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Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is an essential endoscopic tissue sampling method for diagnosing pancreatobiliary diseases; however, determining the presence of target specimens mixed in the blood by conventional observation is challenging due to the small size of the obtained sample. This study investigated the usefulness of a target sample check illuminator (TSCI) that emits a specific wavelength of light to determine the presence of target specimens. Twenty-seven patients who underwent EUS-FNA at our hospital were included. Conventional white light observation was performed for the collected samples, followed by TSCI; six people evaluated the presence of the target specimen on a 5-point scale. The target specimen discrimination score using TSCI (median: 5) was significantly higher than that using conventional white light observation (median: 1) (p < 0.001). No significant difference was observed in the discrimination score between the evaluator (novice vs. expert, p = 0.162) and puncture needle (22G vs. 25G, p = 0.196). The discriminability of TSCI in the samples obtained using EUS-FNA was significantly higher than that of conventional observation. TSCI does not depend on the evaluator or puncture needle for the identification of the target specimen; hence, it can provide a good pathological specimen and may contribute to the improvement of the diagnostic ability.

The coronavirus disease 2019 (COVID-19) is known to cause gastrointestinal symptoms. Recent studies have revealed COVID-19-attributed acute pancreatitis (AP). However, clinical characteristics of COVID-19-attributed AP remain unclear. We performed a narrative review to elucidate relation between COVID-19 and AP using the PubMed database. Some basic and pathological reports revealed expression of angiotensin-converting enzyme 2 and transmembrane protease serine 2, key proteins that aid in the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into the pancreas. The experimental and pathological evaluation suggested that SARS-CoV-2 infects human endocrine and exocrine pancreas cells, and thus, SARS-CoV-2 may have a direct involvement in pancreatic disorders. Additionally, systemic inflammation, especially in children, may cause AP. Levels of immune mediators associated with AP, including interleukin (IL)-1β, IL-10, interferon-γ, monocyte chemotactic protein 1, and tumor necrosis factor-α are higher in the plasma of patients with COVID-19, that suggests an indirect involvement of the pancreas. In real-world settings, some clinical features of AP complicate COVID-19, such as a high complication rate of pancreatic necrosis, severe AP, and high mortality. However, clinical features of COVID-19-attributed AP remain uncertain due to insufficient research on etiologies of AP. Therefore, high-quality clinical studies and case reports that specify methods for differential diagnoses of other etiologies of AP are needed.

Background Endoscopic ultrasonography-guided fine-needle aspiration biopsy (EUS-FNB) enhances the diagnostic capabilities of EUS by providing additional pathological samples. However, detecting the target specimens within the collected samples can be challenging. This study determined the most appropriate wavelength for detecting target specimens within EUS-FNB samples in an animal experiment. Methods EUS-FNB pancreatic tissue samples were collected from a male beagle (weight, 10 kg). The samples were illuminated with monochromatic light of varying wavelengths at 5-nm intervals from 430 to 700 nm. Optimal wavelengths for distinguishing target specimens within samples were determined. Results Transmitted monochromatic light at a wavelength of 605 nm effectively enhanced the contrast between target specimens and blood in EUS-FNB samples. The strengths of the target specimen and blood samples were quantified and analyzed using densitometry in images obtained by irradiating at each wavelength. The contrast between target specimens and blood samples peaked at 600–605 nm. Conclusions Microscopical observations using transmitted light at a wavelength of 605 nm effectively identified target tissues within EUS-FNB samples.

Background and aim Endoscopic retrograde cholangiopancreatography (ERCP)-related tissue acquisition, including fluoroscopy-guided forceps biopsy (F-FB), is a common technique in diagnosing indeterminate biliary lesions. Recently, peroral cholangioscopy (POCS) and POCS-guided forceps biopsy (POCS-FB) has also been used for the diagnosis of indeterminate biliary lesions. However, it is uncertain which of those techniques were superior for the diagnosis of extrahepatic cholangiocarcinoma (ECC). We aimed to evaluate the diagnostic yield and safety of F-FB for indeterminate biliary lesions compared with POCS-FB. Methods Patients who underwent F-FB or POCS-FB to evaluate indeterminate biliary lesions between October 2011 and August 2019 were enrolled retrospectively. We carried out propensity score matching to balance these clinical differences between the F-FB group and POCS-FB group. In the propensity score-matched cohort, we compared the diagnostic performance of F-FB with that of POCS-FB based on the pathological evaluation. We also evaluate adverse events associated with F-FB and POCS-FB. Results We enrolled 113 patients with biliary diseases, and 62 patients were analyzed in the propensity score-matched cohort. Sensitivity, specificity, and accuracy of F-FB were 82.4, 100, and 90.3%, and for POCS-FB, those values were 83.3, 100, and 90.3%, respectively. There were no significant differences in the diagnostic performance between F-FB and POCS-FB. There were also no significant differences in the occurrence of adverse events between F-FB and POCS-FB (41.9 vs 29.0%, P = 0.289). Conclusions The diagnostic yield of F-FB for ECC is similar to that of POCS-FB. POCS-FB is not necessary for the initial pathological diagnosis of indeterminate biliary lesions.

Breakdown voltage enhancement was studied for p-GaN/AlGaN/GaN heterostructure diodes, where residual Si donors during growth were compensated with Mg acceptors doped in the p-GaN layer. As the thicknesses of the p-GaN layer (T p-GaN) decreased from 140 nm, breakdown voltages were increased and maximized at 20 nm, then decreased at 0 nm. Moreover, breakdown voltages of the 20 nm T p-GaN diodes improved with the increase of the drift region lengths. This is because a uniform electric field was obtained by compensation of the residual Si donors with the Mg acceptors. In addition, for a thicker p-GaN layer, the effects of the surface states were suppressed, and injection of a large number of holes under forward bias was observed. Consequently, the thick p-GaN layer is expected to enhance forward current. Adopting the results, the potential of low on-resistance and high current for p-GaN gated anode diodes was demonstrated.

