Long-term outcomes of EUS-guided balloon-occluded gastrojejunostomy bypass for malignant gastric outlet obstruction (with video).

BACKGROUND AND AIMS: EUS-guided gastroenterostomy (EUS-GE) is a minimally invasive technique for gastric outlet obstruction (GOO). EUS-guided balloon-occluded gastrojejunostomy bypass (EPASS) aims to improve stent deployment and minimize migration in EUS-GE. In this study, we evaluated the long-term outcomes of EPASS. METHODS: We retrospectively analyzed 37 patients (mean age, 71 years; 21 men) with symptomatic, nonrefractory GOO who had undergone EPASS. RESULTS: EPASS achieved a 94.6% technical success rate (35/37), including 2 cases of stent misdeployment. The mean procedure time was 27.3 minutes, with a double-balloon tube insertion time of 10.4 minutes. Initial GOO scores improved from .43 to 2.14 and 2.60 at 7 and 28 days after EPASS, respectively. The clinical success rate was 89.2%. The rate of adverse events, including fever and abdominal pain, was 16.2%. The mean overall survival after EPASS was 193.5 days, with no stent occlusion or migration (100% patency). CONCLUSIONS: EPASS demonstrated safety and reliability in EUS-GE, offering a viable option for symptomatic malignant GOO treatment. (Clinical trial registration number: UMIN000011608.).

Long-term outcomes after EUS-guided antegrade intervention for benign bilioenteric anastomotic stricture.

BACKGROUND AND AIMS: Bilioenteric anastomotic stricture (BES) is a well-known adverse event after bilioenterostomy. Recently, EUS-guided antegrade intervention (EUS-AI) has been developed for cases that are difficult to treat by balloon enteroscopy-assisted ERCP. However, no data are available on the long-term outcomes after EUS-AI. The main goal of the present study was to clarify the long-term outcomes of EUS-AI in such patients. METHODS: Between November 2013 and November 2021, 34 patients who were followed for more than 1 year after EUS-AI for BES were identified. The primary endpoint was the rate of stricture resolution. Secondary endpoints were factors associated with stricture resolution, rate of BES recurrence, rate of conversion to surgery, and rate of hepatic fibrosis progression during follow-up. RESULTS: The median follow-up period was 56.7 months. Stricture resolution was achieved in 17 of 34 patients (50%). A multivariate analysis confirmed that the presence of bile duct stones (odds ratio, 9.473; 95% confidence interval, 1.66-53.98; P = .01) was significantly associated with stricture resolution. The stricture recurrence rate was 33%, and the median time from stent removal to recurrence was 31.2 months. Four patients underwent surgery because of recurrent cholangitis. During the median follow-up period of 56.7 months, 25% progressed to hepatic fibrosis based on the Fibrosis-4 index grade. Interestingly, patients without cholangitis during follow-up did not show progression of hepatic fibrosis. CONCLUSIONS: EUS-AI has achieved acceptable long-term clinical outcomes. EUS-AI can be a viable alternative treatment of choice before surgical treatment in patients who are difficult to treat by conventional approaches.

[Bleeding due to acquired factor V inhibitor successfully treated with platelet transfusion during treatment for recurrent prostate squamous cell carcinoma].

A 78-year-old man with prostate squamous cell carcinoma recurrence in his pelvis was admitted to our hospital. Rectal obstruction led to creation of an artificial anus on the transverse colon. Then, docetaxel and radiation therapies were started. A week later, severe hematuria and melena occurred. Activated partial thromboplastin time (APTT) and prothrombin time (PT) were extremely prolonged. Cross-mixing test for APTT and PT revealed an inhibitor pattern, which was diagnosed as acquired factor V inhibitor. Fresh frozen plasma and vitamin K infusions were ineffective, but platelet transfusion successfully stopped the bleeding. Platelet factor V derived from megakaryocytes may affect local hemostasis. The patient received prednisolone (PSL), and the inhibitor disappeared on day 70 and was in remission. PSL could be stopped on day 100. Later, we demonstrated APTT and PT shortening of factor V deficient plasma by the supernatant of activated platelets with collagen.

