Rome Foundation-Asian working team report: Asian functional gastrointestinal disorder symptom clusters.

OBJECTIVE: Functional gastrointestinal disorders (FGIDs) are diagnosed by the presence of a characteristic set of symptoms. However, the current criteria-based diagnostic approach is to some extent subjective and largely derived from observations in English-speaking Western patients. We aimed to identify latent symptom clusters in Asian patients with FGID. DESIGN: 1805 consecutive unselected patients with FGID who presented for primary or secondary care to 11 centres across Asia completed a cultural and linguistic adaptation of the Rome III Diagnostic Questionnaire that was translated to the local languages. Principal components factor analysis with varimax rotation was used to identify symptom clusters. RESULTS: Nine symptom clusters were identified, consisting of two oesophageal factors (F6: globus, odynophagia and dysphagia; F9: chest pain and heartburn), two gastroduodenal factors (F5: bloating, fullness, belching and flatulence; F8 regurgitation, nausea and vomiting), three bowel factors (F2: abdominal pain and diarrhoea; F3: meal-related bowel symptoms; F7: upper abdominal pain and constipation) and two anorectal factors (F1: anorectal pain and constipation; F4: diarrhoea, urgency and incontinence). CONCLUSION: We found that the broad categorisation used both in clinical practice and in the Rome system, that is, broad anatomical divisions, and certain diagnoses with long historical records, that is, IBS with diarrhoea, and chronic constipation, are still valid in our Asian societies. In addition, we found a bowel symptom cluster with meal trigger and a gas cluster that suggests a different emphasis in our populations. Future studies to compare a non-Asian cohort and to match to putative pathophysiology will help to verify our findings.

Arsenic trioxide attenuates STAT-3 activity and epithelial-mesenchymal transition through induction of SHP-1 in gastric cancer cells.

BACKGROUND: We investigated the effect of arsenic trioxide (ATO) for inhibition of signal transducer and activator of transcription 3 (STAT3) and epithelial-mesenchymal transition (EMT) in gastric cancer cells, and the role of SH2 domain-containing phosphatase-1 (SHP-1) during this process. METHODS: We used AGS cells, which showed minimal SHP-1 expression and constitutive STAT3 expression. After treatment of ATO, cellular migration and invasion were assessed by using wound closure assay, Matrigel invasion assay and 3-D culture invasion assay. To validate the role of SHP-1, pervanadate, a pharmacologic phosphatase inhibitor, and SHP-1 siRNA were used. Xenograft tumors were produced, and ATO or pervanadate were administered via intraperitoneal (IP) route. RESULTS: Treatment of ATO 5 and 10 µM significantly decreased cellular migration and invasion in a dose-dependent manner. Western blot showed that ATO upregulated SHP-1 expression and downregulated STAT3 expression, and immunofluorescence showed upregulation with E-cadherin (epithelial marker) and downregulation of Snail1 (mesenchymal marker) expression by ATO treatment. Anti-migration and invasion effect and modulation of SHP-1/STAT3 axis by ATO were attenuated by pervanadate or SHP-1 siRNA. IP injection of ATO significantly decreased the xenograft tumor volume and upregulated SHP-1 expression, which were attenuated by co-IP injection of pervanadate. CONCLUSION: Our data suggest that ATO inhibits STAT3 activity and EMT process by upregulation of SHP-1 in gastric cancer cells.

Clinicopathologic Study of Biliary Intraepithelial Neoplasia in Cholangiocarcinoma.