[Background] Although endoscopic ultrasonography (EUS) is a useful tool for diagnosing pancreatobiliary diseases, not many facilities perform this technique as it is difficult to master. Currently, two new EUS systems exist: EU-ME2/GF-UCT260, manufactured by Olympus, and SU-1/EG-580UT, manufactured by Fujifilm. Some reports have compared new EUS models to older versions, but the operability and image quality of these two latest systems have not been compared. Our study aimed to compare the usefulness of these two types of EUS. [Methods] Forty consecutive patients were recruited and randomized in a two-arm clinical trial; Arm 1: EU-ME2/GF-UCT260 was used only for observation and SU-1/EG-580UT for EUS-fine needle aspiration (FNA); Arm 2: SU-1/EG-580UT was used only for observation and EU-ME2/GF-UCT260 for EUS-FNA. Using a crossover design, we evaluated image findings, ease of scope insertion, and visibility of the gastrointestinal (GI) tract. Each procedure was scored using a 5-point scale (Clinical Trial ID: UMIN000031373). [Results] SU-1/EG-580UT was significantly better in terms of lesion-delineating capacity: lesion border (P < 0.001), internal echo (P < 0.001). Significantly easier scope insertion was observed with SU-1/EG-580UT with respect to any insertion into the piriform recess (P = 0.018), the pylorus ring (P < 0.001), and the superior duodenal angle (P < 0.001). Visibility during gastrointestinal observation was also significantly better with the SU-1/EG-580UT (P < 0.001) than with the EU-ME2/GF-UCT260. [Conclusion] SU-1/EG-580UT EUS demonstrated superior performance during ultrasonic endoscopic GI observation, operability, and ultrasonic image quality. The result of the superior ultrasound imaging quality of SU-1/EG-580UT EUS will aid in the identification of small pancreatic malignancies with unclear borders and prove useful in evaluating mural nodules of IPMN in detail. These findings could result in an increased use of EUS and improve identification and prognosis of patients with pancreatobiliary diseases.

Background: Peroral cholangioscopy (POCS)-guided forceps mapping biopsy (FMB) is a method for the accurate preoperative identification of the extent of the disease of biliary tract cancer (BTC). However, the diagnostic value of POCS-FMB is still uncertain. Objectives: We evaluated the diagnostic utility of POCS-FMB for the identification of lateral extension—superficial intraductal spread longitudinally and continuously from the main lesion—of BTC. Methods: In the retrospective study, patients who received POCS-FMB and surgery for curative resection of BTC between September 2016 and August 2019 at our medical institution were enrolled. The diagnostic accuracy of POCS-FMB for the identification of lateral extension of BTC was evaluated. Furthermore, we also evaluated the factors affecting the diagnostic accuracy of POCS-FMB. Results: A total of 23 patients with BTC were enrolled, and 24 procedures of POCS-FMB from 96 sites of biliary tracts were performed. The sensitivity, specificity, and accuracy of POCS-FMB were 53.8%, 63.9%, and 63.1%, respectively. In the multivariate logistic regression analyses, the biopsy from the bifurcation of biliary tracts was a significant factor affecting the diagnostic accuracy of POCS-FMB (odds ratio 3.538, 95%, confidence interval 1.151–10.875, p = 0.027). Conclusions: The diagnostic accuracy of POCS-FMB for the identification of lateral extension of BTC was insufficient. The biopsy from the bifurcation of biliary tracts was a positive factor affecting the diagnostic accuracy of POCS-FMB.

Background and Aim Endoscopic retrograde cholangiopancreatography (ERCP)‐related tissue acquisition, including fluoroscopy‐guided forceps biopsy (F‐FB), is a common technique in diagnosing indeterminate biliary lesions. Recently, peroral cholangioscopy (POCS) and POCS‐guided forceps biopsy (POCS‐FB) has also been used for the diagnosis of indeterminate biliary lesions. However, it is uncertain which of those techniques were superior for the diagnosis of extrahepatic cholangiocarcinoma (ECC). We aimed to evaluate the diagnostic yield and safety of F‐FB for indeterminate biliary lesions compared with POCS‐FB. Methods Patients who underwent F‐FB or POCS‐FB to evaluate indeterminate biliary lesions between October 2011 and August 2019 were enrolled retrospectively. We carried out propensity score matching to balance these clinical differences between the F‐FB group and POCS‐FB group. In the propensity score‐matched cohort, we compared the diagnostic performance of F‐FB with that of POCS‐FB based on the pathological evaluation. We also evaluate adverse events associated with F‐FB and POCS‐FB. Results We enrolled 113 patients with biliary diseases, and 62 patients were analyzed in the propensity score‐matched cohort. Sensitivity, specificity, and accuracy of F‐FB were 82.4, 100, and 90.3%, and for POCS‐FB, those values were 83.3, 100, and 90.3%, respectively. There were no significant differences in the diagnostic performance between F‐FB and POCS‐FB. There were also no significant differences in the occurrence of adverse events between F‐FB and POCS‐FB (41.9 vs 29.0%, P = 0.289). Conclusions The diagnostic yield of F‐FB for ECC is similar to that of POCS‐FB. POCS‐FB is not necessary for the initial pathological diagnosis of indeterminate biliary lesions., We performed a retrospective study to compare the diagnostic utility of fluoroscopy‐guided forceps biopsy for indeterminate biliary strictures and that of peroral cholangioscopy‐guided forceps biopsy in the propensity score‐matched cohort, and 62 patients were analyzed in the study. Sensitivity, specificity, and accuracy of fluoroscopy‐guided forceps biopsy (F‐FB) were 82.4, 100, and 90.3%, and for peroral cholangioscopy‐guided forceps biopsy (POCS‐FB), those values were 83.3, 100, and 90.3%, respectively. There were no significant differences in the diagnostic performance between F‐FB and POCS‐FB.

