90-year-old woman was admitted to our hospital because of a high-grade fever and appetite loss. On computed tomography scan, a huge cystic lesion about 10 cm in diameter was observed in the pelvic cavity, attached to the vagina and the neck of uterus. Pyometra was strongly suspected; however, a probe could not be inserted into the opening of the uterus because of atrophic changes. Therefore, we decided to perform endoscopic ultrasound (EUS)-guided drainage of the pyometra using the transrectal route. Foul-smelling yellow-brown pus was aspirated. A guide-wire was inserted and a 7 Fr catheter was inserted into the pyometra through an external fistula. We thus completed the treatment of pyometra without surgical resection.

The objectives of this study were to retrospectively evaluate the lesion detection rate of gastric cancer using only virtual gastroscopy generated from MDCT images and the accuracy of invasion depth diagnosis (T staging) using virtual gastroscopy together with contrast-enhanced MDCT with multiplanar reconstruction (MPR) images (virtual gastroscopy with MPR), and to compare the diagnostic performance between virtual gastroscopy with MPR images and endoscopic ultrasound.The subjects consisted of 175 patients with a total of 186 endoscopically proven gastric cancer lesions. All patients underwent dynamic MDCT (arterial and venous phase) for preoperative staging and underwent surgery or endoscopic treatment. In 129 patients (135 lesions) who were also examined using endoscopic ultrasound, the T staging accuracy was also compared between the two modalities. Two endoscopists independently evaluated the lesion detection rate on virtual gastroscopy images alone and determined the T stage on virtual gastroscopy with MPR images. The T staging included the ability to differentiate T1a from T1b lesions.The overall lesion detection rate was 67.7% (126/186). The detection rates of T1a, T1b, and T2 or deeper were 37.8% (28/74), 75.0% (39/52), and 98.3% (59/60), respectively, showing statistically significant differences (p0.001). The T staging accuracies were 82.2% (111/135) using virtual gastroscopy with MPR images and 83.7% (113/135) using endoscopic ultrasound, showing no statistically significant difference (p = 0.850). The main causes of over- and understaging were an ulcer or ulcer scar and poorly differentiated adenocarcinomas, non-solid type, respectively.Virtual gastroscopy with MPR imaging is a useful modality in the T staging of gastric cancer.

Interferon (IFN) induces the double-stranded RNA-dependent protein kinase (PKR) to inhibit viral replication. Two motifs of the PKR-binding domain exist in the E2 and the NS5A regions of the hepatitis C virus (HCV). These regions are called the PKR-eukaryotic transcription factor (elF2-alpha) phosphorylation homology domain (PePHD), and the IFN sensitivity-determining region (ISDR). Both regions are inhibited by PKR. Thus, several studies have reported the relationship between these regions and IFN responsiveness and the HCV viral load. However, the data obtained from these studies remain controversial. The aim of this study was to investigate the genomic heterogeneity of the PePHD and the ISDR in patients with genotype 3a and how this impacts HCV replication and the response to IFN therapy. Twenty-one male patients infected with HCV genotype 3a were studied. The PePHD was well conserved, and mutations were found in only one amino acid position in two patients. Patients with three or more mutations in the ISDR had lower viral loads than those with fewer than two mutations (192.2 ± 176.7 vs. 1279.4 ± 997.6 KIU/ml, P = 0.0277). Ten (71.4%) of 14 patients achieved a sustained virological response to IFN therapy. No specific amino acid substitutions in the PePHD and the ISDR were associated with IFN responsiveness; however, the number of mutations in the ISDR was significantly associated with the HCV viral load. The findings from this study suggest that the ISDR plays an important role in regulating viral replication in patients infected with HCV genotype 3a. J. Med. Virol. 83:1727–1732, 2011. © 2011 Wiley-Liss, Inc.

