Changes in intestinal bacteria and imbalances of metabolites induced in the intestines of pancreatic ductal adenocarcinoma patients in a Japanese population: a preliminary result.

BACKGROUND: The relationship between pancreatic ductal adenocarcinoma (PDAC) and the intestinal environment is not fully understood. The purpose of this study was to elucidate the characteristics of the intestinal environment in PDAC. METHODS: We performed a case-control study of 5 Japanese patients with unresectable PDAC located in the body or tail (PDAC-bt). The number of patients analyzed was limited for this preliminary study. We included 68 healthy subjects, herein control, of pre-printed study in the preliminary study. 16S rRNA amplicon sequencing and metabolomic analysis were performed using fecal samples from the subjects. RESULTS: There was no difference in the Shannon index and Principal Coordinate Analysis between PDAC-bt and the control. However, a significant increase in oral-associated bacteria (Actinomyces, Streptococcus, Veillonella, Lactobacillus) was observed. A significant decrease of Anaerostipes was demonstrated in the feces of PDAC-bt compared with the control. The intestinal propionic acid and deoxycholic acid were significantly lower in PDAC-bt compared with the control. CONCLUSIONS: We showed that the intestinal environment of PDAC-bt is characterized by an increase in oral-associated bacteria and an imbalance of metabolites but without changes in alpha and beta diversity of the gut microbiota profiles.Clinical Trial Registration: www.umin.ac.jp, UMIN 000041974, 000023675, 000023970.

Injury to the muscle layer, increasing the risk of post-colorectal endoscopic submucosal dissection electrocoagulation syndrome.

BACKGROUND AND AIM: In colorectal endoscopic submucosal dissection (ESD), post-ESD electrocoagulation syndrome (PECS) has been recognized as one of the major complications. There are no reports on the relationships between ESD findings and PECS. This study aims to evaluate the risk factors for PECS, including ESD findings such as muscularis propria exposure. METHODS: We performed a retrospective cohort study of patients who underwent colorectal ESD between January 2017 and December 2021 in Japan. The grade of injury to the muscle layer caused by ESD was categorized as follows: Grade 0, no exposure of muscularis propria; Grade 1, muscularis propria exposure; Grade 2, torn muscularis propria; and Grade 3, colon perforation. The risk factors for PECS, including injury to the muscle layer, were analyzed by univariate and multivariate analyses. RESULTS: Out of 314 patients who underwent colorectal ESD, PECS occurred in 28 patients (8.9%). The multivariate analysis showed that female sex (odds ratio [OR] 3.233; 95% confidence interval [95% CI]: 1.264-8.265, P = 0.014), large specimen size (≥ 40 mm) (OR 6.138; 95% CI: 1.317-28.596, P = 0.021), long procedure time (≥ 90 min) (OR 2.664; 95% CI: 1.053-6.742, P = 0.039), and Grade 1 or 2 injury to the muscle layer (OR 3.850; 95% CI: 1.090-13.61, P = 0.036) were independent risk factors for PECS. CONCLUSIONS: Injury to the muscle layer, such as exposure or tear, was identified as a novel independent risk factor for PECS. We should perform colorectal ESD carefully to avoid injuring the muscle layers.

Early Changes in Alpha-Fetoprotein Are a Useful Predictor of Efficacy of Atezolizumab plus Bevacizumab Treatment in Patients with Advanced Hepatocellular Carcinoma.