We have demonstrated an extremely low voltage rectifier by using p-GaN gate AlGaN/GaN high electron mobility transistors. In contrast to conventional GaN rectifiers, the turn-on voltage and on-state current can be decoupled, resulting in low turn-on voltage of 0.05 V and high on-state current achieved simultaneously with p-GaN designs. Furthermore, the role of p-GaN layer on current–voltage characteristics of p-GaN gated anode diode was investigated, indicating the p-GaN layer is the source of hole current. Combined the electron current with hole current, the total current was enhanced significantly with the ohmic p-GaN gate electrode. Finally, full-wave AC to DC rectification was demonstrated by a monolithically-integrated diode bridge rectifier with four p-GaN gated anode diodes. The bridge rectifier is able to operate at an input signal as low as 0.18 V, which is very promising for future power conversion applications.

In the last decade, the incidence rate of detection rate of superficial head, neck and esophageal squamous cell carcinomas has increased with the development of endoscopic imaging techniques. These cancers are thought to arise independently subsequent to tissue exposure to a common carcinogen e.g. alcohol or tobacco. This phenomenon has been termed field cancerization. To determine the molecular background of the development of hypopharyngeal squamous cell carcinomas (HPSCCs) and double esophageal squamous cell carcinomas (DESCCs), the present study immunohistochemically assessed tumor-related protein expression [p53, Fhit (fragile histidine triad), E-cadherin and activation-induced cytidine deaminase (AID)], and subsequently determined the correlation between protein expression and clinicopathological data. Tumor specimens of 9 HPSCCs and 9 DESCCs were endoscopically obtained from 8 patients with HPSCC. The 9 DESCCs, including 5 synchronous and 4 metachronous lesions, were all obtained from four patients with HPSCC. The overexpression of p53 and loss of Fhit expression was immunohistochemically detected in 8 (88.9%) and 8 (88.9%) of the 9 HPSCCs and in 8 (88.9%) and 8 (88.9%) of the 9 DESCCs, respectively, which demonstrated the high frequency of such expression. Additionally, 7 out of 9 HPSCCs, and 7 out of 9 DESCCs demonstrated aberrant expression of p53 and Fhit. The rate of aberrant AID and E-cadherin expression was 67 and 44% in HPSCCs and 44 and 44% in DESCC, respectively. These results suggested that aberrant p53 and Fhit expression was involved in the development of HPSCC and their DESCC, and that their expression may be used for the prediction of DESCC development in patients with HPSCC, thereby acting as a biomarker of field cancerization.

Smoking and alcohol consumption are major risk factors for the development of esophageal squamous cell carcinoma (ESCC). Recent studies have demonstrated that smoking and alcohol consumption may be associated with altered DNA methylation in human cancer development. The aim of the present study was to evaluate methylation-modulated protein expression of tumor-related genes (TRGs) in the early stages of esophageal squamous neoplasia (ESN). ESN tissue samples (n=141) comprising 19 cases of low-grade intraepithelial neoplasia (LGIN), 70 of high-grade intraepithelial neoplasia/carcinoma in situ (HGIN/CIS) and 52 of invasive cancer, were endoscopically resected. The methylation-modulated protein expression of 5 TRGs [fragile histidine triad (FHIT), E-cadherin, MutL homolog 1 (MLH1) /MutS homolog 2 (MSH2) and cyclooxygenase-2 (COX-2)] as well as p53 was examined with immunohistochemistry, and their expression was compared with patient clinicopathological characteristics. Reduced or loss of FHIT, E-cadherin, MLH1/MSH2 and COX-2 expression was detected in 26.3 (5/19), 5.3 (1/19), 0 (0/19) and 63.2% (12/19) of LGIN cases, 61.4 (43/70), 18.6 (13/70), 7.1 (5/70) and 65.7% (46/70) of HGIN/CIS cases, and 78.8 (41/52), 50.0 (26/52), 11.5 (6/52) and 59.6% (31/52) of invasive cancer cases, respectively. Reduced or absent expression of FHIT and E-cadherin was significantly associated with neoplastic progression (FHIT, P=0.0007; E-cadherin, P=0.00014). The mean number of TRGs (FHIT, E-cadherin, MLH1/MSH2, and COX-2) that exhibited reduced or absent expression in LGIN, HGIN/CIS and invasive cancer specimens was 1.12±0.61, 1.66±0.93 and 2.09±0.96, respectively, demonstrating a significant stepwise increment from LGIN to HGIN/CIS and then to invasive cancer (P

Background Programmed cell death-1 (PD-1) inhibitor has been indicated for many types of malignancies. However, these inhibitors also cause immune-related adverse events. Hepatobiliary disorder is a phenotype of immune-related adverse event affecting 0%-4.5% of patients treated with PD-1 inhibitors. Recent studies have reported PD-1 inhibitor-related sclerosing cholangitis (SC); however, the associated clinical and pathological features are unclear. Aim To evaluate the clinical and pathological features of PD-1 inhibitor-related SC through a systematic review of the literature. Methods The review, conducted using electronic databases in PubMed, was restricted to the period from January 2014 to September 2019 and focused on case reports/series on PD-1 inhibitor-related SC published in English. We scanned the references of the selected literature to identify any further relevant studies. Six cases previously studied by us, including three that have not yet been published, were included in this review. Results Thirty-one PD-1 inhibitor-related SC cases were evaluated. Median age of patients was 67 years (range, 43-89), with a male to female ratio of 21:10. The main disease requiring PD-1 inhibitor treatment was non-small cell lung cancer. Agents that caused PD-1 inhibitor-related SC were nivolumab (19 cases), pembrolizumab (10 cases), avelumab (1 case), and durvalumab (1 case). The median number of cycles until PD-1 inhibitor-related SC onset was 5.5 (range, 1-27). Abdominal pain or discomfort (35.5%, 11/31) was the most frequent symptom. Blood serum tests identified liver dysfunction with a notable increase in biliary tract enzymes relative to hepatic enzymes, and a normal level of serum immunoglobulin G4. Biliary dilation without obstruction (76.9%, 20/26), diffuse hypertrophy of the extrahepatic biliary tract (90.5%, 19/21), and multiple strictures of the intrahepatic biliary tract (30.4%, 7/23) were noted. In 11/23 (47.8%) cases, pathological examination indicated that CD8+ T cells were the dominant inflammatory cells in the bile duct or peribiliary tract. Although corticosteroids were mainly used for PD inhibitor-related SC treatment, the response rate was 11.5% (3/26). Conclusion Some clinical and pathological features of PD-1 inhibitor-related SC were revealed. To establish diagnostic criteria for PD-1 inhibitor-related SC, more cases need to be evaluated.

