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.

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.

Long-Term Effects of Rifaximin on Patients with Hepatic Encephalopathy: Its Possible Effects on the Improvement in the Blood Ammonia Concentration Levels, Hepatic Spare Ability and Refractory Ascites.

Background and Objectives: To investigate the long-term efficacy of rifaximin (RFX) for hyperammonemia and efficacy for refractory ascites in patients with cirrhosis. Materials and Methods: We enrolled 112 patients with liver cirrhosis who were orally administered RFX in this study. Changes in the clinical data of patients were evaluated up to 36 months after RFX administration. The primary endpoint was a change in blood ammonia levels. Secondary endpoints included changes in clinical symptoms, Child−Pugh (CP) score, number of hospitalizations, degree of refractory ascites, adverse events, and the relationship between RFX administration and the renin-angiotensin-aldosterone system. Results: An improved rate of overt hepatic encephalopathy (HE) of 82.7% was observed 3 months after RFX administration, which significantly induced a progressive decrease in blood ammonia concentration and an improved CP score up to 36 months. No serious RFX treatment-related adverse events were observed. 36.5% in patients after RFX administration improved refractory ascites. After RFX administration, patients with satisfactory control of hepatic ascites without addition of diuretic had lower renin concentration than those with poor control (p < 0.01). At less than 41 pg/mL renin concentration, the control of refractory ascites was significantly satisfactory (p < 0.0001). Conclusions: RFX reduced blood ammonia concentration and improved hepatic spare ability and the quality of life of patients with long-term HE to up to 36 months. Our study revealed the effects of RFX against refractory ascites, suggesting that renin concentration may be a predictive marker for assessing ascites control.

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.

Novel Endoscopic Therapy for Gastric Varices Using Direct Forward-Viewing Endoscopic Ultrasonography.

Gastric varices (GV) carry a high risk of massive hemorrhage because of potential rupture. To reduce the risk associated with GV, patients need to undergo hemostatic and preventive treatment. The objective of this retrospective study was to evaluate the usefulness of a new method, direct forward-viewing endoscopic ultrasonography (DFV-EUS) for the treatment of GV. We performed endoscopic injection sclerotherapy with histoacryl (EIS-HA) using DFV-EUS for GV in four patients. The paracentesis success rate was 75% (3/4). DFV-EUS has a significant advantage for the treatment of GV in that it can show physicians endoscopic and ultrasound views in real time during the delivery of the sclerosant into the GV. However, the proper use of the ultrasound view must be elucidated through further research for safer and more effective therapy. In the presence of distance between the mucosal surface and vascular lumen or when the blood flow site requires puncture as an additional treatment, DFV-EUS might be a good candidate for the treatment of GV. Altogether, EIS-HA with DFV-EUS might be a new therapeutic option for patients with GV.

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.

Irsogladine maleate alters expression of a tight junction protein in portal hypertensive gastropathy.

BACKGROUND AND AIM: Portal hypertensive gastropathy (PHG) is characterized by noninflammatory edema and vasodilatation of the lamina propria of the mucosal epithelium. In addition, the alterations of intercellular junction proteins and dilatation of the endothelial gaps have been reported. In this study, we examined whether irsogladine maleate (IM), a gastric mucosal protective agent, has the potential to improve PHG by restoration of tight junctions (TJs). METHODS: Twenty-four patients with PHG were registered and randomly assigned into two groups: 12 patients in the IM-administration group and 12 patients in the non-administration group. In the administration group, IM (4 mg/day) was administered orally for 12 weeks. Gastric mucosa with a red color in patients with PHG were obtained endoscopically on the registration day and 12 weeks later. The endoscopic findings were evaluated, an immunohistochemical analysis of claudin-3 (a TJ protein) expression in gastric mucosal tissues by a laser microscope was performed, and claudin-3 expression was quantified by western blot analysis. RESULTS: Irsogladine maleate improved the degree of PHG in 2/12 patients endoscopically, in contrast to none of the 12 patients in the non-administration group. Immunohistochemical analysis showed that expression of claudin-3 increased in 8/12 patients in the IM-administration group and 2/12 patients in the non-administration group (P = 0.036). Western blot analysis revealed that the increase in claudin-3 after 12 weeks was significantly higher in the IM-administration group than in the non-administration group (P = 0.010). CONCLUSIONS: The present pilot study suggested that IM might improve the gastric mucosa in PHG through restoration of TJ-protein claudin-3.

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.

Horizontal Transmission of Hepatitis B Virus Genotype C Among Members of a Wrestling Club in Japan.

