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Background Nonalcoholic steatohepatitis (NASH) is diagnosed with histopathologic testing, but noninvasive surrogate markers are desirable for screening patients who are at high risk of NASH. Purpose To investigate the diagnostic performance of dispersion slope, attenuation coefficient, and shear-wave speed measurements obtained using two-dimensional (2D) shear-wave elastography (SWE) in assessing inflammation, steatosis, and fibrosis and in the noninvasive diagnosis of NASH in patients suspected of having nonalcoholic fatty liver disease (NAFLD). Materials and Methods This prospective study collected data from 120 consecutive adults who underwent liver biopsy for suspected NAFLD and were enrolled between April 2017 and March 2019. Three US parameters (dispersion slope [(m/sec)/kHz], attenuation coefficient [dB/cm/MHz], and shear-wave speed [in meters per second]) were measured using a 2D SWE system immediately before biopsy. The biopsy specimens were scored by one expert pathologist according to the Nonalcoholic Steatohepatitis Clinical Research Network criteria (119 participants underwent a histologic examination). Diagnostic performance was assessed using the area under the receiver operating characteristic curve (AUC) for the categories of inflammation, steatosis, and fibrosis. Results One hundred eleven adults (mean age, 53 years ± 18 [standard deviation]; 57 men) underwent a US examination. Dispersion slope enabled the identification of lobular inflammation, with an AUC of 0.95 (95% confidence interval [CI]: 0.91, 0.10) for an inflammation grade greater than or equal to A1 (mild), 0.81 (95% CI: 0.72, 0.89) for an inflammation grade greater than or equal to A2 (moderate), and 0.85 (95% CI: 0.74, 0.97) for an inflammation grade equal to A3 (marked). Attenuation coefficient enabled the identification of steatosis, with an AUC of 0.88 (95% CI: 0.80, 0.97) for steatosis grade greater than or equal to S1 (mild), 0.86 (95% CI: 0.79, 0.93) for steatosis grade greater than or equal to S2 (moderate), and 0.79 (95% CI: 0.68, 0.89) for steatosis grade equal to S3 (severe). Shear-wave speed enabled the identification of fibrosis, with an AUC of 0.79 (95% CI: 0.69, 0.88) for fibrosis stage greater than or equal to F1 (portal fibrosis), 0.88 (95% CI: 0.82, 0.94) for fibrosis stage greater than or equal to F2 (periportal fibrosis), 0.90 (95% CI: 0.84, 0.96) for fibrosis stage greater than or equal to F3 (septal fibrosis), and 0.95 (95% CI: 0.91, 0.99) for fibrosis stage equal to F4 (cirrhosis). The combination of dispersion slope, attenuation coefficient, and shear-wave speed showed an AUC of 0.81 (95% CI: 0.71, 0.91) for the diagnosis of NASH. Conclusion Dispersion slope, attenuation coefficient, and shear-wave speed were found to be useful for assessing lobular inflammation, steatosis, and fibrosis, respectively, in participants with biopsy-proven nonalcoholic fatty liver disease. © RSNA, 2020

The present, updated document describes the fourth iteration of recommendations for the hepatic use of contrast enhanced ultrasound (CEUS), first initiated in 2004 by the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB). The previous updated editions of the guidelines reflected changes in the available contrast agents and updated the guidelines not only for hepatic but also for non-hepatic applications.The 2012 guideline requires updating as previously the differences of the contrast agents were not precisely described and the differences in contrast phases as well as handling were not clearly indicated. In addition, more evidence has been published for all contrast agents. The update also reflects the most recent developments in contrast agents, including the United States Food and Drug Administration (FDA) approval as well as the extensive Asian experience, to produce a truly international perspective.These guidelines and recommendations provide general advice on the use of ultrasound contrast agents (UCA) and are intended to create standard protocols for the use and administration of UCA in liver applications on an international basis to improve the management of patients.

Background Nonalcoholic fatty liver disease (NAFLD) is common in the general population but identifying patients with high-risk nonalcoholic steatohepatitis (NASH) who are candidates for pharmacologic therapy remains a challenge. Purpose To develop a score to identify patients with high-risk NASH, defined as NASH with an NAFLD activity score (NAS) of 4 or greater and clinically significant fibrosis (stage 2 [F2] or higher). Materials and Methods This was a cross-sectional secondary analysis of data prospectively collected between April 2017 and March 2019 for a group of patients with NAFLD in Japan (Japan NAFLD, the derivation data set) with contemporaneous two-dimensional shear-wave elastography and biopsy-proven NAFLD (age range, 20-89 years). Three US markers (liver stiffness [LS, measured in kilopascals], attenuation coefficient [AC, measured in decibels per centimeter per megahertz], and dispersion slope [DS, measured in meters per second per kilohertz]) were determined, together with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and the AST-to-ALT ratio. The best-fit multivariate logistic regression model for identifying patients with high-risk NASH was determined. Diagnostic performance was assessed by using the area under the receiver operating characteristic curve (AUC). The findings were validated in an independent data set (Korea NAFLD; age range, 20-78 years). Results The Japan NAFLD data set included 111 patients (mean age, 53 years ± 18 [standard deviation]; 57 men), 84 (76%) with NASH. The Korea NAFLD data set included 102 patients (mean age, 48 years ± 18; 43 men), 55 (36%) with NASH. The most predictive model (LAD NASH score) combined LS, AC, and DS. Performance was satisfactory in both the derivation sample (AUC, 0.86; 95% CI: 0.79, 0.93) and the validation sample (AUC, 0.88; 95% CI: 0.80, 0.95). The LAD NASH score showed a positive predictive value of 86.5% and a negative predictive value of 87.5% for high-risk NASH in the derivation sample. Conclusion A score combining three US markers may be useful for noninvasive identification of patients with high-risk nonalcoholic steatohepatitis for inclusion in clinical trials and pharmacologic therapy. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Lockhart in this issue.

