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There is no consensus on the necessity of endoscopic sphincterotomy (ES) to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) after endoscopic stenting in patients with malignant biliary obstruction. We investigated the incidence of PEP after endoscopic biliary stenting for malignant biliary obstruction with or without ES in a multicenter prospective cohort study.We enrolled 807 patients who underwent endoscopic biliary stenting for malignant biliary obstruction with a native papilla at 36 hospitals between April 2017 and March 2018. The incidence of PEP in patients with or without ES was compared for subgroups based on stent type, placement method, and patient background. Univariate and multivariate analysis was performed to investigate the incidence of PEP in all stenting patients.Plastic and metal stents (MS) were inserted in 598 and 209 patients, respectively. The incidence of PEP in patients with or without ES was 7.9% and 7.4%, respectively among all stenting patients. The incidences of PEP with or without ES in plastic stent insertion patients, patients with MS insertion, stent insertions across the papilla, stent insertions across the papilla in patients without main pancreatic duct obstruction, and fully covered MS insertions across the papilla were compared. There was no overall significant difference in the incidence of PEP between those with or without ES. Multivariate logistic regression analysis for the incidence of PEP in all stenting patients revealed obstruction of the main pancreatic duct at the pancreatic head and epinephrine spraying on the papilla were significant factors; there was no significant difference in the incidence of PEP between patients with or without ES.Endoscopic sphincterotomy may not contribute to the prevention of PEP after endoscopic biliary stenting for malignant biliary obstruction, even in cases of insertion with a fully covered MS across the papilla.

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.

The reported incidence of adverse events (AEs) in endoscopic retrograde cholangiopancreatography (ERCP) varies between 2.5% and 14%. The aim of this study was to evaluate the incidence and severity of AEs in biliary ERCP and to specify the risk factors and preventive measures for post-ERCP pancreatitis (PEP).Patients with biliary disease with intact papilla were prospectively enrolled at 36 hospitals between April 2017 and March 2018. The primary outcomes were the incidence and severity of AEs.A total of 16,032 ERCP procedures were performed at the 36 hospitals during the study period and 3739 patients were enrolled. The overall incidence of AEs was 10.1% and ERCP-related mortality was 0.08%. PEP developed in 258 cases (6.9%), bleeding in 33 (0.9%), instrumental AEs in 17 (0.5%), infections in 37 (1.0%), cardiovascular AEs in eight (0.2%), pulmonary AEs in eight (0.2%), drug reaction AE in one (0.03%), pain in 15 (0.4%), and other AEs in 15 (0.4%). Multivariable analysis showed significant risk factors for PEP were: female of younger age, pancreatic guidewire-assisted biliary cannulation, temporary guidewire insertion into the pancreatic duct, total procedure time60 min, and post-ERCP administration of non-steroidal anti-inflammatory drugs. Effective preventive measures were prophylactic pancreatic stenting (PPS) and epinephrine spraying onto the papilla.In patients with intact papilla who underwent biliary ERCP, the incidence of AEs was 10.1% and the mortality was 0.08%. PPS and epinephrine spraying may prevent PEP.This study was registered in the University Hospital Medical Information Network (UMIN000024820).

Peroral cholangioscopy (POCS) is believed to be effective in treating intrahepatic stones; however, reports on its efficacy are few. We reviewed the results of intrahepatic stones treated with fluoroscopic guidance or POCS. This study included 26 patients who underwent endoscopic treatment for intrahepatic stones at our institution between January 2017 and December 2021. We retrospectively evaluated the procedure time and adverse events in the first session and the rate of complete stone removal. Complete stone removal was achieved in 92% (24/26); POCS was required in 16 of 26 (62%) procedures and the complete stone removal was achieved in 15 of 16 (94%) of these procedures. The POCS group had a significantly longer procedure time than the fluoroscopy group. Cholangitis incidence was high; however, no difference was noted between patients with and without POCS, and all cases were mild and treated conservatively. Endoscopic treatment for intrahepatic stones may lead to an increase in the incidence of cholangitis, requires specialized devices such as a cholangioscope, and should be performed in an established institution by experienced staff. POCS is useful for intrahepatic stones formed upstream of the stenosis and intrahepatic stones piled in the bile duct.

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.