Background: Peroral cholangioscopy (POCS)-guided forceps biopsy is a method for diagnosing indeterminate biliary strictures and for the preoperative identification of the exact perihilar and distal margins of biliary tract cancer (BTC). However, POCS-guided forceps biopsy may result in an insufficient amount of specimen at times. Aims: We evaluated the sufficient tissue acquisition rate and the factors affecting the sufficient tissue acquisition of POCS-guided forceps biopsy for the biliary tract. Methods: Patients who underwent POCS-guided forceps biopsy for biliary disease between September 2016 and October 2018 at our hospital were enrolled retrospectively. We evaluated the sufficient tissue acquisition rate of POCS-guided forceps biopsy for the biliary lesion and that for non-stenotic bile duct. In addition, the factors affecting the sufficient tissue acquisition rate of POCS-guided forceps biopsy were evaluated. Results and Conclusions : We enrolled 47 patients with the biliary disease and performed POCS-guided forceps biopsy for biliary lesion and POCS-guided forceps mapping biopsy for non-stenotic bile duct in 40 and 36 patients, respectively. The sufficient tissue acquisition rates of POCS-guided forceps biopsy for biliary lesions and that for non-stenotic bile duct were 86.4%, and 68.9%, respectively. In the multivariate logistic regression analyses, age and previous biliary stenting before POCS were factors affecting the sufficient tissue acquisition rate of POCS-guided forceps biopsy for the biliary lesion. For non-stenotic bile duct, the location of the biliary lesion, endoscopic sphincterotomy, and procedure time of POCS were factors affecting the sufficient tissue acquisition rate of POCS-guided forceps mapping biopsy.

Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA) is a useful procedure that enables reliable pathological diagnoses of pancreatobiliary diseases, subepithelial lesions, and swollen lymph nodes. In recent years, a pathological diagnosis based on EUS-FNA has made it possible to provide accurate treatment methods not only in these fields, but also in respiratory organs and otorhinolaryngology. This review discusses the latest topics pertaining to EUS-FNA as well as procedural tips.

Few studies have compared the diagnostic utility of endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) and endoscopic retrograde cholangiopancreatography (ERCP) tissue sampling for extrahepatic cholangiocarcinoma (ECC). We evaluated the efficacy and safety of EUS-FNA for diagnosing ECC compared with ERCP tissue sampling. Patients who underwent EUS-FNA or ERCP tissue sampling to differentiate ECC from benign biliary disease were enrolled retrospectively between October 2011 and March 2017. We evaluated diagnostic performances of EUS-FNA and ERCP tissue sampling based on pathological evaluation. We compared adverse events in EUS-FNA and ERCP tissue sampling. We enrolled 73 patients with biliary disease and performed EUS-FNA and ERCP in 19 and 54 patients, respectively. Sensitivity, specificity, and accuracy of ERCP tissue sampling were 76.0%, 100%, and 88.9%, respectively, and for EUS-FNA these were 81.8%, 87.5%, and 84.2%, respectively. Statistical values of ERCP tissue sampling and EUS-FNA were not significantly different. The adverse event frequency of EUS-FNA was significantly lower than that of ERCP tissue sampling (0% vs. 25.9%, p = 0.033). The diagnostic ability of EUS-FNA for ECC is similar to that of ERCP tissue sampling. EUS-FNA is a safer tissue sampling modality than ERCP for evaluating biliary disease.

High breakdown voltage (BV) AlGaAs/GaAs/AlGaAs diodes with a pair of hole and electron channels were studied taking account of the residual carbon impurity. The residual acceptor that would affect the charge balance was evaluated by separate growth. Utilizing the residual concentration, the acceptor concentrations (N A) were examined with a fixed donor concentration of 1.1 × 1012 cm−2. For N A of 0.9 × 1012 cm−2, the diode with 113 μm drift region length derived the highest BV of 1800 V. Temperature-dependent I–V measurements revealed the breakdown due to an avalanche multiplication. This implies a uniform electric field across the channels. Then, depletion of both channels was characterized by C–V measurements for obtaining capacitance shut-off voltages of the diodes. The lowest shut-off voltage was obtained for the 0.9 × 1012 cm−2 N A diode. This would be due to the simultaneous depletion of hole and electron channels, i.e. the identical net concentration for acceptor and donor.