BACKGROUNDS AND AIMS: Biliary intraepithelial neoplasia (BilIN) is a precursor of cholangiocarcinoma (CC) and it has been associated with several chronic inflammatory conditions. This study aimed to elucidate the prevalence of BilIN in CC and its clinicopathological significance. METHODS: Medical records of 193 patients with histologically confirmed CC were analyzed. We reviewed the pathology findings of 48 patients who underwent curative surgery for CC. RESULTS: Of the 48 patients analyzed, 34 and 14 patients had extrahepatic and intrahepatic CC respectively. BilIN was detected in 28 patients (58%) and showed a significantly higher prevalence in extrahepatic CC (75%) than in intrahepatic CC (21%; p < 0.001). In the subgroup of 34 patients with extrahepatic CC, 25 and 9 patients were BilIN positive and negative respectively. Poor differentiation and T3 stage were significantly more common in the BilIN-negative group than in the BilIN-positive group (p < 0.05). The expression of MUC5AC, p53, and loss of Smad4 showed no difference between BilIN-positive CC and in BilIN-negative CC, but the Ki-67 expression was significantly higher (p < 0.05). CONCLUSION: BilIN-positive CC showed less invasiveness than negative cases. The Ki-67 expression was significantly higher in BilIN-positive CC.

Usefulness of CA 19-9 for pancreatic cancer screening in patients with new-onset diabetes.

BACKGROUND: Generally, carbohydrate antigen 19-9 (CA 19-9) is not useful for screening pancreatic cancer in the asymptomatic general population. This study aimed to evaluate the utility of CA 19-9 level as a screening indicator of pancreatic cancer in asymptomatic patients with new-onset diabetes. METHODS: We retrospectively reviewed the medical records of patients who visited our health promotion center for health check-ups without cancer related symptoms from January 2005 to January 2014, and were newly diagnosed with diabetes mellitus (DM) within 2 years before their visit. RESULTS: Of the 5111 asymptomatic patients with new-onset DM (<2 years) selected for analyses, 87 (1.7%) eventually developed pancreatic cancer after the health check-up. In the subgroup of 322 patients with high total bilirubin levels (>1.7 mg/dL) at the screening time, 42 (73.7%) of 57 patients with high CA 19-9 levels (>37 IU/mL) had been diagnosed as pancreatic cancer during follow-up period and 12 (4.5%) of 265 patients with normal CA 19-9 levels had finally developed pancreatic cancer (OR = 16.3). In the subgroup of 4789 patients with normal bilirubin levels, pancreatic cancer had been detected in 20 (3.8%) of 522 patients with high CA 19-9 level, while only 13 (0.3%) in 4267 patients with normal CA 19-9 levels (OR = 12.6), respectively. CONCLUSION: CA 19-9 levels after a diagnosis of new-onset DM could be a useful biomarker of pancreatic cancer, especially in patients with high serum bilirubin.

Treatment of Severe Alcoholic Hepatitis With Corticosteroid, Pentoxifylline, or Dual Therapy: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Although both corticosteroids and pentoxifylline are currently recommended drugs for the treatment of patients with severe alcoholic hepatitis, their effectiveness in reducing mortality remains unclear. In this systematic review, we aimed to evaluate the therapeutic and adverse effects of corticosteroids, pentoxifylline, and combination by using Cochrane methodology and therefore determine optimal treatment for severe alcoholic hepatitis. METHODS: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from their inauguration until October 2015. Combinations of the following keywords and controlled vocabularies were searched: alcoholic hepatitis, corticosteroid, and pentoxifylline. RESULTS: A total of 2639 patients from 25 studies were included. The treatment groups did not differ significantly in terms of overall mortality. Analysis of 1-month mortality revealed corticosteroid monotherapy reduced mortality compared with placebo (OR=0.58; 95% CI, 0.34-0.98; P=0.04), but pentoxifylline monotherapy did not. The mortality with dual therapy was similar to corticosteroid monotherapy (OR=0.91; 95% CI, 0.62-1.34; P=0.63). However, dual therapy decreased the incidences of hepatorenal syndrome or acute kidney injury (OR=0.47; 95% CI, 0.26-0.86; P=0.01) and the infection risk (OR=0.63; 95% CI, 0.41-0.97; P=0.04) significantly more than corticosteroid monotherapy did. None of the treatments conferred any medium-term or long-term survival benefits in the present study. CONCLUSIONS: Dual therapy was not inferior to corticosteroid monotherapy and could reduce the incidence of hepatorenal syndrome or acute kidney injury and risk of infection. Therefore, dual therapy might be considered in treatment of patients with severe alcoholic hepatitis.