Background and aims: Mutations in the core and NS5A region of hepatitis C virus (HCV) genotype 1b have been associated with response to interferon (IFN) therapy. Genome-wide association studies have revealed that the single-nucleotide polymorphism (SNP) of interleukin 28B (IL28B) contributes to IFN response. The aim of this study was to investigate whether the SNP of IL28B (rs8099917) and amino acid substitutions in the core and NS5A region affect the response to IFN therapy. Methods: A total of 299 patients (157 men, 142 women; mean age, 55.9 ± 10.3 years) infected with HCV genotype 1b were studied. The fibrosis stage was diagnosed as F0 (n=23), F1 (n=121), F2 (n=62), F3 (n=32) and F4 (n=7) by liver biopsy. Results: Of the 299 patients, 138 achieved sustained virological response (SVR). On univariate analysis, predictors of SVR were age

通常型膵癌に比較して膵内分泌腫瘍では，主膵管途絶を呈することは稀である．我々はERPにて主膵管途絶を来たした膵内分泌腫瘍の2例を経験した.症例1は40歳代男性.心窩部痛で近医受診し，膵腫瘍を指摘.当院精査にて膵内分泌腫瘍と診断し，膵体尾部切除術施行.リンパ節転移を認めwell-differentiated endocrine carcinomaであった.症例2は40歳代男性.主膵管拡張精査目的で当院受診し，膵体部に8mm大の膵腫瘍を認め，膵癌疑いで膵体尾部切除術施行.膵内神経浸潤を認め，well-differentiated endocrine tumor（uncertain behavior）と診断.また造影EUSでは，2症例ともに造影効果の乏しい画像所見を呈した．膵内分泌腫瘍における主膵管途絶所見と造影EUSにおける非典型的造影パターンは悪性度の高い膵内分泌腫瘍を示唆する重要な所見と考えられた．

We propose a computing platform for parallel machine learning. Learning from large-scale data has become common, so that parallelization techniques are increasingly applied to machine learning algorithms in order to reduce calculation time. Problems of parallelization are implementation costs and calculation overheads. Firstly, we formulate MapReduce programming model specialized in parallel machine learning. It represents learning algorithms as iterations of following two phases: applying data to machine learning models and updating model parameters. This model is able to describe various kinds of machine learning algorithms, such as k-means clustering, EM algorithm, and linear SVM, with comparable implementation cost to the original MapReduce. Secondly, we propose a fast machine learning platform which reduces the processing overheads at iterative procedures of machine learning. Machine learning algorithms iteratively read the same training data in the data application phase. Our platform keeps the training data in local memories of each worker during iterative procedures, which leads to acceleration of data access. We evaluate performance of our platform on three experiments. Our platform executes k-means clustering 2.85 to 118 times faster than the MapReduce approach, and shows 9.51 times speedup with 40 processing cores against 8 cores. We also show the performance of Variational Bayes clustering and linear SVM implemented on our platform.

膵疾患の診断における超音波内視鏡検査（EUS）の有用性は世界中で広く認められている．造影EUS（CE-EUS）は，いわゆる第二世代超音波造影剤Sonazoid®（第一三共）を使用することで，膵疾患に対する良質な造影イメージと持続的な観察を実現した．造影EUSによる持続観察後，Time-intensity curve（TIC）を作成し定量的解析を行うと，膵管癌はピーク後のecho-intensityの速やかな低下が特徴的であった．また，B-mode画像診断，肉眼的な造影イメージ診断に，TICを用いた定量的評価を加えることで，膵疾患の良悪性の鑑別診断能の向上が得られる．

Background Management of small-bowel polyps in Peutz-Jeghers syndrome (PJS) by using fluoroscopic enteroclysis (FE), double-balloon enteroscopy (DBE), and videocapsule enteroscopy (VCE) remains incompletely determined. Objective To evaluate the usefulness of FE, VCE, and DBE and compute the polyp growth rate. Design Single-center retrospective study. Setting Tertiary referral hospital. Patients Between June 2003 and January 2010, 18 consecutive patients with PJS were enrolled. Main Outcome Measurements Polyp detection rates among FE, VCE, and DBE, histology of resected polyps, and the polyp growth rate. Results Total enteroscopy rate was higher at VCE (89%) than at DBE (52%; 27% in patients with ≥2 previous laparotomies and 90% in patients with ≤1 [ P = .001]). FE demonstrated fewer polyps than DBE, whereas VCE had detection rates similar to those of DBE. Of 387 DBE-resected and 22 surgically resected polyps, histologic analysis of 110 retrieved polyps showed adenoma or adenocarcinoma in 30.0% of polyps >20 mm and in only 1.3% of polyps ≤20 mm ( P 10 mm (X1; P = .0366) and colorectal polyps >5 mm (X2; P = .002) were independent predictors of the growth rate of small-bowel polyps (Y), and a forward stepwise selection model was constructed: Y=0.136 × X1 + 0.289 × X2 − 0.589 ( R 2 = 0.665). Limitations Small sample size. Conclusions DBE and VCE were useful for the management of small-bowel polyps in PJS. VCE may replace barium examinations for surveillance after polyp resection at intervals depending on the polyp growth rate.

