Updated techniques and evidence for endoscopic ultrasound-guided tissue acquisition from solid pancreatic lesions.

Endoscopic ultrasound-guided tissue acquisition (EUS-TA), including fine-needle aspiration (EUS-FNA) and fine-needle biopsy (EUS-FNB), has revolutionized specimen collection from intra-abdominal organs, especially the pancreas. Advances in personalized medicine and more precise treatment have increased demands to collect specimens with higher cell counts, while preserving tissue structure, leading to the development of EUS-FNB needles. EUS-FNB has generally replaced EUS-FNA as the procedure of choice for EUS-TA of pancreatic cancer. Various techniques have been tested for their ability to enhance the diagnostic performance of EUS-TA, including multiple methods of sampling at the time of puncture, on-site specimen evaluation, and specimen processing. In addition, advances in next-generation sequencing have made comprehensive genomic profiling of EUS-TA samples feasible in routine clinical practice. The present review describes updates in EUS-TA sampling techniques of pancreatic lesions, as well as methods for their evaluation.

Value of image enhancement of endoscopic ultrasound for diagnosis of gastrointestinal subepithelial lesions.

Objectives: Among subepithelial lesions (SELs), gastrointestinal stromal tumors (GISTs) should be identified and surgically treated at an early stage. However, it is difficult to diagnose SELs smaller than 20 mm. In recent years, endoscopic ultrasound (EUS) elastography (EUS-EG) and contrast-enhanced harmonic EUS (CH-EUS) have been reported to be useful for the diagnosis of SELs, although the diagnostic accuracy of a combination of EUS techniques with image enhancement is unknown. Methods: Patients with SELs who underwent EUS-guided tissue acquisition, EUS shear-wave elastography (EUS-SWE), EUS strain elastography (EUS-SE), and CH-EUS from January 2019 to June 2023 were enrolled. To assess the diagnostic accuracy for differentiating GISTs from other SELs, shear-wave velocity on EUS-SWE, the strain ratio on EUS-SE, and vascularity on CH-EUS were determined and their diagnostic accuracies were compared. Results: Forty-three patients were enrolled. When the cut-off value was set at 3.27 m/s, the sensitivity, specificity, and diagnostic accuracy of shear-wave velocity were 28.6%, 86.2%, and 34.9%, respectively. When the cut-off value was set at 3.79, the sensitivity, specificity, and diagnostic accuracy of the strain ratio were 93.1%, 64.3%, and 83.7%, respectively. The sensitivity, specificity, and diagnostic accuracy of CH-EUS were 79.3%, 92.3%, and 83.7%, respectively. When EUS-SE was combined with CH-EUS, the sensitivity and diagnostic accuracy were the highest among binary combinations of image enhancement modalities. Conclusions: EUS-SE and CH-EUS are useful for differentiating GISTs from other SELs. Furthermore, the use of both modalities may further improve the identification of GISTs.

Proposal of classification and terminology of interventional endoscopic ultrasonography/endosonography.

Interventional endoscopic ultrasonography/endosongraphy (I-EUS) procedures have rapidly evolved since their introduction three decades ago; however, the classification and terminology for these procedures remain unstandardized. To address this, the Subcommittee for Terminology of I-EUS in the Japan Gastroenterological Endoscopy Society was established to define classifications and a glossary of I-EUS terms. They categorized I-EUS procedures into five types based on purpose and method: (i) EUS-guided sampling; (ii) EUS-guided through-the-needle examination; (iii) EUS-guided drainage/anastomosis (EUS-D/A); (iv) trans-endosonographically/EUS-guided created route (ESCR) procedures; and (v) EUS-guided delivery. EUS-guided sampling includes tissue acquisition and fluid sampling, classified by needle type into fine needle aspiration and fine needle biopsy. Through-the-needle examinations include imaging, measurements, and biopsies. EUS-D/A includes organ drainage/anastomosis, fluid collection drainage, and digestive tract anastomosis. In the EUS-D/A route, "anastomosis" is used for organ-to-organ procedures, whereas "tract" is for fluid drainage. ESCR is a newly proposed term for procedures via anastomosis or tract, such as endoscopic necrosectomy and EUS-guided antegrade stenting. The term "trans-luminal drainage/anastomosis stent" is used for stents that maintain the ESCR rather than treating strictures. EUS-guided delivery involves the delivery of substances, such as fluids, drugs, medical devices, and energy. This proposed categorization and terminology aimed to clarify I-EUS procedures and will require updates as new techniques and concepts emerge.