Rome foundation Asian working team report: Real world treatment experience of Asian patients with functional bowel disorders.

BACKGROUND AND AIM: Information on real world treatment experiences of patients with functional bowel disorders is lacking from Asia. This study aimed to describe the medication exposure and treatment satisfaction of patients presenting to gastroenterology clinics across a sampling of Asian cities. METHODS: From March 2011 to October 2013, adult patients presenting to hospital-based gastroenterology outpatient clinics in 11 cities across Asia, who fulfilled screening criteria for any functional gastrointestinal disorder, were asked to complete a validated culturally adapted translation of the Rome III diagnostic questionnaire, a checklist of medications received in the preceding 3 months and questions on treatment satisfaction. RESULTS: A total of 1376 patients (female 755, male 621, 41.36 ± 13.25 years) comprising irritable bowel (621, 45.1%), unspecified functional bowel disorder (372, 27.8%), functional constipation (202, 14.7%), functional bloating (144, 10.5%), and functional diarrhea (56, 4.1%) completed the study. Of 1105 patients with a previous consultation, 509 (46.1%) were dissatisfied with their treatment, with ineffective treatment being the commonest reason. Satisfaction with previous consultation was lowest by diagnosis for functional constipation (29.2%), and the most bothersome symptom was straining (37.5%). Of 1046 patients who had taken medications for their gastrointestinal symptoms in the last 3 months, 793 (75.8%) had received two or more drugs. For irritable bowel syndrome patients, treatment with proton pump inhibitors and antispasmodics was recorded in 57% and 31%, with overlapping epigastric pain and heartburn predicting proton pump inhibitors use. CONCLUSIONS: More attention should be given to treatment gaps with regards to possible under-treatment with antispasmodics in irritable bowel syndrome and to critically evaluating the efficacy of constipation management.

Epigenetic regulation and anti-tumorigenic effects of SH2-containing protein tyrosine phosphatase 1 (SHP1) in human gastric cancer cells.

SH2-containing protein tyrosine phosphatase 1 (SHP1) is an important negative regulator in cytokine-mediated signal transduction and cell cycling. Recent studies have demonstrated that SHP1 promoter methylation is frequently observed in gastric adenocarcinoma tissues. In this in vitro study, we attempted to reveal promoter hypermethylation and to investigate effects of SHP1 in gastric carcinoma cell lines. We observed that both gene and protein expression of SHP1 were negative in 8 of 10 gastric cancer cell lines (SNU-1, SNU-5, SNU-16, SNU-638, SNU-719, MKN-28, MKN-45, AGS). Methylation-specific PCR (MSP) showed a methylation-specific band only in the 10 gastric cancer lines. Bisulfite pyrosequencing in AGS, MKN-28, and SNU-719 cells indicated that methylation frequency was as high as 94.4, 92.6, and 94.5 %, respectively, in the three cell lines. Treatment of SNU-719, MKN-28, and AGS cells with 5-Aza-2'-deoxycytidine (5-Aza-dc) led to re-expression of SHP1 in these cells. Introduction of exogenous SHP1 in SNU-719 and MKN-28 cells by transient transfection substantially downregulated protein expression of constitutive phosphor-Janus kinase 2 (JAK2) (tyrosine 1007/1008) and phosphor-signal transducers and activators of transcription 3 (STAT3) (tyrosine 705), which in turn decreased expression of STAT3 target genes including those encoding cyclin D1, MMP-9, VEGF-1, and survivin. Induction of SHP1 significantly inhibited cell proliferation, migration and invasion in SNU-719 and MKN-28 cells. Taken together, epigenetic silencing of SHP1 is frequently caused by promoter hypermethylation in gastric carcinoma cells. Overexpression of SHP1 downregulates the JAK2/STAT3 pathway to modulate various target genes and inhibit cell proliferation, migration, and invasion in gastric cancer cells.

Radiation recall gastritis secondary to combination of gemcitabine and erlotinib in pancreatic cancer and response to PPI - a case report.