Background Peroral cholangioscopy (POCS)-guided forceps biopsy is a method for diagnosing indeterminate biliary strictures and for the preoperative identification of the exact perihilar and distal margins of biliary tract cancer (BTC). However, POCS-guided forceps biopsy may result in an insufficient amount of specimen at times. Therefore, we evaluated the adequate tissue acquisition rate and the factors affecting the adequate tissue acquisition of POCS-guided forceps biopsy for the biliary tract. Methods Patients who underwent POCS-guided forceps biopsy for biliary disease between September 2016 and October 2018 at our hospital were enrolled retrospectively. We evaluated the adequate tissue acquisition rate of POCS-guided forceps biopsy for the biliary lesion and that for non-stenotic bile duct. In addition, the factors affecting the adequate tissue acquisition rate of POCS-guided forceps biopsy were evaluated. Results We enrolled 47 patients with biliary disease and performed POCS-guided forceps biopsy for biliary lesion and POCS-guided forceps mapping biopsy for non-stenotic bile duct in 40 and 36 patients, respectively. The adequate tissue acquisition rates of POCS-guided forceps biopsy for biliary lesions and that for non-stenotic bile duct were 86.4%, and 68.9%, respectively. In the multivariate logistic regression analyses, age, and previous biliary stenting before POCS were factors affecting the adequate tissue acquisition rate of POCS-guided forceps biopsy for the biliary lesion. For non-stenotic bile duct, the location of the biliary lesion, endoscopic sphincterotomy (EST), and procedure time of POCS were factors affecting the adequate tissue acquisition rate of POCS-guided forceps mapping biopsy. Conclusions Previous biliary stenting was a factor affecting a low tissue acquisition rate of POCS-guided forceps biopsy for the biliary lesion. In the POCS-guided forceps mapping biopsy, the location of the biliary lesion, EST, and procedure time were factors affecting tissue acquisition rates.

Background and aim Pancreatic ductal adenocarcinoma (PDAC) is difficult to detect in its early stages with the poorest prognosis of all cancers. To improve the prognosis, a precise diagnosis is needed when we suspect PDAC. Although endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA) is a widely accepted modality for the diagnosis of PDAC, its sensitivity is 85-89%, and approximately 10% of PDAC cases cannot be diagnosed. The main causes that interrupt the diagnosis of PDAC by using EUS-FNA are tumor size, presence of a vessel or the main pancreatic duct along the puncture route, and difficulty in withdrawing anticoagulant. Pancreatic juice cytology (PJC), the sensitivity of which is 33.3-65.8%, is a method for the diagnosis of PDAC cases in which carrying out of EUS-FNA is difficult. To diagnose PDAC appropriately, we need to improve the diagnostic ability of PJC. Methods We examined PJC using synthetic secretin for 138 cases of pancreatic tumor and pancreatic non-cancerous diseases. Results Sensitivity of PJC improved from 50.9% to 74.0% as a result of synthetic secretin loading, and 13 PDAC cases that had not been able to be diagnosed with EUS-FNA could be diagnosed pathologically by PJC. Although there were 12 patients with mild pancreatitis (8.7%) as a complication, all were relieved with conservative treatment. Conclusion Adding synthetic secretin to PJC is useful for cases in which it is difficult to carry out EUS-FNA for PDAC.

A number of tumor-associated genes have been associated with gastric cancer development. The present study evaluated differences in tumor-associated protein expression and phenotype among early gastric neoplasms, and correlated these data with those of the background mucosa. The expression of activation-induced cytidine deaminase (AID), p53 and MLH1 in 151 early gastric neoplasms [22 gastric adenomas, 92 intramucosal carcinomas (MCs), and 37 submucosal carcinomas (SMCs)] was examined immunohistochemically and compared with that of the corresponding background mucosal condition. The cellular phenotypes of the neoplasms and the corresponding background intestinal metaplasia were also determined. Aberrant AID, p53 and MLH1 expression was detected in 36.4, 0 and 0% of the adenomas, in 35.9, 32.6 and 16.3% of the MCs, and in 56.8, 62.2 and 21.6% of the SMCs, respectively. The frequency of aberrant AID and p53 expression in the SMCs was significantly increased compared with that in the MCs (AID, P

Background and Aim. Pancreatic juice cytology (PJC) is considered optimal for differentially diagnosing pancreatic masses, but the accuracy of PJC ranges from 46.7% to 93.0%. The aim of this study was to evaluate the clinical impact of measuring the KL-6 concentration of pancreatic juice for diagnosing pancreatic masses.Methods. PJC and the KL-6 concentration measurements of pancreatic juice were performed for 70 consecutive patients with pancreatic masses (39 malignancies and 31 benign).Results. The average KL-6 concentration of pancreatic juice was significantly higher for pancreatic ductal adenocarcinomas (PDACs) (167.7±396.1 U/mL) and intraductal papillary mucinous carcinomas (IPMCs) (86.9±21.1 U/mL) than for pancreatic inflammatory lesions (17.5±15.7 U/mL,P=0.034) and intraductal papillary mucinous neoplasms (14.4±2.0 U/mL,P=0.026), respectively. When the cut-off level of the KL-6 concentration of pancreatic juice was 16 U/mL, the sensitivity, specificity, and accuracy of the KL-6 concentration of pancreatic juice alone were 79.5%, 64.5%, and 72.9%, respectively. Adding the KL-6 concentration of pancreatic juice to PJC when making a diagnosis caused the values of sensitivity and accuracy of PJC to increase by 15.3% (P=0.025) and 8.5% (P=0.048), respectively.Conclusions. The KL-6 concentration of pancreatic juice may be as useful as PJC for diagnosing PDACs.