Positive diagnoses of gastric tumors from photodynamic diagnosis (PDD) images after the administration of 5-aminolevulinic acid are subjectively identified by expert endoscopists. Objective methods of tumor identification are needed to reduce potential misidentifications. We developed two methods to identify gastric tumors from PDD images. Method one was applied to segmented regions in the PDD endoscopic image to determine the region in LAB color space to be attributed to tumors using a multi-layer neural network. Method two aimed to diagnose tumors and determine regions in the PDD endoscopic image attributed to tumors using the convoluted neural network method. The efficiencies of diagnosing tumors were 77.8% (7/9) and 93.3% (14/15) for method one and method two, respectively. The efficiencies of determining tumor region defined as the ratio of the area were 35.7% (0.0–78.0) and 48.5% (3.0–89.1) for method one and method two, respectively. False-positive rates defined as the ratio of the area were 0.3% (0.0–2.0) and 3.8% (0.0–17.4) for method one and method two, respectively. Objective methods of determining tumor region in 5-aminolevulinic acid-based endoscopic PDD were developed by identifying regions in LAB color space attributed to tumors or by applying a method of convoluted neural network.

The stomach is an important digestive organ with a variety of biological functions. However, due to the complexity of its cellular and glandular composition, the precise cellular biology has yet to be elucidated. In this study, we conducted single-cell RNA sequence analysis of the human stomach and constructed a 137,610-cell dataset, the largest cell atlas reported to date. By integrating this single-cell analysis with spatial cellular distribution analysis, we were able to clarify novel aspects of the developmental and tissue homeostatic ecosystems in the human stomach. We identified LEFTY1+ as a potential stem cell marker in both gastric and intestinal metaplastic glands. We also revealed skewed distribution patterns for PDGFRA+BMP4+WNT5A+ fibroblasts that play pivotal roles in, or even precede, the phenotypic changes from gastric to metaplastic mucosa. Our extensive dataset will function as a fundamental resource in investigations of the stomach, including studies on development, aging, and carcinogenesis.

Numerous cancer histopathology specimens have been collected and digitised as whole slide images over the past few decades. A comprehensive evaluation of the distribution of various cells in a section of tumour tissue can provide valuable information for understanding cancer and making accurate cancer diagnoses. Deep learning is one of the most suitable techniques to achieve these goals; however, the collection of large, unbiased training data has been a barrier to producing accurate segmentation models. Here, we developed a pipeline to generate SegPath, the largest annotation dataset that is over one order of magnitude larger than publicly available annotations, for the segmentation of haematoxylin and eosin (H&E)-stained sections for eight major cell types. The pipeline used H&E-stained sections that were destained and subsequently immunofluorescence-stained with carefully selected antibodies. The results showed that SegPath is comparable to, or significantly outperforms, conventional pathologist annotations. Moreover, we revealed that annotations by pathologists are biased toward typical morphologies; however, the model trained on SegPath can overcome this limitation. Our results provide foundational datasets for the histopathology machine learning community.

Efficient molecular targeting therapies for most gastric cancers (GCs) are currently lacking, despite GC being one of the most frequent and often devastating malignancies worldwide. Thus, identification of novel therapeutic targets for GC is in high demand. Recent advancements of high-throughput nucleic acid synthesis methods combined with next-generation sequencing (NGS) platforms have made it feasible to conduct functional genomics screening using large-scale pooled lentiviral libraries aimed at discovering novel cancer therapeutic targets. In this study, we performed NGS-based functional genomics screening for human GC cell lines using an originally constructed 6,399 shRNA library targeting all 2,096 human metabolism genes. Our screening identified aspartyl-tRNA synthetase (DARS) as a possible candidate for a therapeutic target for GC. In-house tissue microarrays containing 346 cases of GC combined with public datasets showed that patients with high expression levels of DARS protein exhibited more advanced clinicopathologic parameters and a worse prognosis, specifically among diffuse-type GC patients. Both in vitro and in vivo experiments concretely evidenced that DARS inhibition achieved robust growth suppression of GC cells. Moreover, RNA sequencing of GC cell lines under shRNA-mediated DARS knockdown suggested that DARS inhibition exerts its effect through the inactivation of multiple p-ERK pathways. This MAPK-related growth suppression by DARS inhibition would also be applicable to other cancers; thus, it is warranted to investigate the expression and clinical significance of DARS in a wide spectrum of malignancies. Taken together, NGS-based high-throughput pooled lentiviral screening showed DARS as a novel prognostic marker and a promising therapeutic target for GC. © 2022 The Authors. The Journal of Pathology published by John Wileyamp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Gastric cancer (GC) is a major health concern in many countries. GC is a heterogeneous disease stratified by histopathological differences. However, these variations are not used to determine GC management. Next-generation sequencing (NGS) technologies have become widely used, and cancer genomic analysis has recently revealed the relationships between various malignant tumors and genomic information. In 2014, studies using whole-exome sequencing (WES) and whole-genome sequencing (WGS) for GC revealed the entire structure of GC genomics. Genomics with NGS has been used to identify new therapeutic targets for GC. Moreover, personalized medicine to provide specific therapy for targets based on multiplex gene panel testing of tumor tissues has become of clinical use. Recently, immune checkpoint inhibitors (ICIs) have been used for GC treatment; however, their response rates are limited. To predict the anti-tumor effects of ICIs for GC and to select patients suitable for ICI treatment, genomics also provides informative data not only of tumors but also of tumor microenvironments, such as tumor-infiltrating lymphocytes. In therapeutic strategies for unresectable or recurrent malignant tumors, the target is not only the primary lesion but also metastatic lesions, and metastatic lesions are often resistant to chemotherapy. Unlike colorectal carcinoma, there is a heterogeneous status of genetic variants between the primary and metastatic lesions in GC. Liquid biopsy analysis is also helpful for predicting the genomic status of both primary and metastatic lesions. Genomics has become an indispensable tool for GC treatment and is expected to be further developed in the future.

