Endoscopic papillectomy for ampullary adenoma and early adenocarcinoma: Analysis of factors related to treatment outcome and long-term prognosis.

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 < 0.001) and the need for surgery (P = 0.005). The presence of adenocarcinoma had no significant effect. CONCLUSION: Although remission was achieved in more than 95% of our patients, we observed a high rate of recurrence at the long-term follow-up, which was significantly associated with intraductal extension but not with the presence of adenocarcinoma.

Rescuing the aberrant sex development of H3K9 demethylase Jmjd1a-deficient mice by modulating H3K9 methylation balance.

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.

Association of interleukin 28B polymorphism and mutations in the NS5A region of hepatitis C virus genotype 2 with interferon responsiveness.

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 < 0.001). SVR was achieved in 65.9% of patients with wild-type IFN sensitivity-determining region (ISDR) and 83.5% of patients with mutant type (P < 0.001). There were no significant differences in other factors, including sex, alanine aminotransferase, platelet count, HCV viral load, HCV genotype, and IL28B genotype. The factors related to SVR on multivariate analysis were age (P = 0.019) and ISDR (P = 0.003). CONCLUSIONS: ISDR sequence variations are significantly associated with IFN responsiveness in patients with HCV genotype 2. The SNP of IL28B was not associated with SVR in patients with HCV genotype 2.

Effect of peginterferon alfa-2b and ribavirin on hepatocellular carcinoma prevention in older patients with chronic hepatitis C.

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 (< 65 years) among 1280 CH-C patients treated with peginterferon alfa-2b and ribavirin. Cumulative incidence of HCC was determined by Kaplan-Meier analysis, and factors associated with liver carcinogenesis were analyzed by Cox proportional hazards regression. RESULTS: Older patients had a significantly lower SVR rate and a significantly higher discontinuation rate of treatment than younger patients. Fifty patients developed HCC during median follow-up period of 47 months. Cox proportional hazards regression analysis indicated that the following were independent risk factors associated with the development of HCC: older age, male, advanced fibrosis, non-SVR in all patients: higher gamma-glutamyltranspeptidase, and non-SVR in older patients. Older patients who achieved SVR had a significantly reduced rate of HCC compared with those who did not achieve SVR, especially those who had gamma-glutamyltranspeptidase over 44 IU/L. CONCLUSIONS: The SVR rate was lower and the combination therapy discontinuation rate was higher in older CH-C patients than in younger patients. However, older patients who achieved SVR had a markedly lower rate of HCC development compared with older patients who did not achieve SVR.

Preoperative endoscopic nasobiliary drainage in 164 consecutive patients with suspected perihilar cholangiocarcinoma: a retrospective study of efficacy and risk factors related to complications.

OBJECTIVE: To assess the clinical benefits of preoperative endoscopic nasobiliary drainage (ENBD) in patients with perihilar cholangiocarcinoma. BACKGROUND: The advantages of ENBD have been previously reported. However, no studies to date have examined a large number of patients, including those with Bismuth-Corlette (B-C) type III to IV tumors. In addition, sufficient data on the risk factors associated with ENBD complications are not available. METHODS: This study involved 164 consecutive patients with suspected perihilar cholangiocarcinoma (128 patients with B-C type III-IV tumors) who had undergone unilateral ENBD between January 2007 and December 2010. The success and efficacy of this procedure and the risk factors for post-ENBD cholangitis and pancreatitis were retrospectively evaluated. RESULTS: The ENBD procedure was successful in 153 (93.3%) of the 164 patients. Of these 164 patients, 65 had serum total bilirubin (TB) levels of 2.0 mg/dL or more before the drainage. The first unilateral ENBD was successfully performed in 60 of the 65 patients, and the TB level decreased to less than 2.0 mg/dL after ENBD in 50 of these 60 patients (83.3%). The significant predictive factors for ENBD efficacy included the pre-ENBD TB level (P = 0.032; 95% confidence interval [CI], 1.01-1.23) and post-ENBD cholangitis (P = 0.012; 95% CI, 1.61-43.2). Post-ENBD cholangitis occurred in 47 (28.8%) of the 163 patients, and a previous endoscopic sphincterotomy (EST) was found to be a significant risk factor for post-ENBD cholangitis (P = 0.008; 95% CI, 1.30-5.46). Post-ENBD pancreatitis occurred in 33 (20.1%) of the 164 patients (26 grade 1 patients, 4 grade 2 patients, and 3 grade 3 patients). The significant risk factors included undergoing pancreatography (P < 0.001; 95% CI, 2.44-31.1) and the absence of previous EBS or ENBD (P < 0.001; 95% CI, 3.03-29.2). CONCLUSIONS: Unilateral ENBD of the future remnant lobe(s) exhibited a high success rate, suggesting that it is an effective and suitable preoperative drainage method for perihilar cholangiocarcinoma even in patients with B-C type III to IV tumors. To reduce the postprocedural complications, ENBD should be performed without EST or pancreatography.