Distal malignant biliary obstruction (MBO) leads to obstructive jaundice as a result of when the bile excretion from the liver is disturbed and induces hepatic failure and sepsis, which when complicated with cholangitis, it becomes necessary to perform drainage for the MBO. For biliary drainage, we can perform a surgical bypass operation, percutaneous transhepatic biliary drainage (PTBD), endoscopic biliary drainage (EBD) via duodenal papilla, or endoscopic ultrasound (EUS)-guided biliary drainage (EUS-BD), which is a transgastrointestinal biliary drainage. Although currently we usually perform EBD for distal MBO to begin with, the choice is different for biliary drainage in patients in whom EBD has failed in a preoperative case or an unresectable case. In other words, we choose PTBD for preoperative cases, and PTBD or EUS-BD according to the ability of the institution for their procedures when EBD has failed. It is desirable not to choose a plastic stent (PS) but a self-expandable metallic stent (SEMS), in particular for the unresectable cases of pancreatic cancer it is desirable not to choose an uncovered SEMS but a covered SEMS in EBD. Nevertheless, further examinations are expected to decide which, a covered or uncovered SEMS, we should choose in unresectable biliary tract cancer (BTC) and whether we should select PS, SEMS or ENBD in preoperative cases.

Objective Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection may be involved in the development of cholangiocarcinoma. The prevalence of HBV and HCV infection was examined in patients with intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC). Methods The levels of HBV surface antigens (HBsAg), antibodies against HBV core antigens (HBcAb) and hepatitis C virus antibodies (HCV-Ab) were determined in sera obtained from 145 consecutive patients (50 patients with ICC, 95 patients with ECC). Results The seroprevalence of HBsAg was 10% in the ICC patients and 4.2% in the ECC patients. The prevalence of HCV-Ab was 20% in the ICC patients and 7.4% in the ECC patients. Conclusion The prevalence of HBsAg and HCV-Ab is 0.8-2.2% and 1-2%, respectively, in the Japanese population living in the Tottori area. Furthermore, HBV and HCV infection is a possible risk factor for the development of cholangiocarcinoma. Therefore, the surveillance of ICC and ECC is needed in HBV and HCV carriers.

Background: Peroral cholangioscopy (POCS) has become a widely-used technique in diagnosing indeterminate biliary strictures, enabling optical viewing of the biliary system and targeted biopsies under direct vision. The diagnostic utility of the new endoscopic scraper, Trefle&reg, for extrahepatic cholangiocarcinoma (ECC) has also been reported. However, the diagnostic utility of POCS-guided and Trefle&reg, assisted tissue acquisition for ECC has never been compared empirically. We evaluated the efficacy and safety of Trefle&reg, assisted tissue acquisition for diagnosing ECC compared with POCS-guided tissue sampling. Methods: Patients who underwent Trefle&reg, assisted tissue acquisition or POCS-guided forceps biopsy to differentiate ECC from benign biliary disease between April 2014 and March 2018 were enrolled retrospectively. We evaluated the diagnostic performance of Trefle&reg, assisted tissue acquisition and POCS-guided forceps biopsy based on pathological evaluation. We also compared adverse events associated with Trefle&reg, assisted tissue acquisition with those of POCS-guided forceps biopsy. Results: We enrolled 34 patients with biliary disease and performed Trefle&reg, assisted tissue acquisition and POCS-guided forceps biopsy in 14 and 20 patients, respectively. Sensitivity, specificity, and accuracy of Trefle&reg, assisted tissue acquisition were 87.5%, 83.3%, and 85.7%, respectively, and for POCS-guided forceps biopsy, these were 90.0% each. Statistical values of Trefle&reg, assisted tissue acquisition and POCS-guided tissue acquisition were not significantly different. There were no significant differences in the occurrence of adverse events between the Trefle&reg, assisted tissue acquisition and the POCS-guided forceps biopsy (35.7% vs. 25.0%, p = 0.770). Compared with patients who underwent POCS procedure, endoscopic sphincterotomy was performed for fewer patients who underwent Trefle&reg, assisted tissue acquisition (p &lt, 0.001). Conclusions: The diagnostic ability of Trefle&reg, assisted tissue acquisition for ECC is similar to that of POCS-guided tissue acquisition. Trefle&reg, assisted tissue acquisition might also help to preserve the sphincter of Oddi and its digestive function.

The adenoma-carcinoma sequence (ACS) and the serrated pathway are two distinct developmental routes leading to the formation of colorectal carcinoma (CRC). However, the mechanism triggered by the serrated pathway remains unclear. Therefore, to clarify the molecular and clinicopathological characteristics of the serrated tumorigenic pathway, immunohistochemistry was used to examine the expression of Fragile Histidine Triad (FHIT), cyclooxygenase-2 (COX-2), MutL homolog 1 (MLH1), MutS protein homolog 2 (MSH2) and P53 in endoscopically resected samples of 62 serrated polyps. These samples included 20 hyperplastic polyps (HPs), 16 traditional serrated adenomas (TSAs), 26 sessile serrated adenoma/polyps (SSA/Ps), 20 non-serrated adenomas, 20 carcinoma in adenomas (CIAs) and 18 early pure CRCs without any adenoma component (EPCs). FHIT expression was markedly reduced or absent in 50% of TSA samples, 92.3% of SSA/Ps and 44% of EPCs, but only rarely in HPs, non-serrated adenomas and CIAs. COX-2 expression was more common in non-serrated adenomas compared with in serrated polyps, and was present in 25 and 3.2% of the cases respectively (P

This study aimed to compare the tissue stiffness of pancreatic ductal adenocarcinoma (PDAC) with that of pancreatic parenchyma using virtual touch quantification (VTQ). SWV was measured in 34 PDAC lesions and in pancreatic parenchyma of both controls and patients. SWVs in PDAC lesions were significantly higher than in pancreatic parenchyma in both healthy controls and in patients with PDAC. The area under the ROC for diagnosis of PDAC was 0.94 for pancreatic parenchyma in healthy controls, and 0.85 for pancreatic parenchyma in patients with PDAC. VTQ can provide a useful and additional information for diagnosis of PDAC.

