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Background and Aim Percutaneous radiofrequency ablation (RFA) is a minimally invasive and curative local treatment for hepatocellular carcinoma (HCC). However, serious concerns remain regarding critical recurrences such as metastasis, dissemination, and/or seeding due to RFA. In August 2006, we introduced selective feeding artery ablation before tumor ablation to reduce the risk of critical recurrence by blocking tumor blood flow. The aim of the present study was to clarify whether feeding artery ablation before tumor ablation can reduce the risk of critical recurrence after RFA. Methods This study retrospectively analyzed 279 patients with primary, solitary, and hypervascular HCC ≤5 cm in diameter who were treated with RFA alone between April 2001 and August 2013. Critical recurrence was defined as intra‐ or extrahepatic metastasis, dissemination, or seeding that was difficult to treat radically. Results Of the 279 HCC patients, 157 patients were treated with conventional RFA alone, and 122 patients underwent RFA with prior feeding artery ablation. Although no significant differences were seen in the rates of local tumor progression‐free survival, overall recurrence‐free survival, or overall survival between a conventional RFA group and a prior feeding artery ablation group, significant differences were seen in rates of critical recurrence‐free survival and cancer‐specific survival (5‐year, 69 vs 81%, P = 0.01 and 76 vs 88%, P = 0.03, respectively). On multivariate analysis, prior feeding artery ablation, tumor diameter, and alpha‐fetoprotein were independent factors related to critical recurrence. Conclusions Feeding artery ablation before tumor ablation may reduce the risk of critical recurrence., To reduce the risk of critical recurrence such as metastasis, dissemination, and/or seeding, we conducted selective ablation of the feeding artery before tumor ablation. Our retrospective analysis of 279 patients with primary, solitary, hypervascular hepatocellular carcinoma ≤5 cm in diameter who were treated with radiofrequency ablation alone revealed that feeding artery ablation before tumor ablation could reduce the risk of critical recurrence.

BACKGROUND AND AIM Chronic pancreatitis (CP) leads to permanent impairment of exocrine and endocrine functions. The endoscopic ultrasonography (EUS)-based Rosemont classification plays an important role in diagnosing CP. However, it is based on subjective judgment. In contrast, EUS shear wave measurement (EUS-SWM) has been established to be a precise method for evaluating tissue hardness. This study aimed to evaluate the utility of EUS-SWM in diagnosing CP and determining exocrine and endocrine dysfunctions. METHODS We evaluated 40 patients who underwent EUS-SWM between January 2019 and January 2020. They were classified into the normal pancreas and early, probable, and definite CP groups following the Japan Pancreatic Society criteria. EUS-SWM value was compared between the normal pancreas group and the early, probable, and definite CP groups. The relationship between EUS-SWM value and exocrine/endocrine dysfunctions was also assessed. The cut-off value of EUS-SWM for diagnosing CP and exocrine/endocrine dysfunctions was investigated. RESULTS The EUS-SWM value was positively correlated with the Japan Pancreatic Society criteria stages. The probable and definite CP groups had significantly higher EUS-SWM values than the normal group. The areas under the receiver operating characteristic curve for the diagnostic accuracy of EUS-SWM for CP, exocrine dysfunction, and endocrine dysfunction were 0.92, 0.78, and 0.63, respectively. The cut-off values of 1.96, 1.96, and 2.34 for diagnosing CP, exocrine dysfunction, and endocrine dysfunctions had 83%, 90%, and 75% sensitivity, respectively, and 100%, 65%, and 64% specificity, respectively. CONCLUSIONS Endoscopic ultrasonography shear wave measurement provides objective assessment and can thus be an alternative diagnostic tool for diagnosing CP and exocrine/endocrine dysfunctions.

Benign esophageal strictures (BES) cause dysphagia and decrease patients' quality of life. Although mechanical dilation is the standard of care for BES, in some patients, dysphagia is unrelieved despite repeated procedures. The biodegradable stent was developed to resolve refractory BES, with reported favorable outcomes, but it is unapproved in Japan. Thus, we evaluated the safety and efficacy of the biodegradable stent (BDS) for patients with refractory BES for regulatory approval.This was a nonrandomized single-arm prospective trial conducted at eight institutions. We included patients with BES after ≥ 5 times of dilation or ≥ one time of radial incision and cutting whose dysphagia score (DS) was 2 or worse and an endoscope could not admit. The primary endpoint was the proportion of patients whose DS improvement of ≤ 1 was maintained at 3 months.Thirty patients (median age: 69 years, male/female: 27:3) were enrolled and treated; BDS placement failed in 1 patient. Fourteen patients maintained their DS improvement until 3 months after placement (proportion of DS improvement at 3 months 46.7% [95% CI: 28.3-65.7]), and the median dysphagia-free survival was 98 days [95% CI: 68-123]. Most adverse events could be managed conservatively; however, a patient with BES after chemoradiotherapy (CRT) developed an esophago-left atrium fistula and died approximately 4 months after stent placement.The BDS was effective for refractory BES and the safety was acceptable. However, the indication for this procedure in patients RECEIVING CRT for esophageal cancer should be carefully considered.

Continuous duodenal levodopa/carbidopa intestinal gel delivery by a gastrostomy infusion system improves control of Parkinson’s disease. The overall complication rates of percutaneous endoscopic gastrojejunostomy were reported to be 41% and 59% for immediate and delayed adverse events, respectively. A 72-year-old woman underwent percutaneous endoscopic gastrojejunostomy using the delivery system noted above. Abdominal pain and vomiting occurred 3 months later. Esophagogastroduodenoscopy showed a longitudinal ulcer extending from the lower gastric body to the ileum end, with small intestinal telescoping. Colonoscopy showed a large bezoar of food residue that was attached around the tip of the tube, reaching the ascending colon, which may have acted as an anchor. Thus, the gastric antrum and small intestine were shortened with telescoping. This complication was resolved by crushing the bezoar with forceps during colonoscopy and can be prevented by consuming a fiber-free diet and periodic exchanges of the tube using esophagogastroduodenoscopy.

A 68-year-old man with epigastric pain was admitted for acute pancreatitis and obstructive jaundice caused by Primary pancreatic malignant lymphoma. Computed tomography showed diffuse enlargement of the whole pancreas and dilation of the main pancreatic duct and bile duct. Endoscopic retrograde cholangiopancreatography was performed to decompress these dilated ducts. After two courses of chemotherapy, follow-up computed tomography incidentally revealed migration of the pancreatic duct stent, which had perforated the contralateral duodenal wall to enter the peritoneal cavity. In the present case, pancreatic duct stent deviation was attributed to tumor shrinkage resulting from chemotherapy. In addition, stent migration into the peritoneal cavity occurred due to repeated mechanical manipulation of the pancreatic duct stent, presumably leading to partial ulceration of the duodenal wall and delayed wound healing during chemotherapy. This case may provide valuable information on the migration of pancreatic duct stents as a rare, stent-related late complication during chemotherapy.