BACKGROUND: Radiation recall gastritis is rare but can be induced after concurrent chemoradiation for pancreatic cancer. We report a patient with pancreatic cancer who developed radiation-recall gastritis related to a combination of gemcitabine and erlotinib. CASE PRESENTATION: A 54-year-old female with unresectable pancreatic cancer received gemcitabine in combination with radiation therapy followed by chemotherapy with gemcitabine and erlotinib. After completing 2 cycles of chemotherapy, the patient had epigastric pain, nausea, and vomiting. Abdominal computed tomography (CT) scan revealed diffuse wall thickening of the stomach, and esophagogastroduodenoscopy (EGD) showed multiple gastric ulcers. The patient was treated with proton pump inhibitors (PPI) and was continued on maintenance chemotherapy. Two months later, the patient presented with the similar symptoms and persistent gastric ulcers were observed during subsequent EGD. Nevertheless, the patient's symptom had resolved with PPI therapy. Thus, the patient underwent maintenance chemotherapy with gemcitabine and erlotinib for additional 4 cycles. Eventually, follow-up abdominal CT Scan and EGD at 6 months demonstrated resolution of the gastric ulcers. CONCLUSIONS: Physicians should be aware of the possibility of radiation recall gastritis associated with a combination of gemcitabine and erlotinib. Administration of PPIs may mitigate the adverse effects of gemcitabine and erlotinib in the presence of radiation recall gastritis; however further studies are warranted.

Endoscopic versus surgical resection of GI stromal tumors in the upper GI tract.

BACKGROUND AND AIMS: Endoscopic resection has been performed for treatment of GI stromal tumors (GISTs) in the upper GI tract. However, the therapeutic roles of the endoscopic procedure remain debatable. We aimed in this retrospective study to evaluate the feasibility and long-term follow-up results of endoscopic resection of GISTs in the upper GI tract, compared with surgery. METHODS: Between March 2005 and August 2014, 130 cases of GIST in the upper GI tract were resected. We compared baseline characteristics and clinical outcomes including R0 resection rate and recurrence rate between the endoscopy group (n = 90) and surgery group (n = 40). RESULTS: The most common location of GIST was the stomach body in the endoscopy group, whereas it was the duodenum in the surgery group (P = .001). Tumor size was significantly smaller (2.3 vs 5.1 cm; P < .001), and procedure time (51.8 ± 36.2 vs 124.6 ± 74.7 minutes; P < .001) and hospital stay (3.3 ± 2.4 vs 8.3 ± 5.4 days; P < .001) were significantly shorter in the endoscopy group than in the surgery group. The R0 resection rate was 25.6% in the endoscopy group, whereas it was 85.0% in the surgery group (P = .001), and 50.0% of resected tumors belonged to a very low-risk group in the endoscopy group, whereas 35.0% and 30.0% belonged to low-risk and high-risk in the surgery group (P = .001). However, during 45.5 months of follow-up, the recurrence rate was not significantly different between the 2 groups (2.2% vs 5.0%; P = .586). CONCLUSIONS: Endoscopic resection might be an alternative therapeutic modality for GISTs in the upper GI tract in selective cases.

The roles of HOXB7 in promoting migration, invasion, and anti-apoptosis in gastric cancer.

BACKGROUND AND AIM: The aim of this study was to compare HOXB7 expression level between gastric cancer and non-cancerous gastric tissues. Additionally, the functional effects of HOXB7, including its pro-migration or invasion and anti-apoptosis roles, were evaluated in gastric cancer cells. METHODS: Both gene and protein expression levels of HOXB7 were examined in gastric cancer cell lines, and HOXB7 expression was compared between primary or metastatic gastric cancer tissues and chronic gastritis or intestinal metaplasia tissues. Functional studies included a wound healing assay, a Matrigel invasion assay, and an Annexin-V assay were performed, and Akt/PTEN activity was measured by western blotting. RESULTS: Both gene and protein expression levels of HOXB7 could be clearly detected in various gastric cancer cell lines except MKN-28 cell. HOXB7 expression was significantly higher in primary or metastatic gastric cancer tissues than in chronic gastritis or intestinal metaplasia tissues. HOXB7 knockdown led to inhibition of cell invasion and migration, had an apoptotic effect, downregulated phosphor-Akt, and upregulated PTEN in AGS and SNU-638 cells. Reinforced expression of HOXB7 caused the opposite effects in MKN-28 and MKN-45 cells. CONCLUSION: Our study suggests that HOXB7 has an oncogenic role in gastric cancer, which might be related to the modulation of Akt/PTEN activity to induce cell migration/invasion and anti-apoptotic effects.