New ultrasound methods that can be used to quantitatively assess liver fat content have recently been developed. These quantitative ultrasound (QUS) methods are based on the analysis of radiofrequency echoes detected by the transducer, allowing calculation of parameters for quantifying the fat in the liver. In this position paper, after a section dedicated to the importance of quantifying liver steatosis in patients with non-alcoholic fatty liver disease and another section dedicated to the assessment of liver fat with magnetic resonance, the current clinical studies performed using QUS are summarized. These new methods include spectral-based techniques and techniques based on envelope statistics. The spectral-based techniques that have been used in clinical studies are those estimating the attenuation coefficient and those estimating the backscatter coefficient. Clinical studies that have used tools based on the envelope statistics of the backscattered ultrasound are those performed by using the acoustic structure quantification or other parameters derived from it, such as the normalized local variance, and that performed by estimating the speed of sound. Experts' opinions are reported.

To investigate the usefulness of shear-wave speed and dispersion slope measurements obtained, using an ultrasound elastography system in rat livers with various degrees of necroinflammation and fibrosis. A total of 25 male Sprague Dawley rats were randomly divided into 5 groups of 5 rats each: G0 (control), G1 (CCl4 injected twice a week for 1 wk), G2 (CCl4 injected four times a wk for 1 wk), G3 (CCl4 injected twice a wk for 6 wk) and G4 (CCl4 injected twice a wk for 10 wk). The shear-wave speed (m/s) and the dispersion slope ([m/s]/kHz) were measured. Histologic features (inflammation, necrosis and fibrosis) were used as reference standards. In multivariable analysis with histologic features as independent variables, the fibrosis grade was significantly related to shear-wave speed (p < 0.05) and the necrosis grade was significantly related to dispersion slope (p < 0.05). Dispersion slope is more useful than shear-wave speed for predicting the degree of necroinflammation.

Aim The efficacy and safety of rifaximin in the treatment of hepatic encephalopathy (HE) are widely known, but they have not been confirmed in Japanese patients with HE. Thus, two prospective, randomized studies (a phase II/III study and a phase III study) were carried out. Methods Subjects with grade I or II HE and hyperammonemia were enrolled. The phase II/III study, which was a randomized, evaluator-blinded, active-comparator, parallel-group study, was undertaken at 37 institutions in Japan. Treatment periods were 14 days. Eligible patients were randomized to the rifaximin group (1200 mg/day) or the lactitol group (18-36 g/day). The phase III study was carried out in the same patients previously enrolled in the phase II/III study, and they were all treated with rifaximin (1200 mg/day) for 10 weeks. Results In the phase II/III study, 172 patients were enrolled. Blood ammonia (B-NH3 ) concentration was significantly improved in the rifaximin group, but the difference between the two groups was not significant. The portal systemic encephalopathy index (PSE index), including HE grade, was significantly improved in both groups. In the phase III study, 87.3% of enrolled patients completed the treatment. The improved B-NH3 concentration and PSE index were well maintained from the phase II/III study during the treatment period of the phase III study. Adverse drug reactions (ADRs) were seen in 13.4% of patients who received rifaximin, but there were no severe ADRs leading to death. Conclusion The efficacy of rifaximin is sufficient and treatment is well tolerated in Japanese patients with HE and hyperammonemia.

Staphylococcus lugdunensis produces a tannase with activity that may be associated with the onset of colon carcinoma. To clarify this feature of colon carcinoma-associated S. lugdunensis, we obtained isolates from healthy subjects and patients with colon adenomas and carcinomas and analyzed their genetic backgrounds. In total, 40 S. lugdunensis isolates from 288 rectal swabs collected between 2002 and 2008 were used. These isolates were classified into four groups according to the diseases of the subjects: healthy (n = 13), colon carcinoma (n = 13), colon adenoma (n = 9), and unknown (n = 5). The isolates were also classified by pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing. In addition, an antimicrobial susceptibility test and detection of resistance genes were performed for all isolates. According to the PFGE analysis, 40 isolates could be classified into five groups. Among the groups, carcinoma and colon adenoma patients were significantly more frequently (40.9%) classified into group D (p