Colonoscopy is currently considered the optimal method to detect colorectal neoplasia; however, some adenomas remain undetected. While indigo carmine staining with a dye-spray catheter has demonstrated promising results for reducing the miss rate, we investigated the oral indigo carmine method. The aim of this study was to determine whether oral indigo carmine intake before standard colonoscopy increases the adenoma (and adenocarcinoma) detection rate (ADR) or the mean number of adenomas per patient (MAP).The oral indigo carmine method was performed from April 2018 to July 2020 in two hospitals. Data were collected in a prospective manner and compared to the conventional group whose data were collected retrospectively and consecutively from January 2016 to March 2018. All data were anonymized.Among the 704 patients included, colonoscopies were completely performed in 693 patients (347 in the indigo group). The ADR did not significantly differ between the groups: 42.3% vs. 40.3% (indigo vs. conventional group; odds ratio: 1.13; 95% confidence interval: 0.9-1.33,The routine use of oral indigo carmine does not lead to a higher ADR despite the higher MAP.

OBJECTIVES Detective flow imaging for endoscopic ultrasonography (DFI?EUS) is a new imaging modality developed for detecting fine vessels without using ultrasound contrast agents. This study aimed to evaluate its utility by comparing it with a type of directional power Doppler (eFLOW) for subepithelial lesions (SELs). METHODS Between January 2019 and January 2020, 28 patients with SELs undergoing DFI?EUS and eFLOW?EUS were enrolled. DFI?EUS and eFLOW?EUS assessing the vascularity in SELs were compared in terms of the rates of identification of intratumoral vessels. We also investigated how large vessels were depicted in both modalities based on surgical specimens as well as the detection rates of intratumoral vessels in gastrointestinal stromal tumors (GISTs) and non?GISTs using either DFI?EUS or eFLOW?EUS. RESULTS Among 28 patients, 23 with pathological confirmation by EUS?guided fine?needle aspiration biopsy (EUS?FNAB) specimens were included. Of those 23 patients, the 10 who underwent surgical resection were selected for analysis. The rate of detection of intratumoral vessels in SELs was significantly higher on DFI?EUS (80%) than on eFLOW?EUS (30%) (P\xA0=\xA00.03). Comparison with surgical specimens revealed that detection rate for vessels with maximum size of less 1000\xA0μm was higher in DFI?EUS (66%) than that in eFLOW?EUS (0%). GIST patients had significantly higher positive rates (90%) of intratumoral vessels than non?GIST patients (31%) on DFI in 23 cases including EUS?FNAB specimens (P\xA0=\xA00.045). CONCLUSIONS Detective flow imaging?EUS is more sensitive for depicting intratumoral vessels than eFLOW?EUS. Evaluation of intratumoral vessels on DFI?EUS is useful for identifying GISTs without contrast agents.

Background and aim Nodular gastritis is caused by Helicobacter pylori infection and is associated with the development of diffuse-type gastric cancer. This study examined the clinical characteristics of patients with nodular gastritis, including cancer incidence before and after H. pylori eradication. Methods This was a retrospective study of patients who underwent upper endoscopy and were positive for H. pylori infection. We examined the clinical findings and follow-up data after H. pylori eradication in patients with and without nodular gastritis. Results Of the 674 patients with H. pylori infections, nodular gastritis was observed in 114 (17%). It was more prevalent in women (69%) and young adults. Among patients with nodular gastritis, six (5%) had gastric cancer, all of which were of the diffuse type. Among the 19 (4%) patients with gastric cancer and no nodular gastritis, 16 had intestinal-type cancer. White spot aggregates in the corpus, a specific finding in patients with nodular gastritis, were more frequently observed in patients with gastric cancer than in those without (83% vs 26%, P = 0.0025). Of 82 patients with nodular gastritis who had H. pylori eradicated successfully, none developed gastric cancer over a 3-year follow-up period, while 7 (3%) of 220 patients without nodular gastritis developed gastric cancer after H. pylori eradication. Conclusions In patients with nodular gastritis, white spot aggregates in the corpus may indicate a higher risk of developing diffuse-type gastric cancer. Nodular gastritis may be an indication for eradication therapy to reduce the risk of cancer development after H. pylori eradication.

Background and aim Blood markers are not always regarded as satisfactory surrogate biomarkers for predicting endoscopic activity in ulcerative colitis (UC). However, those biomarkers have been evaluated solely based on endoscopic activity at the most severe colorectal location, taking no account of the extent of inflammation. This study aimed to examine whether integrated evaluation of severity and extent of endoscopic activity improves the performance of blood biomarkers for UC. Methods We performed a retrospective study of UC patients who underwent colonoscopy and blood tests in our hospital. Blood tests were C-reactive protein (CRP), serum albumin (ALB), and platelet count (PLT). We compared blood markers with two versions of endoscopic activity assessed by Mayo endoscopic subscore (MES): the maximum score of MES in the colorectum (mMES, range: 0-3) and the cumulative score of MES of six colorectal regions (cMES, range: 0-18). Results All three blood markers correlated well with both mMES and cMES, and each marker showed better correlation with cMES than mMES (Spearman rank correlation coefficient: PLT: 0.54 vs 0.47, ALB: -0.65 vs -0.52, and CRP: 0.52 vs 0.38, respectively). The predictability, including sensitivity and specificity, of each marker for endoscopic activity was also better for cMES, resulting in higher degrees of area under the curve (mMES vs cMES: PLT: 0.75 vs 0.83, ALB: 0.77 vs 0.90, and CRP: 0.75 vs 0.90, respectively). Conclusion When incorporating the extent of inflammation, blood markers are better at predicting endoscopic activity of UC than previously considered and could be used as a reliable biomarker in clinical practice.

Background/aims Endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) has been used to diagnose gastrointestinal submucosal tumors (SMTs). Although rapid on-site evaluation (ROSE) has been reported to improve the diagnostic accuracy of EUS-FNA for pancreatic lesions, on-site cytopathologists are not routinely available. Given this background, the usefulness of ROSE by endosonographers themselves for pancreatic tumors has also been reported. However, ROSE by endosonographers for diagnosis of SMT has not been reported. The aim of this study was to evaluate the diagnostic accuracy of EUS-FNA with ROSE by endosonographers for SMT, focusing on diagnosis of gastrointestinal stromal tumor (GIST), compared with that of EUS-FNA alone. Methods Twenty-two consecutive patients who underwent EUS-FNA with ROSE by endosonographers for SMT followed by surgical resection were identified. Ten historical control subjects who underwent EUS-FNA without ROSE were used for comparison. Results The overall diagnostic accuracy for SMT was significantly higher in cases with than without ROSE (100% vs. 80%, p=0.03). The number of needle passes by FNA with ROSE by endosonographers tended to be fewer, although accuracy was increased (3.3±1.3 vs. 5.9±3.8, p=0.06). Conclusions ROSE by endosonographers during EUS-FNA for SMT is useful for definitive diagnosis, particularly for GIST.

