Feasibility and safety of endoscopic ultrasound-guided biliary drainage in inexperienced centers: a multicenter study in Southwest Japan.

BACKGROUND AND AIMS: Endoscopic ultrasound-guided biliary drainage (EUS-BD) has shown promising procedural outcomes in high-volume centers. While inferior procedural outcomes were reported in inexperienced centers during the early days of EUS-BD, the current outcomes are unknown. This study aimed to clarify the feasibility and safety of EUS-BD in centers that recently introduced EUS-BD. METHODS: This multicenter retrospective study was conducted at 22 centers that introduced EUS-BD between 2017 and 2022. A maximum of 20 initial EUS-BD cases at each center were evaluated. The clinical outcomes and experience of 84 endoscopists who performed these procedures were examined. The primary outcomes were the rate of technical success and adverse events (AEs). The secondary outcomes were risk factors associated with technical failure and procedure-related AEs. RESULTS: A total of 255 patients were enrolled. The technical success rate was 91.4% (233/255). Among technical failure cases (n=22), guidewire manipulation failure was the most common cause (n=12), followed by tract dilation failure (n=5). The AE rate was 10.2% (26/255). Multivariate analysis identified a puncture target diameter of <5 mm (odds ratio, 3.719; 95% confidence interval, 1.415-9.776; p=0.008) and moderate ascites extending to the liver surface (odds ratio, 3.25; 95% confidence interval, 1.195-8.653; p=0.021) as independent risk factors for technical failure and procedure-related AEs, respectively. Endoscopists' procedural experience was not a risk factor for technical failure or procedure-related AEs. CONCLUSIONS: The feasibility and safety of EUS-BD were maintained during the induction phase at inexperienced centers. These will be helpful in better understanding the current status of EUS-BD.

Radial force and wire structure determine the onset of covered self-expandable metal stent migration in endoscopic ultrasound-guided hepaticogastrostomy: Measurement of sliding-resistance force using a porcine model.

BACKGROUND: Self-expandable metal stent (SEMS) migration after endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) is a severe complication. The migration risk could be related to the surface friction of SEMS, assumed to be affected by the wire structure and mechanical properties, including radial force (RF); however, their relevance remains unclear. This experimental study aimed to assess the mechanical properties of SEMS involved in the onset of stent migration by measuring the sliding-resistance force (SF) as the SEMS moves through the stomach wall. METHODS: The SF of seven types of 8-mm diameter SEMS (four braided and three laser-cut types) and porcine stomach wall was measured with a universal testing machine. The SF of each SEMS was measured three times, and the average maximum SF (SFmax) was used for analysis. The correlation between SFmax and RF of each SEMS was evaluated. RESULTS: SFmax and RF showed a very strong positive correlation (r = 0.92). Compared to the regression line predictions in the scatter plots of SFmax and RF, the SFmax of laser-cut and braided type SEMSs had positive and negative residuals, respectively. CONCLUSIONS: Selecting a laser-cut type SEMS with a higher RF may more effectively prevent the onset of stent migration against the stomach wall in EUS-HGS.

Inhibitory Effect of Pyra-Metho-Carnil on the Differentiation and Maturation of Macrophages in Normal and Cancer Microenvironments.

BACKGROUND/AIM: In a previous study, we have demonstrated heightened Pyra-Metho-Carnil (PMC) efficacy in nude mice with intact innate immunity that lack T and B cells. This has prompted hypothesizing that PMC may target macrophages that promote cancer growth. In this study, we conducted co-culture experiments with macrophages derived from THP-1 human monocyte cell lines and spheroids representing normal and cancer microenvironments. We then performed RNA sequencing and flow cytometry analysis to elucidate the mechanisms by which PMC affects macrophage differentiation and maturation. MATERIALS AND METHODS: THP-1 cells were differentiated by phorbol 12-myristate 13-acetate (PMA) and matured by PMA and lipopolysaccharide (LPS) either with or without PMC. Co-cultures were performed using stimulated THP-1 cells and HKe3-wild-type KRAS or HKe3-mutant (mt) KRAS spheroids. We then performed RNA-seq analysis of THP-1 cells stimulated by PMA (either with or without PMC) and flow cytometry analysis of mice peripheral blood obtained after PMC administration. RESULTS: THP-1 cells matured by PMA and LPS specifically increased the area of HKe3-mtKRAS cancer spheroids and the addition of PMC to THP-1 cells was found to inhibit cancer spheroid growth. RNA-seq data suggested that PMC treatment of THP-1 cells stimulated with PMA suppressed cell motility regulatory functions via down-regulation of the NF[Formula: see text]B pathway. Furthermore, flow cytometry results showed that PMC treatment suppressed monocyte maturation in B6 mice. CONCLUSION: The high level of in vivo tumor suppression caused by PMC may be due to inhibition of the differentiation and maturation of tumor-associated macrophages via the NF[Formula: see text]B signaling pathway.