[Background] The 5-aminolevulinic acid (ALA)-based photodynamic diagnosis is based on the accumulation of photosensitizing protoporphyrin IX in the tumor after ALA administration. However, the mechanisms connecting exogenous ALA and tumor fluorescence in pancreatic cancer remain unclear. We aimed to elucidate the mechanism underlying the ALA-induced fluorescent. [Methods] Human pancreatic duct epithelial cells (hPDECs) and pancreatic cancer cell lines were used. The expressions of ALA-associated enzymes and membrane transporters in these cell lines were investigated. ALA-induced fluorescence was also investigated. [Results] The expression of oligopeptide transporter-1 (PEPT-1), through which ALA is absorbed, was significantly higher in AsPC-1 cells and lower in MIA PaCa-2 cells than in hPDECs. AsPC-1 cells showed rapid and intense fluorescence after ALA administration, and that was attenuated by PEPT-1 inhibition. ALA-induced fluorescence was not sufficiently strong in MIA PaCa-2 cells to distinguish the cells from hPDECs. [Conclusion] We revealed the association of PEPT-1 with ALA-induced fluorescence. Cancers expressing PEPT-1 could be easily distinguished by this technique from normal cells. These findings help develop novel diagnostic modalities for pancreatic cancer.

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 report the case of a 68-year-old woman who had abdominal pain and slightly elevated biliary enzymes. Magnetic resonance cholangiopancreatography detected biliary duct stenosis, while contrast-enhanced magnetic resonance imaging showed that the right hepatic artery transversed the extrahepatic bile duct at the level of bifurcation of the bile duct. We performed endoscopic retrograde cholangiopancreatography and peroral cholangioscopy with the SpyGlass DS™ system. Then, mild extrinsic pulsatile compression of the bile duct was observed at stricture level with an intact bile duct epithelium. Therefore, she was diagnosed with right hepatic artery syndrome and underwent cholecystectomy. Six months later, her biliary enzyme level decreased, and the recurrence of pain gradually decreased.

A 65-year-old man had a history of cholecystectomy and treatment for cholelithiasis with a common bile duct incision. Owing to frequent cholangitis, he underwent choledochojejunostomy. Twenty years after the surgery, he was hospitalized for cholangitis and was suspected of having hilar cholangiocarcinoma based on imaging findings. Percutaneous transhepatic cholangioscopy using a SpyGlass™ DS (Boston Scientific, Marlborough, USA) showed gallstones and bile sludge in the bile ducts, but no tumors were noted. Electrohydraulic shockwave lithotripsy with double-balloon enteroscopy enabled complete stone removal; a direct visual biopsy with peroral cholangioscopy showed no malignancy in the bile duct.