Background/Aims: Rosemont classification (RC) with endoscopic ultrasonography (EUS) is important for diagnosing chronic pancreatitis (CP) but is based only on subjective judgement. EUS shear wave measurement (EUS-SWM) is a precise modality based on objective judgment, but its usefulness has not been extensively studied yet. This study evaluated the utility of EUS-SWM for diagnosing CP and estimating CP severity by determining the presence of endocrine dysfunction along with diabetes mellitus (DM). Methods: Between June 2018 and December 2018, 52 patients who underwent EUS and EUS-SWM were classified into two groups according to RC: non-CP (indeterminate CP and normal) and CP (consistent and suggestive of CP). The EUSSWM value by shear wave velocity was evaluated with a median value. The EUS-SWM value was compared with RC and the number of EUS features. The diagnostic accuracy and cutoff value of EUS-SWM for CP and DM and its sensitivity and specificity were calculated. Results: The EUS-SWM value significantly positively correlated with the RC and the number of EUS features. The EUS-SWM values that were consistent and suggestive of CP were significantly higher than that of normal. The area under the receiver operating characteristic (AUROC) curve for the diagnostic accuracy of EUS-SWM for CP was 0.97. The cutoff value of 2.19 had 100% sensitivity and 94% specificity. For endocrine dysfunction in CP, the AUROC was 0.75. The cutoff value of 2.78 had 70% sensitivity and 56% specificity. Conclusions: EUS-SWM provides an objective assessment and can be an alternative diagnostic tool for diagnosing CP. EUS-SWM may also be useful for predicting the presence of endocrine dysfunction. (Gut Liver 2020;14:659-664)

Background/Aims This study aimed to predict sustained viral response (SVR) to low-dose pegylated interferon (PEG-IFN) plus ribavirin of elderly and/or cirrhotic patients with genotype 2 hepatitis C virus (HCV) using viral response within 2 weeks. Methods Low-dose PEG-IFN-α-2b plus ribavirin was administered to 50 elderly and/or cirrhotic patients with genotype 2 HCV for 24 weeks. The dynamics of HCV RNA and HCV core antigen levels within 2 weeks were measured. Results The patients’ median age was 66 years. There were 21 male and 29 female patients. The median baseline HCV RNA level was 5.7 log IU/mL. Rapid viral response was achieved in 17 patients (34%), SVR in 28 (56%), and two (4%) discontinued treatment. Univariate analysis of factors contributing to SVR showed significant differences for sex, baseline virus level, and response within 4 weeks. When 40 fmol/L was set as the cutoff value for the core antigen level at 1 week, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for predicting SVR were 93%, 75%, 84%, 88%, and 85%, respectively. Conclusions Low-dose PEG-IFN plus ribavirin was a safe and cost-effective treatment for elderly and/or cirrhotic patients with genotype 2 HCV, and the viral response within 2 weeks was a useful predictor of SVR.

Background/Aims Transpapillary forceps biopsy is an effective diagnostic technique in patients with biliary stricture. This prospective study aimed to determine the usefulness of the wire-grasping method as a new technique for forceps biopsy. Methods Consecutive patients with biliary stricture or irregularities of the bile duct wall were randomly allocated to either the direct or wire-grasping method group. In the wire-grasping method, forceps in the duodenum grasps a guide-wire placed into the bile duct beforehand, and then, the forceps are pushed through the papilla without endoscopic sphincterotomy. In the direct method, forceps are directly pushed into the bile duct alongside a guide-wire. The primary endpoint was the success rate of obtaining specimens suitable for adequate pathological examination. Results In total, 32 patients were enrolled, and 28 (14 in each group) were eligible for analysis. The success rate was significantly higher using the wire-grasping method than the direct method (100% vs 50%, p=0.016). Sensitivity and accuracy for the diagnosis of cancer were comparable in patients with the successful procurement of biopsy specimens between the two methods (91% vs 83% and 93% vs 86%, respectively). Conclusions The wire-grasping method is useful for diagnosing patients with biliary stricture or irregularities of the bile duct wall.

We have previously reported that serum pepsinogen (PG) can quantify the level of gastric mucosal atrophy, and that H. pylori eradication reduces cancer development in subjects with mild atrophy identified by serum PG levels. The aim of this study was to elucidate the predictive ability of serum PG levels for the development of metachronous gastric cancer (MGC) after endoscopic resection (ER) of primary cancer in association with H. pylori eradication. A retrospective chart review was performed, and 330 patients who underwent ER for initial early gastric cancer were enrolled. Presence or absence of H. pylori, serum PG levels, and endoscopic atrophy at ER were evaluated. H. pylori eradication was performed at the patient's request after ER. The incidence of MGC in these patients was analyzed. Of 330 patients, 47 developed MGC. Endoscopic extensive atrophy was observed more frequently in patients with MGC (p = 0.001). Although PG I or PG II alone did not significantly differ according to development of MGC, the proportion of PG I/II ≤ 3.0, which is one of the criteria of PG test-positive, was significantly higher in patients with MGC (83 vs. 69%, p = 0.04). H. pylori eradication after ER did not affect MGC development (p = 0.2). On multivariate analysis, serum PG I/II ratio ≤ 3.3 was significantly associated with the development of MGC (hazard ratio: 3.66, 95% confidence interval: 1.47-12.25, p = 0.004). The risk of MGC after ER could be quantitatively predicted by the PG I/II ratio regardless of H. pylori status.

Background and Aim The preventive effect of Helicobacter pylori (HP) eradication on metachronous gastric cancer development after endoscopic resection remains controversial. The aim of the present study was to identify specific endoscopic features that correlated with the risk of metachronous gastric cancer development after endoscopic submucosal dissection (ESD) using both endoscopic findings before ESD and changes of findings after HP eradication. Methods This retrospective study investigated 122 consecutive patients who underwent ESD for early gastric cancer and successful HP eradication after ESD. Endoscopic findings linked with HP before ESD and changes after HP eradication were evaluated according to the development of metachronous cancer. Results Most patients showed severe atrophy and intestinal metaplasia (IM) before ESD (97% and 83%, respectively). Improvement of spotty redness, improvement of diffuse redness, emergence of patchy redness, and emergence of map-like redness were frequent findings after HP eradication (52%, 50%, 54%, and 32%, respectively). Kaplan–Meier curves indicated that patients without IM before ESD never developed metachronous cancer, whereas patients with emergence of map-like redness after HP eradication were significantly more likely to develop metachronous cancer (log–rank test, P = 0.031 and P

We recently published in your journal a 3-year multicentre prospective cohort study demonstrating the usefulness of an epigenetic cancer risk marker for gastric metachronous cancers.1 This study achieved the first proof of concept of epigenetic cancer risk diagnosis in any type of cancer but, due to the short follow-up period, a relatively small number of events were observed, resulting in a marginally significant difference (p=0.042). It was anticipated that a longer follow-up could lead to a clearer difference and HR with a smaller 95% CI. We now report the 5-year follow-up data, which show highly significant results. Among the 826 enrolled patients, 795 patients received annual follow-ups by endoscopy for a median period of 5.46 years (IQR: 3.95–6.09). By the end, 133 patients had developed a metachronous gastric cancer. Among them, 116 patients developed a metachronous gastric cancer detected 1 year after the enrolment (authentic metachronous cancer). Statistical analyses were conducted in the same manner as previously …

Background and aim Treatment efficiency of walled-off necrosis (WON) using endoscopic ultrasound-guided drainage (EUS-D) with a double pigtail stent (DPS) is limited. Endoscopic necrosectomy is often carried out if EUS-D fails. However, endoscopic necrosectomy is associated with significant morbidity and mortality. Thus, we developed transmural nasocyst continuous irrigation (TNCCI) as an alternative therapeutic option for WON. This study aimed to evaluate the usefulness of TNCCI therapy for WON. Methods Between April 2009 and March 2018, 19 of 39 patients admitted with WON underwent EUS-D. Ten consecutive patients also received TNCCI therapy (TNCCI group) between May 2015 and March 2018. TNCCI was carried out by inserting an external tube from the gastroduodenal lumen into the WON under endoscopic ultrasonography guidance and then continuously irrigating the WON with saline at a rate of 40 ml/h. Nine consecutive patients who underwent EUS-D without TNCCI therapy between April 2009 and April 2015 were used for comparison (control group). Various parameters were compared between the TNCCI and control groups. Results Time taken to reduce WON (6 vs 32 days, P = 0.001), implementation rate of endoscopic necrosectomy (0% vs 55.6%, P = 0.01), and number of endoscopic necrosectomy sessions per patient (0 vs 0.8 ± 1.0, P = 0.008) were significantly lower in the TNCCI group than in the control group. Conclusions Walled-off necrosis can be effectively and safely treated by endoscopic drainage with a DPS and TNCCI. This technique can be an alternative therapeutic option before carrying out endoscopic necrosectomy.