Structural factors influencing the clinical performance of 0.025-inch guidewires for pancreatobiliary endoscopy: An experimental study.

Background and study aims To develop a pancreatobiliary endoscopic guidewire with good clinical performance, an understanding of its structure is necessary. This study aimed to investigate the structural factors influencing the clinical performance of pancreatobiliary endoscopic guidewires. Methods Eight types of 0.025-inch guidewires were evaluated. The following structural properties were measured: tip length, tip deflection height, tip weight (TW), ratio of tip core weight to TW, shaft coating type (flat or uneven), outer diameter, and core wire diameter (CWD). Four performance tests were conducted to evaluate shaft stiffness as bending force (BF), shaft lubricity as friction force (FF), torque response as torque response rate (TRR), and seeking ability as total insertion success (TIS) in a technical test using a 3D bile duct model. The correlation coefficients of each variable were analyzed. Results The BF and CWDs were strongly correlated, as well as the FF and CWDs and BF. Among the guidewires with similar CWDs, the guidewires with uneven coating had significantly lower FF than those with flat coating. The TRR was strongly correlated with the CWDs; furthermore, guidewires with lower FF had better TRR. TIS was strongly correlated with the TRR, TWs, and ratio of the tip core weight to TW. Conclusions CWD affects shaft stiffness; CWD and coating type affect shaft lubricity and torque response. Because TRR and TW are correlated with seeking ability, an appropriate combination of core wire thickness, TW, and coating design is required to develop a guidewire with good seeking ability.

Disappearance of Hepatocellular Adenoma in a Patient with Cornelia de Lange Syndrome after Treatment with Transcatheter Arterial Embolization.

Cornelia de Lange syndrome (CdLS) is a congenital disorder occasionally associated with congenital portosystemic shunt (CPSSs). We herein report a patient with CdLS and CPSS who developed hepatocellular adenomas (HCAs). The patient presented to our hospital for the further investigation of newly diagnosed liver tumors. Imaging findings and pathological examination results indicated that the liver tumors were inflammatory HCAs that subsequently shrank following transcatheter arterial embolization (TAE). Patients with CdLS and CPSS are at risk of developing HCAs, and TAE may be an effective management strategy for HCA in these patients.

Preoperatively diagnosed intraductal oncocytic papillary neoplasm of the pancreas with prominent invasion: a case report.

Previously considered as one of the less-invasive subtypes of intraductal papillary mucinous neoplasm, intraductal oncocytic papillary neoplasm (IOPN) has recently been acknowledged as a new entity of pancreatic tumor. We herein present a case of preoperatively diagnosable IOPN invasion in the stomach and colon. A 78-year-old woman was referred to our hospital for evaluation of anorexia and gastroesophageal reflux. Upper gastrointestinal endoscopy revealed a gastric subepithelial lesion with ulcerated mucosa that required hemostasis. Computed tomography revealed a 96-mm-diameter solid tumor with a well-defined border and centrally positioned necrotic area, extending from the stomach to the transverse colon and pancreatic tail. Because it was suspected to be a pancreatic solid tumor with direct stomach invasion, endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) was performed, which led to a preoperative diagnosis of IOPN. Moreover, laparoscopic pancreatosplenectomy, proximal gastrectomy, and transverse colectomy were performed. Analysis of the surgical specimen revealed that the tumor was IOPN and had invaded the stomach and transverse colon. Lymph node metastasis was also confirmed. These findings indicate that IOPN can manifest as an invasive tumor, and EUS-FNB may be equally helpful for assessing the invaded area of a cystic lesion as it is for a solid lesion.

High predictive ability of apparent diffusion coefficient value for wall-invasion pattern of advanced gallbladder carcinoma.