CXCL12-CXCR4 Axis Is Required for Contact-Mediated Human B Lymphoid and Plasmacytoid Dendritic Cell Differentiation but Not T Lymphoid Generation.

We investigated the involvement of CXCL12-CXCR4 interactions in human lymphohematopoiesis by coculture with telomerized human stromal cells. CXCR4 expression was low in CD34+CD38-CD45RA-CD10-CD7-CD19- immature hematopoietic stem/precursor cells (HSPCs) but higher in CD34+CD38-CD45RA+CD10+CD7+/-CD19- early lymphoid precursors and even higher in CD34+CD38+CD45RA+CD10+CD7-CD19+ pro-B cells. Inhibition of the effect of stromal cell-produced CXCL12 by an anti-CXCR4-blocking Ab suppressed the generation of CD45RA+CD10-CD7+CD19- early T lymphoid precursors (ETPs) and CD45RA+CD10+CD7-CD19+/- B lymphoid precursors on stromal cells, but it did not affect the generation of ETPs in conditioned medium of stromal cell cultures. Replating assays showed that contact with stromal cells was critical for HSPC-derived CD45RA+CD10+CD7-CD19- B lineage-biased precursors to differentiate into CD19+ pro-B cells, which was suppressed by the anti-CXCR4 Ab. Conversely, HSPC-derived ETPs possessed T and B lymphoid and monocytic differentiation potential; stromal cell contact was not required for their growth but rather promoted B lymphoid differentiation. The anti-CXCR4 Ab did not affect the growth of ETPs in conditioned medium, but it suppressed their B lymphoid differentiation on stromal cells. CD14-CD11c-HLA-DR+CD123highCD303+ plasmacytoid dendritic cells developed from HSPCs and ETPs exclusively in contact with stromal cells, which was suppressed by the anti-CXCR4 Ab. These data indicate that CXCL12 plays an essential role in stromal cell contact-mediated B lymphoid and plasmacytoid dendritic cell differentiation from immature hematopoietic and early T lymphoid precursors with a multilineage differentiation potential, but it does not participate in contact-independent generation of early T lymphoid precursors.

Caenorhabditis elegans brc-1 mutation increases the number of COSA-1 foci in him-8 and zim-2 mutants.

Crossover designation factors such as COSA-1 are concentrated at the specific DNA double-strand break (DSB) sites to promote crossover formation. zim-1 mutants, which show defects in the homologous chromosome pairing of chromosomes II and III, increase the COSA-1 foci/normal bivalent state compared to the expected value. The excess designation was suppressed by an additional mutation in brc-1 in zim-1 mutants. We demonstrated that the number of COSA-1 foci in him-8 and zim-2 mutants, showing defects in the pairing of the X and V chromosomes, respectively, increased compared to the expected value, and brc-1 mutation accelerated the number of COSA-1 foci in oogenesis.

Early and late effects of endoscopic interventions in patients with malignant afferent loop syndrome: A single-center experience and literature review.

BACKGROUND/PURPOSE: Afferent loop syndrome (ALS) is a rare adverse event after gastrointestinal surgery requiring appropriate early decompression treatment. Several endoscopic interventions have been attempted for treatment, including endoscopic enteral metal stent placement (EMSP), endoscopic ultrasound (EUS)-guided entero-enterostomy (EUS-EE), and EUS-guided hepaticogastrostomy (EUS-HGS). However, there are limited data on outcomes, including duration of stent patency. In this study, we evaluated the usefulness of each endoscopic intervention for malignant ALS. METHODS: We retrospectively investigated nine patients with malignant ALS who underwent EMSP, EUS-EE, or EUS-HGS. Information on technical success, clinical efficacy, adverse events, stent dysfunction, and overall survival was collected and analyzed. RESULTS: The most common symptoms were abdominal pain and cholangitis. ALS was treated by EMSP in three patients, EUS-EE in three patients, and EUS-HGS in three patients. Stent placement was successful and clinically effective in all patients with no adverse events. During follow-up, stent dysfunction occurred in two patients treated by EUS-HGS. Eight patients died of primary disease during a median follow-up of 157 days. CONCLUSIONS: Each of the available endoscopic interventions for malignant ALS can be expected to produce similar outcomes, including duration of stent patency. The choice of endoscopic intervention should be made based on the characteristics of each treatment.