Performance evaluation of endoscopic ultrasonography needles: Experimental study.

Background and study aims The relative procedural performance of needles for endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/B) is unclear. The present study therefore compared six types of 22-gauge FNA/B needles using a bench simulator. Methods Resistance forces during needle puncture and removal, needle tip damage before and after procedure, leakage after puncture of mucinous cyst models, the shape of the puncture surface at the puncture site, amounts of samples extracted, ranges of needle deflection angles, and needle deformation after multiple procedures were compared using six types of needles. Results Maximum resistance forces during puncture and removal were highest for ProCore needles and lowest for Expect needles. None of the needles had damage after puncturing. SharkCore needles showed the highest amount of leakage, whereas FNA needles showed no leakage. The puncture tracts of FNA needles remained in the form of a flap at the puncture site, whereas FNB needles broke off the target material creating a hole. The target material removed was supplemented within the puncture needle. TopGain needles produced significantly larger samples than ProCore, EZShot3 Plus, and Expect needles. FNB needles produced larger and more core samples than FNA needles. EZShot3 Plus needles had the highest range of needle deflection angle using an elevator device and the lowest needle deformation after 20 punctures at full endoscopic angle and a full elevator. Conclusions The performance of the six needles differed in various ways. Understanding the characteristics of each needle may allow for selection of the appropriate needle for each situation.

Endoscopic biliary drainage for distal bile duct obstruction due to pancreatic cancer.

Approximately 60% of pancreatic cancers occur in the pancreatic head and may present as obstructive jaundice due to bile duct invasion. Obstructive jaundice often leads to poor general conditions and acute cholangitis, interfering with surgery and chemotherapy and requiring biliary drainage. The first choice of treatment for biliary drainage is the endoscopic transpapillary approach. In unresectable tumors, self-expandable metal stents (SEMSs) are most commonly used and are classified into uncovered and covered SEMSs. Recently, antireflux metal stents and large- or small-diameter SEMSs have become commercially available, and their usefulness has been reported. Plastic stents are infrequently used in patients with resectable biliary obstruction; however, owing to the recent trend in preoperative chemotherapy, SEMSs are frequently used because of the long time to recurrent biliary obstruction. Endoscopic ultrasound-guided biliary drainage (EUS-BD) is often performed in patients who are not eligible for the transpapillary approach, and favorable outcomes have been reported. Different EUS-BD techniques and specialized stents have been developed and can be safely used in high-volume centers. The indications for EUS-BD are expected to further expand in the future.

Endoscopic Ultrasound and Intraductal Ultrasound in the Diagnosis of Biliary Tract Diseases: A Narrative Review.

Endoscopic ultrasound (EUS) and intraductal ultrasound (IDUS) play very important roles in the field of biliary tract disease. Because of their excellent spatial resolution, the detection of small lesions and T- or N-staging of tumors have become possible. Additionally, contrast-enhanced EUS and the new imaging technique of detective flow imaging are reported to be useful for differential diagnosis. Furthermore, EUS-guided tissue acquisition is used not only for pathological diagnosis but also to collect tissue samples for cancer genome profiling. This review provides an overview of diagnosis utilizing the features and techniques of EUS and IDUS.

WONDER-02: plastic stent vs. lumen-apposing metal stent for endoscopic ultrasound-guided drainage of pancreatic pseudocysts-study protocol for a multicentre randomised non-inferiority trial.