INTRODUCTION: The aim of this study was to investigate the early changes in alpha-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) levels in patients with advanced hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab and to evaluate the relationship between changes in these tumor markers and treatment efficacy. METHODS: Of 58 consecutive patients who started atezolizumab plus bevacizumab at our institution, 50 patients with information on antitumor response obtained at 6 weeks after therapy were enrolled in this study and their treatment outcomes were retrospectively evaluated. RESULTS: According to the Response Evaluation Criteria in Solid Tumors at 6 weeks, the objective response (OR) rate was 22.0% and the disease control (DC) rate was 78.0%. In patients who achieved OR at 6 weeks, median AFP and DCP ratios at weeks 1, 2, 3, and 6 were significantly lower than those in patients who did not achieve OR. AFP ratios in patients who did not achieve DC at 6 weeks (Non-6W-DC group) were significantly higher than in those who achieved DC at week 6 (6W-DC group). Median overall survival in the Non-6W-DC group was significantly shorter than in the 6W-DC group (156 days vs. not reached, p = 0.0008). An AFP ratio of 1.4 or higher at 3 weeks had a specificity of 88.0% and a sensitivity of 88.9% for predicting Non-6W-DC. Median progression-free survival was significantly shorter in patients with an AFP ratio of 1.4 or higher at 3 weeks than in those with an AFP ratio of <1.4 (42 days vs. 210 days, p = 0.0003). CONCLUSION: Early changes in AFP might be useful for predicting the antitumor efficacy of atezolizumab plus bevacizumab in patients with advanced HCC. An AFP ratio of 1.4 or higher at 3 weeks might be an early predictor of refractoriness to atezolizumab plus bevacizumab therapy.

Novel image enhancement technology that helps find bleeding points during endoscopic submucosal dissection of gastric neoplasms.

BACKGROUND AND AIM: The management of bleeding during endoscopic submucosal dissection (ESD) is critical and related to the procedure time. We collaborated on a new image enhancement algorithm with parameter optimization for clinical use being developed by FUJIFILM Co. and processed white light image data offline to evaluate the effectiveness of this technology. This study aims to evaluate the clinical usefulness of this technology. METHODS: Eighteen video scenes of bleeding points from five gastric ESDs were selected and processed by the new image enhancement algorithm. The time until a bleeding point was found, visibility of a bleeding point, and color abnormality of the submucosal layer were evaluated by ESD experts, ESD trainees, and endoscopy trainees. The color differences between the bleeding point and the surroundings in CIE-L*a*b* color space were calculated in the original and enhanced images. RESULTS: The time until a bleeding point was found in the enhanced videos was significantly shorter than that in the original videos (11.10 s vs 13.85 s) (P = 0.017). On a 5-point (-2 to +2) Likert scale of visibility, the enhanced image was slightly superior to the original (+0.45), and the appearance of the submucosa was comparable between images (+0.14). The color difference among the bleeding areas on the enhanced images was significantly larger than that on the original images (10.93 vs 8.36). CONCLUSION: This novel image enhancement algorithm emphasizes the color difference between a bleeding point and the surrounding area, which would help find bleeding points faster during ESD for the less experienced endoscopists.

Immunohistochemical staining for IMP3 in patients with duodenal papilla tumors: assessment of the potential for diagnosing endoscopic resectability and predicting prognosis.

BACKGROUND: Endoscopic papillectomy of duodenal papillary tumors (PT) is indicated for adenomas or well-differentiated adenocarcinomas that do not involve the sphincter of Oddi. However, there is currently no reliable pre-operative method to diagnose the infiltration in the sphincter of Oddi.' Insulin-like growth factor 2 mRNA protein 3 (IMP3) staining is reportedly associated with advanced disease stage and clinical outcomes in many carcinomas. The aim of this retrospective study was to investigate the ability of diagnosing sphincter of Oddi involvement in PT and predicting the prognoses using IMP3 immunohistochemistry. METHODS: Twenty-five resected specimens from patients with PT and 24 biopsy specimens from the same patients excluding one were immunostained for IMP3. The percentage of positive cells in the tumor was evaluated and compared with the final pathological diagnosis and prognosis. RESULTS: The final pathological diagnoses were adenoma in 5 patients and adenocarcinoma in 20 patients (no sphincter of Oddi involvement in 5 and involvement in 15). The ability to diagnose sphincter of Oddi involvement based on the percentage of IMP3-positive cells in resected specimens and tissue biopsies was the area under the curve 0.8 and 0.78, respectively, of the receiver operating characteristic curve, and the accuracies were 80.0% and 75.0% (cutoff value: 10%), respectively. Moreover, patients with an IMP3-positive cell rate of ≥ 10% had a significantly worse prognosis (log-rank test P = 0.01). CONCLUSION: IMP3 immunostaining of resected and biopsy specimens from PT patients enables the diagnosis of sphincter of Oddi involvement objectively and is also effective in predicting the prognosis.