Aim: Hemolytic anemia is a well-known adverse effect of interferon and ribavirin combination treatment. Herein, we analyzed the impact of early elevation of serum bilirubin level as a marker for predicting severe anemia during treatment. Methods: We studied 245 chronic hepatitis C patients who received pegylated interferon and ribavirin combination treatment, and divided them using two different threshold levels: (i) elevation of total bilirubin of 0.5 mg/dL or more within 1 week of starting treatment; and (ii) drop of hemoglobin (Hb) by 3 g/dL or more within 4 weeks of starting treatment. We compared the dynamics in each group and then investigated independent factors for predicting a severe Hb drop (≥3 g/dL) at 4 weeks after beginning treatment and dose reduction of ribavirin. Results: Total bilirubin levels at 1 week were significantly higher in patients with a Hb drop of 3 g/dL or more as compared to those with a drop of less than 3 g/dL (P

Two randomized controlled trials comparing endoscopic nasobiliary drainage (ENBD) and internal endoscopic biliary drainage (internal EBD) for acute suppurative cholangitis (ASC) showed no significant difference in efficacy and both preferred internal EBD to ENBD. In this study, the necessity of ENBD was re-examined. Over five years, 59 patients underwent an emergency endoscopic procedure for ASC in our institute. If drainage was needed, we selected internal EBD as a first choice and ENBD was used in patients predicted to have early obstruction of the tube or retrograde infection of the bile duct. The rate of ENBD, for which reason ENBD was selected, and the efficacy of drainage were examined retrospectively. In the 59 patients, 40 patients had the stones completely removed without drainage, five internal EBD and two ENBD were performed without removal of stones and five internal EBD and seven ENBD were performed after removal of stones. In terms of white blood cell count and direct bilirubin level, no significant difference was observed between ENBD and internal EBD patients. ENBD was mainly selected for the patients with multiple biliary strictures, hemorrhage tendency and excessive purulent bile. Even though internal drainage is suitable in many ASC patients, ENBD is necessary in selected patients.

Objectives: The aim of this study was to evaluate the efficacy and indication of combination therapy with ribavirin plus peginterferon-α-2b in chronic hepatitis C virus (HCV) patients aged 65 years and older. Methods: Five hundred and ninety-one consecutive HCV patients were treated with combination therapy. These patients were divided into elder patients (≥65 years) (n=115) and younger patients (

Mutations in two regions of hepatitis C virus (HCV) have been implicated in influencing response to interferon (IFN) therapy. Substitutions in the NS5A region of HCV have been associated with response to IFN therapy, and this region has been known as the IFN sensitivity-determining region (ISDR). The mutations in the core region of HCV have also been reported to predict IFN response. The aim of this study was to investigate whether amino acid substitutions in the core region and ISDR among patients with HCV genotype 1b affect the response to IFN therapy. A total of 213 patients who completed IFN treatment were randomly selected. All patients received pegylated-IFN-alpha 2b once each week, plus oral ribavirin daily for 48 weeks. Of the 213 patients, 117 (54.9%) showed early virologic response (EVR), with HCV-negativity, at 12 weeks. Factors related to EVR on multivariate analysis were non-Gln70 and Leu91 in the core region, and ISDR mutant-type. One hundred and two (47.9%) showed a sustained virologic response (SVR). SVR occurred more frequently in patients without Gln70 (55.4%) than in those with Gln70 (21.3%) (P < 0.0001). SVR was achieved in 43.6% of patients with wild-type ISDR and 62.5% of patients with mutant-type (P = 0.0227). Of the 34 patients who simultaneously had non-Gln70 and mutant-type ISDR, 26 (76.5%) achieved SVR. Factors related to SVR on multivariate analysis were non-Gln70 and ISDR mutant-type. In conclusion, amino acid substitutions in the core region and ISDR were useful for predicting the response to IFN in patients with HCV genotype 1b.