Potential versatile uses of a novel ultra-thin peroral cholangioscope.

Tonozuka and colleagues report the usefulness of a newly developed ultra-thin mother-baby type peroral cholangioscope with a tip external diameter of 2.3 mm for a case of biliary stricture in which conventional peroral cholangioscope insertion was challenging. The novel scope allows simple and low-cost peroral cholangioscopy, making it highly versatile.

Novel self-assembling hemostatic agent with a supportive role in hemostatic procedures for delayed bleeding after endoscopic papillectomy.

PuraStat is a newly developed self-assembling hemostatic gel which is expected to be applied to bleeding from various lesions of the gastrointestinal tract. Yamamoto and colleagues describe the practical use of this hemostatic gel for delayed bleeding after endoscopic papillectomy, with accompanying video.

Endoscopic retrieval of a proximally migrated fully covered self-expandable metal stent using biopsy forceps with a guiding sheath cannula.

Transpapillary endoscopic biliary drainage is the gold standard for resolving malignant biliary obstruction. Stent migration occasionally occurs and is troublesome to retrieve. Yamamoto and colleagues report with accompanying video on the successful retrieval of a proximally migrated stent using biopsy forceps through a guiding sheath cannula.

A novel peroral digital cholangioscope with a large accessory channel: An experimental study.

BACKGROUND/PURPOSE: A peroral cholangioscope (POCS) can allow direct visualization of the biliary mucosa and its use is becoming more widespread due to improvements in functionality, image quality, and operability, as well as the development of related devices. Recently, a novel mother-baby peroral cholangioscope (nMB-POCS) with a large (2-mm) accessory channel has been developed. In this study, we evaluated the feasibility of this novel POCS in a dry simulation and animal model. METHODS: We evaluated the ease of insertion and maneuverability of the nMB-POCS, the image quality, and the passage of the devices into the accessory channel and into the common bile duct in a dry and live porcine model. RESULTS: In both models, the nMB-POCS could be easily inserted into the duodenoscope and into the distal bile duct and hilum. The image quality was good, and it was possible to observe the surface structure and the vascular network of the bile duct mucosa in detail. CONCLUSIONS: The nMB-POCS with its larger accessory channel is expected to improve the efficiency of diagnosis and  treatment, and reduce the procedure time. Clinical studies in patients are warranted.

A fatal case of massive hemobilia caused by invasive pancreatic cancer with median arcuate ligament syndrome: A case report.

INTRODUCTION: In median arcuate ligament syndrome (MALS), the celiac artery is compressed, causing an arcade to develop in the pancreatic head, leading to ischemic symptoms and aneurysms. PATIENT CONCERNS: The patient was diagnosed with borderline resectable pancreatic cancer (PC) and MALS. Endoscopic biliary drainage with a covered metal stent (CMS) was performed for the obstructive jaundice. After the jaundice improved, a modified FOLFIRINOX regimen was initiated. Several days later, cardiopulmonary arrest occurred after hematemesis occurred. Cardiopulmonary resuscitation was performed, his blood pressure stabilized, and emergent upper endoscopy was performed. The CMS was dislodged and active bleeding was observed in the papillae. The CMS was replaced, and temporary hemostasis was achieved. Contrast-enhanced computed tomography revealed a diagnosis of extravasation from the posterior superior pancreaticoduodenal artery (PSPDA) into the biliary tract. Transcatheter arterial embolization was performed. However, the patient was subsequently diagnosed with hypoxic encephalopathy and died on day 14 of hospitalization. DIAGNOSIS: Biliary hemorrhage due to invasion of pancreatic cancer from the PSPDA associated with MALS. INTERVENTION: None. OUTCOMES: Biliary hemorrhage from the PSPDA was fatal in the patient with invasive PC with MALS. LESSONS: Since MALS associated with PC is not a rare disease, the purpose of this study was to keep in mind the possibility of fatal biliary hemorrhage.

Objective evaluation of the resistance forces of 22-gauge EUS-FNA and fine-needle biopsy needles.