BACKGROUND In adulthood, most cases of acute hepatitis B virus (HBV) infection are transmitted either by sexual contact or by contaminated needles, but there are other modes of transmission. We report on three cases of HBV infection among members of a wrestling club. CASE REPORT A 19-year-old male wrestling athlete was admitted with acute hepatitis B. Five months later, 2 other men, who were members of the same wrestling club, were diagnosed with HBV infection. The full-length sequences of the HBV DNA were identical in all three cases and classified as subgenotype C2 on phylogenetic analysis. This is the most common genotype found in Japan. No history of sexual or bleeding contact with acquaintances outside the club was noted in any of these cases. This suggests horizontal transmission within the wrestling club. CONCLUSIONS The possibility of HBV transmission through bleeding wounds and sweat is a concern in contact sports such as wrestling. Hence, hepatitis B vaccination is recommended for unvaccinated contact-sports players.

Reduction in Tumor Stain at 2 Weeks after Treatment Initiation Is a Predictor of the Efficacy of Lenvatinib in Patients with Unresectable Hepatocellular Carcinoma.

BACKGROUND AND AIMS: Lenvatinib is an oral anticancer drug for patients with unresectable advanced hepatocellular carcinoma (HCC). We evaluated whether a reduction in tumor stain at 2 weeks after lenvatinib treatment in patients with unresectable HCC is a predictor of early treatment efficacy at 12 weeks. PATIENTS AND METHODS: Of the 23 patients who initiated lenvatinib treatment between April 2018 and January 2019, treatment efficacy was measured in 15 patients for more than 12 weeks after treatment. Changes in tumor stain, tumor size on contrast-enhanced computed tomography (CT), and serum levels of tumor markers were evaluated 2 weeks after lenvatinib treatment. Therapeutic efficacy was assessed by tumor stain and tumor size by contrast-enhanced CT within the first 12 weeks, according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) guidelines. RESULTS: At 12 weeks, efficacy evaluation of 15 patients revealed that 11 of them experienced partial responses, for a response rate of 73.3%. In the first 2 weeks, 13 patients (86.7%) experienced a decreased tumor stain, including 10 responders (90.9%) and 3 non-responders (75.0%). All patients in the non-responder group had required a lenvatinib dose reduction due to adverse events within 12 weeks. On contrast-enhanced CT, the change rate of tumor stain to HCC at 2 weeks after treatment was <0.8 among 10 responders (90.9%) and 1 non-responder (25.0%; p = 0.033). No significant differences between responders and non-responders were observed with regard to most characteristics at baseline and at 2 weeks after treatment initiation. However, significant differences were observed between groups in the presence or absence of a dose suspension period, the presence or absence of lenvatinib dose reduction from the maximum value during the first 2 weeks, and decreased tumor stain at 2 weeks after treatment initiation. CONCLUSION: Reduction in tumor stain at 2 weeks after lenvatinib treatment may be an early biomarker of efficacy at 12 weeks in patients with unresectable HCC.

Exploratory Research on the Relationship between Human Gut Microbiota and Portal Hypertension.

Objective The relationship between gut microbiota and portal hypertension remains unclear. We investigated the characteristics of the gut microbiota in portal hypertension patients with esophago-gastric varices and liver cirrhosis. Methods Thirty-six patients (12 patients with portal hypertension, 12 healthy controls, and 12 non-cirrhosis patients) were enrolled in this university hospital study. Intestinal bacteria and statistical analyses were performed up to the genus level using the terminal restriction fragment length polymorphism method targeting 16S ribosomal RNA genes, with diversified regions characterizing each bacterium. Results Levels of Lactobacillales were significantly higher (p=0.045) and those of Clostridium cluster IV significantly lower (p=0.014) in patients with portal hypertension than in other patients. This Clostridium cluster contains many butanoic acid-producing strains, including Ruminococcace and Faecalibacterium prausnitzii. Clostridium cluster IX levels were also significantly lower (p=0.045) in portal hypertension patients than in other patients. There are many strains of Clostridium that produce propionic acid, and the effects on the host and the function of these bacterial species in the human intestine remain unknown. Regarding the Bifidobacterium genus, which is supposed to decrease as a result of cirrhosis, no significant decrease was observed in this study. Conclusion In the present study, we provided information on the characteristics of the gut microbiota of portal hypertension patients with esophago-gastric varices due to liver cirrhosis. In the future, we aim to develop probiotic treatments following further analyses that include the species level, such as the intestinal flora analysis method and next-generation sequencers.