Background/Aims Although daclatasvir with asunaprevir was approved in Japan for interferon ineligible or intolerant patients, patients aged ≥75 years were excluded in the phase III trial. The present study aimed to evaluate the safety and efficacy of this therapy for elderly patients aged ≥75 years and to clarify whether an extremely high sustained virological response (SVR) rate can be achieved, even in a real-world setting when patients with resistance-associated substitutions (RASs) to nonstructural protein 5A (NS5A) inhibitors or prior simeprevir failure are excluded. Methods Daclatasvir (60 mg) and asunaprevir (100 mg) were orally administered daily for 24 weeks. Patients without pre-existing NS5A RASs and simeprevir failure were enrolled in this study. Results Overall, 110 patients were treated. The median age was 73 years old. The SVR rates of total patients, those aged ≥75 years, and those aged ＜75 years were 97% (107/110), 98% (46/47), and 97% (61/63), respectively. The treatment of two patients (2%) was discontinued because of adverse events. Conclusions Daclatasvir with asunaprevir was a safe treatment, even in patients aged ≥75 years. When patients without pre-existing NS5A RASs and prior simeprevir failure were selected, an extremely high SVR rate could be achieved irrespective of age.

Entecavir requires long-term administration. Pegylated interferon (PEG-IFN) therapy leads to significant reduction of hepatitis B surface antigen (HBs Ag) levels. This study aimed to assess the safety and efficacy of adding PEG-IFN-α-2a to entecavir toward cessation of entecavir. A total of 23 patients treated with entecavir underwent add-on PEG-IFN-α-2a therapy (90 μg per week) for 48 weeks. Viral response (VR) was defined as more than 50% reduction of baseline hepatitis B surface antigen (HBs Ag) level at 72 weeks from the start of therapy. Complete response (CR) was defined as the decline of HBs Ag levels α-2a to entecavir has limited efficacy. The percentage reduction of HBs Ag level at week 12 may be a useful predictor for VR.

Background Epigenetic alterations accumulate in normal-appearing tissues of patients with cancer, producing an epigenetic field defect. Cross-sectional studies show that the degree of the defect may be associated with risk in some types of cancer, especially cancers associated with chronic inflammation. Objective To demonstrate, by a multicentre prospective cohort study, that the risk of metachronous gastric cancer after endoscopic resection (ER) can be predicted by assessment of the epigenetic field defect using methylation levels. Design Patients with early gastric cancer, aged 40–80 years, who planned to have, or had undergone, ER, were enrolled at least 6 months after Helicobacter pylori infection discontinued. Methylation levels of three preselected genes (miR-124a-3, EMX1 and NKX6-1) were measured by quantitative methylation-specific PCR. Patients were followed up annually by endoscopy, and the primary endpoint was defined as detection of a metachronous gastric cancer. Authentic metachronous gastric cancers were defined as cancers excluding those detected within 1 year after the enrolment. Results Among 826 patients enrolled, 782 patients had at least one follow-up, with a median follow-up of 2.97 years. Authentic metachronous gastric cancers developed in 66 patients: 29, 16 and 21 patients at 1–2, 2–3 and ≥3 years after the enrolment, respectively. The highest quartile of the miR-124a-3 methylation level had a significant univariate HR (95% CI) (2.17 (1.07 to 4.41); p=0.032) and a multivariate-adjusted HR (2.30 (1.03 to 5.10); p=0.042) of developing authentic metachronous gastric cancers. Similar trends were seen for EMX1 and NKX6-1. Conclusions Assessment of the degree of an epigenetic field defect is a promising cancer risk marker that takes account of life history.

BACKGROUND/AIMS The present study aimed to clarify whether virological response within 2 weeks after therapy initiation can predict a null response to pegylated interferon α-2b plus ribavirin therapy in patients with high viral load genotype 1b hepatitis C. METHODS The participants consisted of 72 patients with high viral load genotype 1b. The dynamics of viral load within 2 weeks were measured. RESULTS Significant differences between null responders and nonnull responders were noted for interleukin (IL)-28B genotype, amino acid 70 substitution, α-fetoprotein, low-density lipoprotein cholesterol, hyaluronic acid, and viral response. The area under the curve (AUC) for the receiver operating characteristic curve of the hepatitis C virus (HCV) RNA level decline at 2 weeks (AUC=0.993) was the highest among the factors predicting the null response. When the cutoff value for the HCV RNA level decline at 2 weeks was set at 0.80 log, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in predicting a null response were 82%, 96%, 82%, 96%, and 94%, respectively. In comparison, values for the non-TT and mutant type of amino acid 70 substitution were similar to those for HCV RNA level decline at 2 weeks. CONCLUSIONS Virological response at 2 weeks or the combination of IL-28B and amino acid 70 substitution are accurate predictors of a null response.

Liquid-based cytology (LBC) is a thin-layer slide preparation procedure that was developed to overcome the cell crowding and contamination associated with smear cytology (SC). The present study compared diagnostic efficacy between SC alone and SC combined with LBC (SLBC) using endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) samples of pancreatic lesions. We retrospectively analyzed data derived from 311 consecutive patients. Specimens obtained via EUS-FNA from 179 patients between December 2011 and May 2016 were analyzed by SC, and those obtained from 132 patients between June 2016 and October 2017 were analyzed by SLBC. The 2 groups were compared in terms of adequate sample rate, diagnostic accuracy, sensitivity, and specificity using propensity score matching. SC and SLBC were compared using propensity score-matching in 204 patients (n = 102 per group). The adequate sample rate did not differ significantly between SLBC (100%) and SC (99.0%, P = 1). Diagnostic sensitivity, negative predictive value and accuracy were better for SLBC than for SC in terms of cytological (93.2% vs 67.4%, 68.4% vs 23.1%, and 94.1% vs 69.6%, P

Our study investigated the relationship between gastric cancer development and activity of Helicobacter pylori-associated chronic gastritis or the resulting chronic atrophic gastritis (CAG). A cohort of 4,655 healthy asymptomatic subjects, in whom serum pepsinogen (PG) and H. pylori antibody titer had been measured to assess the activity and stage of H. pylori-associated chronic gastritis, was followed for up to 16 years, and cancer development was investigated. In subjects with a serologically diagnosed healthy stomach (H. pylori-negative/CAG-negative), cancer incidence rate was low, at 16/100,000 person-years. With the establishment of H. pylori infection and progression of chronic gastritis, significant stepwise cancer risk elevations were seen from CAG-free subjects (H. pylori-positive/CAG-negative) [hazard ratio (HR) = 8.9, 95% confidence interval (CI) = 2.7-54.7] to subjects with CAG (H. pylori-positive/CAG-positive) (HR = 17.7, 95% CI = 5.4-108.6) and finally to subjects with metaplastic gastritis (H. pylori-negative/CAG-positive) (HR = 69.7, 95% CI = 13.6-502.9). In H. pylori-infected CAG-free subjects, significantly elevated cancer risk was observed in the subgroup with active inflammation-based high PG II level or potent immune response-based high H. pylori antibody titer; the former was associated with a particularly high risk of diffuse-type cancer, and both subgroups showed high cancer incidence rates of around 250/100,000 person-years, comparable to that in subjects with CAG. No such risk elevation was observed in H. pylori-infected subjects with CAG. These results clearly indicate that gastric cancer develops mainly from the gastritis-atrophy-metaplasia-cancer sequence and partly from active inflammation-based direct carcinogenesis, and that serum levels of PG and H. pylori antibody titer provide indices of cancer development in H. pylori-infected subjects.