BACKGROUND: Endoscopic ultrasound (EUS)-guided transluminal drainage has become a first-line treatment modality for symptomatic pancreatic pseudocysts. Despite the increasing popularity of lumen-apposing metal stents (LAMSs), plastic stents may resolve non-necrotic fluid collections effectively with lower costs and no LAMS-specific adverse events. To date, there has been a paucity of data on the appropriate stent type in this setting. This trial aims to assess the non-inferiority of plastic stents to a LAMS for the initial EUS-guided drainage of pseudocysts. METHODS: The WONDER-02 trial is a multicentre, open-label, non-inferiority, randomised controlled trial, which will enrol pancreatic pseudocyst patients requiring EUS-guided treatment in 26 centres in Japan. This trial plans to enrol 80 patients who will be randomised at a 1:1 ratio to receive either plastic stents or a LAMS (40 patients per arm). In the plastic stent group, EUS-guided drainage will be performed using two 7-Fr double pigtail stents. In the LAMS group, the treatment will be performed in the same way except for LAMS use. The step-up treatment will be performed via endoscopic and/or percutaneous procedures at the trial investigator's discretion. The primary endpoint is clinical success, which is defined as a decrease in a pseudocyst size to ≤ 2 cm and an improvement in inflammatory indicators (i.e. body temperature, white blood cell count, and serum C-reactive protein). Secondary endpoints include technical success, adverse events including mortality, pseudocyst recurrence, and medical costs. DISCUSSION: The WONDER-02 trial will investigate the efficacy and safety of plastic stents compared to a LAMS in EUS-guided treatment of symptomatic pancreatic pseudocysts with a particular focus on the non-inferior efficacy of plastic stents. The findings will help establish a new treatment algorithm for this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT06133023 registered on 9 November 2023. UMIN000052647 registered on 30 October 2023. jRCT1032230444 registered on 7 November 2023.

Serum trypsin as an early predictor of post-endoscopic retrograde cholangiopancreatography pancreatitis.

BACKGROUND: Serum amylase (AMY) levels measured 2-6 h after ERCP are a predictor of post-ERCP pancreatitis (PEP). Trypsin is one of the pancreatic enzymes elevated in the development of PEP. The study assessed whether serum trypsin (TRY) can predict early-stage PEP. METHODS: This prospective study included patients who underwent ERCP from June 2022 to May 2023. TRY, AMY, serum pancreatic AMY (P-AMY), and serum lipase (LIP) levels were measured immediately after ERCP and 2 h later. The primary outcome was the diagnostic abilities of TRY levels measured immediately (0 h-TRY) and 2 h after (2 h-TRY) ERCP to predict PEP (compared with the other serum pancreatic enzymes). RESULTS: Of 130 patients analyzed, 18 developed PEP. The sensitivity and specificity of 0 h-TRY were 83.3% and 69.6%, respectively, and those of 2 h-TRY were 88.9% and 72.3%, respectively. The area under the curve (AUC) for 0 h-TRY was significantly higher than that for 0 h-AMY (p = .006) and 0 h-P-AMY (p = .012), whereas the AUCs for 0 h-TRY and 0 h-LIP did not differ significantly (p = .563). The AUC for 2 h-TRY for predicting PEP was significantly higher than that for 2 h-AMY (p = .025), whereas there was no significant differences between the AUCs for 2 h-TRY and 2 h-P-AMY(p = .146), or between those for 2 h-TRY and 2 h-LIP (p = .792). The median increase ratio (expressed as a ratio relative to baseline) in TRY was highest among all of serum pancreatic enzymes tested immediately after ERCP (5.35, 1.72, 1.94, and 4.44 for TRY, AMY, P-AMY, and LIP, respectively). CONCLUSION: Measuring TRY immediately after ERCP is useful for the early prediction of PEP.

Endoscopic ultrasonography for microvascular imaging without contrast enhancement in the differential diagnosis of pancreatic lesions.