Cholangiocarcinoma Risk as Long-term Outcome After Hepatic Resection in the Hepatolithiasis Patients.

BACKGROUND: Hepatolithiasis is a well-known risk factor of cholangiocarcinoma. Despite advances in diagnostic modalities, diagnosing cholangiocarcinoma in patients with hepatolithiasis still challenging and there are not enough reports on the incidence of cholangiocarcinoma in patient with hepatolithiasis after treatment. We aimed to evaluate the incidence and clinical characteristics of cholangiocarcinoma in patients with hepatolithiasis who underwent liver resection or non-resection. METHODS: Among a total of 257 patients who received treatment for hepatolithiasis, 236 patients were eligible for analysis. Exclusion criteria were follow-up period less than 9 months, preoperative diagnosis of cholangiocarcinoma, occurrence of cholangiocarcinoma within 1 year after treatment. Completeness of stone clearance was defined when there was no intrahepatic duct stone during whole follow-up period. A retrospective study was done to analyze the patients' characteristics, the results and complications of the procedure, and the long-term outcomes for these patients. Kaplan-Meier method and cox proportional regression were used for statistical analysis. RESULTS: 95 patients underwent hepatic resection (resection group) and 144 patients did not (non-resection group). Complete stone clearance was 71% (67/95) in resection group and 41% (58/141) in non-resection group (p < 0.001). The incidence of cholangiocarcinoma was 6.8% (16/236) during follow-up period (mean 41 ± 41 months). Cholangiocarcinoma occurred 6.3% (6/95) and 7.1% (10/141) in resection and non-resection group, respectively. There was no significant difference in survival between two groups (p = 0.254). In analysis of according to completeness of stone clearance regardless of treatment modality, cholangiocarcinoma incidence was higher in patients with residual stone (10.4%) than complete stone removal (3.3%) (p = 0.263). On multivariate analysis, none of the factors (age, gender, CA19-9, stone location, bile duct stenosis, liver atrophy, stone recurrence, residual stone, and hepatic resection) showed relationship with the incidence of cholangiocarcinoma. CONCLUSION: Hepatic resection for hepatolithiasis is considered to have a limited value in preventing cholangiocarcinoma and the patients should be carefully followed even after hepatic resection. A combination of different treatment modalities is necessary to decrease the residual stone and improve the outcome of the patients with hepatolithiasis.

Comparison of the methods for tumor response assessment in patients with hepatocellular carcinoma undergoing transarterial chemoembolization.

BACKGROUND & AIMS: Recently, new methods, including the concept of viable enhancing tumor such as EASL and mRECIST, have been proposed for substitution of the conventional WHO and RECIST criteria in hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE). Herein, we evaluated the differences of four methods and compared the association of these methods with the prognosis of HCC patients undergoing TACE. METHODS: We retrospectively reviewed 114 consecutive newly diagnosed HCC patients who underwent TACE as initial treatment. We evaluated the intermethod agreement (κ values) between the methods and compared their association with the prognosis of HCC patients. RESULTS: The κ values for EASL vs. WHO, EASL vs. RECIST, mRECIST vs. WHO, and mRECIST vs. RECIST were low, of 0.102, 0.088, 0.112, and 0.122, respectively. However, good correlations were observed for WHO vs. RECIST and EASL vs. mRECIST (κ=0.883, κ=0.759, respectively p<0.001). The median OS was 32.3 months. Hazard ratios (HR) for survival in responders compared with non-responders were 0.21 (95% CI; 0.12-0.37, p<0.001) for EASL and 0.27 (95% CI; 0.15-0.48, p<0.001) for mRECIST. The mean survival of responders was significantly longer than that of non-responders in both EASL (40.8 vs. 16.9 months, p<0.001) and mRECIST (41.1 vs. 20.7 months, p<0.001). In multivariate analysis, EASL response (HR 0.21, 95% CI 0.11-0.40, p<0.001) and mRECIST response (HR; 0.31, 95% CI, 0.17-0.59, p<0.001) were independently associated with survival. CONCLUSIONS: The response assessment by EASL and mRECIST could reliably predict the survival of HCC patients undergoing TACE and could be applicable in practice in preference to the conventional WHO and RECIST criteria.