Idiopathic portal hypertension (IPH), causing aberrant portal hemodynamics, is a disease with an as yet unidentified cause and no treatment has been established so far. The Japanese research group on IPH in Japan was set up in 1975 by the Ministry of Health, Labour and Welfare, furthermore extra-hepatic portal obstruction (EHO) and Budd-Chiari syndrome (BCS) have been added to the research subjects and further work has continued. The aims of the research group are to accurately evaluate the current status of the three diseases in Japan, elucidate the disease aetiology and pathogenesis, and develop new treatments. Due to the long-term efforts of the Japanese research group, aberrant portal hemodynamics has been investigated to date in a variety of aspects, from epidemiological and pathological studies to molecular biology analysis. As a result, it has been shown that there are abnormal genes in the liver, specific for IPH. In addition, pathological findings of BCS were internationally compared and the difference in findings between Japan and Western countries has been clarified. Furthermore, it was found that complication rates of hepatocellular carcinoma (HCC) in BCS were higher in Japan. Based on the research, "Diagnosis and treatment of aberrant portal hemodynamics (2001)", including diagnostic criteria for aberrant portal hemodynamics, was published in 2001. In 2013, it was revised to "Diagnosis and treatment guidelines for aberrant portal hemodynamics (2013)" after the incorporation of diagnosis and treatment in accordance with its current status. This article is protected by copyright. All rights reserved.

The present, updated document describes the fourth iteration of recommendations for the hepatic use of contrast-enhanced ultrasound, first initiated in 2004 by the European Federation of Societies for Ultrasound in Medicine and Biology. The previous updated editions of the guidelines reflected changes in the available contrast agents and updated the guidelines not only for hepatic but also for non-hepatic applications. The 2012 guideline requires updating as, previously, the differences in the contrast agents were not precisely described and the differences in contrast phases as well as handling were not clearly indicated. In addition, more evidence has been published for all contrast agents. The update also reflects the most recent developments in contrast agents, including U.S. Food and Drug Administration approval and the extensive Asian experience, to produce a truly international perspective. These guidelines and recommendations provide general advice on the use of ultrasound contrast agents (UCAs) and are intended to create standard protocols for the use and administration of UCAs in liver applications on an international basis to improve the management of patients.

Shear wave (SW) dispersion imaging is a newly developed imaging technology for assessing the dispersion slope of SWs, which is related to tissue viscosity in diffuse liver disease. Our preclinical and preliminary clinical studies have shown that SW speed is more useful than dispersion slope for predicting the degree of fibrosis and that dispersion slope is more useful than SW speed for predicting the degree of necroinflammation. Thus, dispersion slope, which reflects viscosity, may provide additional pathophysiological insight into diffuse liver disease.

Esophageal varices (EV) are often complicated in cirrhotic patients, and bleeding from EV induces high mortality rate. Endoscopic screening for EV and hepatic venous pressure gradient (HVPG) is recommended for all cirrhotic patients; however, these are invasive procedures. Liver stiffness (LS) measurement (LSM) is a noninvasive technique using elastographic method by ultrasonography or magnetic resonance imaging and is a very useful examination method to assess significant fibrosis and to rule out liver cirrhosis (LC). LS values are thought to increase gradually alongside the increment of HVPG in line with the progresses of LC state. However, regarding the presence of EV, spleen stiffness (SS) is a more accurate predictor with high area under receiver operating characteristic curve than LS. The measurement of SS values can reveal cirrhotic patients with high-risk EV. Moreover, measuring the spleen/liver stiffness ratio by elastography made it possible to noninvasively, specifically, and accurately diagnose idiopathic portal hypertension or extrahepatic portal vein obstruction.

Background and Aims There are currently no prospective, controlled trials of needle puncture speed in EUS-guided FNA (EUS-FNA). In this study, we prospectively evaluated the accuracy of histological diagnosis and the tissue acquisition rate of EUS-FNA by using the door-knocking method (DKM) with a standard 22-gauge needle. Methods From November 2013 to August 2014, 82 patients who had solid pancreatic masses underwent EUS-FNA in which the conventional method (CM) and DKM with 2 respective passes in turn were used. The primary outcomes of this study were the accuracy of histological diagnosis and the rates of tissue acquisition in 2 FNA procedures by using these 2 methods. Results Although the successful tissue acquisition rate for histology was not significantly different with the DKM and CM (91.5% vs 89.0%, P = .37), the high cellularity tissue acquisition rate for histology with the DKM was significantly superior to that with the CM (54.9% vs 41.5%, P = .03). However, adequate quality rate and accuracy were not different in the DKM and CM (78.0% vs 80.5%, P = .42 and 76.8% vs 78.0%, P = .50, respectively). In the transgastric puncture group, although the adequate quality rate and accuracy were similar in the DKM and CM (84.1% vs 79.4%, P = .30 and 84.1% vs 76.2%, P = .11, respectively), the tissue acquisition rate tended to be higher with the DKM than the CM (93.7% vs 85.7%, P = .06). Moreover, the high cellularity tissue acquisition rate was significantly better with the DKM than the CM (63.5% vs 39.7%, P = .002). On the other hand, in the transduodenal puncture group, although the tissue acquisition rate was similar with the DKM and CM (84.2% vs 100%, P = .13), the adequate quality rate and accuracy were significantly lower with the DKM than with the CM (57.9% vs 84.2%, P = .03 and 52.6% vs 84.2%, P = .02, respectively). Conclusion EUS-FNA by using a 22-gauge needle with the DKM did not improve the accuracy of histological diagnosis, but enabled acquisition of a larger amount of tissue specimen by using transgastric puncture. (Trial Registration: http://www.umin.ac.jp/english/: UMIN000012127.)