Alpha-fetoprotein (AFP) and des-gamma-carboxyprothrombin (DCP) are widely used as tumor markers to diagnose hepatocellular carcinoma (HCC). Some advanced HCCs demonstrate neither AFP nor DCP. This study investigated the characteristics and prognosis of AFP (

Photodynamic therapy (PDT) induces cancer cell death by generating reactive oxygen species (ROS). In this process, photosensitizers accumulate in cancer cells irradiated by laser light of a specific wavelength, leading to ROS generation. Verteporfin (VP), a second-generation photosensitizer, is used in PDT for age-related macular degeneration. However, the antitumor effects of VP-PDT remain poorly defined. This study investigated the antitumor effects of VP-PDT on esophageal cancer (EC) cell lines in vitro. Two types of EC cell lines, the KYSE30 cell line, derived from highly differentiated esophageal carcinoma, and the KYSE170 cell line, derived from moderately differentiated carcinoma, were used in this study. VP-PDT exerted effective anticancer effects in both cell lines. Our results revealed that the low-density lipoprotein receptor, albumin receptor, and heme carrier protein-1 in VP uptake were not involved in VP uptake. However, cells rich in intracellular glutathione were resistant to VP-PDT. Our study outcomes suggest that lowering intracellular glutathione via a glutathione synthesis inhibitor or sulfasalazine can increase the effectiveness of VP-PDT-mediated anticancer effects.

A γ-glutamyl hydroxymethyl rhodamine green probe (gGlu-HMRG) reacts with γ-glutamyltranspeptidase (GGT) and immediately produces fluorescence, is clinically applied for real-time cancers’ visualization. Since Helicobacter pylori produces GGT, this study aimed to investigate whether gGlu-HMRG can be used to detect H. pylori infections. A wild-type H. pylori strain and the ggt gene-disrupted mutant were cultured and treated with gGlu-HMRG. This fluorescent probe assay was used to quantify GGT activity of H. pylori ex vivo using gastric biopsy specimens. The H. pylori diagnostic capabilities of the assay were determined from altered fluorescence intensity (FI) values at 5 min (FIV-5) and 15 minutes (FIV-15). Distinct fluorescence was identified in wild H. pylori strain, using gGlu-HMRG, whereas no fluorescence was observed in ggt gene-disrupted mutant strain. On ex vivo imaging of gGlu-HMRG, fluorescence intensity increased markedly with time in H. pylori-positive specimens; however, the H. pylori-negative specimens displayed a slight increase in FI. FIV-5 and FIV-15 differed significantly between H. pylori-positive and -negative specimens. FIV-15 differed significantly between H. pylori-positive and -eradicated group. This assay sensitivity and specificity were 75.0% and 83.3% in the antrum and 82.6% and 89.5% in the stomach body. GGT-activatable fluorescence probe is applicable for rapid diagnosis of H. pylori.

This randomized trial aimed to compare the safety and efficacy of the GAGLESS mouthpiece for esophagogastroduodenoscopy (EGD) with that of the conventional mouthpiece. In all, 90 participants were divided into the GAGLESS mouthpiece and conventional mouthpiece groups. The primary endpoint was the severity of pain using the visual analog scale (VAS), and secondary endpoints were examination time, past history of endoscopy, success of the procedure, systolic (SBP) and diastolic (DBP) blood pressure, oxygen saturation, pulse rate before and after EGD, and adverse events. Endoscopy was completed in all cases, and no complications were observed. VAS, when passing the scope through the pharynx, was 2.5 ± 2.4 and 2.0 ± 1.9 cm (p = 0.24) in the conventional and GAGLESS groups, respectively, and that, throughout the examination, was 2.5 ± 2.4 and 1.7 ± 1.5 cm (p = 0.06), respectively. The difference in blood pressure between the GAGLESS and conventional groups was not significant for SBP (p = 0.08) and significant for DBP (p = 0.03). The post-EGD difference in DBP was significantly lower in the GAGLESS group than in the conventional group. The results indicate that GAGLESS mouthpieces had a lower VAS during endoscopy than the conventional mouthpieces, and the changes in blood pressure were smaller with the GAGLESS mouthpiece.

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.

Cancer histological images contain rich biological and clinical information, but quantitative representation can be problematic and has prevented the direct comparison and accumulation of large-scale datasets. Here, we show successful universal encoding of cancer histology by deep texture representations (DTRs) produced by a bilinear convolutional neural network. DTR-based, unsupervised histological profiling, which captures the morphological diversity, is applied to cancer biopsies and reveals relationships between histologic characteristics and the response to immune checkpoint inhibitors (ICIs). Content-based image retrieval based on DTRs enables the quick retrieval of histologically similar images using The Cancer Genome Atlas (TCGA) dataset. Furthermore, via comprehensive comparisons with driver and clinically actionable gene mutations, we successfully predict 309 combinations of genomic features and cancer types from hematoxylin-and-eosin-stained images. With its mounting capabilities on accessible devices, such as smartphones, universal encoding for cancer histology has a strong impact on global equalization for cancer diagnosis and therapies.