Background and study aims: Specimens collected by fine needle are microscopic and contain blood; therefore, the presence of a target specimen within a sample is often difficult to confirm. Although rapid on-site evaluation (ROSE) during endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNA) is beneficial, many health care facilities are unable to apply this technique due to a lack of cytopathologists. The aim of this study was to develop and validate a device that detects the target specimen within pancreatic tumor EUS-FNA samples. Patients and methods: Fifty-eight consecutive patients with solid pancreatic masses were studied for a preliminary case series at a tertiary-care university hospital (Tottori University Hospital, Yonago, Japan). The material collected was checked with a target sample check illuminator (TSCI) and was evaluated by one cytopathologist. Results: The agreement rate between the TSCI and histopathology was 93.7 %. Further testing procedures were not needed in 91.4 % of patients, and the mean number of needle punctures was 1.2 after a single pass using TSCI. No adverse events were encountered with the procedure. Conclusions: With the introduction of the TSCI in EUS-FNA, it became possible to both collect the minimum necessary target samples by EUS-FNA and to end further procedures, even without performing ROSE.

Pancreatic cancer is the fifth leading cause of cancer death and has the lowest survival rate of any solid cancer. Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA) is currently capable of providing a cytopathological diagnosis of pancreatic malignancies with a higher diagnostic power, with a sensitivity and specificity of 85%-89% and 98%-99%, compared to pancreatic juice cytology (PJC), whose sensitivity and specificity are only 33.3%-93% and 83.3%-100%. However, EUS-FNA is not effective in the cases of carcinoma in situ and minimally invasive carcinoma because both are undetectable by endoscopic ultrasonography, although PJC is able to detect them. As for the frequency of complications such as post endoscopic retrograde cholangiopancreatography pancreatitis, EUS-FNA is safer than PJC. To diagnose pancreatic cancer appropriately, it is necessary for us to master both procedures so that we can select the best methods of sampling tissues while considering the patient's safety and condition.

The patient was a 68-year-old man with pancreatic cancer exhibiting invasion into the superior mesenteric artery and stenosis of the third part of the duodenum. He subsequently received a duodenal stent for malignant gastric outlet obstruction. On day 43 after the placement of the duodenal stent, he reported feeling poorly, with hypotension and hematemesis. High-density areas were observed from the stomach to the rectum on computed tomography. We diagnosed the origin of bleeding as the last third of the duodenum; unfortunately, the patient died. This is the first report of massive gastrointestinal tract bleeding as a late complication of self-expandable metallic stent placement for malignant gastric outlet obstruction.