Branched-chain alpha-keto acid dehydrogenase (BCKDH) kinase (BDK) is responsible for the regulation of BCKDH complex, which is the rate-limiting enzyme in the catabolism of branched-chain amino acids (BCAAs). In the present study, we investigated the expression and activity of hepatic BDK in spontaneous type 2 diabetes using hyperinsulinemic Zucker diabetic fatty rats aged 9weeks and hyperglycemic, but not hyperinsulinemic rats aged 18weeks. The abundance of hepatic BDK mRNA and total BDK protein did not correlate with changes in serum insulin concentrations. On the other hand, the amount of BDK bound to the complex and its kinase activity were correlated with alterations in serum insulin levels, suggesting that hyperinsulinemia upregulates hepatic BDK. The activity of BDK inversely corresponded with the BCKDH complex activity, which was suppressed in hyperinsulinemic rats. These results suggest that insulin regulates BCAA catabolism in type 2 diabetic rats by modulating the hepatic BDK activity.

This paper introduces the brief summary of the recent collaboration test results on thermal barrier coatings (TBCs) in the JSMS Subcommittee, which covers the measurements of elastic modulus, tensile strength, residual stress and thermal conductivity of the TBC specimens. Here, the round-robin TBC specimens consisting of 8% yttria stabilized zirconia, CoNiCrAlY alloy bond coat and Ni-base superalloy were prepared by plasma spraying method. The isothermal exposure and the thermal cycles were applied to the TBC specimens by several conditions at high temperatures, to measure both the residual stress and the remaining adhesion strength of the ceramic top, as well as to characterize the thermally grown oxide at the top coat/bond coat interface. The round-robin test results clearly demonstrated that the adhesion strength was significantly changed by the application of thermal cycles and the isothermal exposure. Of particular important results was found in the remaining adhesion strength that were strongly dependent on the testing method to give the thermal cycles.

Lamivudine (LMV) prophylaxis is effective in preventing hepatitis B virus (HBV) reactivation in patients with chronic hepatitis B undergoing chemotherapy. However, the optimal duration of LMV prophylaxis remains unclear. We report herein the case of a woman with localized follicular B-cell lymphoma who received chemotherapy with LMV prophylaxis. She achieved complete response to lymphoma, and LMV treatment was continued for 8 months after completion of chemotherapy. HBV status was still inactive. LMV was then stopped, but reactivation of hepatitis developed 1 month after cessation of LMV. LMV was restarted, resulting in successful treatment of reactivated hepatitis. Interferon (IFN) was used for 6 months before withdrawal of LMV, which was successfully ceased without flare hepatitis. This report describes the utility of sequential therapy with LMV and IFN to treat flare after withdrawal of LMV in hepatitis B carriers who receive LMV prophylaxis during chemotherapy and to prevent flare after withdrawal of LMV.

OBJECTIVES Pancreatic cystic (PC) lesions are not necessarily rare, and it is important to diagnose whether PC lesions are neoplastic such as intraductal papillary mucinous neoplasm (IPMN) because of its malignant potential. Reports on PC lesions in hemodialysis (HD) patients are remarkably limited. The aim of this study was to clarify the prevalence and characteristics of PC lesions in HD patients. METHODS We reviewed 1012 consecutive HD patients and 11,100 patients (controls) without renal disease who underwent transabdominal ultrasonography between January 2003 and December 2005. Patients' sex ratio (female-to-male) was less, and the age was older in HD patients. Clinical findings of these patients were examined. RESULTS The prevalence both of PC lesions and IPMNs was significantly higher in HD patients than in controls (9.3% vs 1.3% and 2.8% vs 0.2%, P < 0.0001). The incidence of IPMNs in HD patients with PC lesions was higher than that in controls with PC lesions (29.8% vs 17.0%, P = 0.021). Multivariate logistic regression analysis revealed that the odds ratios of PC lesions and IPMNs were 6.38 (95% confidence interval, 4.82-8.45) and 9.39 (95% confidence interval, 5.36-16.49) in HD patients compared with controls. CONCLUSION The prevalence of PC lesions in HD patients is higher, and HD patients with PC lesions have high prevalence of IPMNs.