All endoscopic centers should establish infection control strategies (ICS) tailored to individual resources based upon updated national and academic guidance for COVID‐19 without superseding local advisories and institutional guidelines1. Endoscopic administrators have to customize control measures and adjust with the rapidly evolving local and global pandemic and prepare for the upcoming resurgence due to relaxation of social distancing norms. In this regard, Zhang et al. have reported their stringent ICS in Peking Union Medical College Hospital (PUMCH) based on the guidance of the Chinese Society of Digestive Endoscopy and have shared their experiences from the pandemic and the subsequent recovery2.

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.

In December 2019, the World Health Organization (WHO) was informed of cases of pneumonia of unknown etiology detected in Wuhan, China. Severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), a novel coronavirus, was identified and SARS‐CoV‐2 related disease, called coronavirus disease 2019 (COVID‐19), has spread worldwide. The WHO has declared COVID‐19 to be a pandemic on March 11, 2020. Clinical symptoms of the COVID‐19 includes cough (67.8%), fever (43.8%), fatigue (38.1%), production of sputum (33.7%), and shortness of breath (18.7%). Gastrointestinal symptoms of COVID‐19 include nausea or vomiting (5.0%), as well as diarrhea (3.8%) 1. It is estimated that 1.2% of infected subjects are asymptomatic, but the rate of severe disease is 13.9% with an overall mortality rate of 2.3% 2.

Summary The patient-derived xenograft (PDX) model is a versatile tool used to study the tumor microenvironment (TME). However, limited studies have described multi-tumor PDX screening strategies to detect hub regulators during cancer-stroma interaction. Transcriptomes of cancer (human) and stroma (mouse) components of 70 PDX samples comprising 9 distinctive tumor types were analyzed in this study. PDX models recapitulated the original tumors' features, including tumor composition and putative signaling. Particularly, kidney renal clear cell carcinoma (KIRC) stood out, with altered hypoxia-related pathways and a high proportion of endothelial cells in the TME. Furthermore, an integrated analysis conducted to predict paracrine effectors in the KIRC cancer-to-stroma communication detected well-established soluble factors responsible for the hypoxia-related reaction and the so-far unestablished soluble factor, apelin (APLN). Subsequent experiments also supported the potential role of APLN in KIRC tumor progression. Therefore, this paper hereby provides an analytical workflow to find hub regulators in cancer-stroma interactions., Graphical abstract, Highlights • Analysis of multi-tumor PDXs discloses hub regulators in cancer-stroma interplay • PDX transcriptomes reproduced original tumor's biological characteristics • Kidney cancer (KIRC) TME is featured with altered hypoxia-related reactions • Apelin is documented as a potential paracrine effector in KIRC-to-stroma interplay, Cancer systems biology; Cancer

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.

IntroductionNon-alcoholic fatty liver disease (NAFLD) has a wide spectrum, eventually leading to cirrhosis and hepatic carcinogenesis. We previously reported that a series of microRNAs (miRNAs) mapped in the 14q32.2 maternally imprinted gene region (Dlk1-Dio3 mat) are related to NAFLD development and progression in a mouse model. We examined the suitability of miR-379, a circulating Dlk1-Dio3 mat miRNA, as a human NAFLD biomarker.MethodsEighty NAFLD patients were recruited for this study. miR-379 was selected from the putative Dlk1-Dio3 mat miRNA cluster because it exhibited the greatest expression difference between NAFLD and non-alcoholic steatohepatitis in our preliminary study. Real-time PCR was used to examine the expression levels of miR-379 and miR-16 as an internal control.ResultsCompared to normal controls, serum miR-379 expression was significantly up-regulated in NAFLD patients. Receiver operating characteristic curve analysis suggested that miR-379 is a suitable marker for discriminating NAFLD patients from controls, with an area under the curve value of 0.72. Serum miR-379 exhibited positive correlations with alkaline phosphatase, total cholesterol, and low-density-lipoprotein cholesterol levels in patients with early stage NAFLD (Brunt fibrosis stage 0 to 1). The correlation between serum miR-379 and cholesterol levels was lost in early stage NAFLD patients treated with statins. Software-based predictions indicated that various energy metabolism–related genes, including insulin-like growth factor-1 (IGF-1) and IGF-1 receptor, are potential targets of miR-379.ConclusionsSerum miR-379 exhibits high potential as a biomarker for NAFLD. miR-379 appears to increase cholesterol lipotoxicity, leading to the development and progression of NAFLD, via interference with the expression of target genes, including those related to the IGF-1 signaling pathway. Our results could facilitate future research into the pathogenesis, diagnosis, and treatment of NAFLD.

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.