OBJECTIVES: Detective flow imaging endoscopic ultrasonography (DFI-EUS) is a recent imaging modality developed for detecting fine vessels without the need for ultrasound contrast agents. The aim of the present study was to evaluate the utility of DFI-EUS for solid pancreatic lesions and to compare the diagnostic ability for pancreatic cancer (PC) between DFI-EUS, directional power Doppler (eFLOW) EUS, and contrast-enhanced harmonic (CH)-EUS. METHODS: Patients with a pancreatic lesion who underwent DFI-EUS, eFLOW-EUS, and CH-EUS between March 2019 and November 2023 were retrospectively enrolled. Final diagnoses were confirmed by pathologic examination of EUS-guided tissue acquisition and/or resected specimens. Lesions were categorized into the three patterns of poor, mild, and rich vascularity on DFI-EUS and eFLOW-EUS, and hypo-, iso-, and hypervascular on CH-EUS. PC was defined as a poor pattern on DFI-EUS and eFLOW-EUS, and a hypovascular pattern on CH-EUS. RESULTS: The final diagnoses of 90 examined tumors were PC (n = 57), inflammatory mass (n = 6), autoimmune pancreatitis (n = 13), neuroendocrine tumor (n = 9), and others (n = 5). The sensitivity, specificity, and accuracy for diagnosis of PC were 93%, 82%, and 88%, respectively, on DFI-EUS, 97%, 42%, and 77% on eFLOW-EUS, and 95%, 89%, and 92% on CH-EUS. The accuracy of DFI-EUS was significantly superior to eFLOW-EUS (P = 0.005), but no significant difference was found between DFI-EUS and CH-EUS. CONCLUSION: DFI-EUS is more sensitive for depicting vasculature than eFLOW-EUS, and has higher diagnostic sensitivity for PC. Evaluation of vascularity on DFI-EUS is useful for the differential diagnosis of pancreatic lesions without the need for intravenous contrast agent.

Endoscopic ultrasound-guided hepaticogastrostomy vs. antegrade metal stent placement keeping an access route in patients with malignant biliary obstruction.

BACKGROUND: Few studies have compared endoscopic ultrasound (EUS)-guided hepaticogastrostomy (HGS) with EUS-guided antegrade metal stent placement (AGMS). The purpose of this study was to compare times to recurrent biliary obstruction (TRBO) in patients who underwent HGS using metal stents (MS) and those who underwent AGMS keeping access routes with plastic stents (AGMS-AR). METHODS: This study retrospectively evaluated consecutive patients who underwent HGS or AGMS between September 2016 and December 2022. TRBO, overall survival (OS), and adverse event (AE) rates were compared in the two groups. The risk factors for RBO were determined using a multivariable Cox proportional hazards model. RESULTS: This study included 32 patients in the HGS group and 30 in the AGMS-AR group. Technical success rate was significantly higher in the HGS than in the AGMS-AR group (100 vs. 80%; P = 0.009). The technical success rate without tract dilation was significantly higher in the AGMS-AR than in the HGS group (83 vs. 38%; P < 0.001). RBO rates were significantly higher in the HGS than in the AGMS-AR group (53 vs. 17%; P = 0.024), whereas AE rates did not differ significantly. TRBO differed significantly in the HGS and AGMS-AR groups (159 days vs. not reached, P = 0.011), whereas OS did not differ significantly. Multivariable analysis revealed that HGS was an independent risk factor for RBO (hazard ratio, 6.48, P = 0.014). CONCLUSION: TRBO was significantly longer in patients who underwent AGMS with PS than HGS. AGMS with PS may be effective after the failure of ERCP in patients with malignant biliary obstruction.

Multicenter study comparing EUS-guided hepaticogastrostomy and ERCP for malignant biliary obstruction in patients with accessible papillae.