Comparison of the efficacy of ribavirin plus peginterferon alfa-2b for chronic hepatitis C infection in patients with and without coagulation disorders.

Many patients with coagulation disorders are infected with hepatitis C virus (HCV) that advances to end stage liver disease, resulting in an increased number of deaths. The efficacy of ribavirin and peginterferon combination therapy for chronic HCV infection in patients with coagulation disorders has not been clarified fully. The aim of this study was to evaluate the efficacy and tolerability of combination therapy in this patient population compared with patients who are infected with HCV and do not have coagulation disorders. A total of 226 consecutive chronic hepatitis C patients were treated with combination therapy and divided into two groups: patients with (n = 23) and without coagulation disorders (n = 203). Clinical characteristics, sustained virological response rates obtained by an intention-to-treat analysis, and combination therapy discontinuation rates were compared between the two groups. The sustained virological response rates did not differ significantly between patients with and without coagulation disorders (65.2% vs. 47.8% by intention-to-treat analysis). According to a multivariate analysis, age, alanine aminotransferase, gamma-glutamyltransferase, and HCV genotype were associated significantly with a sustained virological response, whereas whether a patient had a coagulation disorder did not affect the sustained virological response. In conclusion, combination therapy for chronic hepatitis C was comparably effective between patients with and without coagulation disorders and did not result in adverse bleeding.

Impact of recipient age and preoperative fasting blood glucose level as the risk factors of living donor liver transplantation in cirrhotic patients in the recent comprehensive era with knowledge of indications: Recent status in a Japanese single center.

AIM: Recently, knowledge for indications of living donor liver transplantation (LDLT) has been robustly accumulated in. For further improvement, risks should be reexamined in recent cases. In this study, we investigated preoperative risk factors in cirrhotic patients who underwent LDLT in recent era. METHODS: Seventy-four cirrhotic patients who underwent LDLT at our institution between 2003 and 2011 were included. Recipient and donor age and sex, existence of hepatocellular carcinoma (HCC), preoperative Model for End-Stage Liver Disease score, fasting blood glucose (FBG), triglyceride, total cholesterol, serum creatinine, hemoglobin A1c, graft : recipient weight ratio, ABO compatibility and choice of calcineurin inhibitor were analyzed. A proportional hazard model was applied and P < 0.05 was considered statistically significant. RESULTS: In multivariate analysis, recipient age (hazard ratio = 1.188, P = 0.011) and FBG (hazard ratio = 1.009, P = 0.016) showed as significant independent factors. Theoretical mortalities were 9.2%, 21.9% and 51.7% in patients with normal FBG at 55, 60 and 65 years old, respectively, and 34.3% and 53.6% in patients with FBG of 150 and 200 mg/dL, respectively, at 60 years old. CONCLUSION: Recipient age and FBG remain important risk factors for LDLT in cirrhotic patients even in the recent era. These factors should be considered for selecting liver transplant candidates in cirrhotic patients.

Pegylated interferon monotherapy in patients with chronic hepatitis C with low viremia and its relationship to mutations in the NS5A region and the single nucleotide polymorphism of interleukin-28B.

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.

An increase in lesion density can predict lower local recurrence after transarterial chemoembolization in patients with hepatocellular carcinoma.

BACKGROUND/AIMS: The purpose of this retrospective study was to determine the characteristics of hepatocellular carcinoma (HCC) associated with lower, local recurrence rates after transcatheter arterial chemoembolization (TACE). METHEDOLOGY: From 2005 to 2012, 93 consecutive patients with 125 nodules were included in this study. Patients were included if they had fewer than 3 hypervascular tumors, smaller than 4cm in diameter. Patients were excluded if they had a lack of iodized oil accumulation in target nodules on non-enhanced computed tomography (CT) immediately after TACE treatment. Mean lesion density in Hounsfield units (HU) was measured on non-enhanced CT imaging immediately after and 1 week after TACE. RESULTS: The median lesion density on CT was 625HU (range 138-1911) immediately after and 431HU (range 89-2145) 1 week after TACE. Multivariate analysis using the Cox proportional hazard model revealed that an increase in lesion density (hazard ratio (HR), 0.18; p=0.002), des-gamma-carboxy prothrombin concentration (HR, 2.21; p=0.01), and lesion density on CT 1 week after TACE (HR, 0.46; p=0.02) were significant independent predictors associated with the lower, local recurrence rate after TACE treatment. CONCLUSIONS: In HCC without increased lesion density 1 week after TACE, it is possible to consider alternative or adjuvant treatments.