Asian consensus report on functional dyspepsia.

BACKGROUND AND AIM: Environmental factors such as food, lifestyle and prevalence of Helicobacter pylori infection are widely different in Asian countries compared with the West, and physiological functions and genetic factors of Asians may also be different from those of Westerners. Establishing an Asian consensus for functional dyspepsia is crucial in order to attract attention to such data from Asian countries, to articulate the experience and views of Asian experts, and to provide a relevant guide on management of functional dyspepsia for primary care physicians working in Asia. METHODS: Consensus team members were selected from Asian experts and consensus development was carried out by using a modified Delphi method. Consensus teams collected published papers on functional dyspepsia especially from Asia and developed candidate consensus statements based on the generated clinical questions. At the first face-to-face meeting, each statement was reviewed and e-mail voting was done twice. At the second face-to-face meeting, final voting on each statement was done using a keypad voting system. A grade of evidence and strength of recommendation were applied to each statement according to the method of the GRADE Working Group. RESULTS: Twenty-nine consensus statements were finalized, including seven for definition and diagnosis, five for epidemiology, nine for pathophysiology, and eight for management. Algorithms for diagnosis and management of functional dyspepsia were added. CONCLUSIONS: This consensus developed by Asian experts shows distinctive features of functional dyspepsia in Asia and will provide a guide to the diagnosis and management of functional dyspepsia for Asian primary care physicians.

Efficacy of S-pantoprazole 20 mg compared with pantoprazole 40 mg in the treatment of reflux esophagitis: a randomized, double-blind comparative trial.

BACKGROUND: S-isomer (S) pantoprazole is known to be more effective and less dependent on cytochrome 2C19 than R-isomer (R)-pantoprazole. AIM: The purpose of this study was to compare the efficacy and safety of S-pantoprazole 20 mg versus pantoprazole 40 mg for treatment of reflux esophagitis. METHODS: This multi-center, double-blind, randomized trial enrolled patients with endoscopically documented reflux esophagitis. Patients were assigned to receive either 20 mg S-pantoprazole or 40 mg pantoprazole once daily for 4 weeks. Endoscopy and symptoms were assessed after 4 weeks of treatment. In patients whose reflux esophagitis was not resolved at 4 weeks, treatment was extended to 8 weeks and symptoms were reassessed. Heartburn, chest pain, acid regurgitation, globus, and overall symptoms were rated. The primary efficacy endpoint was healing of esophagitis, and secondary endpoints were symptomatic and endoscopic improvement. RESULTS: Sixty-seven patients in the S-pantoprazole group (52 male, mean age 51 years) and 62 in the pantoprazole group (61 male, mean age 50 years) were analyzed per protocol. The healing rate of reflux esophagitis was 85 % at 4 weeks and 94 % at 8 weeks in the S-pantoprazole group, which did not differ from those in the pantoprazole group (84 and 97 %, respectively). After treatment, individual and overall gastroesophageal reflux disease (GERD) symptoms and esophagitis improved compared with baseline inflammation in both groups. Intergroup differences in symptoms and endoscopic healing were not significant. CONCLUSION: The efficacy and safety of 20 mg S-pantoprazole were comparable to those of 40 mg pantoprazole for treatment of reflux esophagitis and symptomatic improvement of GERD.

HBsAg seroclearance in chronic hepatitis B: implications for hepatocellular carcinoma.