AIM Rapid virological response (RVR), defined as serum hepatitis C virus (HCV) RNA negativity at 4 weeks, is the most useful predictor of sustained virological response (SVR) to standard pegylated interferon (PEG IFN) plus ribavirin therapy for patients infected with genotype 2 HCV. The aim of the present study was to predict SVR using viral response within 2 weeks of therapy initiation. METHODS Of 64 HCV genotype 2 patients with a high viral load treated with standard PEG IFN-α-2b plus weight-based ribavirin for 24 weeks, 58 patients whose adherence was more than 67% were analyzed. RNA and core antigen levels were measured at four time points: the day of therapy initiation, the following day, and at 1 and 2 weeks. RESULTS SVR was achieved in 73% (47/64) of patients. Univariate analysis of SVR contributing factors showed significant differences with age, bodyweight, white blood cell count, platelet count, fibrosis marker levels, baseline core antigen level and viral response. The area under the receiver-operator curve (AUC) of the core antigen level at 1 week (AUC, 0.940) was the highest among the significant SVR predicting factors. Setting 100 fmol/L as the cut-off value for core antigen level at 1 week, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy for predicting SVR were 100%, 86%, 96%, 100% and 97%, respectively, and for predicting RVR were 66%, 93%, 97%, 46% and 72%, respectively. CONCLUSION The HCV core antigen level at 1 week after therapy initiation is the most useful predictor for SVR.

Background No mouthpiece has been designed to control salivary flow during endoscopic procedures. A new continuous suction mouthpiece (CSM) was developed, and its usefulness for percutaneous endoscopic gastrostomy (PEG) was evaluated. Patients and Methods Seventy-two patients who were scheduled to undergo PEG or the exchange of a gastrostomy button or tube were assigned to one of two groups: the group using the CSM and the group using the conventional mouthpiece. Aspiration pneumonia, procedure duration, extent of salivary flow, frequency of saliva suction, and number of choking episodes during the procedures were evaluated and compared between the two groups. Results The same number of patients was randomly allocated to each group. There were no significant differences between the two groups in sex, age, procedure type, duration of procedure,depth of sedation, and indication for the procedure. The grade of salivary flow was significantly lower in patients with the CSM than in patients with the conventional mouthpiece (P

Aim Elderly and/or cirrhotic patients with hepatitis C virus (HCV) are at high risk of adverse effects during interferon therapy. The aim of the present study was to evaluate the efficacy, safety and predictive factors for sustained virological response (SVR) of low-dose pegylated interferon-α-2a (PEG IFN-α-2a) monotherapy in elderly and/or cirrhotic patients with HCV genotype-2 or genotype-1 low level infection. Methods Sixty-four elderly (≥65 years) and/or cirrhotic patients with HCV genotype-2 or genotype-1 low level (

Background/Aims: The present study aimed to evaluate the safety and efficacy of simeprevir-based triple therapy with reduced doses of pegylated interferon (PEG-IFN) and ribavirin for interferon (IFN) ineligible patients, such as elderly and/or cirrhotic patients, and to elucidate the factors contributing to a sustained virologic response (SVR). Methods: One hundred IFN ineligible patients infected with genotype 1b hepatitis C virus (HCV) were treated. Simeprevir (100 mg) was given orally together with reduced doses of PEG-IFN-α 2a (90 μg), and ribavirin (200 mg less than the recommended dose). Results: The patients` median age was 70 years, and 70 patients were cirrhotic. Three patients (3%) discontinued treatment due to adverse events. The SVR rate was 64%. Factors that significantly contributed to the SVR included the γ-glutamyl transferase and α-fetoprotein levels, interleukin- 28B (IL28B) polymorphism status, and the level and reduction of HCV RNA at weeks 2 and 4. The multivariate analysis showed that the IL28B polymorphism status was the only independent factor that predicted the SVR, with a positive predictive value of 77%. Conclusions: Simeprevir-based triple therapy with reduced doses of PEG-IFN and ribavirin was safe and effective for IFN ineligible patients infected with genotype 1b HCV. IL28B polymorphism status was a useful predictor of the SVR. (Gut Liver 2017;11:551-558)

In a previous population-based case-control study, we demonstrated an elevated risk of colorectal neoplasia with Helicobacter pylori (H. pylori) infection. The present study investigated the effects of H. pylori-associated chronic gastritis on the development of colorectal neoplasia by analyzing the recurrence of colorectal neoplasia subsequent to endoscopic resection. Ninety-nine patients who had undergone endoscopic resection of colorectal neoplasia were monitored under colonoscopy, and the recurrence of colorectal neoplasia was prospectively investigated. The stage of H. pylori-associated chronic gastritis in each subject was evaluated using a combination of two serum tests: H. pylori antibody and pepsinogen. In the present cohort, colorectal neoplasia recurred at a rate of 15,296/100,000 person-years during the study period. After adjusting for the confounding factors, chronic atrophic gastritis (CAG) was identified as an independent risk factor [adjusted hazard ratio (HR), 2.72; 95% confidence interval, 1.33-5.57], while H. pylori-infected non-atrophic gastritis was not identified as an independent risk factor for recurrent colorectal neoplasia. Colorectal neoplasia recurred earlier and was significantly more frequent in patients with CAG (22,573/100,000 person-years) compared to patients without CAG (11,089/100,000 person-years; P=0.029, log-rank test). Patients with more extensive CAG showed a higher risk of recurrence. These results demonstrated a significant elevation of the risk of recurrent colorectal neoplasia with the establishment and progression of CAG, indicating the involvement of H. pylori infection in the development of colorectal neoplasia. The two serum tests were useful clinical markers for noninvasively evaluating the risk of each individual for recurrent colorectal neoplasia subsequent to endoscopic resection.