Background and aims: In hemostasis for colonic diverticular bleeding, the incidence of recurrent bleeding is higher in deep colonic diverticulum than in shallow. We aimed to improve and evaluate barium impaction therapy using an enteroscopic overtube with balloon. Patients and method: We performed barium impaction therapy in three patients with a diagnosis of deep colonic diverticular bleeding. The tip of the overtube was inserted to reach the cecum using the conventional method. After deflating the colon, the enteroscope was removed. The balloon in the tube was inflated, followed by barium filling via the tube. Sufficient pressure was applied by ensuring no regurgitation into the small intestine side. The entire colon was continuously filled with barium in stages. Results: Post-treatment bleeding was controllable without adverse events in all three patients. Conclusion: This novel barium impaction therapy using an enteroscopic overtube with balloon was effectively performed without adverse events.

AIM Protein and energy malnutrition is a severe problem for patients with liver cirrhosis (LC) and fasting often induces starvation which is a vitally important outcome. Dietary restriction is essential for endoscopic injection sclerotherapy (EIS) in patients with risky esophageal varices, thereby creating the possible exacerbation of nutritional state and inducing liver dysfunction. Whether EIS induces nutritional deficiency in LC patients and the effects of branched-chain amino acid (BCAA)-enriched nutrient are prospectively investigated. METHODS A total of 61 LC patients were randomly divided into an EIS monotherapy group (non-BCAA group, n = 31) and an EIS combined with BCAA therapy group (n = 30). Platelet count, blood chemistry and somatometry values were prospectively measured at five time points. RESULTS The platelet counts before treatment were at the same level in both groups (P = 0.72). Three months after treatment, the counts decreased in the non-BCAA group; however, they increased in the BCAA group (P = 0.019). Body mass index, triceps skin fold thickness and arm muscle circumference significantly decreased in both groups. The BCAA and tyrosine ratio value increased only in the BCAA group (P

Background and Aims Although endoscopic submucosal dissection (ESD) is a significant advancement in therapeutic endoscopy, it is a complicated technique and requires considerable expertise. In this exploratory study, we evaluated the efficacy of a simple traction method that uses dental floss and a hemoclip (DFC) and was developed to overcome the technical difficulties of ESD. Methods In total, 238 early gastric cancers treated by ESD between May 2012 and December 2014 at Tokyo Medical University were retrospectively reviewed. Lesions treated by conventional ESD (n = 185) and by ESD with DFC (ESD-DFC) (n = 53) were compared. Multivariable analyses and propensity score matching were used to compensate for the differences in age, sex, resected specimen size, lesion location, lesion position, presence of ulceration, and operator level. The procedure time, rate of en bloc and complete resection, and rates of adverse events were evaluated between the 2 groups. Results Propensity score matching analysis created 43 matched pairs. Adjusted comparisons between ESD-DFC and conventional ESD showed similar treatment outcomes (en bloc resection rate: 97.7% vs 100%, P = .315; complete resection rate: 90.7% vs 95.3%, P = .397; perforation during ESD rate: 2.3% vs 2.3%, P = 1.000; post-ESD bleeding rate: 4.7% vs 4.7%, P = 1.000) but a significantly shorter procedure time for ESD-DFC (82.2 ± 79.5 minutes vs 118.2 ± 71.6 minutes, P = .002). Conclusion ESD-DFC facilitated rapid ESD with good visualization and traction while ensuring high curability and safety.

The aim of the present study was to investigate two methods of determining liver stiffness in rats with various degrees of non-alcoholic steatohepatitis induced by a methionine- and choline-deficient (MCD) diet by comparing each finding with reference to histopathological liver findings. Twenty male Wister rats were fed an MCD diet for up to 32 weeks, and four were fed a normal diet. Ultrasound-based shear wave elastography (SWE) and mechanical compression testing using an Instron Universal Testing machine were performed on each rat at designated time points. After each examination, liver histopathology was analyzed to evaluate the degrees of steatosis, inflammation, and fibrosis based on non-alcoholic fatty liver disease (NAFLD) activity score, and each finding was compared with reference to liver histopathologic findings. Median liver stiffness values measured using SWE showed a stepwise increase with increasing histological inflammation score (P = 0.002), hepatic fibrosis stage (P = 0.029), ballooning score (P = 0.012), and steatosis grade (P = 0.030). Median liver stiffness measured using an Instron machine showed a stepwise increase only with increasing histological fibrosis stage (P = 0.033). Degree of liver stiffness measured by SWE and the Instron machine differed. SWE reflected mainly inflammation, whereas Instron machine-derived values primarily reflected fibrosis. This is the main source of discrepancies between measurements made with these two modalities.