GOALS AND BACKGROUND: The long-term clinical course, including the development of hepatocellular carcinoma (HCC) after hepatic B surface antigen (HBsAg) seroclearance is not established. We discovered that the incidence of HCC and the risk factors for HCC in chronic hepatitis B (CHB) patients after HBsAg seroclearance. STUDY: During 28 years, 96 CHB patients with HBsAg seroclearance were retrospectively reviewed. These patients continued to undergo HCC surveillance. The median follow-up time from initial visit was 166.5 months (range, 7 to 321 mo). RESULTS: The mean age at the initial visit and at the time of seroclearance was 39.2 ± 10.6 years and 46.4 ± 9.9 years, respectively. The mean age at the time of HBsAg seroclearance was significantly lower (P=0.03) in patients with spontaneous HBsAg seroclearance than patients with treatment-associated HBsAg seroclearance. During a median of 56 months (range, 7 to 238 mo) of follow-up after HBsAg seroclearance, 6 (6.5%) patients developed HCC. The mean age at the time of developing HCC was 55.8 ± 10.3 years. On univariate analysis, the evidence of liver cirrhosis from the time of HBsAg seroclearance and age more than 45 years at the time of HBsAg seroclearance were significant risk factors for HCC development. In multivariate analysis, the evidence of liver cirrhosis at HBsAg seroclearance was the only significant risk factor for HCC development. CONCLUSIONS: HCC can develop after HBsAg seroclearance in patients with known cirrhosis. Patients who achieved HBsAg seroclearance at older age (>45) may have undiagnosed cirrhosis and hence remain at risk for HCC. HCC surveillance should be carried out for both of those patient populations.

Change in serum hepatitis B surface antigen level and its clinical significance in treatment-naïve, hepatitis B e antigen-positive patients receiving entecavir.

BACKGROUND/AIM: We investigated changes in hepatitis B surface antigen (HBsAg) level and its correlation with clinical outcomes in treatment-naive chronic hepatitis B (CHB) patients undergoing entecavir therapy. PATIENTS AND METHODS: Among 51 hepatitis B e antigen (HBeAg)-positive treatment-naive CHB patients receiving entecavir for more than 1 year, 28 were enrolled. HBsAg levels were measured at baseline, 6 months, and 12 months after treatment using the Architect HBsAg QT assay (Abbott, dynamic; range: 0.05 to 125,000 IU/mL). Serum alanine aminotransferase, HBeAg, anti-HBe, and hepatitis B virus (HBV) DNA (Cobas Taqman: low detection limit 1.84 log10 copies/mL) were measured at baseline and every 3 months. The HBsAg response was defined as an HBsAg level that decreased more than 1 log10 IU/mL from baseline level at 12 months after entecavir treatment. RESULTS: Twenty-eight patients were treated for a median period of 21 months (range: 18 to 24 mo). Serum HBsAg level showed a mean of 4.0, 3.7, and 3.6 log10 IU/mL at pretreatment, 6, and 12 months, respectively, and declined significantly (P<0.001). Serum HBV DNA level showed a mean of 8.1, 3.1, and 2.4 log10 copies/mL at pretreatment, 6, and 12 months, respectively, and declined significantly (P<0.001). The decline in HBsAg level was significantly correlated with that of the HBV DNA level at 12 months from baseline (γ=0.391, P=0.044). Five patients showed an HBsAg response, and cumulative incidence of HBeAg loss at 1 year after entecavir treatment was 80% versus 30% in patients with an HBsAg response and those without, respectively (P=0.034). CONCLUSIONS: Monitoring changes in quantitative HBsAg level could be a useful parameter for assessing the response to entecavir therapy in HBeAg-positive treatment-naive CHB patients.

Effects of sphingolipid synthesis inhibition on cholesterol gallstone formation in C57BL/6J mice.