Background and Objectives: EUS-guided tissue acquisition is routinely performed for the diagnosis of gastrointestinal tract and adjacent organ lesions. Recently, various types of needles have been developed. However, how the shape of the needle tip and echoendoscope tip angle affect puncturability, has not been clarified. The aim of this experimental study was to compare the puncturability of several 22-gauge EUS-FNA and EUS-guided fine-needle biopsy (EUS-FNB) needles, and to evaluate the effects of the needle tip shape and echoendoscope tip angle on tissue puncturability. Materials and Methods: The following six major FNA and FNB needles were evaluated: SonoTip® ProControl, EZ Shot 3 Plus, Expect™ Standard Handle, SonoTip® TopGain, Acquire™, and SharkCore™. The mean maximum resistance force against needle advancement was evaluated and compared under several conditions using an echoendoscope. Results: The mean maximum resistance force of the needle alone was higher for the FNB needles than for the FNA needles. The mean maximum resistance force of the needle in the echoendoscope with free angle demonstrated that the resistance forces were between 2.10 and 2.34 Newton (N). The mean maximum resistance force increased upon increases in angle of the tip of echoendoscope, particularly in the FNA needles. Among the FNB needles, SharkCore™ had the lowest resistance force (2.23 N). The mean maximum resistance force of the needle alone, the needle in the echoendoscope with free angle, and the needle in the echoendoscope with full-up angle for SonoTip® TopGain were all similar to that of Acquire™. Conclusion: SonoTip® TopGain had similar puncturability to Acquire™ in all tested situations. Regarding the puncturability, SharkCore™ is most suitable for insertion into target lesions, when tight echoendoscope tip angle is necessary.

Impact of using scope holder on Interventional Endoscopy (with video).

Highlight Tsuchiya and colleagues developed a scope holder to maintain good scope positioning during interventional endoscopic ultrasound. The scope holder not only reduces the burden on the endoscopist but also reduces the radiation exposure of the caregiver. This is the first report on a scope holder for flexible endoscopes.

A bifurcation concept for B-lymphoid/plasmacytoid dendritic cells with largely fluctuating transcriptome dynamics.

Hematopoiesis was considered a hierarchical stepwise process but was revised to a continuous process following single-cell RNA sequencing. However, the uncertainty or fluctuation of single-cell transcriptome dynamics during differentiation was not considered, and the dendritic cell (DC) pathway in the lymphoid context remains unclear. Here, we identify human B-plasmacytoid DC (pDC) bifurcation as large fluctuating transcriptome dynamics in the putative B/NK progenitor region by dry and wet methods. By converting splicing kinetics into diffusion dynamics in a deep generative model, our original computational methodology reveals strong fluctuation at B/pDC bifurcation in IL-7Rα+ regions, and LFA-1 fluctuates positively in the pDC direction at the bifurcation. These expectancies are validated by the presence of B/pDC progenitors in the IL-7Rα+ fraction and preferential expression of LFA-1 in pDC-biased progenitors with a niche-like culture system. We provide a model of fluctuation-based differentiation, which reconciles continuous and discrete models and is applicable to other developmental systems.

Two Cases of Hemorrhagic Ampullary Lesions Successfully Treated by Endoscopic Papillectomy.

We herein report two cases of hemorrhagic ampullary lesions in which endoscopic papillotomy was performed to control bleeding and resulted in successful treatment. Both patients were pathologically diagnosed with an underlying pathology characterized by inflammatory cell infiltration and capillary proliferation. They also had disposing factors for bleeding, such as antithrombotic therapy and idiopathic thrombocytopenic purpura. Endoscopic treatment was selected because the risk of surgical resection was high due to the patients' hemorrhagic condition. Both patients were successfully treated without any serious adverse events and had an uneventful postoperative course with no relapse of bleeding.

Clinical Outcomes of Digital Cholangioscopy-Guided Procedures for the Diagnosis of Biliary Strictures and Treatment of Difficult Bile Duct Stones: A Single-Center Large Cohort Study.