Probe-based confocal laser endomicroscopy for the diagnosis of pancreatic ductal structures.

BACKGROUND AND AIM: The image-based diagnosis of pancreatic diseases can be difficult and requires pathological evaluation. Probe-based confocal laser endomicroscopy (pCLE) enables real-time observation of the microscopic tissue pattern of lesion and may be a useful assistance for the diagnosis. This study aimed to evaluate the feasibility and utility of pCLE for the diagnosis of pancreatic diseases. METHODS: Thirty patients who underwent endoscopic retrograde cholangiopancreatography with pCLE for the evaluation of indeterminate pancreatic diseases from June 2015 to October 2018 were included in this study. The pCLE findings were interpreted according to the Miami Classification. RESULTS: Among a total of 30 patients, 12, 10, 4, and 4 patients received the definitive diagnoses of pancreatic ductal adenocarcinoma (PDAC), main duct intrapapillary mucinous neoplasm, autoimmune pancreatitis, and chronic pancreatitis, respectively. The diagnostic accuracy of pCLE for PDAC and pancreatitis (96.7% and 93.3%, respectively) was higher than that of cytology (76.7% and 63.3%, respectively) (P = 0.0227 and 0.0048, respectively). The sensitivity of pCLE for PDAC was significantly higher (91.7%) than that of cytology (41.7%) (P = 0.0094). Moreover, the specificity of pCLE for pancreatitis was significantly higher than that of cytology (90.9% vs 50%; P = 0.0029). However, the diagnostic accuracies of pCLE and cytology for main duct intrapapillary mucinous neoplasm did not differ significantly (96.7% and 86.7%, respectively). CONCLUSIONS: Probe-based confocal laser endomicroscopy may be effective for the diagnosis of pancreatic diseases as adjunct modality. It requires technical learning and further evaluation of its usefulness.

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

OBJECTIVES: There are few reports on the long-term prognosis of papillary tumors after endoscopic papillectomy. Here, we report a retrospective study of the therapeutic effects, long-term prognosis, and affecting factors. METHODS: The inclusion criteria were papillary adenoma with/without an adenocarcinoma component on biopsy results and ≤10 mm intraductal extension, and the exclusion criteria were moderate to poorly differentiated adenocarcinoma on biopsy results. If no residual lesion was confirmed ≥6 months after the last endoscopic treatment, remission was defined. Subsequently, follow-up endoscopy was scheduled once a year. Surgery was required in the case of adenocarcinoma recurrence or intraductal lesions >10 mm. The rates of adverse events, remission, recurrence, and need for surgery were examined. The affecting factors were calculated. RESULTS: There were a total of 253 subjects, including 65 with adenocarcinoma. Pancreatitis (7.5%), bleeding (9.1%) and perforation (2.8%) were observed as adverse events. Among 221 subjects with ≥6 months of follow-up, 212 (95.9%) were in remission. The cumulative recurrence rate using the Kaplan-Meier analysis at 5 years was 16.9% (22 cases), with the need for surgery in 5.9% (5 cases). Intraductal extension on preoperative diagnosis was the only significant risk factor for both recurrence (P < 0.001) and the need for surgery (P = 0.005). The presence of adenocarcinoma had no significant effect. CONCLUSION: Although remission was achieved in more than 95% of our patients, we observed a high rate of recurrence at the long-term follow-up, which was significantly associated with intraductal extension but not with the presence of adenocarcinoma.

Endoscopic ultrasound-guided needle-based confocal laser endomicroscopy in gastrointestinal subepithelial lesions: Feasibility study.