BACKGROUND: One advantage of endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) is that it is difficult for reflux cholangitis, caused by duodenal pressure increasing due to duodenal obstruction, to occur. In addition, since stent deployment is performed away from the malignant stricture site, longer stent patency than with endoscopic retrograde cholangiopancreatography (ERCP) may be obtained. However, no study has previously compared EUS-HGS and ERCP for patients without duodenal obstruction or surgically altered anatomy. The aim of the present study was to compare clinical outcomes between EUS-HGS and ERCP in normal anatomy patients without duodenal obstruction. METHOD: In the ERCP group, patients who initially underwent biliary drainage were included. In the EUS-HGS group, patients who underwent EUS-HGS due to failed biliary cannulation were included. Patients with an inaccessible papilla, such as with surgically altered anatomy or duodenal obstruction, were excluded. RESULTS: A total of 314 patients who underwent ERCP and EUS-HGS were enrolled in this study. Of the 314 patients, 289 underwent biliary stenting under ERCP guidance, and 25 patients underwent biliary stenting under EUS-HGS. After propensity score-matching analysis, the adverse event rate tended to be lower in the EUS-HGS group than in the ERCP group. Although overall survival was not significantly different between the EUS-HGS and ERCP groups (p = .228), stent patency was significantly longer in the EUS-HGS group (median 366.0 days) than in the ERCP group (median 76.5 days). CONCLUSIONS: EUS-HGS had a lower adverse event rate, shorter procedure time, and longer stent patency than ERCP in cases of normal anatomy without duodenal obstruction.

Rat Tracheal Cartilage Regeneration Using Mesenchymal Stem Cells Derived From Human iPS Cells.

Tracheal cartilage provides structural support to the airways to enable breathing. However, it can become damaged or impaired, sometimes requiring surgical resection and reconstruction. Previously, we clinically applied an artificial trachea composed of a polypropylene mesh and collagen sponge, with a favorable postoperative course. However, the artificial trachea presents a limitation, as the mesh is not biodegradable and cannot be used in pediatric patients. Compared to a polypropylene mesh, regenerated cartilage represents an ideal material for reconstruction of the damaged trachea. The use of mesenchymal stem cells (MSCs) as a source for cartilage regeneration has gained widespread acceptance, but challenges such as the invasiveness of harvesting and limited cell supply persist. Therefore, we focused on the potential of human-induced pluripotent stem cell (hiPSC)-derived mesenchymal stem cells (iMSCs) for tracheal cartilage regeneration. In this study, we aimed to regenerate tracheal cartilage on an artificial trachea as a preliminary step to replace the polypropylene mesh. iMSCs were induced from hiPSCs through neural crest cells and transplanted with a polypropylene mesh covered with a collagen sponge into the damaged tracheal cartilage in immunodeficient rats. Human nuclear antigen (HNA)-positive cells were observed in all six rats at 4 weeks and in six out of seven rats at 12 weeks after transplantation, indicating that transplanted iMSCs survived within the tracheal cartilage defects of rats. The HNA-positive cells coexpressed SOX9, and type II collagen was detected around HNA-positive cells in four of six rats at 4 weeks and in three of seven rats at 12 weeks after transplantation, reflecting cartilage-like tissue regeneration. These results indicate that the transplanted iMSCs could differentiate into chondrogenic cells and promote tracheal cartilage regeneration. iMSC transplantation thus represents a promising approach for human tracheal reconstruction.

TOKYO criteria 2024 for the assessment of clinical outcomes of endoscopic biliary drainage.

The consensus-based TOKYO criteria were proposed as a standardized reporting system for endoscopic transpapillary biliary drainage. The primary objective was to address issues arising from the inconsistent reporting of stent outcomes across studies, which has complicated the comparability and interpretation of study results. However, the original TOKYO criteria were not readily applicable to recent modalities of endoscopic biliary drainage such as biliary drainage based on endoscopic ultrasound or device-assisted endoscopy. There are increasing opportunities for managing hilar biliary obstruction and benign biliary strictures through endoscopic drainage. Biliary ablation has been introduced to manage benign and malignant biliary strictures. In addition, the prolonged survival times of cancer patients have increased the importance of evaluating overall outcomes during the period requiring endoscopic biliary drainage rather than solely focusing on the patency of the initial stent. Recognizing these unmet needs, a committee has been established within the Japan Gastroenterological Endoscopy Society to revise the TOKYO criteria for current clinical practice. The revised criteria propose not only common reporting items for endoscopic biliary drainage overall, but also items specific to various conditions and interventions. The term "stent-demanding time" has been defined to encompass the entire duration of endoscopic biliary drainage, during which the overall stent-related outcomes are evaluated. The revised TOKYO criteria 2024 are expected to facilitate the design and reporting of clinical studies, providing a goal-oriented approach to the evaluation of endoscopic biliary drainage.