The Efficacy and Therapeutic Outcome of Bipolar Radiofrequency Ablation for the Treatment for Hepatocellular Carcinoma in the Real-World Setting, Compared with Monopolar Radiofrequency Ablation Conducted during the Same Period.

BACKGROUND: Several reports have suggested that the bipolar radiofrequency ablation (RFA) system is useful for the treatment of hepatocellular carcinoma (HCC). We evaluated the efficacy and safety of the bipolar RFA system for HCC treatment in the real-world setting. METHODS: A total of 155 patients with 224 HCC tumors were enrolled. First, we examined the characteristics and outcomes of two RFA systems, monopolar and bipolar. Second, we identified the factors associated with local tumor progression in 72 patients with 104 HCC tumors, who could be followed up for at least 3 months after treatment and had been treated with the bipolar RFA system. RESULTS: Of the baseline characteristics, tumor size and location were associated with the selection of the bipolar RFA system. A sufficient ablative zone margin (≥5 mm) was obtained by bipolar RFA in 81 of 94 (86.1%). The 1- and 2-year local tumor progression rates were 15.6 and 26.3%, respectively. An alpha-fetoprotein-L3 (AFP-L3) ratio >10% (HR: 7.64; 95% CI: 1.7-39.8, p = 0.007) and an insufficient ablative zone margin (<5 mm) (HR: 4.53; 95% CI: 1.02-20.3, p = 0.047) were related to local tumor progression in Cox regression analysis. Although severe adverse events were not observed in most cases, severe hepatic infarction occurred in 1 patient. CONCLUSIONS: The bipolar RFA system is safe and effective for HCC treatment. Tumor localization within the liver is an important factor associated with bipolar RFA. Careful follow-up or reconsideration of treatment is necessary for cases with AFP-L3 ratio >10% or insufficient ablative zone margin (<5 mm), which were associated with local tumor progression.

Two Cases of Hepatocellular Carcinoma Arising Over 20 Years after a Sustained Virologic Response Following Interferon Therapy for Chronic Hepatitis C.

The development of hepatocellular carcinoma (HCC) after a sustained virologic response (SVR) due to interferon (IFN) therapy for hepatitis C virus infection remains a serious problem. We herein report 2 cases of HCC that developed more than 20 years after SVR with IFN therapy for chronic hepatitis C. The patients were 89- and 72-year-old men with HCC that developed 24-25 years after an SVR with IFN therapy. These patients regularly underwent imaging examinations; therefore, the HCC was detected in the early stage, when it was still curable. Both cases suggest that long-term surveillance after an SVR is effective for the detection of HCC, and radical treatment is possible.

IL28B gene polymorphism is correlated with changes in low-density lipoprotein cholesterol levels after clearance of hepatitis C virus using direct-acting antiviral treatment.

BACKGROUND: Direct-acting antivirals (DAAs) rapidly clear hepatitis C virus (HCV), but the lipid dynamics after DAA treatment remain unknown. Low-density lipoprotein (LDL) cholesterolemia is the predicting factor for the onset and death of atherosclerotic cardiovascular diseases. Thus, in this study, we examined the frequency and risk of hyper-LDL cholesterolemia in HCV patients who achieved sustained virologic response (SVR) with DAA treatment. METHODS: A total of 121 patients with HCV genotype 1b, who achieved SVR with DAA treatment, were examined for serum levels of total cholesterol, LDL-cholesterol (LDL-C), high-density lipoprotein, and triglycerides from the start of treatment until 2 years after SVR (SVR-2y). ΔLDL-C was defined as the change in LDL-C levels from treatment initiation to SVR-2y. Hyper-LDL cholesterolemia was defined as ≥ 140 mg/dL LDL-C at SVR-2y. Stepwise multiple regression analysis was performed to determine whether ΔLDL-C and hyper-LDL cholesterolemia are associated with other factors, including viral kinetics. RESULTS: A total of 63, 3, and 55 patients were administered daclatasvir + asunaprevir, ombitasvir + paritaprevir + ritonavir, and ledipasvir + sofosbuvir, respectively. ΔLDL-C in patients with the IL28B (rs8099917) TG/GG genotype was significantly higher than in those with IL28B TT (27.3 ± 27.0 and 9.6 ± 27.3 mg/dL; P < 0.001). In addition, IL28B TG/GG was an independent risk factor for hyper-LDL cholesterolemia (odds ratio: 8.47; P < 0.001). CONCLUSIONS: An IL28B polymorphism is associated with ΔLDL-C and hyper-LDL cholesterolemia after achieving SVR. Thus, lipid markers should be carefully monitored in patients who achieve SVR with DAA.