BACKGROUND AND AIM: Needle-based confocal laser endomicroscopy (nCLE) allows for real-time optical biopsies during endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). Little is known about nCLE imaging of gastrointestinal subepithelial lesions (GI-SEL); therefore, we determined its feasibility. METHODS: We carried out EUS, nCLE, and finally FNA in 25 patients with GI-SEL between November 2015 and December 2018. We retrospectively compared nCLE findings with pathological findings of EUS-FNA or surgical specimens. For concordance analysis, two endoscopists independently validated representative nCLE images 5 months or more after examinations. RESULTS: Adequate sample acquisition rate of EUS-FNA was 67% per needle pass and 96% per patient. EUS-FNA was diagnostic in 80% (20/25), suspicious in 4% (1/25), and nondiagnostic in 16% (4/25). nCLE image acquisition rate was 100% and its concordance rate with final pathology was 88% (22/25), which was not significantly different from diagnostic and suspicious EUS-FNA. nCLE could differentiate GI stromal tumors (GISTs) from leiomyoma, in that GISTs were characterized by contrast-enhanced densely populated spindle cell tumors with unenhanced rod-shaped nuclei in 93% of 14 patients, whereas leiomyomas were characterized by narrower spindle cell tumors with fewer and smaller unenhanced nuclei in 100% of three patients. In rectal metastasis from lung adenocarcinoma, some pleomorphic dark nests were observed. At concordance analysis between the two endoscopists' validation results, κ value was 0.560 (P < 0.001), indicating moderate agreement. There were no adverse events associated with nCLE and EUS-FNA. CONCLUSION: Needle-based confocal laser endomicroscopy can be safe and useful for on-site detection of abnormalities of GI-SEL (UMIN 000013857).

Randomized Phase II Study of Consecutive-Day versus Alternate-Day Treatment with S-1 as Second-Line Chemotherapy in Advanced Pancreatic Cancer.

OBJECTIVE: To evaluate the efficacy and safety of alternate-day administration of S-1 as second-line chemotherapy for unresectable pancreatic cancer in a multicenter, randomized, phase II study. METHODS: Patients with histologically proven, unresectable pancreatic cancer treated with chemotherapy not including S-1 as first-line therapy were randomly assigned to receive either daily or alternate-day treatment with S-1. The primary end point was overall survival (OS), and the secondary end points were progression-free survival (PFS), time to treatment failure (TTF), response rate, and adverse events. RESULTS: A total of 77 patients were enrolled, of which 75 were included in the final analysis. The median OS was 4.5 months in the daily group and 4.4 months in the alternate-day group (HR 1.178; 95% CI 0.741-1.875), with no significance in PFS and TTF. The response rate was 2.8% in the daily group and 0% in the alternate-day group. Grade 3 or higher adverse events occurred with significantly higher incidence in the daily group (47.2 vs. 25.6%, p = 0.044). CONCLUSION: As a second-line chemotherapy for unresectable pancreatic cancer, although the efficacy in both groups was comparable and we can expect fewer toxicities with alternate-day administration of S-1, the noninferiority of alternate-day treatment to daily treatment with S-1 was not verified.

Comparison of 8- and 10-mm diameter fully covered self-expandable metal stents: A multicenter prospective study in patients with distal malignant biliary obstruction.

OBJECTIVES: The time to recurrent biliary obstruction (TRBO) of unresectable distal malignant biliary obstruction is generally thought to be longer when a self-expandable metal stent (SEMS) with a thicker inner diameter is used for drainage, but the dependence on the inner diameter using a fully covered SEMS (FCSEMS) is uncertain. The objective of this multicenter prospective study was to compare TRBO and adverse events, such as cholecystitis and pancreatitis, in treatment of patients with unresectable malignant biliary obstruction using 8- and 10-mm diameter FCSEMS. METHODS: Eighteen tertiary-care centers participated in the study. Patients were allocated to the 8- and 10-mm diameter groups. TRBO, non-inferiority of the 8-mm FCSEMS, overall survival time, frequency and type of adverse events, and non-recurrent biliary obstruction (RBO) rate at the time of death were compared between the two groups. RESULTS: Median TRBO did not differ significantly between the 8-mm (n = 102) and 10-mm (n = 100) groups (275 vs 293 days, P = 0.971). The hazard ratio of the 8- to 10-mm groups was 0.90 (80% confidence interval, 0.77-1.04; upper limit lower than the acceptable hazard ratio [1.33] of the null hypothesis). Based on these findings, the 8-mm diameter stent was determined to be non-inferior to the 10-mm diameter stent. Survival time, incidence of adverse events and non-RBO rate at the time of death did not differ significantly between the two groups. CONCLUSIONS: Time to RBO with an 8-mm diameter FCSEMS was non-inferior to that with a 10-mm diameter FCSEMS. This finding is important for development of future SEMS.