Durvalumab or placebo plus gemcitabine and cisplatin in participants with advanced biliary tract cancer (TOPAZ-1): updated overall survival from a randomised phase 3 study.

BACKGROUND: In the preplanned interim analysis of the TOPAZ-1 study, durvalumab plus gemcitabine-cisplatin significantly improved overall survival versus placebo plus gemcitabine-cisplatin in participants with advanced biliary tract cancer. We aimed to report updated overall survival and safety data from TOPAZ-1 with additional follow-up and data maturity beyond the interim analysis. METHODS: TOPAZ-1 was a phase 3, randomised, double-masked, placebo-controlled, global study done at 105 sites in 17 countries. Participants aged 18 years or older with unresectable, locally advanced, or metastatic biliary tract cancer were randomly assigned (1:1) to durvalumab plus gemcitabine-cisplatin or placebo plus gemcitabine-cisplatin using a computer-generated randomisation scheme, stratified by disease status and primary tumour location. Participants received durvalumab (1500 mg) or placebo on day 1 of each cycle every 3 weeks for up to eight cycles, plus gemcitabine (1000 mg/m2) and cisplatin (25 mg/m2) intravenously on days 1 and 8 of each cycle every 3 weeks for up to eight cycles, followed by durvalumab (1500 mg) or placebo monotherapy every 4 weeks until disease progression or other discontinuation criteria were met. Investigators and participants were masked to study treatment. The primary endpoint was overall survival. TOPAZ-1 met its primary endpoint at the preplanned interim analysis, and the study is active but no longer recruiting participants. Updated overall survival and safety data from TOPAZ-1, with additional follow-up (data cutoff Feb 25, 2022) and data maturity beyond the interim analysis, are reported here. Efficacy was assessed in the full analysis set (all randomly assigned participants). Safety was assessed in the safety analysis set (all participants who received at least one dose of study treatment). The TOPAZ-1 study is registered with ClinicalTrials.gov, NCT03875235. FINDINGS: From April 16, 2019, to Dec 11, 2020, 914 participants were enrolled, 685 of whom were randomly assigned (341 to the durvalumab plus gemcitabine-cisplatin group and 344 to the placebo plus gemcitabine-cisplatin group). 345 (50%) participants were male and 340 (50%) were female. Median follow-up at the updated data cutoff was 23·4 months (95% CI 20·6-25·2) in the durvalumab plus gemcitabine-cisplatin group and 22·4 months (21·4-23·8) in the placebo plus gemcitabine-cisplatin group. At the updated data cutoff, 248 (73%) participants in the durvalumab plus gemcitabine-cisplatin group and 279 (81%) participants in the placebo plus gemcitabine-cisplatin group had died (median overall survival 12·9 months [95% CI 11·6-14·1] vs 11·3 months [10·1-12·5]; hazard ratio 0·76 [95% CI 0·64-0·91]). Kaplan-Meier-estimated 24-month overall survival rates were 23·6% (95% CI 18·7-28·9) in the durvalumab plus gemcitabine-cisplatin group and 11·5% (7·6-16·2) in the placebo plus gemcitabine-cisplatin group. Maximum grade 3 or 4 adverse events occurred in 250 (74%) of 338 participants in the durvalumab plus gemcitabine-cisplatin group and 257 (75%) of 342 in the placebo plus gemcitabine-cisplatin group. The most common maximum grade 3 or 4 treatment-related adverse events were decreased neutrophil count (70 [21%] vs 86 [25%]), anaemia (64 [19%] vs 64 [19%]), and neutropenia (63 [19%] vs 68 [20%]). INTERPRETATION: Durvalumab plus gemcitabine-cisplatin showed robust and sustained overall survival benefit with no new safety signals. Findings continue to support the regimen as a standard of care for people with untreated, advanced biliary tract cancer. FUNDING: AstraZeneca.