the modality and long-term outcomes of both non-invasive (US/CT/MRI) and invasive (EUS) surveillance in these patients. The purpose of this study was to evaluate each modality in the detection of pancreatic cancer during surveillance of IPMN to validate the current guidelines. Methods: Between June 2007 and January 2014, 535 asymptomatic high-risk individuals (HRIs) with either pancreatic cysts (O5mm) or a dilated main pancreatic duct (O2.5mm) were examined periodically at a single center, using pancreatic protocol US (pUS) (every 3 or 6 month) and CT or MRI (once a year). EUS was performed when any changes such as hypoechoic mass, new nodule or rapid change in cyst size were detected by pUS. ERCP was recommended for cytology when the size of the cyst became bigger than 3cm, the main pancreatic duct was dilated bigger than 3mm, a newly narrowed part appeared or the size of the cyst or main pancreatic duct changed rapidly. EUS-FNA was performed when an invasive nodule or a hypoechoic mass was detected. Contrast harmonic pUS/EUS was also performed when necessary. Results: Thirteen cases of IPMN with malignancy were confirmed during follow up (2.4% incidence rate). 8 males and 5 females (mean ageZ69.3 yrs). Seven patients had an IPMN with associated carcinoma (2: invasive, 5: non-invasive), Six patients had a pancreatic ductal adenocarcinoma concomitant with IPMN. The median total follow up period until the detection of cancer was 34 months (range 9 64 mo). The number of patients in cancer stages 0, IA, IIA, IIB, III, was 5, 3, 2, 1 and 2, respectively. Of the thirteen patients with IPMN, at the time of cancer diagnosis, 7 had cysts of!2cm, 3 had cysts of 2-3cm, and 3 had cysts of O3cm. The 7 patients with cysts less than 2 cm were found to have multiple cysts. Invasive cancer showed hypo-vascularity in pUS/CE-EUS. All pancreatic cancers smaller than 10mm were detected using pUS or EUS but not by CT or MRI. Conclusion: Contrary to current guidelines for the management of IPMN, more surveillance is recommended for patients of IPMN with multiple small cysts because pancreatic cancer can develop in those cases. pUS or EUS are recommended to detect pancreatic cancer in early stages during surveillance rather than CT/MRI. 1037 Serum Human Telomerase Reverse Transcriptase Messenger RNA As a Novel Marker for Pancreatic Ductal Adenocarcinoma Kazuya Matsumoto*, Norimasa Miura, Yohei Takeda, Takumi Onoyama, Soichiro Kawata, Kenichi Harada, Yoshikazu Murawaki Department of Gastroenterology, Tottori University School of Medicine, Yonago, Japan; Department of Pathophysiological and Therapeutic Science, Tottori University, Yonago, Japan Background: Endoscopic ultrasound-guided fine needle aspiration biopsy (EUSFNA) used as a diagnostic modality for a pancreatic mass has an accuracy of 8591%. However, the institutions that are capable of performing EUS-FNA are limited. The conventional biomarkers for pancreatic ductal adenocarcinoma (PDAC) have an accuracy of at most around 70%, and are especially difficult to use to distinguish between a PDAC and a pancreatic inflammatory lesion or a benign stricture of the main pancreatic duct (MPD), and between intra-ductal papillary mucinous carcinoma (IPMC) and intra-ductal papillary mucinous neoplasm (IPMN). Therefore, a novel surrogate marker is needed for clinical use. Using a very small amount of mRNA from the human serum, we have established a method to quantify human telomerase reverse transcriptase mRNA (hTERT mRNA) expression. Objective: We examined the usefulness of the serum hTERT mRNA as a biomarker for PDAC. Methods: Eighty-three cases (45 pancreatic cancers, 38 non-pancreatic cancers) were treated in our hospital from December 2011 to October 2012. After removing the cellular component from the serum by centrifugal separation, we did RNA extraction and purification with a DNase treatment, finally hTERT mRNA levels were measured by using a KAPA SYBR FAST Universal One-Step qRT-PCR Kit with SYBR Green I (KAPA BIOSYSTEMS, Boston, USA). Results: The serum hTERT mRNA was significantly higher for PDAC (5285.6 15320.0 copy/serum 10ml) than for pancreatic inflammatory lesions or benign strictures of the MPD (1050.9 807.5 copy/serum 10ml, P! 0.05). Furthermore, the average serum hTERT mRNA of IPMC was significantly higher (2863.6 1291.8 copy/serum 10ml) than that of IPMN (846.5 926.1 copy/ serum 10ml, P! 0.05). Using a cut-off value of 924 (copy/serum 10ml), calculated based on a receiver-operating characteristic curve analysis, the pancreatic malignancies diagnostic ability of hTERT mRNA had a sensitivity of 97.8%, a specificity of 76.3%, a positive-predictive value (PPV) of 83.0%, a negative-predictive value (NPV) of 96.7% and an accuracy of 88.0%. Compared with conventional tumor markers, the sensitivity, NPV and the accuracy of hTERTmRNA for pancreatic malignancies were significantly improved. Regarding the T factor in the pancreatic malignancies, the sensitivity of T1/ T2/ T3/ T4 was 100%/ 100% 100%/ 96.8%, respectively. Conclusion: The measurement of serum hTERT mRNA was useful for the differential diagnosis of pancreatic malignancies. 1038 Characteristics and Outcomes of Pancreatic Cystic Neoplasms With Indeterminate CEA Levels Obtained by Endoscopic Ultrasound Guided Fine-Needle Aspiration (EUS-FNA): Results of a Multicenter Study Diana Jaiyeola*, David Grande, Sachin Wani, Brian C. Brauer, Norio Fukami, Raj J. Shah, Stuart K. Amateau, Roy D. Yen, Richard D. Schulick, Barish H. Edil, Lindsay Hosford, www.giejournal.org Vol Timothy Donahue, V. Raman Muthusamy, Rabindra R. Watson, Alireza Sedarat, Jitin Makker, Phillip S. Ge, Daniel Mullady, Steven A. Edmundowicz, Riad R. Azar, Faris Murad, Vladimir M. Kushnir, Dayna S. Early, Srinivas Gaddam, Dyanna Gregory, Rajesh N. Keswani, Srinadh Komanduri NorthwesternUniversity,Chicago, IL; University of Colorado, Denver, CO; UCLA, Los Angeles, CA; Washington University in St. Louis, St. Louis, MO Introduction: Carcinoembryonic antigen (CEA) levels measured from fluid obtained by EUS-FNA of pancreatic cystic neoplasms (PCN) are used to distinguish between mucinous and non-mucinous cysts. While high accuracy rates with levels O200 ng/ ml for mucinous lesions has been reported, management of PCN with indeterminate CEA levels (5-200ng/ml) is unclear. Aim: To compare clinical parameters and outcomes in patients with indeterminate CEA PCN to patients with CEA O200. Methods: This is a retrospective, multicenter study of consecutive patients undergoing EUS for evaluation of pancreatic cysts. Demographics and EUS morphology, and FNA results were recorded. Univariate analysis to compare those with indeterminate CEA levels (5-200) to those with CEA O200 ng/ml was performed followed by multivariate logistic regression to identify predictors of operative intervention. Results: A total of 3112 patients (59% female, 56% Caucasian) were referred for EUS evaluation of PCN at four tertiary care centers from 2008-2013. The majority of cysts (1828, 58.7%) were identified on body imaging (CT: 54.4%, MR: 10.3%) performed for evaluation of gastrointestinal symptoms (Table 1). EUS-FNA was performed in 2385 (76.6%) cases of which 1141 (47.6%) had CEA levels!200, 565 (23.8%) had CEA levels O200, and 679 (28.6%) patients had only cytology available. Mean EUS cyst size was significantly greater in those with CEA! 200 (29.2mm 22.9 vs. 24.2mm 15.6, (p!0.01)), while median CEA levels were 37 (18-58, CEA!200) and 687 (362-2818,CEA O200). EUS findings of mural nodularity and cytologic findings of mucin, atypia, and cancer were significantly greater in the high CEA cohort(Table 1). A total of 148 (13.0%) patients with CEA!200 were recommended to stop any further imaging compared to 2 (0.4%) of patients with CEA O200 (pZ0.01). As such, a significantly larger percentage (40.2% vs. 14.0%, p!0.01) of patients with CEA O200 were referred for surgical consultation. On multivariate logistic regression, cyst size (pZ0.003, OR: 1.13/10mm increase (1.07-5.21), CEA levelsO200 (pZ0.01, OR: 1.08 (1.01-3.04) and abnormal cytology (pZ0.04, OR 2.06 (1.34-4.21) were independent predictors of operative intervention. However, despite these findings, a total of 185 (16.2%) patients with CEA! 200 had mucinous or malignant cytology. Conclusions: This large multicenter outcomes study demonstrates that cyst fluid CEA levels O200 are suboptimal for evaluation of PCN as 16% of mucinous or malignant cysts are missed using this cutoff. Despite this, endosonographers and surgeons continue to make clinical decisions based on a cyst fluid CEA O200. The current study demonstrates the importance of continued surveillance of patients with indeterminate CEA levels and the need for more sensitive diagnostic strategies for PCN. Table 1. Clinical Parameters and Outcomes for PCN with indeterminate and elevated CEA levels