OBJECTIVE Elderly gastrointestinal bleeding (GIB) patients sometimes cannot be discharged home. In some cases, they die after hemostasis, even following appropriate treatment. This study investigates the clinical backgrounds and outcomes of elderly Japanese GIB patients. METHODS The medical records of 185 patients (123 men, 62 women; mean age 68.2 years; range 10-99 years) with GIB symptoms who underwent esophagogastroduodenoscopy or colonoscopy to detect or treat the source of GIB were retrospectively reviewed. We compared the outcomes between patients ≤70 (n=85) and >70 (n=100) years. The clinical backgrounds of the patients who died or changed hospitals to undergo rehabilitation or receive palliative care were evaluated, as were the association of four factors with these poor outcomes: GIB (re-bleeding or uncontrolled bleeding), endoscopic procedure-related complications, exacerbation of the pre-existing comorbidity, and any complications that were not directly related to GIB. RESULTS Of the patients ≤70 and >70 years of age, three (3.5%) and 17 (17.0%), respectively, were transferred to another hospital (p=0.003). One (1.2%) and five (5.0%), respectively, died (p=0.144). All three patients ≤70 years old that changed hospitals did so because their comorbidities became worse. The reasons for changing hospitals in the 17 patients >70 years of age included exacerbation of a pre-existing comorbidity (41.1%, 7/17), other complications (35.4%, 6/17), GIB itself (17.6%, 3/17), and endoscopic procedure-related complications (5.9%, 1/17). CONCLUSION Although non-elderly and elderly GIB patients had similar mortality rates, many more elderly patients could not be discharged home for various reasons.

Eradication of Helicobacter pylori causes improvement of gastric atrophy and intestinal metaplasia. Gastric acid secretion levels in corpus predominant gastritis increase after eradication. These changes can increase the risk of reflux esophagitis and low-dosage aspirin ulcers. Although eradication may reduce the overall risk of gastric cancer, a certain degree of risk remains, related to the extent of atrophy and intestinal metaplasia. Many post-eradication gastric cancers are the early depressed type, with low levels of epithelial atypia, and therefore can be difficult to distinguish endoscopically from benign erosion. Further research is required in this area.

A 58-year-old Japanese woman came to our institution because of leg edema and abdominal distention. She had developed acute pancreatitis 5 times in the past 3 years. Dilation of the bile duct and main pancreatic duct without obstruction was observed on computed tomography and magnetic resonance cholangiopancreatography. The presence of Strongyloides stercoralis was highly suspected from the biopsy sample from the duodenal papilla. Polymerase chain reaction amplification and sequencing of small subunit rDNA from paraffin-embedded specimens identified the worm as S. stercoralis. All of the symptoms were considered to be associated with S. stercoralis infection. Therefore, the patient was treated with oral administration of ivermectin. Subsequently, symptoms and laboratory data improved. There has been no recurrence of the symptoms to date.

The clearance of the esophagus is to transport food boluses from the pharynx to the stom- ach through peristaltic motion. This occurs through the primary peristaltic wave, triggered by swallowing, passing from the upper to lower esophagus in a sequence of contractions and relaxations. Investigation modalities for evaluation of esophageal clearance function include esophageal manometry (included high resolution manometry), esophageal radiography (barium swallow), esophageal scintigraphy, ultrasonography, impedance methods and com- bination with transnasal endoscopy and manometry. Of these, evaluation of esophageal clear- ance is conducted quantitative assessment of esophageal motility as well as transient lower esophageal sphincter relaxation(TLESR) in reflux esophagitis.

Purpose Irreversible electroporation (IRE) differs from thermal radiofrequency (RF) ablation, especially in terms of the reparative process in the ablation zone induced. To elucidate this, the systemic immune responses after 2 mechanistically different types of ablation (IRE and RF ablation) were evaluated in patients with hepatocellular carcinoma (HCC). Materials and Methods Twenty-one patients with HCC who underwent either RF ablation (n = 11) or IRE (n = 10) were studied. Peripheral blood samples were collected from all patients at 4 timepoints: before ablation, within 1 hour after ablation, 1 day after ablation, and 4 days after ablation. The phenotypes and functions of immune cells in peripheral blood and serum levels of cytokines and chemokines were monitored and analyzed using the mixed-effects model. Follow-up radiological images were also obtained to assess temporal changes in the ablation zone. Results The most significant difference was seen in the levels of macrophage migration inhibitory factor (MIF) in the IRE group compared to the RF ablation group (P = .0011): the serum levels of MIF in the IRE group significantly increased immediately after IRE and then rapidly decreased to the pre-ablation range 1 day after IRE, but, in contrast, no consistent trend was observed in the RF ablation group. The axial diameter (P = .0009) and area (P = .0192) of the ablation zone of IRE were significantly smaller than those of RF ablation 1 year after ablation. Conclusions IRE was found to be associated with a significant early increase in MIF levels, which may facilitate the early reparative process and result in significant shrinkage of the ablation zone.