Usefulness of shear wave elastography as a quantitative diagnosis of chronic pancreatitis.

BACKGROUND AND AIM: Chronic pancreatitis (CP) is sometimes diagnosed at the progressed stage. For the early diagnosis of CP, endoscopic ultrasonography (EUS) may be a useful method, but its diagnostic criteria is based on subjective judgment. Shear wave elastography (SW-EG) using transabdominal ultrasonography, which quantifies tissue elasticity as an absolute value, may be an objective and noninvasive method for the diagnosis of CP. METHODS: Eighty-five patients with known or suspected CP who underwent both EUS and SW-EG from October 2012 to July 2016 were included in this study. Patients were categorized into four stages using Rosemont classification and into three stages using Japan Pancreas Society clinical diagnostic criteria 2009 that was EUS-based criteria for the diagnosis of CP. SW-EG was measured five times in the pancreatic parenchyma, and the median value was defined as the pancreatic elastic modulus (PEM). RESULTS: Pancreatic elastic modulus was significantly positively correlated with Rosemont classification stage (rs  = 0.54), Japan Pancreas Society stage (rs  = 0.41), and the number of EUS features (rs  = 0.47). Area under the receiver operating characteristic curve for the accuracy of SW-EG (consistent with CP and suggestive of CP vs normal and indeterminate for CP) was 0.77 (sensitivity 77.1%, specificity 64.9%). In a multivariate linear regression analysis including various EUS features related to PEM, hyperechoic foci with shadowing and lobularity with honeycombing were independent features related to PEM. CONCLUSIONS: Chronic pancreatitis may be diagnosed noninvasively and objectively using SW-EG without performing EUS.

Natural history of pancreatic cystic lesions: A multicenter prospective observational study for evaluating the risk of pancreatic cancer.

BACKGROUND AND AIM: The aim of this study is to elucidate the natural history of pancreatic cystic lesions (PCLs), including branch duct-type intraductal papillary mucinous neoplasm (BD-IPMN), via midterm follow-up analysis of a multicenter prospective observational study (NSPINAL study). METHODS: From July 2011 to October 2016, 881 patients with PCLs were enrolled in NSPINAL study, and 664 patients with > 12 months of follow up were analyzed. Every patient was asymptomatic, and endoscopic ultrasound was performed at the initial diagnosis to exclude high-risk individuals. Follow up included endoscopic ultrasound, computed tomography, or magnetic resonance imaging at least once a year. Serial morphological changes and the pancreatic cancer (PC) incidence, including malignant progression of PCLs, were evaluated. RESULTS: The 664 patients (358 men) were followed for a median of 33.5 months (interquartile range 29). The cyst and main pancreatic duct sizes were 16.6 ± 9.3 and 2.3 ± 1.0 mm, respectively. Morphologically, 518 cases were multilocular, 137 were unilocular, and 9 had a honeycomb pattern; 269 cases involved multifocal lesions. Ninety-six patients (14.5%) showed worsening progression on imaging. There were two resectable and four unresectable cases of pancreatic ductal adenocarcinoma and three cases of malignant BD-IPMN. The 3-year risk of developing PC was 1.2%. The standardized incidence ratio for PC among PCLs was 10.0 (95% confidence interval 3.5-16.5), and the standardized incidence ratio among BD-IPMN was 16.6 (95% confidence interval 5.1-28.1). Multivariate analysis showed that development of symptoms and worsening progression were significant predictors of PC. CONCLUSIONS: Malignant progression of PCLs, including PC development, is not uncommon. Patients with PCLs should be carefully monitored to detect pancreatic ductal adenocarcinoma at early stages.

HLA-DQ gene polymorphisms are associated with hepatocellular carcinoma and hepatitis B surface antigen in chronic hepatitis B virus infection.