Aim: Although frequent vomiting reflexes during esophagogastroduodenoscopy (EGD) causes suffering in patients, very few studies have investigated the characteristics of subjects who frequently develop vomiting reflexes. This study examined the incidence of the vomiting reflex and related factors, especially upper gastrointestinal symptoms, among individuals undergoing transoral EGD. Methods: Subjects included 488 consecutive adults (mean age, 56.1 ± 8.9 years) who underwent transoral EGD for gastric cancer screening between February 2010 and March 2011. All procedures were performed by an endoscopist with 15 years of experience. Based on a questionnaire survey using the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG), symptoms (dyspepsia and acid reflux symptoms) and the number of vomiting reflexes during EGD were recorded. Results: Of the 488 subjects, 271 (56%) developed vomiting reflexes (mean, 4.2 times). This reflex-positive group was younger (54.3 ± 9.5 years) than the reflex-negative group (58.3 ± 7.7 years, P

Epigenomic damage induced by Helicobacter pylori infection is accumulated in gastric mucosae before the development of malignancy. In individuals without current H. pylori infection, DNA methylation levels of specific CpG islands (CGIs) are associated with gastric cancer risk. Because risk estimation in individuals with past infection is clinically important, we here aimed to identify the risk markers that reflect epigenomic damage induced by H. pylori infection, and that are informative in these individuals. Gastric mucosae were obtained from 55 gastric cancer patients (GC-Pt) (21 with current infection and 34 with past infection) and 55 healthy volunteers (HV) (7 never-infected, 21 with current infection, and 27 with past infection). Hypermethylated CGIs were searched for by methylated DNA immunoprecipitation-CGI microarray, and methylation levels were analyzed by quantitative methylation-specific polymerase chain reaction (PCR). By microarray analysis of a pool of three samples from GC-Pt with past infection and another pool of samples from HV with past infection, 15 hypermethylated CGIs in the former pool were isolated. Seven of them had significantly higher methylation levels in GC-Pt with past infection (n = 10) than in HV with past infection (n = 10) (P

A 67-year-old woman with compensated cirrhosis type B associated with hepatocellular carcinoma was started on sorafenib for multiple pulmonary metastases. The patient developed right upper quadrant pain and high fever 4 weeks later. Imaging revealed marked enlargement of the gallbladder without calculi. Following percutaneous transhepatic gallbladder aspiration, her symptoms resolved, but the gallbladder remained enlarged. Laparoscopic cholecystectomy was performed. Arteriolar occlusion with intimal thickening in the muscular layer of the gallbladder was seen sporadically. The fact that this patient had no risk factors for acalculous cholecystitis suggested that the cholecystitis resulted from ischemia, implying a strong causal relationship with sorafenib.

Aim: Continuation of pegylated interferon (PEG-IFN) plus ribavirin at the recommended dose is difficult in elderly patients and/or patients with cytopenia or complications. Whether the therapeutic efficacy of low-dose PEG-IFN plus ribavirin therapy could be predicted based on virological response within 2 weeks of therapy initiation was evaluated. Methods: A total of 106 patients with a high viral load of genotype-1b hepatitis C virus (HCV) underwent low-dose PEG-IFN plus ribavirin therapy. PEG-IFN alpha 2b (0.75 µg/kg per week) and ribavirin (600–800 mg/day) were administered for 48 weeks. Results: Sustained virological response (SVR) was achieved in 37%, and treatment was discontinued in 9%. On univariate analysis of SVR-contributing factors, significant differences were noted in the white blood cell count, platelet count, fibrosis markers, and viral reduction within 2 weeks from therapy initiation. On multivariate analysis, the platelet count and the reduction in the HCV core antigen level at week 2 were independent factors. The positive predictive value (PPV) and the negative predictive value (NPV) for SVR based on a 1-log or greater HCV-RNA level reduction at week 2 were 65% and 90%, respectively, and those based on HCV core antigen level at week 2 were 64% and 97%, respectively. PPV and NPV based on a 2-log or greater reduction of the RNA level were 86% and 67%, respectively, and those based on the core antigen level were 93% and 69%, respectively. Conclusion: Evaluation of viral reduction at week 2 after therapy initiation is useful for predicting SVR to low-dose PEG-IFN plus ribavirin therapy.

AIM Evaluation of malignant potential is important to determine the treatment strategy for small hepatocellular carcinoma (HCC). The aim of the present study was to establish a method of assessing the malignant potential of small hypervascular HCC using B-mode ultrasonography. METHODS One hundred and thirteen arterial hypervascular HCC nodules under 3 cm diagnosed by biopsy or surgical resection (20.5 ± 6.3 mm) were classified into two groups ultrasonographically: type 1 with (n = 27) and type 2 without (n = 86) a halo. Type 2 was categorized into three subgroups: type 2a, homogenous hyperechoic (n = 9); type 2b, hypoechoic with a smooth margin (n = 35); and type 2c, hypoechoic with an irregular or unclear margin (n = 42). RESULTS The mean diameter of type 2a nodules was significantly smaller than that of other HCC types (P

Background Both double-balloon enteroscopy (DBE) and video capsule endoscopy (VCE) have similar diagnostic yields for patients with overt obscure gastrointestinal bleeding (OGIB). However, the choice of initial modality is still controversial. The aim of this study was to show the clinical outcome of the strategy of initial VCE, followed by DBE. Methods Eighty-nine consecutive overt OGIB patients who had undergone VCE as the initial examination were analyzed. The interpreters of VCE evaluated the necessity of performing DBE, and the antegrade or retrograde route was chosen, depending on the transit time of the capsule. Results Thirty-seven patients (42 %) underwent DBE depending on the findings of VCE. Of these, bleeding sites in the small bowel were identified in 29 patients with the initially selected route (21 antegrade and 8 retrograde). The remaining 8 later underwent DBE by the other route, but 7 had no bleeding lesion, which was confirmed by second-look VCE. One remaining patient had a jejunal varix found by VCE, but DBE from either side could not reach the lesion. The sensitivity and negative predictive value of VCE were 100 %, both for the presence of small bowel lesions and the requirement of hemostasis in the small bowel; this indicated that VCE never misses relevant findings in the small bowel, and that negative VCE findings correspond to the lack of necessity for further examination. Conclusions VCE as the initial examination can efficiently identify overt OGIB patients who require DBE. The strategy of initial VCE for overt OGIB appears to be reasonable.

To investigate the effects of Japanese apricot (JA) consumption on gastroesophageal reflux disease (GERD)-related symptoms.Participants included individuals living in Minabe-cho, a well-known JA-growing region, who received specific medical check-ups by the local community health service in 2010. GERD-related symptoms were examined in 1303 Japanese individuals using a validated questionnaire, the Frequency Scale for Symptoms of GERD (FSSG), which consists of 7 questions associated with acid reflux symptoms and 5 questions asking about gastrointestinal dysmotility symptoms. Each question was answered using a 4-point scale, with higher scores indicating more severe GERD-related symptoms. Subjects were divided into two groups according to their intake of dried and pickled JA: daily intake (≥ 1 JA daily) (392 subjects) and none or occasional intake (1 JA daily) (911 subjects). FSSG scores were compared between subjects who consumed JA daily and those who did not. Next, subjects were stratified by age, gender and Helicobacter pylori (H. pylori) status for subanalyses.Those who ate JA daily were significantly older than those who did not (60.6 ± 10.5 years vs 56.0 ± 11.0 years, P0.001). Total FSSG scores were significantly lower in subjects with daily JA intake than in those with none or only occasional intake (2.13 ± 3.14 vs 2.70 ± 3.82, P = 0.005). In particular, subjects who consumed JA daily showed significantly improved FSSG dysmotility scores compared with subjects who did not (1.05 ± 1.58 vs 1.46 ± 2.11, P0.001). In contrast, the FSSG reflux score did not differ between subjects with and without daily intake of JA (1.08 ± 1.90 vs 1.24 ± 2.11, P = 0.177). Subanalysis indicated that improvement in dysmotility by JA intake was specifically observed in non-elderly (1.24 ± 1.68 vs 1.62 ± 2.22, P = 0.005) and H. pylori-negative subjects (0.99 ± 1.58 vs 1.57 ± 2.06, P0.001). GERD patients (total FSSG score ≥ 8) were less frequently observed among subjects with daily intake of JA as compared to those without daily intake of JA (6.1% vs 9.7%, P = 0.040).Daily JA intake may improve digestive dysmotility symptoms, resulting in relief of GERD symptoms. The effect is more obvious in non-elderly and H. pylori-negative subjects.