Objective To evaluate irreversible electroporation (IRE) for locally advanced pancreatic cancer (LAPC). Methods This study was approved by our local review board. Eight patients with histologically proven LAPC ≤5 cm were prospectively enrolled to undergo ultrasound-guided IRE. The primary endpoint was complications within 90 days. Secondary outcomes were the overall survival (OS) and time to local progression. Safety was assessed using Common Terminology Criteria for Adverse Events Version 4.0. Results All patients were treated successfully. The median procedure time was 150 min. The median largest tumor diameter was 29.5 mm (20.0-48.0 mm) in the pancreatic head (n=5) and body (n=3). Open (n=4) and percutaneous (n=4) approaches were used. No patients died within 90 days after IRE. There were 5 minor complications in 3 patients and 4 major complications in 3 patients. The incidence rates of major complications did not differ significantly between the approaches. The median time to local progression after IRE was 12.0 months, and the median OS was 17.5 months from IRE and 24.0 months from the diagnosis, with no significant differences between the approaches. Conclusions Percutaneous and open IRE may be acceptable for patients with LAPC (despite some major adverse events) and may represent a useful new therapeutic option.

This clinical study was conducted to evaluate the safety and short-term outcomes of irreversible electroporation (IRE) for the treatment of patients with hepatocellular carcinoma (HCC) in Japan. The study was designed in a prospective setting. Five patients (3 men and 2 women; mean age, 66.6 ± 5.8 years) with 6 HCCs were enrolled and treated using percutaneous ultrasound (US)-guided IRE. Safety was assessed based on adverse events and laboratory values. Local control was assessed using contrast-enhanced US with a perflubutane microbubble contrast agent, contrast-enhanced multiphase CT, and gadoxetic acid-enhanced MRI (EOB-MRI) at designated points. The tumors ranged in diameter from 11 to 28 mm (mean diameter, 17.5 ± 6.3 mm). Five of the 6 tumors (83 %) were successfully treated, with no local recurrence to date (mean follow-up 244 ± 55 days). In 1 lesion located in liver segment 1, residual tumor was diagnosed at 7 days after intervention by follow-up EOB-MRI. No serious complications related to the IRE procedure were observed. The results of this study suggest that image-guided percutaneous IRE can achieve satisfactory local disease control, particularly for small HCCs, and is well tolerated by patients.

Background Currently, few reports exist on EUS-guided hepatic abscess drainage (EUS-HAD) and EUS-guided biloma drainage (EUS-BLD) using a metal stent. Objective We evaluated the technical success rate and efficacy of EUS-HAD and EUS-BLD for patients with hepatic abscess (HA) and infected biloma. Design Retrospective case series. Setting Single tertiary referral medical center. Patients We evaluated 7 HA and 6 infected biloma patients who were treated between August 2013 and August 2014 at Tokyo Medical University Hospital. Interventions EUS-HAD or EUS-BLD using a short (length, 2 or 3 cm) or long (length, 6 or 8 cm) self-expandable fully covered metal stent. Main Outcome Measurements Technical success, clinical success, and adverse event. Results The overall technical success rate was 100% in both EUS-HAD and EUS-BLD. The clinical success rates of EUS-HAD and EUS-BLD at the first session were 71.4% and 83.3%, respectively. Direct endoscopic necrosectomy was required in 1 case each of HA and infected biloma. The final clinical success rate was 100%. There were no procedure-related adverse events or cases of recurrence during the follow-up period (median, 83.5 days; range, 24-396 days). Limitations Small sample size and no control group. Conclusions EUS-HAD and EUS-BLD using a metal stent can be performed safely and effectively for HA and infected biloma.

Background and Aim Newly developed ultrathin transnasal endoscope, the GIF-XP290N, makes possible a resolving power similar to the GIF-H260 at a distance of 3 mm. We conducted surveillance of subjects with Barrett's esophagus using this ultrathin transnasal endoscopy. In Japan the lower margin of the lower esophageal palisade vessels is defined the gastroesophageal junction in deep inspiration. We diagnose Barrett's esophagus if columnar epithelium is present on the oral side of the gastroesophageal junction. Methods and Results Barrett's esophagus was confirmed in 116 out of 135 subjects (85.9%), with 17 cases of short-segment Barrett's esophagus (SSBE) and 99 of ultra-short-segment Barrett's esophagus. Close observation of the Barrett's esophagus mucosal structural pattern using narrow band imaging revealed 29 cases with an oval or round pattern, 29 with a long straight pattern, 47 with a villous pattern, 8 with a cerebriform pattern, and 6 with an irregular pattern according to Goda classification. Mucosal biopsies from all subjects with SSBE are examined. Histological examination revealed intestinal metaplasia in only eight subjects. We grouped the oval/round and long straight patterns as closed type, and the villous, cerebriform, and irregular patterns as open type. Analysis of the relationship between these mucosal patterns and background factors revealed a significant correlation between intestinal metaplasia and the open-type pattern. Conclusion We consider this new ultrathin transnasal endoscopy to be a useful technique for surveillance of Barrett's esophagus, especially SSBE.