PURPOSE: The wall-invasion pattern classification of advanced gallbladder carcinoma (GBC) has been reported. However, its association with clinical findings remains unclear. We aimed to clarify relationships between clinicopathological characteristics, prognosis, and apparent diffusion coefficient (ADC) values of advanced GBC based on the wall-invasion pattern. METHODS: We reviewed the data of 37 patients who had undergone advanced GBC cholecystectomy at our institution between 2009 and 2021. Clinicopathological findings, prognosis, and ADC values were retrospectively analyzed. RESULTS: Based on the wall-invasion pattern, patients were classified into infiltrative growth (IG) type (n = 22) and destructive growth (DG) type (n = 15). In the DG-type, the incidence of venous invasion (P = 0.027), neural invasion (P = 0.008), and lymph node metastasis (P = 0.047) was significantly higher than in the IG-type, and recurrent-free survival (RFS) was significantly shorter (P = 0.015); the median RFS was 11.4 months (95% confidence interval, 6.3-16.5 months) in the DG-type and not reached in the IG-type. The ADC value in the DG-type was significantly lower than in the IG-type (median, 1.19 × 10-3 mm2/s vs. 1.86 × 10-3 mm2/s, P < 0.001). The area under the receiver operating characteristic curve for the ADC values to differentiate wall-invasion patterns was 0.95 (95% confidence interval, 0.87-1.00). The optimal cutoff ADC value was 1.45 × 10-3 mm2/s (sensitivity, 92.9%; specificity, 90.9%). CONCLUSIONS: The wall-invasion pattern of advanced GBC is associated with its aggressiveness and prognosis, and can be predicted by ADC values with high accuracy.

A novel self-assembling peptide hemostatic gel as an option for initial hemostasis in endoscopic sphincterotomy-related hemorrhage: a case series.

Endoscopic sphincterotomy (EST) is a fundamental procedure of therapeutic endoscopic retrograde cholangiopancreatography, with post-EST bleeding as a serious adverse event. Although there are various hemostatic methods for post-EST bleeding, there is no consensus regarding the treatment choice. PuraStat is a novel self-assembling peptide developed as a hemostatic agent. We report six cases of EST-related hemorrhage with initial hemostasis achieved using PuraStat. The cases were observed in four men and two women, with an average age of 77.8 years. EST was performed for biliary drainage in four cases and for stone removal in two cases. Bleeding occurred during the same session as EST in five of six cases, with the remaining case showing bleeding 4 days after EST. As all patients with EST-related hemorrhage presented oozing with stable vital signs, we selected PuraStat as first-line hemostasis in each case. We applied PuraStat using a dedicated catheter with the tip pressed against the bleeding point. Hemostasis was confirmed without additional procedure in all cases. No adverse events were noted after the procedures. As PuraStat hemostasis is effective, feasible, and safe for EST-related hemorrhage, PuraStat may be an option for initial hemostasis, although it is limited to oozing.

Standardized Methods Using EUS-guided Fine-needle Biopsy and a Minimal Medium Creates Three Pancreatic Cancer Organoids.

BACKGROUND/AIM: Recently, endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) has been conducted for diagnosing pancreatic ductal adenocarcinoma (PDAC), after which obtained samples were used in organoid cultures. However, no standardized method for PDAC organoid cultures exists. Therefore, to standardize or simplify sample collection and culture methods for PDAC organoids, we performed a floating culture using non-minced specimens obtained by EUS-FNB in a minimal medium, lacking growth factors or inhibitors for pancreatic organoids. PATIENTS AND METHODS: A total of 38 patients with clinically diagnosed PDAC were enrolled in the study. First, EUS-FNB was conducted using a 22- or 25-gauge biopsy needle. Then, a surplus of samples was collected for organoid formation after rapid on-site cytological evaluations of sample adequacy. Subsequently, the established organoids were compared with clinical data and pathological diagnosis, following periodic observations and evaluations for morphology. RESULTS: PDAC organoids were successfully created in 24 of the 38 cases (63.2%), including four cases with pathologically inconclusive EUS-FNB results. Afterward, PDAC organoid morphology was classified into ductal, dormant, and adhesive small cluster (ASC) types. Although the ductal and ASC types were seen separately, they were also seen together in other cases, which we named "mixed type". CONCLUSION: We propose a feasible and straightforward method for establishing organoids, especially for diagnosing PDAC, particularly when the result of EUS-FNB is pathologically inconclusive. Furthermore, PDAC organoids are morphologically classified into three types reported for the first time.

Eosinophilic Granuloma of the Liver Mimicking Metastatic Liver Tumor.