Should plastic stents be avoided in all unresectable malignant perihilar biliary strictures?

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.

Efficacy and safety of tolvaptan for refractory fluid collection and edema in the terminal cancer patients.

Objective: Tolvaptan, a vasopressin V2 receptor antagonist, is an oral diuretic. Patients with terminal cancer develop marked fluid retention, and oral diuretics other than tolvaptan have been used as treatments without clear therapeutic effects. Herein, we aimed to study the efficacy and safety of tolvaptan in patients with terminal cancer. Methods: Tolvaptan was administered at a dose of 7.5 mg/day to 29 patients (median, 72 years) between August 2017 and February 2020. The duration of tolvaptan treatment ranged from 1 to 85 days (mean, 18.5 days). Results: Median albumin (Alb) and transthyretin (TTR) levels on admission were 2.3 g/dL (1.2-4.2 g/dL) and 8.9 mg/dL (2.1-38.2 g/dL), respectively. Median Alb and TTR levels 1 month after treatment initiation remained at 2.3 g/dL (0.8-2.9 g/dL) and 8.6 mg/dL (0.8-23.7 mg/dL), respectively. Regarding renal function indicators, median blood urea nitrogen (BUN) and creatinine levels on admission were 19.9 mg/dL (8.6-49.3 mg/dL) and 0.81 mg/dL (0.38-2.25 mg/dL), respectively. Median BUN and creatinine levels 1 month after treatment initiation were 23.4 mg/dL (13.5-34.0 mg/dL) and 0.91 mg/dL (0.39-2.41 mg/dL), respectively. No patients had hypernatremia on admission, and no effects of tolvaptan on the blood sodium level were found 1 month after treatment initiation. The median potassium level on admission was 4.2 mEq/dL (2.9-5.0 mEq/dL); tolvaptan treatment had no effects on blood potassium level. Conclusions: Tolvaptan is effective and safe for treating fluid retention refractory to conventional diuretics in patients with terminal cancer.

N-of-1 Trial of Electrical Sensory Stimulation Therapy on the Tibial Innervated Area during Gait in a Case of Post-stroke Sensory Disturbance.

Background: Transcutaneous electrical sensory nerve stimulation (TESS) is used to enhance the recovery of sensorimotor function in post-stroke hemiparesis. However, TESS efficacy for post-stroke gait disturbance remains unknown. We hypothesized that TESS on the area innervated by the tibial nerve, targeting the superficial plantar sensation, combined with gait training would improve gait function in patients with gait disturbance caused by severe superficial sensory disturbance after stroke. Case: A 42-year-old man was referred to the convalescent rehabilitation hospital 4 months after a left pontine hemorrhage. He showed severe superficial sensory disturbance without motor paresis in the right lower leg and planta pedis. Gait training with TESS on the tibial nerve innervated area was performed, targeting plantar sensation according to an N-of-1 study design of a single-case ABCAB that included two 10-min sessions of gait training without TESS (phase A), two gait training sessions with TESS targeting the right plantar sensation (phase B), and one session with TESS targeting the upper leg sensation as control (phase C). The patient showed increased gait distance and stride length, improved superficial sensation on the right planta pedis, and improved balance after phase B, but not after phases A and C. Discussion: Gait training with TESS on the tibial nerve innervated area improved gait ability, superficial plantar sensation on the targeted side, and balance function in a post-stroke patient with sensory disturbance. Gait training with TESS may be effective for gait dysfunction caused by sensory disturbance in patients with central nervous system disorders.

Prevalence of hepatitis C virus genotype 1a in Japan and correlation of mutations in the NS5A region and single-nucleotide polymorphism of interleukin-28B with the response to combination therapy with pegylated-interferon-alpha 2b and ribavirin.

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.

Enteroscopic and radiologic diagnoses, treatment, and prognoses of small-bowel tumors.

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.

Endoscopic and imaging findings in protein-losing enteropathy.