Background and aim Identification of the esophageal gastric junction (EGJ) is of crucial importance for the consistent detection of Barrett’s esophagus (BE). In Japan, the distal end of the lower esophageal palisade vessels is used to define the EGJ. However, in Western countries, the EGJ is defined as the proximal margin of the gastric folds. In this prospective study, we compared the variation in endoscopic diagnosis of BE using the Japanese criteria (J-criteria) and the Prague C & M criteria (P-criteria) as a landmark of the EGJ.

† † Background/Aims: Propofol sedation for elderly patients during time-consuming endoscopic procedures is controversial. Therefore, we investigated the safety of using propofol in elderly patients during upper gastrointestinal therapeutic endoscopy. Methods: The medical records of 160 patients who underwent therapeutic endoscopic procedures under gastroenterologist-guided propofol sedation at a single institution were retrospectively reviewed. The subjects were divided into two groups: a younger group, patients

There are currently no plastic pancreatic duct stents that have been designed for endoscopic ultrasonography (EUS)-guided placement. This study prospectively evaluated the feasibility and efficacy of a new, single-pigtail, plastic stent. Eight patients with main pancreatic duct stricture or stenotic pancreatojejunostomy underwent EUS-guided placement of the pancreatic duct stent. The stent was placed successfully in all cases (8/8). Treatment success was achieved in all cases (8/8). A mild adverse event associated with the procedure was observed in one patient but there were no other adverse events during a mean follow-up of 7.4 months. This new pancreatic duct stent appears to be feasible and effective for EUS-guided stenting.

We herein report a case of severe acute cholangitis complicated by bacterial meningitis. A 56-year-old Japanese man was admitted to our hospital due to a consciousness disorder that had developed while he was being treated for acute cholangitis. The levels of both hepatobiliary enzymes and inflammatory markers were high, and computed tomography revealed common bile duct stones and cholangiectasis. A diagnosis of acute cholangitis was made, and meningitis was subsequently confirmed on a cerebrospinal fluid analysis. The patient recovered successfully after receiving emergency endoscopic drainage and antibiotic therapy. This case demonstrates that a disturbance of consciousness complicated by acute cholangitis may result from septic encephalopathy as well as meningitis via bloodstream infections.

Background and Aim Endoscopic sphincterotomy (ES) combined with large balloon dilation (ESLBD) can be useful for extracting large and multiple bile duct stones. Although there are many studies on the feasibility and short-term outcome, there are few reports about mid- to long-term outcome after ESLBD. The aim of our study is to prospectively evaluate the mid-term outcome of ESLBD. Methods One hundred eighty-three patients who underwent ESLBD between November 2006 and May 2012 were included. The patients were followed up periodically after the procedure until April 2013. Papillary dilation was performed at the time of initial ES or prior ES. Early and late adverse events and stone recurrence were evaluated in this study. Results The patients' mean age was 76.6 ± 10.7 years. Surgically altered anatomy was present: Billroth I gastrectomy (2), Billroth II gastrectomy (13), and gastrectomy with Roux-en Y reconstruction (18). Seventy-eight (42.6%) patients had periampullary diverticulum. Prior ES had been performed in 40 (21.9%) patients. The mean follow-up period was 43.5 ± 19.7 months (range 11–78). Eight (4.4%) patients had stone recurrence. There was rare stone recurrence after initial ESLBD treatment and native gastrointestinal anatomy. Univariate and multivariate analyses showed that prior ES and previous history of stone recurrence were predictive of stone recurrence (P

Background and Aim The new developed ultrathin transnasal endoscope, the GIF-XP290N, makes possible a resolving power similar to the GIF-H260 at a distance of 3 mm. In this study, using the GIF-XP290N, we evaluated whether endoscopic diagnosis (discrimination between benign and malignant) of gastric lesions is possible using nonmagnified narrow-band imaging (NBI) endoscopy. Methods The subjects were 255 consecutive patients who underwent screening of the gastrointestinal tract using new ultrathin transnasal endoscopy. Their average age was 65.2 ± 11.4 years. The male-female ratio was 2.5:1. All cases were examined using conventional white-light imaging (WLI) and nonmagnified NBI. When a depressed lesion was detected in the stomach, it was examined using WLI, then NBI close examination (at about 3 mm). We observed the mucosal structure of the lesion using close visualization with NBI. Concerning mucosal structural changes, we looked for a clear demarcation line between the lesion and the surrounding mucosa, and loss, irregularity, or nonuniformity of the lesion mucosal microsurface pattern. Results A total of 52 depressed lesions were examined. The histological diagnosis was cancer for 8 lesions, and noncancer for 44 lesions. WLI examination yielded a sensitivity of 50.0% (4/8), specificity of 63.6% (28/44), and accuracy 61.5% (32/52). On the other hand, NBI close examination yielded a sensitivity of 87.5% (7/8), specificity of 93.2% (41/44), and accuracy of 92.3% (48/52), significantly higher. Conclusion NBI close examination using ultrathin transnasal endoscopy enables mucosal diagnosis even without magnification and was considered to be an effective technique for improving endoscopic diagnosis.