Background and Aim Esophageal varices are usually treated with endoscopic injection sclerotherapy (EIS) or endoscopic band ligation (EBL). However, frequent recurrences of varices after those procedures have been problematic. Argon plasma coagulation (APC) after EIS may be effective for preventing varix recurrence and, in recent years, we have routinely carried out APC after EIS. The aim of the present study was to verify the effectiveness of APC for preventing recurrence of varices after EIS. Methods A case–control study was carried out using a historical control cohort in a single center. The varix recurrence rate in 62 patients (34 men and 28 women, median age; 69 years) who underwent APC after EIS for hemorrhagic or risky esophageal varices (APC group) was compared with that of control patients who did not undergo APC after EIS (control group). Age-, sex-, and liver function-matched two control subjects were selected for one case subject (control group). Recurrence of varices was defined as rupture of varices or reappearance of risky varices. Results The 1-year and 2-year recurrence rates of the APC group were 9.7% and 11.3%, respectively. In contrast, the rates of the control group were 29.0% and 34.7%, respectively. Kaplan–Meier curves showed a significantly lower recurrence rate in the APC group (P = 0.013, log–rank test). No APC-related severe adverse events were observed. Conclusion APC after EIS was safe and could significantly prevent recurrence of esophageal varices. Therefore, the addition of APC should be routinely carried out after EIS.

A previous multicenter prospective randomized study from Japan showed that Helicobacter pylori eradication reduced the development of metachronous gastric cancer (MGC) after endoscopic resection for early gastric cancer. MGC risk, however, is not eliminated; yet few studies have evaluated its long-term incidence and risk factors. In this study, we investigated the incidence of and risk factors for MGC in patients who underwent endoscopic resection for early gastric cancer with successful H. pylori eradication.A total of 594 patients who underwent endoscopic resection for early gastric cancer and successful H. pylori eradication at three institutions (National Cancer Center Hospital, University of Tokyo Hospital, and Wakayama Medical University Hospital) were analyzed retrospectively. Annual endoscopic surveillance was performed after initial endoscopic resection. MGC was defined as a gastric cancer newly detected at least 1 year after successful H. pylori eradication.Ninety-four MGCs were detected in 79 patients during the 4.5-year median follow-up period. Kaplan-Meier analysis showed the cumulative incidence of MGC 5 years after successful H. pylori eradication was 15.0 %; the incidence of MGC calculated by use of the person-year method was 29.9 cases per 1000 person-years. Multivariate analysis using the Cox proportional hazards model revealed that male sex, severe gastric mucosal atrophy, and multiple gastric cancers before successful H. pylori eradication were independent risk factors for MGC. Eleven percent of MGCs (10 of 94) were detected more than 5 years after successful H. pylori eradication.Surveillance endoscopy for MGC in patients who have undergone endoscopic resection for early gastric cancer should be performed even after successful H. pylori eradication.

We report a case of a 16-year-old male who suffered from Crohn's disease (CD) with esophageal involvement, showing remarkable improvement with granulocyte/monocyte adsorption (GMA). The patient had been diagnosed as ileocolic CD and was treated with 5-aminosalicylate. He was admitted to our hospital with symptoms of fever, diarrhea, and odynophagia. Endoscopic examinations revealed that the exacerbation of ileocolic ulcers, and advent of ulcers in esophagus. Because of the patient's refusal to receive corticosteroids, immunomodulators, or biologics, he underwent GMA twice a week. After 10 sessions of GMA, he entered remission with significant decrease in clinical activity. In addition, endoscopic examinations showed remarkable improvement of ileocolic ulcers and disappearance of esophageal lesions. No adverse events were observed. GMA could be effective for manifestations of CD in gastrointestinal tract other than ileum or colon. J. Clin. Apheresis, 2011. © 2011 Wiley-Liss, Inc.

The aim of the present study was to predict sustained virological response (SVR) to telaprevir with pegylated interferon (PEG-IFN) and ribavirin using viral response within 2 weeks after therapy initiation. Thirty-six patients with genotype 1 hepatitis C virus (HCV) and high viral load were treated by telaprevir-based triple therapy. SVR was achieved in 72% (26/36) of patients. Significant differences between the SVR group and non-SVR group were noted regarding response to prior PEG-IFN plus ribavirin, interleukin (IL)28B polymorphism, amino acid substitution at core 70, cirrhosis, hyaluronic acid level, and HCV-RNA reduction within 2 weeks. Setting 4.56 logIU/mL as the cut-off value for HCV-RNA reduction at 2 weeks, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for predicting SVR were 77%, 86%, 95%, 50%, and 79%, respectively, and for neither the IL28B minor allele nor core 70 mutant were 80%, 71%, 91%, 50%, and 78%, respectively. In conclusion, evaluation of viral reduction at 2 weeks or the combination of IL28B polymorphism and amino acid substitution at core 70 are useful for predicting SVR to telaprevir with PEG-IFN and ribavirin therapy.

Background Pegylated interferon (PEG-IFN) plus ribavirin therapy is still recommended for elderly and/or cirrhotic patients. This study examined whether sustained virological response (SVR) to low-dose PEG-IFN-α2a plus ribavirin therapy for elderly and/or cirrhotic patients could be predicted based on viral reduction within 2 weeks after therapy initiation or interleukin IL-(28B) polymorphism and viral mutations. Methods Participants comprised 115 elderly (≥65 years) and/or cirrhotic patients with genotype-1b and high viral load. Reduced doses of PEG-IFN-α2a (90 μg/kg/week) and ribavirin (400-800 mg/day) were administered for 48-72 weeks based on virological response of each patient. Results SVR was achieved in 34% (39/115), and treatment was discontinued in 15% (17/115). Univariate analysis identified age, α-fetoprotein, fibrosis marker, interferon sensitivity-determining region (ISDR), IL-28B polymorphism and level of viral reduction within 2 weeks as factors contributing significantly to SVR. However, no significant differences were noted in core amino acid substitutions. Multivariate analysis identified age, hyaluronic acid, ISDR and viral reduction as factors independently associated with SVR. Positive predictive value (PPV) and negative predictive value (NPV) of SVR based on the level of viral reduction at 2 weeks (cutoff level, 1.7 log IU/ml) were 83% and 84%, respectively. The PPV of SVR based on IL-28B major and ISDR mutant was 70%, and the NPV of SVR based on IL-28B minor and wild-type ISDR was 89%. Conclusions Evaluations of viral reduction at 2 weeks or both IL-28B and ISDR are useful to predict SVR to low-dose PEG-IFN-α2a plus ribavirin therapy for elderly and/ or cirrhotic patients.