AIM: Genome-wide association studies have revealed that single nucleotide polymorphism (SNP) of human leukocyte antigen (HLA)-DQ is associated with the clearance of hepatitis B surface antigen (HBsAg) in acute hepatitis B virus (HBV) infection. We examined the effects of SNPs on the development of hepatocellular carcinoma (HCC) and markers of HBV in chronic HBV infection. METHODS: The SNPs of HLA-DQ (rs2856718 and rs7453920) were determined in 299 patients with chronic HBV infection. RESULTS: In 224 hepatitis B e antigen (HBeAg)-negative patients, those with rs2856718 genotype AG + GG had significantly lower hepatitis B core-related antigen levels (P = 0.0184), less frequent treatment with nucleotide/nucleoside analogs (NAs) (P = 0.0433), and less frequent HCC development (P = 0.0256) than those with genotype AA. Multivariate analysis selected age (P = 0.0460), platelet count (P = 0.0481), γ-glutamyl transpeptidase (P = 0.0030), and nucleotide/nucleoside analog treatment (P = 0.0003) as factors independently associated with HCC development. HBeAg-negative patients with rs7453920 genotype GG had significantly lower HBsAg levels (P < 0.0001), a higher prevalence of HBV genotype C (P = 0.0063), and a lower prevalence of the wild-type basal core promoter region (P = 0.0045) than those with genotype AA + AG. Multivariate analysis selected age (P < 0.0001), platelet count (P = 0.0021), HBV DNA levels (P = 0.0314), wild type of precore region (P = 0.0015), and rs7453920 (P < 0.0001) as factors independently associated with HBsAg levels. CONCLUSION: This study revealed an association between rs2856718 and HCC development and an association between rs7453920 and HBsAg levels.

Quantitative evaluation of pancreatic tumor fibrosis using shear wave elastography.

BACKGROUND & AIMS: There is no established non-invasive method for diagnosis of pancreatic fibrosis. Shear wave elastography (SW-EG) may be a candidate for this purpose. The aims of this study were to assess the reproducibility of SW-EG in the normal imaging pancreas (Phase 1) and to evaluate the diagnostic performance of SW-EG for pancreatic fibrosis classified histologically (Phase 2). METHODS: Phase 1: This included 127 cases that underwent SW-EG of the normal imaging pancreas. SW-EG was measured at least five times in the pancreatic parenchyma and the median of repeated measurements was defined as the pancreatic elastic modulus (PEM). Phase 2: This included 53 cases that underwent SW-EG of the pancreatic parenchyma preoperatively and in which pancreas parenchyma were evaluated histologically. Histological fibrosis was graded in 4 stages: normal, mild, moderate, and severe. RESULTS: Phase 1: Median PEM in the head, body, and tail of the pancreas were 3.23, 3.17, and 2.91 kPa, respectively, with no significant difference among regions (P = 0.554). The intraclass correlation coefficient showed good reproducibility (ρ = 0.71) after 5 measurements. Phase 2: There was a significant positive correlation between PEM and the histological pancreatic fibrosis stage (rs = 0.63, P < 0.001). Areas under the receiver operating characteristic curve for the accuracy of SW-EG for diagnosis of pancreatic fibrosis were 0.85 (≥mild), 0.84 (≥moderate), and 0.87 (severe). CONCLUSION: SW-EG can be used to determine the stage of pancreatic fibrosis non-invasively with high accuracy and reproducibility.

Prospective multicenter study on the usefulness of EUS-guided FNA biopsy for the diagnosis of autoimmune pancreatitis.