An Infection Model for SARS-CoV-2 Using Rat Transplanted with hiPSC-Airway Epithelial Cells.

Investigating the infection mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the airway epithelium and developing effective defense strategies against infection are important. To achieve this, establishing appropriate infection models is crucial. Therefore, various in vitro models, such as cell lines and primary cultures, and in vivo models involving animals that exhibit SARS-CoV-2 infection and genetically humanized animals have been used as animal models. However, no animal model has been established that allows infection experiments with human cells under the physiological environment of airway epithelia. Therefore, we aimed to establish a novel animal model that enables infection experiments using human cells. Human induced pluripotent stem cell-derived airway epithelial cell-transplanted nude rats (hiPSC-AEC rats) were used, and infection studies were performed by spraying lentiviral pseudoviruses containing SARS-CoV-2 spike protein and the GFP gene on the tracheae. After infection, immunohistochemical analyses revealed the existence of GFP-positive-infected transplanted cells in the epithelial and submucosal layers. In this study, a SARS-CoV-2 infection animal model including human cells was established mimicking infection through respiration, and we demonstrated that the hiPSC-AEC rat could be used as an animal model for basic research and the development of therapeutic methods for human-specific respiratory infectious diseases.

Lusutrombopag Reduces the Risk of Hemoperitoneum Caused by Percutaneous Radiofrequency Ablation for Hepatocellular Carcinoma Compared with Platelet Transfusion.

INTRODUCTION: Patients with liver cirrhosis develop thrombocytopenia and an increased risk of bleeding events after invasive procedures. Lusutrombopag, a thrombopoietin receptor agonist, can increase the platelet count. This study assessed whether lusutrombopag reduces the risk of hemoperitoneum following percutaneous radiofrequency ablation for hepatocellular carcinoma, compared with platelet transfusion. METHODS: Participants in the present study comprised patients with severe thrombocytopenia (platelet count <50,000/µL) enrolled between November 2012 and March 2020, excluding patients with idiopathic thrombocytopenia or anticoagulant use. Hemoperitoneum rate, hemostasis rate, hemoglobin reduction rate, rate of achieving a platelet count ≥50,000/µL, and increases in platelet count and factors contributing to hemoperitoneum were retrospectively analyzed. RESULTS: This study enrolled 41 patients, comprising 18 patients administered lusutrombopag and 23 patients who received platelet transfusion. The major hemoperitoneum rate after RFA was tend to be lower in the lusutrombopag group (0%) than in the platelet transfusion group (21.7%). All of the major hemoperitoneum was observed in the platelet transfusion group. Hemoglobin reduction rate was lower in the lusutrombopag group (-0.17%) than in the platelet transfusion group (6.79%, p = 0.013). Hemostasis rate was lower in the lusutrombopag group (0%) than in the platelet transfusion group (21.7%, p = 0.045). The rate of achievement of platelet counts ≥50,000/µL the day after RFA was higher in the lusutrombopag group (100%) than in the platelet transfusion group (60.9%, p = 0.005). CONCLUSION: Lusutrombopag may be able to perform RFA more safely with respect to the hemoperitoneum caused by percutaneous radiofrequency ablation compared with platelet transfusion.

Efficacy of the traction method for gastric endoscopic submucosal dissection: a randomized controlled trial (with videos).