Although Spy DS (SpyGlass DS Direct Visualization System) is considered to be useful for the diagnosis of bile duct strictures and the treatment of bile duct stones, there is limited data to date validating its efficacy. We hence retrospectively evaluated the clinical outcomes of the use of Spy DS in a large number of patients. A total of 183 patients who underwent Spy DS-guided procedures for indeterminate bile duct strictures (n = 93) and bile duct stones (n = 90) were analyzed retrospectively. All patients (93/93) with bile duct strictures successfully underwent visual observation, and 95.7% (89/93) of these patients successfully underwent direct biopsy. The sensitivity, specificity, and overall accuracy were 94.7%, 83.3%, and 90.3%, respectively, for visual impression; 80.9%, 100%, and 89.2%, respectively, for histopathological analysis of a direct biopsy; and 96.5%, 91.7%, and 94.6%, respectively, for visual impression combined with biopsy. Successful visualization of the stones was achieved in 98.9% (89/90) of the patients, and complete stone removal was achieved in 92.2% (83/90) of the patients, with an average of 3.3 procedures. The adverse events rate was 17.5% (32/183; cholangitis in 15 patients, fever the following day in 25, pancreatitis in 1, hemorrhage in 1, and gastrointestinal perforation in 1). No administration of antibiotics before the procedure was found to be a statistically significant risk factor for the development of fever after the procedure (p < 0.01). Spy DS-guided procedures are effective for the diagnosis and treatment of bile duct lesions and can be performed with a low risk of serious adverse events.

The feasibility of pancreatic duct stenting using a novel 4-Fr plastic stent with a 0.025-in. guidewire.

Pancreatic duct stenting is a well-established method for reducing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. However, there is no consensus on the optimal type of plastic stent. This study aimed to evaluate the feasibility and safety of a new 4-Fr plastic stent for pancreatic duct stenting. Forty-nine consecutive patients who placed the 4-Fr stent into the pancreatic duct (4Fr group) were compared with 187 consecutive patients who placed a conventional 5-Fr stent (control group). The primary outcome was technical success. Complications rate, including post-ERCP pancreatitis (PEP) were the secondary outcomes. Propensity score matching was introduced to reduce selection bias. The technical success rate was 100% in the 4Fr group and 97.9% in the control group (p = 0.315). Post-ERCP amylase level was significantly lower in the 4-Fr group than the control group before propensity score matching (p = 0.006), though without statistical significance after propensity score matching (p = 0.298). The rate of PEP in the 4Fr group (6.1%) was lower than the control group (15.5%), though without statistical significance before (p = 0.088) and after (p = 1.00) propensity score matching. Pancreatic duct stenting using a novel 4-Fr plastic stent would be at least similar or more feasible and safe compared to the conventional plastic stent.

Urgent and early EUS-guided biliary drainage in patients with acute cholangitis.

BACKGROUND AND OBJECTIVES: EUS-guided biliary drainage (EUS-BD) has been reported as an effective alternative drainage technique. However, clinical data on EUS-BD for patients with acute cholangitis (AC) are limited. The aim of this study was to analyze the clinical outcomes of EUS-BD in patients with AC. PATIENTS AND METHODS: Nineteen patients with AC who underwent urgent or early drainage (within 96 h) by EUS-guided hepaticoenterostomy (EUS-HES) between January 2014 and November 2019 were retrospectively reviewed. Furthermore, the clinical outcomes of EUS-HES using a plastic stent in the AC group (n = 15) were compared to those in the non-AC group (n = 88). RESULTS: In the 19 AC cases, the technical and clinical success rate was 100% with 5.3% of moderate adverse events (biliary peritonitis [n = 1]). Regarding the comparison between the AC group and the non-AC group, the clinical success rate was 100% in both groups and the adverse event rate was not statistically significantly different (P = 0.88). Although the recurrent biliary obstruction (RBO) rate was not statistically significantly different (P = 0.43), the early RBO rate was statistically significantly higher in the AC group (26.7% vs. 3.4%, P < 0.001). Kaplan-Meier curves showed that AC was associated with a shorter time to RBO (P = 0.046). The presence of AC was found to be an independent risk factor of early RBO (odds ratio = 10.3; P = 0.005). CONCLUSIONS: Urgent or early biliary drainage (within 96 h) by EUS-BD can be a feasible and safe alternative procedure for patients with AC, although there is a tendency of early RBO.