BACKGROUND AND AIMS: In the International Consensus Diagnostic Criteria (ICDC), autoimmune pancreatitis (AIP) is classified into types 1 and 2, and its definite histopathology diagnosis can be made based only on surgical or core biopsy specimens. Although EUS-guided FNA (EUS-FNA) biopsy is a safe technique for the collection of pancreatic tissue, no consensus viewpoint has been reached with regard to the role of EUS-FNA biopsy in the diagnosis of AIP. This study investigated the utility of pancreatic tissue collected by EUS-FNA biopsy by using a standard 22-gauge aspiration needle in the diagnosis of AIP. METHODS: Patients with suspected AIP were prospectively enrolled in Nagoya University Hospital and Nagoya University-affiliated institutions. Pancreatic tissue was collected from each by EUS-FNA biopsy with a standard 22-gauge aspiration needle. RESULTS: Fifty patients were registered, including 45 with a final diagnosis of AIP. Lymphoplasmacytic infiltration and abundant immunoglobulin G4-positive plasmacyte infiltration (>10/high-power field) were detected in 36 (72%) and 27 (54%) patients, respectively. Obliterative phlebitis and storiform fibrosis were not detected in our study. Granulocytic epithelial lesions (GEL) were observed in 3 patients. The sensitivity, specificity, positive predictive value, and negative predictive value of EUS-FNA biopsy to definitively diagnose AIP were 7.9% (3/38), 100% (12/12), 100% (3/3), and 25.5% (12/47), respectively. Pathology evaluation of pancreatic tissue collected by EUS-FNA biopsy improved the diagnostic accuracy in 8 (16%) of the 50 patients. CONCLUSIONS: In this study, EUS-FNA biopsy by using a standard 22-gauge aspiration needle is not an effective diagnostic method for most patients with AIP. The combination of level 2 histology diagnosis of AIP with other findings specified in the ICDC slightly improved the diagnostic accuracy, although it still remains insufficiently accurate for routine clinical use.( CLINICAL TRIAL REGISTRATION NUMBER: 000006297.).

The prognostic factors and trajectory of HRQOL in patients with pancreatic cancer who received psychiatric intervention.

BACKGROUND AND AIM: Patients with advanced pancreatic cancer have severe pain, anxiety, and depression, and these symptoms deteriorate quality of life (QOL). Previous study reported that early psychiatric intervention for advanced cancer patients may improve QOL. We evaluated the trajectory of health-related QOL (HRQOL) in patients with pancreatic cancer after an early psychiatric intervention. METHODS: A prospective cohort study was performed in 108 pancreatic cancer patients who received consultation liaison psychiatry from November, 2011 to October, 2014 at Nagoya University Hospital. Longitudinal changes in HRQOL and the association between aspects of HRQOL and survival were evaluated using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire core 30 before treatment and every month after the start of treatment. RESULTS: Physical functioning significantly decreased after 1, 3, and 6 months of treatment compared with baseline, but global health status (GHS), role functioning, emotional functioning, and social functioning showed a tendency to improve. Severe impairment of GHS, fatigue, and appetite loss were apparent at 3 months prior to death. In multivariate analysis, pain was a significant prognostic factor for survival (hazard ratio [HR], 1.109; 95% confidence interval [CI], 1.021-1.204; P = 0.013), in addition to poor performance status (HR, 5.473; 95%CI, 2.338-12.816; P < .0001) and distant metastases at diagnosis (HR, 3.274; 95%CI, 1.872-5.725; P < .0001). CONCLUSIONS: Early psychiatric intervention in patients with pancreatic cancer may maintain HRQOL. More effective pain management and reduction of psychological distress are important for patients with pancreatic cancer.

Risk factors and clinical characteristics of the depressive state induced by pegylated interferon therapy in patients with hepatitis C virus infection: A prospective study.

AIM: Pegylated interferon (PegIFN) therapies for hepatitis C virus (HCV) infection often induce a depressive state. This study aimed to identify the risk factors for and clinical characteristics of PegIFN-induced depressive state. METHODS: Sixty-nine subjects with HCV who received PegIFN therapy were enrolled. Before beginning therapy, all subjects were evaluated using the Neuroticism-Extraversion-Openness Five-Factor Inventory and the List of Threatening Events Questionnaire. Beck Depression Inventory (BDI) scores were also evaluated at baseline, 2-4 weeks after initiating therapy, and every 4 weeks thereafter. RESULTS: During the study, 18 subjects (24.3%) developed a depressive state (BDI ≥ 10). A bimodal peak of onset was observed during the early (2-8 weeks) and late (after 20 weeks) therapy phases. Moreover, we observed that baseline BDI scores (odds ratio [OR] = 1.40, P = 0.0104) and neuroticism (OR = 1.14, P = 0.0275) were significant risk factors for developing a depressive state. To determine the specific characteristics of this condition, we compared the BDI subscales between the 'PegIFN-induced' and 'general' depressive state reported previously. We found that the score at 'somatic symptoms' was higher in the 'PegIFN-induced' group. CONCLUSION: Our results indicate the following: (i) PegIFN-induced depressive state most frequently develops during the first 8 weeks of therapy; (ii) baseline BDI and neuroticism scores are risk factors for PegIFN-induced depressive state; and (iii) the core symptoms of PegIFN-induced depressive state are different from those of 'general' depression.