We herein report a case of coagulation necrosis with granulation and eosinophilic infiltration of the liver. A 37-year-old woman was diagnosed with a new mass lesion in the liver 1 month after breast cancer surgery and admitted for a further examination. Because the tumor occurred immediately after surgery, it was considered essential to determine whether or not it was a metastatic liver tumor from breast cancer. A percutaneous liver tumor biopsy revealed eosinophilic granuloma of the liver, which is considered to have a high possibility of visceral larva migrans with suspected gnathostomiasis infection. A detailed medical history and histological diagnosis are important for making a differential diagnosis.

Gastroesophageal Varices and Hyperplastic Nodules of the Liver in a Patient with Anorexia Nervosa.

We report a case of anorexia nervosa (AN) with gastroesophageal varices (GEV) in a 36-year-old woman. The patient presented to our hospital with progressive bloating due to severe ascites. She had no history of alcohol intake. Esophagogastroduodenoscopy and enhanced computed tomography revealed GEV and multiple hepatic nodules, respectively. The histological examination of a liver biopsy specimen revealed similar features to nonalcoholic fatty liver disease and showed hyperplastic nodules that were suspected to be related to the uneven distribution of portal blood flow in the liver. In conclusion, patients with long-term AN should undergo abdominal imaging to detect signs of portal hypertension.

Elobixibat, an ileal bile acid transporter inhibitor, ameliorates non-alcoholic steatohepatitis in mice.

BACKGROUND: Recent studies have suggested that several types of toxic bile acids (BAs) are involved in the pathogenesis of non-alcoholic steatohepatitis (NASH). In the present study, we aimed to determine whether elobixibat, an ileal bile acid transporter (IBAT) inhibitor, would ameliorate NASH in mice. METHODS: C57BL/6N mice were fed a methionine and choline-deficient (MCD) to induce NASH or standard diet as control for 8 weeks (n = 5 per group). The MCD diet-fed mice were administered elobixibat 5 days a week for 4 weeks by gavage (n = 5). The effects of the treatments on liver histopathology, proinflammatory cytokine concentrations, intestinal epithelial tight junctions, and the intestinal microbial composition were then assessed. RESULTS: In MCD-fed mice, hepatic fibrosis and inflammatory cell infiltration developed, and the serum aspartate transaminase activity and BA concentration were higher than the control. In addition, the proinflammatory cytokine concentrations were high in the liver and mesenteric lymph nodes (MLN), and the expression of intestinal epithelium tight junction proteins, claudin1, was increased. In the intestinal microbial composition, the abundance of the Lachnospiraceae and Ruminococcaeae were decreased, whereas that of the Enterobacteriaceae was increased. Treatment with elobixibat reduced the serum BA and increased the fecal BA concentration, and ameliorated the liver inflammation and fibrosis. It also reduced the expression of proinflammatory cytokines in the liver and MLNs, and transforming growth factor-ß expression in the liver. Finally, elobixibat normalized intestinal tight junction protein level and the composition of the intestinal microbiota. CONCLUSION: Elobixibat ameliorates NASH-related histopathology, reduces cytokine expression, and normalizes the intestinal microbial composition in MCD-fed mice, which suggests that it may represent a promising candidate for the therapy of NASH.

Hepatitis B virus core-related antigen is useful for surveillance of hepatocellular carcinoma recurrence in a patient with occult hepatitis B virus infection: Case report.

Serum HBV core-related antigen (HBcrAg) is useful for detecting HCC in patients with occult HBV infection. Surveillance for HCC is needed in patients who are positive for HBcrAg, even if they are negative for HBsAg and HBV DNA.

Autoimmune Hepatitis with Concomitant Idiopathic Thrombocytopenic Purpura Diagnosed by Transjugular Liver Biopsy.

Patients with autoimmune hepatitis (AIH) may sometimes have concomitant idiopathic thrombocytopenic purpura (ITP). Severe thrombocytopenia in ITP interferes with percutaneous liver biopsy for pathological diagnosis of AIH. Here, we report a case of AIH with ITP in a 63-year-old woman. The patient presented to our hospital with liver dysfunction and thrombocytopenia. For histological examination, transjugular liver biopsy (TJLB) was performed, leading to a diagnosis of AIH. Corticosteroids treatment led to an improvement in her liver enzyme levels and platelet count. In conclusion, patients with AIH may sometimes have concomitant ITP. TJLB was effective for making the diagnosis of AIH with severe thrombocytopenia due to ITP.