We investigated the feasibility of using real-time tissue elastography (EG) with transcutaneous ultrasonography (EG-US) for pancreatic diseases.A preliminary study (phase I) and a prospective (phase II) study were conducted. Phase I: subjects were 10 volunteers, 5 with cancer, 2 with endocrine tumor, 5 with chronic pancreatitis, 14 with intraductal papillary-mucinous neoplasm. To determine the characteristic EG images (diagnostic criteria for phase II), B-mode images were compared with EG images and histopathologic findings. Phase II: 53 consecutive patients were enrolled. The visualization rate by EG-US in lesions visualized by B mode was assessed, and the correct diagnosis rate by B mode alone (B diagnosis) or in combination with EG-US was evaluated.Phase I: normal parenchyma was a homogeneous color. In cancer, EG-US showed a markedly hard area with soft spots inside. Endocrine tumor was uniform and soft comparable to parenchyma. Chronic pancreatitis showed a mixture of various colors. Phase II: we identified 77.4% (41/53) of the lesions and observed 60.0% (15/25) of the cancers, 100% (3/3) of the endocrine tumor, 92.0% (23/25) of the cases of chronic pancreatitis cases on EG-US. The B-diagnosis rates ranged from about 70% to 80%. The diagnosis rates of the combination were more than 90% of lesions of each type.The EG-US is feasible in the diagnosis of pancreatic diseases.

Objective: Hepatitis B virus (HBV) has been classified into 8 genotypes that have different geographic distributions. The clinical outcomes of acute hepatitis are dependent on genotype. The aim of this study was to investigate the distribution of HBV subgenotypes and basal core promoter (BCP)/precore (PC) regions in acute hepatitis patients in Central Vietnam to clarify the distributions and the clinical and virological differences. Methods: 27 patients with acute hepatitis B were studied. HBV subgenotypes and BCP/PC variants were determined by direct sequencing of the preS, BCP/PC regions, respectively. Results: HBV subgenotypes B4/Ba (n = 22) and C1/Cs (n = 5) were detected. Of the 27 patients, 3 developed fulminant hepatic failure, and all were infected with B4/Ba. Three patients had a BCP mutation, and 10 patients had a PC mutation in subgenotype B4/Ba. Three patients with C1/Cs had a BCP mutation. Two of 3 patients who progressed to fulminant hepatic failure had T1762, A1764, and A1896 simultaneously. None of the patients with acute, self-limited hepatitis carried these triple mutations. Conclusion: The prevalent HBV subgenotypes in patients with acute hepatitis B in Central Vietnam were B4/Ba and C1/Cs. BCP/PC variants have an association with the development of fulminant hepatic failure in subgenotype B4/Ba.

The branched-chain alpha-keto acid dehydrogenase (BCKDH) complex is the most important regulatory enzyme in branched-chain amino acid (BCAA) catabolism. We examined the regulation of hepatic BCKDH complex activity in spontaneous type 2 diabetes Otsuka Long-Evans Tokushima Fatty (OLETF) rats and Zucker diabetic fatty rats. Hepatic BCKDH complex activity in these rats was significantly lower than in corresponding control rats. The amount of BCKDH complex in OLETF rats corresponded to the total activity of the complex. Activity and abundance of the bound form of BCKDH kinase, which is responsible for inactivation of the complex, showed an inverse correlation to BCKDH complex activity in OLETF rats. Dietary supplementation of 5% BCAAs for 10 weeks markedly increased BCKDH complex activity, and decreased the activity and bound form of BCKDH kinase in the rats. These results suggest that BCAA catabolism in type 2 diabetes is downregulated and enhanced by BCAA supplementation.