OBJECTIVES: Protein-losing enteropathy (PLE) is often difficult to diagnose. We evaluated the diagnostic yields of underlying diseases of PLE among esophagogastroduodenoscopy, colonoscopy, fluoroscopic conventional enteroclysis (FCE), videocapsule endoscopy (VCE), and double-balloon enteroscopy (DBE) and prognosis after treatment. METHODS: Between June 2003 and August 2010, 25 consecutive patients with PLE confirmed by fecal α1-antitrypsin clearance (n=18) and technetium 99m human serum albumin scintigraphy (n=19) were enrolled, investigated, and treated. RESULTS: Of 25 patients, 4 (16%) with intestinal lymphangiectasia secondary to macroglobulinemia (n=1), amyloidosis (n=2), and strongyloidiasis (n=1) were diagnosed at preceding esophagogastroduodenoscopy or colonoscopy, and 7 (32%) with primary intestinal lymphangiectasia and chronic nonspecific multiple ulcers unrelated to nonsteroidal anti-inflammatory drugs of the small intestine were newly diagnosed at FCE or VCE. Other 11 (44%) patients with primary intestinal lymphangiectasia, small-bowel tumors, amyloidosis, chronic nonspecific multiple ulcers unrelated to nonsteroidal anti-inflammatory drugs of the small intestine, Crohn's disease, and small-bowel ulcers due to polyarteritis nodosa were diagnosed only at DBE with biopsy. Three patients with primary intestinal lymphangiectasia, cirrhosis after living donor liver transplantation, and congestive heart failure were not diagnosed at any small-bowel examination. The overall diagnostic yield of FCE, VCE, and DBE was 62% (8/13), 83% (14/17), and 88% (22/25), respectively. Eight patients (32%) died of underlying disorders regardless of medical treatment over the follow-up period. CONCLUSIONS: DBE with pathologic findings of biopsy specimens was useful for the differential diagnosis of PLE. Noninvasive VCE might be preferable and useful for screening and follow up of PLE without stricture. Prognosis of a subgroup of PLE was poor regardless of treatment.

Clinical impact of HFE mutations in Japanese patients with chronic hepatitis C.

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.

Peripancreatic vascular involvements of autoimmune pancreatitis.

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.

Usefulness of flexible spectral imaging color enhancement (FICE) for the detection of angiodysplasia in the preview of capsule endoscopy.

BACKGROUNDS/AIMS: Flexible spectral imaging color enhancement (FICE) is an image enhancement system that can obtain bright and high-contrast images. FICE for capsule endoscopy (CE) is available during interpretation of Given Imaging, but its usefulness is rarely reported. The aim of this study is to evaluate the preview of angiodysplasia by FICE in comparison with the conventional preview. METHODOLOGY: The accumulated CE data of 50 patients with angiodysplasia were randomly assigned to 2 equally sized groups of conventional reading and FICE reading. One experienced doctor analyzed them for the first time in a quick-view mode and the mean reading time, sensitivity and specificity for detecting angiodysplasia by each method were evaluated for comparisons including suspected blood indicator. RESULTS: The mean reading time was 14min for both conventional reading and FICE reading. The two previews of angiodysplasia were significantly superior to the function of suspected blood indicator (p<0.01). The sensitivity and specificity of conventional reading for detecting angiodysplasia were 80% and 100%, respectively. Those of FICE reading were 91% and 86%, respectively. FICE reading was superior in term of sensitivity, while it resulted in more false positive lesion findings and lower specificity. However, such false-positive findings by FICE reading can be correctly identified at a glance by converting the image to conventional mode. CONCLUSIONS: This study demonstrates that FICE enables accurate detection of angiodysplasia in the preview of CE.

Real-time viewing of video capsule endoscopy for on-going mid GI bleeding.

RAPID Access Real-Time (RT) has the ability to provide an endoscopist with the presence of bleeding and its location for cases with on-going mid GI bleeding. However, to date, the clinical benefits of this device remain unknown as studies on it have not yet been published. We present a case of recurrent GI bleeding where video capsule endoscopy (VCE) with real time viewing helped them decide on the route of double-balloon enteroscopy (DBE). Since the bleeding image of RT had not been obtained over 150 minutes after passing the pylorus, the patient underwent retrograde DBE. In the middle of the ileum, active bleeding from Dieulafoy's lesion was found and we treated it successfully. It was suggested the effectiveness of VCE in reference to the determination of RT for on-going mid GI bleeding.

Transpapillary biliary forceps biopsy to distinguish benign biliary stricture from malignancy: how many tissue samples should be obtained?

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.