Measurement of liver stiffness as a non-invasive method for diagnosis of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is one of the major causes of liver disease worldwide. To detect early stages of NAFLD and start treatment or to monitor the changes in trials of new drugs, non-invasive diagnostic methods are needed, such as biochemical markers or liver stiffness measurement (LSM). LSM with transient elastography (TE) and acoustic radiation force impulse (ARFI) has been shown to be useful in NAFLD, although the cut-off values have varied among reports. Magnetic resonance elastography and real-time tissue elastography also can be useful for the diagnosis of NAFLD, although the number of studies is limited. Fibrosis is absent in 8-40% of patients with non-alcoholic steatohepatitis (NASH), making it difficult to diagnose NASH by LSM because LSM is usually associated with fibrotic stage. The presence of inflammation or hepatocyte ballooning may affect LSM and aid the diagnosis of NASH without fibrosis. However, obesity significantly increases the failure of LSM and its interference is more conspicuous in TE than in ARFI. The newly implemented XL probe of TE has overcome the difficulty to some degree. Nonetheless, the effects of obesity, hepatocyte ballooning, steatosis and inflammation on LSM values have not yet been adequately investigated, although they are likely to affect LSM values. Further studies are needed to establish the clinical utility of LSM in NAFLD.

Current status of tissue harmonic imaging in endoscopic ultrasonography (EUS) and EUS-elastography in pancreatobiliary diseases.

Endoscopic ultrasonography (EUS) has high spatial and contrast resolution, and is thought to be one of the most reliable and efficient diagnostic modalities for pancreatobiliary diseases. Recent progress in EUS, especially in the development of the electronic scanning method, has enabled the application of several utilities and software of a high-end transabdominal ultrasound apparatus as an image-enhanced EUS. Tissue harmonic imaging (THI) is a novel US acquisition method that provides better US images by using second harmonic signals. The potential advantages of THI are improved lateral resolution, reduced side lobe artifact and an increased signal-to-noise ratio. EUS-elastography is another novel technique that provides information about the distributed pattern of tissue hardness. Clinical benefits of EUS-elastography for the differential diagnosis of pancreatic tumors and the evaluation of pancreatic fibrosis have been reported. It is necessary to develop a unified and objective method of imaging and analysis to increase the use of EUS-elastography in the future.

The NAFLD Index: A Simple and Accurate Screening Tool for the Prediction of Non-Alcoholic Fatty Liver Disease.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is a common debilitating condition in many industrialized countries that increases the risk of cardiovascular disease. The aim of this study was to derive a simple and accurate screening tool for the prediction of NAFLD in the Japanese population. METHODS: A total of 945 participants, 279 men and 666 women living in Hokkaido, Japan, were enrolled among residents who attended a health check-up program from 2010 to 2014. Participants with an alcohol consumption > 20 g/day and/or a chronic liver disease, such as chronic hepatitis B, chronic hepatitis C or autoimmune hepatitis, were excluded from this study. Clinical and laboratory data were examined to identify predictive markers of NAFLD. RESULTS: A new predictive index for NAFLD, the NAFLD index, was constructed for men and for women. The NAFLD index for men = -15.5693+0.3264 [BMI] +0.0134 [triglycerides (mg/dl)], and for women = -31.4686+0.3683 [BMI] +2.5699 [albumin (g/dl)] +4.6740[ALT/AST] -0.0379 [HDL cholesterol (mg/dl)]. The AUROC of the NAFLD index for men and for women was 0.87(95% CI 0.88-1.60) and 0.90 (95% CI 0.66-1.02), respectively. The cut-off point of -5.28 for men predicted NAFLD with an accuracy of 82.8%. For women, the cut-off point of -7.65 predicted NAFLD with an accuracy of 87.7%. CONCLUSION: A new index for the non-invasive prediction of NAFLD, the NAFLD index, was constructed using available clinical and laboratory data. This index is a simple screening tool to predict the presence of NAFLD.