In endemic areas, including Japan, basal core promoter (BCP) and precore (PC) variants of hepatitis B virus (HBV) have been reported to be associated with the clinical outcome of acute hepatitis B patients. However, the associations of BCP/PC variants with clinical outcomes have not been observed in nonendemic areas. HBV subgenotypes, which show geographic variations in prevalence, may underlie this discrepancy in clinical outcomes. Little is known about the differences in the clinical and virological features of HBV subgenotypes and BCP/PC variants. The aim of this study was to investigate the distributions of subgenotypes and BCP/PC variants to identify clinical differences in acute hepatitis B patients.One hundred thirty-nine patients with acute hepatitis were enrolled. Nested polymerase chain reaction was used to amplify the pre-S region of HBV for genotyping and the BCP/PC regions for variant screening.HBV subgenotypes A1 (n = 3), A2 (n = 28), B1 (n = 3), B2 (n = 9), C1 (n = 5), C2 (n = 84), C variant (n = 1), D2 (n = 3), and H (n = 3) were detected. BCP/PC variants were not associated with progression to chronic hepatitis. Patients infected with subgenotype C2 who progressed to fulminant hepatic failure frequently carried variants at nucleotides non-T1753 and non-T1754 and T1762, A1764, and A1896.BCP/PC variants would be associated with progression to fulminant hepatitis in subgenotype C2. Knowledge of HBV subgenotypes and BCP/PC variants is useful for developing strategies to treat acute hepatitis B patients.

Although obscure gastrointestinal bleeding cannot be detected by colonoscopy or upper endoscopy, wireless video capsule endoscopy (VCE) is capable of imaging it. Few data are available on medical therapy for patients with nonsteroidal anti-inflammatory drug (NSAID)-induced small-intestinal mucosal injuries. The aim of this study was to compare prevention by rebamipide and placebo of NSAID-induced smallintestinal injury in healthy subjects. Ten healthy subjects who provided written informed consent were enrolled. Rebamipide or placebo plus diclofenac was administered with omeprazole for 7 days, and for an additional 7-day period with treatments reversed in the same subjects, with a 4-week washout period between treatments. VCE of the small intestine was performed four times, before and after each of the two study periods. The number of subjects with small-intestinal mucosal injuries was higher in the placebo group (8/10) than in the rebamipide group (2/10) (P = 0.023). Two cases of ulcer and one of bleeding were observed in the placebo group, while no ulcer or bleeding was observed in the rebamipide group. Rebamipide had significantly higher efficacy than placebo in preventing NSAID-induced small-intestinal mucosal injury.

A 54-year-old man, with the chief complaints of hematuria, pollakisuria, and pneumaturia, was referred to our hospital, with a diagnosis of giant urinary bladder adenocarcinoma with massive invasion to the rectum. On the basis of the radiological diagnosis and findings of hematoxylin and eosin (H&E) of biopsy specimens, it was difficult to conclude whether the adenocarcinoma originated in the bladder or in the rectum. The immunohistochemical staining of the biopsy specimens showed cytokeratin 7 (CK7)(-) and CK20(+), which supported the notion that the adenocarcinoma possibly originated from the rectum. Although the prognosis of T4 bladder adenocarcinomas has been reported to be quite poor in comparison with that of transitional cell carcinomas, the postoperative prognosis of T4 rectal adenocarcinomas has been reported to be more favorable and such tumors are recommended to be surgically resected. Because no distant metastasis was detected, the patient underwent total pelvic exenteration with a reconstruction of the ileal conduit. Although the resected tumor measured 12 cm in diameter with n1 metastasis, the radial margin was cancer-negative, and the tumor was curatively resected. The immunohistochemical diagnosis of the resected tumor showed carcinoembryonic antigen(+), CK7(-), CK20(+), thrombomodulin(-), and uroplakin(-), which supported the rectal origin. At present the patient is undergoing postoperative adjuvant chemotherapy for rectal cancer.