BACKGROUND: Sphingolipids play a very important role in cell membrane formation, signal transduction and plasma lipoprotein metabolism. The first rate-limiting step in the sphingolipid biosynthetic pathway is catalyzed by serine palmitoyltransferase (SPT), and myriocin is a potent and specific inhibitor of SPT. We investigated the impact of SPT inhibition on cholesterol gallstone formation in C57BL/6J mice. METHODS: Three groups of eight-week-old C57BL/6J mice were utilized. Each group consisted of 20 mice; group A, B, and C were fed normal chow, lithogenic diet with phosphate buffered saline, and lithogenic diet with myriocin (0.3 mg/kg), respectively, for 6 weeks. The ceramide levels in both serum and bile were assessed by high performance liquid chromatography analysis. Protein expression of ERK, JNK and p38 in the extracted gallbladder were determined by Western-blot analysis. RESULTS: Myriocin treatment caused a significant decrease in the rate of cholesterol gallstone formation. The lithogenic diet mice (group B) showed the highest ceramide activities in both the serum and bile among all the tested groups and there was significant suppression of the ceramide levels in both the serum and bile of the myriocin-treated mice (group C, p < 0.05). Phosphorylation of p38 in the gallbladder was increased in the lithogenic-diet mice and the expression of phosphorylated p38 was significantly suppressed in the myriocin treated mice. CONCLUSIONS: SPT inhibition by myriocin suppressed gallstone formation and the levels of ceramide in both the serum and bile. p38 in the cellular signaling pathways might be associated with cholesterol gallstone formation.

Asian consensus on irritable bowel syndrome.

BACKGROUND AND AIMS: Many of the ideas on irritable bowel syndrome (IBS) are derived from studies conducted in Western societies. Their relevance to Asian societies has not been critically examined. Our objectives were to bring to attention important data from Asian studies, articulate the experience and views of our Asian experts, and provide a relevant guide on this poorly understood condition for doctors and scientists working in Asia. METHODS: A multinational group of physicians from Asia with special interest in IBS raised statements on IBS pertaining to symptoms, diagnosis, epidemiology, infection, pathophysiology, motility, management, and diet. A modified Delphi approach was employed to present and grade the quality of evidence, and determine the level of agreement. RESULTS: We observed that bloating and symptoms associated with meals were prominent complaints among our IBS patients. In the majority of our countries, we did not observe a female predominance. In some Asian populations, the intestinal transit times in healthy and IBS patients appear to be faster than those reported in the West. High consultation rates were observed, particularly in the more affluent countries. There was only weak evidence to support the perception that psychological distress determines health-care seeking. Dietary factors, in particular, chili consumption and the high prevalence of lactose malabsorption, were perceived to be aggravating factors, but the evidence was weak. CONCLUSIONS: This detailed compilation of studies from different parts of Asia, draws attention to Asian patients' experiences of IBS.

Long-term outcomes of prophylactic endoscopic histoacryl injection for gastric varices with a high risk of bleeding.

PURPOSE: Endoscopic histoacryl injection (EHI) is reported to be an effective treatment modality for bleeding gastric varices (GVs) but controversial as a prophylactic treatment for non-bleeding GVs because efficacy and safety have yet to be determined. The aim of this study was to evaluate safety and long-term outcomes of prophylactic EHI for non-bleeding GVs with a high risk of bleeding. METHODS: Thirty-three patients (23 males/10 females, mean age 56.6 years old) with a high risk of gastric variceal bleeding (large tumorous (27), red color sign (14) or rapidly growing in size (1)) underwent EHI. According to the grade of GVs, 25 patients belonged to F3, seven to F2, and one to F1. In terms of the locations of GVs, four patients belonged to type IGV1, 21 to type GOV2, and eight to type GOV1. RESULTS: Obliteration of GVs was achieved in all of the treated patients. Twenty-three patients required one session and ten needed more than two sessions to obliterate their GVs. A mean volume of histoacryl used per session was 2.0 ml. Complications related to the procedure included immediate bleeding in two patients and bacteremia in one patient. The mean duration of follow-up was 12.2 months and eradication of GVs was achieved in 21 (95%) of 22 patients who were followed-up more than 3 months. Index GVs recurred in three of 21 patients (14%) and re-bleeding in index GVs after EHI occurred in two of 26 patients (8%). CONCLUSIONS: Prophylactic EHI can be a promising procedure for eradication of non-bleeding GVs in case with a high risk of bleeding.