Background: Some patients with common bile duct (CBD) stones develop cholangitis requiring drainage, while others do not. The aims of this study were to elucidate the clinical differences among patients with CBD stones who required and did not require emergent drainage, and to identify risk factors for the development of cholangitis requiring emergent drainage in patients with silent CBD stones. Methods: Clinical characteristics of consecutive patients with CBD stones who underwent endoscopic removal of stones or biliary drainage were analyzed retrospectively. Results: Of 101 patients analyzed, 32 had moderate or severe cholangitis as the indication for emergent drainage, and the remaining 69 did not. Patients who required emergent drainage were more likely to have gallstones (P = 0.029), dilated CBD ( > 10 mm) (P = 0.004) and larger CBD stones (P = 0.019). By multivariate analysis, CBD dilation was the only significant differentiating clinical characteristic of the patients who required emergent drainage (OR = 3.75, 95% CI: 1.41-9.96, P = 0.008). Of the 35 patients with silent bile duct stones, eight required emergent endoscopic drainage during the waiting period. CBD dilation was also the only significant risk factor for the development of moderate or severe cholangitis among patients with silent bile duct stones (OR = 10.18, 95% CI: 1.09-94.73, P = 0.042). Conclusions: Dilated CBD ( > 10 mm) was the only risk factor identified for requirement of early drainage in patients with CBD stones. Those who have silent CBD stones with CBD dilatation should undergo early drainage. Gastroenterology Research. 2013;6(6):219-226 doi: http://dx.doi.org/10.4021/gr587w

Chronic inflammation triggered by Helicobacter pylori causes altered DNA methylation in stomach mucosae, which is deeply involved in gastric carcinogenesis. This study aimed to elucidate the correlation between altered mucosal DNA methylation levels and activity of H. pylori-related gastritis, because inflammatory activity shows particular correlations with the development of diffuse-type cancer.Methylation levels in stomach mucosae of 78 healthy volunteers were determined by real-time methylation-specific PCR or bisulfite pyrosequencing. Examined loci were the promoter CpG islands of six genes (FLNc, HAND1, THBD, p41ARC, HRASLS, and LOX) and the CpG sites of non-coding repetitive elements (Alu and Satα) that are reportedly altered by H. pylori infection. Activity of H. pylori-related gastritis was evaluated using two serum markers: H. pylori antibody titer and pepsinogen II.Methylation levels of the six CpG islands were consistently increased, and those of the two repetitive elements were consistently decreased in a stepwise manner with the activity of gastric inflammation as represented by serum marker levels. Each serum marker level was well correlated with the overall DNA methylation status of stomach mucosa, and these two serologic markers were additive in the detection of the mucosa with severely altered DNA methylation.Alteration in mucosal DNA methylation level was closely correlated with activity of H. pylori-related gastritis as evaluated by serum markers. The observed correlation between altered DNA methylation levels and activity of H. pylori-related gastritis appears to be one of the relevant molecular mechanisms underlying the development of diffuse-type cancer.

This study aimed to elucidate groups at high risk of developing cancer among patients with serologically identified Helicobacter pylori infection and nonatrophic stomach. Annual endoscopy was performed for a mean of 5.4 years in 496 asymptomatic middle-aged men who were H. pylori antibody-positive and pepsinogen (PG) test-negative. Subjects were stratified according to the activity of H. pylori-associated gastritis measured by serum levels of PG and H. pylori antibody, and/or by endoscopic findings of rugal hyperplastic gastritis (RHG), and cancer development was investigated. During the study period, seven cases of cancer developed in the cohort (incidence rate, 261/100,000 person-years), with 85.7% developing in the group showing a PGI/II ratio ≤ 3.0, reflecting active inflammation-based high PGII levels. Cancer incidence was significantly higher in this group (750/100,000 person-years) than in groups with less active gastritis. Furthermore, cancer incidence for this group was significantly higher in the subgroup with high H. pylori antibody titers than in the low-titer subgroup. Meanwhile, endoscopic findings revealed that 11.7% of subjects showed RHG reflecting localized highly active inflammation, and cancer risk was significantly higher in patients with RHG than in patients without. Combining the two serum tests and endoscopic examination for RHG allowed identification of subjects with more active gastritis and higher cancer risk. No cancer development was observed in these high-risk subjects after H. pylori eradication. Subjects with highly active gastritis identified by the two serological tests and endoscopic RHG constitute a group at high risk of cancer development with H. pylori-infected nonatrophic stomach.

Helicobacter pylori (HP) is recognized as a major pathogenic factor for persistent inflammation in the human stomach (Dooley et al., 1989; Marshall & Warren, 1984). In 1994, the International Agency for Research on Cancer (IARC) classified HP infection as a definite class I carcinogen (International Agency for Research on Cancer (IARC), 1994). HP triggers chronic inflammation of the infected stomach mucosa and is considered a major risk factor for gastric cancer (GC) and associated precursor lesions. Long-lasting inflammation in the stomach mucosa leads to a cascade of molecular and morphological changes, representing the gastritis-atrophymetaplasia-dysplasia-cancer sequence (Correa, 1992). The HP infection rate is higher in Japan than in Western countries, with nearly all cases of GC occurring in subjects with underlying HP-related chronic gastritis. HP infection is widely accepted as a major risk factor for the development of GC and its precursor lesions, based on extensive evidence derived from many studies (Blaser et al., 1995; EUROGAST Study Group, 1993; Forman et al., 1991; Hirayama et al., 1999; Honda et al., 1998; Huang et al., 1998; Nomura et al., 1991; Parsonnet et al., 1991; Shimizu et al., 1999; Sipponen et al., 1992; Sugiyama et al., 1998; Talley et al., 1991; Tokieda et al., 1999; Uemura et al., 2001; Watanabe et al., 1998; Zheng et al., 2004). However, in countries such as Japan, where the HP infection rate is high, prediction of GC risk based solely on the presence or absence of HP infection does not offer sufficient specificity. Elucidation of groups at high risk based on the natural history of GC is clearly necessary. The identification of useful markers of GC risk is thus hoped for. Evaluating HPrelated chronic gastritis and determining which subjects are at high risk for developing GC is very important, and would likely increase the efficacy of GC screening by endoscopic or other examinations (Enomoto et al., 2010a; Mukoubayashi et al., 2007; Ohata et al., 2005), and strategic approaches to metachronous multiple GC after endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) performed as minimally invasive treatment for early GC (Gotoda, 2007; Kakushima & Fujishiro, 2008; Nakajima et al., 2006). In addition, in terms of GC prevention, it has become clear that HP-related chronic gastritis cannot be ignored as an origin of carcinogenesis.

AIM: To evaluate the association of Helicobacter pylori (H.pylori)-related chronic gastritis stage with upper gastrointestinal symptoms and gastroesophageal reflux disease (GERD). METHODS: Subjects underwent upper gastrointestinal endoscopy, a questionnaire using a frequency scale for symptoms of GERD (FSSG), and measurements of serum H.pylori-antibody and pepsinogen (PG) levels. They were classified into the following 4 groups in terms of H.pylori-related chronic gastritis stage: Group A (n = 219), H.pylori(-)PG(-); Group B (n = 310), H.pylori(+)PG(-); Group C (n = 279), H.pylori(+)PG(+); and Group D (n = 17), H.pylori(-)PG(+). RESULTS: Reflux esophagitis occurred in 30.6% of Group A, 14.5% of Group B, 6.8% of Group C, and 0% of Group D (P < 0.001). Scores for acid reflux symptoms decreased significantly with chronic gastritis stage (from Group A to D) (P < 0.05), while scores for dysmotility symptoms did not differ significantly. The prevalence of non-erosive reflux disease (NERD) did not differ among groups. However, in subjects with GERD, the prevalence of NERD tended to increase with chronic gastritis stage (P = 0.081). CONCLUSION: Acid reflux symptoms and the prevalence of reflux esophagitis can be assessed by measuring both serum H.pylori-antibody and PG levels.