BACKGROUND AND AIMS: To overcome the technical difficulties associated with gastric endoscopic submucosal dissection (ESD), a novel traction device that can alter the direction of traction was developed. This study compared the efficacy and safety of conventional ESD versus those of traction-assisted gastric ESD. METHODS: Patients with a single gastric epithelial neoplasm were randomized to receive conventional (n = 75) or traction-assisted (n = 73) gastric ESD. The primary outcome was ESD procedure time. RESULTS: There were no differences between the conventional and traction-assisted groups with respect to treatment results or adverse events. The mean procedure time was similar for both groups (78.9 vs 88.3 minutes, respectively; P = .3); however, times for the traction device tended to be shorter for lesions in the lesser curvature of the upper or middle stomach (84.6 vs 123.2 minutes; P = .057). CONCLUSIONS: Traction-assisted ESD for lesions in the lesser curvature of the upper or middle stomach were shorter, thereby reducing the procedure time of conventional ESD. (Clinical trial registration: University Hospital Medial Information Network Clinical Trials Registry, identifier 000044450.).

Safety of skipping the tract dilation step for EUS-guided biliary drainage in patients with unresectable malignant biliary obstruction (with video).

BACKGROUND: Thin delivery system stents can be inserted directly without the need for a tract dilation step and are expected to reduce bile leakage during endoscopic ultrasound-guided biliary drainage (EUS-BD). The present study retrospectively compared the safety and efficacy of EUS-BD using a thin metal stent (< 7.5 Fr) with those of EUS-BD using a conventional stent (≥ 7.5 Fr). METHODS: The present study enrolled 112 patients who underwent EUS-BD using metal stents for unresectable malignant biliary obstruction between April 2016 and July 2022. The primary endpoint was the rate of adverse events (AEs). The secondary endpoints were clinical success rate, procedure time, procedure success rate in the absence of the tract dilation step, recurrent biliary obstruction rate, time to biliary obstruction, and overall survival. Risk factors associated with early AEs were also evaluated. RESULTS: The rate of early AEs was significantly lower (12% vs. 35%, P = 0.013) and the procedure success without the tract dilation step was significantly higher (82% vs. 33%, P < 0.001) in the thin than in the conventional delivery system stent group. None of the other secondary endpoints differed significantly between the two groups. Multivariate analysis showed that employing the tract dilation step during EUS-BD was a significant independent risk factor for early AEs (skipping vs. employing; HR, 9.66; 95% CI, 1.13-83.0, P = 0.028). CONCLUSION: Employing the tract dilation step during EUS-BD was a significant risk factor for early AEs. Metal stents with a delivery diameter < 7.5 Fr can be inserted directly without the tract dilation step, resulting in lower early AE rates.

Changes in the Proportion of Each Cell Type After hiPSC-Derived Airway Epithelia Transplantation.

No radical treatment is available for the regeneration of dysfunction and defects in airway epithelia. Artificial tracheae made of polypropylene and collagen sponge were used in clinical studies to reconstitute tracheae after resection. For early epithelialization of the luminal surface of the artificial trachea, a model was established, that is, an artificial trachea covered with human-induced pluripotent stem cell-derived airway epithelial cells (hiPSC-AECs) was transplanted into a tracheal defect in an immunodeficient rat. Unlike the cell types of hiPSC-derived cells that are currently used in clinical studies, AECs maintain tissues by proliferation and differentiation of basal cells into various cell types that constitute AECs constantly. Therefore, post-transplantation, the proportion of each cell type, such as ciliated and goblet cells, may change; however, no studies have examined this possibility. In this study, using our hiPSC-AEC-transplanted rat model, we investigated changes in the proportion of each cell type in hiPSC-AECs pre-transplantation and post-transplantation. As a result, the proportion of each cell type changed post-transplantation. The proportion of ciliated, basal, and club cells increased, and the proportion of goblet cells decreased post-transplantation. In addition, the proportion of each cell type in engrafted hiPSC-AECs is more similar to the proportion of each cell type in normal proximal airway tissue than the proportion of each cell type pre-transplantation. The results of this study are useful for the development of therapeutic techniques using hiPSC-AEC transplantation.