Recently, a novel fully covered and biflanged metal stent (BFMS)dedicated to the drainage of walled-off necrosis(WON) was developed. The aim of this study was to retrospectively evaluate the safety, efficacy, and cost performance of drainage of WON using the novel BFMS compared with a traditional plastic stent.A total of 70 patients with symptomatic WON were treated under endoscopic ultrasound (EUS) guidance. Initial drainage was conducted using the single gateway technique with placement of one or more plastic stents or a single BFMS.If drainage was unsuccessful,direct endoscopic necrosectomy (DEN)was performed.There were no statistically significant differences in rates of technical success, clinical success,and adverse events between plastics stents and BFMS, despite the size of WON in the BFMS group being significantly larger than that in the plastic stent group (105.6 vs. 77.1 mm; P=0.003).The mean procedure times for the first EUS-guided drainage and for re-intervention were significantly shorter in the BFMS group than in the plastic stent group (28.8±7.1 vs. 42.6±14.2, respectively,for drainage, P0.001; and 34.9±8.5 vs.41.8±7.6, respectively, for re-intervention, P0.001). There was no statistically significant difference in the total cost between plastic stent and BFMS use in the treatment of WON ($5352vs. $6274; P=0.25).Plastic stents and BFMS were safe and effective for the treatment of WON. In particular,BFMS placement appeared to be preferable for initial EUS-guided drainage and additional reintervention(e.g. DEN) as it reduced the procedure time. Prospective randomized controlled trials are warranted.

Pancreatic pseudocysts and walled-off necrosis are typical late complications of acute pancreatitis, and they require drainage in symptomatic cases presenting with infection. Transgastrointestinal endoscopic treatment with endoscopic ultrasound-guided drainage has become common and yields a good treatment outcome for pancreatic pseudocyst. Walled-off necrosis, however, contains necrotic tissue, and thus many cases additionally require an invasive treatment that includes endoscopic necrosectomy. Methods that involve a procedure-specific large-diameter metal stent, additional endoscopic drainage techniques, and the hybrid approach method of adding percutaneous drainage have been described, and considerable advances in these methods have now made it possible to cure almost all cases of walled-off necrosis with endoscopic treatment alone. However, without being restricted to endoscopic treatments, a wide range of options including surgery should be considered as treatments for walled-off necrosis.

Minimally invasive interventions for choledocholithiasis are preferable in elderly patients because they tend to have multiple underlying disorders or a decreased activity of daily living. Endoscopic sphincterotomy and endoscopic papillary balloon dilation have been recognized as first-line treatments for choledocholithiasis excluding difficult cases such as large stones or multiple stones. Recently, the safety and efficacy of endoscopic papillary large balloon dilation (EPLBD) for difficult choledocholithiasis cases have been reported, although scarcely in elderly patients. To investigate whether EPLBD can be safety and effectively performed in patients aged 75 years or older. The medical records of 165 patients who underwent EPLBD from November 2006 to August 2013 were analyzed retrospectively. The patients were divided into 2 groups: Group A (≥75 years); Group B (

Aim The combination therapy of pegylated interferon-α and ribavirin (PEG IFN/RBV) is one of the effective treatments for chronic hepatitis C (CHC) patients. Natural killer (NK)-cell activity was reported to be impaired in patients with hepatitis C virus (HCV). The aim of this study was to examine whether PEG IFN/RBV therapy could restore NK activity in CHC patients. Methods In 19 CHC patients, PEG IFN/RBV therapy was performed. Just before (0M), at 3 months of the therapy (3M) and at 6 months after completion of the therapy (6M), NK activity and the frequency of NK cells, CD56dimNK cells and CD56brightNK cells in peripheral blood was estimated by creatinine release assay and flow cytometry. Statistical analysis was performed by anova and Mann–Whitney U-test. Results anova showed that NK activity significantly improved at 6M (vs 0M, P

Although midazolam is widely used during endoscopic procedures by endoscopists, propofol has been recently favored for its rapid action and metabolism. The aim of this study is to compare the clinical advantages between propofol and midazolam use during screening esophagogastroduodenoscopy (EGD) for gastric cancer and post-procedure management at a medical clinic.One hundred six healthy patients aged 20-69 years requesting sedation for screening EGD from October 2012 to May 2013 at a single clinic in Japan were randomly assigned to propofol (n = 54) or midazolam (n = 52). Medications were given by bolus injection, and the dose was adjusted by body weight. Sedation level and tolerability during EGD and recovery time were assessed. Sedation level and tolerability were evaluated by American Society of Anesthesiologists responsiveness levels and four levels of the gag reflex, respectively. For safety purposes, endoscopists and nurses were trained in administering propofol and an anesthesiologist was on call at all times.No statistically significant differences were found between the two groups in sedation level and patient tolerability. Full recovery time in the propofol group (4.7 min) was significantly shorter than that in the midazolam group (24 min, P 0.01).Regarding post-procedure management of patients in a medical clinic, propofol use might not necessitate a recovery room and excessive assessment tasks because of rapid recovery time without any prolonged reaction, which causes patient compliance. (UMIN000009142.).