Impact of endoscopic ultrasound-guided fine-needle biopsy on the diagnosis of subepithelial tumors: A propensity score-matching analysis.

BACKGROUND AND AIM: Immunohistological evaluations are essential for diagnosing subepithelial tumors (SET). However, endoscopic ultrasound-guided sampling using fine-needle aspiration (FNA) needles is limited in its ability to procure core tissue for immunostaining. Fine-needle biopsy (FNB) needles may mitigate this limitation. The present study aimed to examine the efficacy of FNB needles for procuring samples that enable the diagnosis of SET. METHODS: One hundred sixty patients were included in the study and separated into those whose samples were obtained using FNB needles (FNB group) and those whose samples were procured using FNA needles (FNA group). Groups were compared regarding the conclusive diagnosis rate and unwarranted resection rate. Propensity score matching was introduced to reduce selection bias. RESULTS: Rates at which conclusive diagnoses were reached through adequate immunohistological evaluations were 82% and 60% in the FNB and FNA groups, respectively; this difference was significant (P = 0.013). Unwarranted resection rate was significantly lower in the FNB group (2%) than in the FNA group (14%; P = 0.032). Multivariate analyses showed that lesions ≤20 mm were a significant risk factor for lower conclusive diagnosis rates following the use of FNB needles (P = 0.017). CONCLUSIONS: Fine-needle biopsy needles can be useful for obtaining samples that facilitate the diagnosis of SET and for avoiding unwarranted resections. However, FNB needles may be less advantageous for small SET.

Severe Biliary Stricture Dilation Using the Soehendra Stent Retriever with a Short-Type Balloon Enteroscope in Patients with Surgically Altered Anatomies.

BACKGROUND: Balloon enteroscopy (BE) can be used for endoscopic retrograde cholangiography (ERC) to treat biliary strictures in patients with surgically altered anatomies. However, biliary strictures, including bilioenteric anastomotic strictures, are often very severe and dilation catheters cannot pass through them. The Soehendra stent retriever (SSR) is like a screw drill and can be useful for dilating severe strictures, but the utility of SSR during BE-assisted ERC (BE-ERC) is unclear. This study aimed to examine the efficacy and safety of a dilation technique using the SSR during BE-ERC. METHODS: Between 2014 and 2018, 28 patients with surgically altered gastrointestinal anatomies and severe biliary strictures underwent BE-ERC, and the SSR was used for the dilation procedures. We evaluated the technical success, therapeutic success, and adverse event rates associated with SSR dilation. RESULTS: The technical success rate was 93% (26/28). The procedures undertaken on two patients with non-anastomotic strictures failed technically because the SSR was not long enough to reach the strictures. The therapeutic success rate was 96% (25/26) for the patients whose procedures were technically successful. The adverse event rate was 7% (2/28), and the adverse events were mild and improved with conservative management. No bleeding or duct perforations occurred. CONCLUSIONS: Although the indications for using the SSR in patients with non-anastomotic strictures should be considered based on the distance between the tip of the scope and the stricture's location, SSR dilation may be a useful option during BE-ERC if a biliary stricture is very severe.

Assessing the diagnostic yield of controllable biopsy-forceps for biliary strictures.

OBJECTIVE: Biliary forceps biopsies are essential for differentially diagnosing biliary strictures and evaluating the preoperative superficial intraductal spread of bile duct cancers; however, these biopsies are technically demanding and time consuming. Using controllable biopsy-forceps (C-BF), which enable the tip's angle to be adjusted by up to 90°, may facilitate the procedure and improve the diagnostic yield for biliary biopsies. This study aimed to examine the efficacy of C-BF associated with the diagnosis of biliary strictures. MATERIALS AND METHOD: Between 2009 and 2015, 110 patients with biliary strictures underwent biliary biopsies using C-BF. We retrospectively evaluated the diagnostic yield of C-BF for biliary strictures and determined the success rate associated with obtaining adequate samples during mapping biopsies to evaluate the superficial intraductal tumor spread. RESULTS: The technical success rate for biliary biopsies using C-BF was 99% (109/110). The sensitivity, specificity and accuracy of the diagnoses of biliary strictures were 60% (46/77), 100% (33/33) and 72% (79/110), respectively. Regarding the mapping biopsy procedures, adequate samples were successfully obtained from 96% (22/23), 92% (11/12), 80% (12/15), 75% (9/12) and 31% (5/16) of the intrapancreatic common bile ducts, upper common bile ducts, confluences of the hepatic ducts, right intrahepatic bile ducts and left intrahepatic bile ducts, respectively. CONCLUSIONS: C-BF may facilitate biliary cannulation and mapping biopsies of the common bile duct and the right intrahepatic bile duct. However, given that the diagnostic sensitivity was 60%, further modifications are expected and necessary to maximize the utility of the controllable mechanism.

Hemothorax following Uncomplicated Endoscopic Variceal Sclerotherapy and Ligation for Esophageal Varices.

Endoscopic variceal sclerotherapy and ligation are standard treatment modalities used for the management of esophageal varices. Reportedly, sclerotherapy and ligation are associated with complications such as hematuria, pulmonary thrombus formation, pleural effusion, renal dysfunction, and esophageal stenosis. However, hemothorax following sclerotherapy and ligation has not yet been reported. We treated a patient who presented with liver cirrhosis and polycythemia vera and later developed hemothorax following the above-mentioned procedures. An 86-year-old man diagnosed with liver cirrhosis due to chronic hepatitis type B and alcohol abuse underwent variceal sclerotherapy using ethanolamine oleate to treat his esophageal varices. Oozing from the esophageal varices continued even after the sclerotherapy procedure; therefore, we performed endoscopic variceal ligation. The patient developed left-sided hemothorax within 24 h after treatment of his varices, and an emergency thoracotomy was performed. A pulmonary ligament of the left lung was bulging and ripping because of mediastinal hematoma, and oozing was noted. Cessation of bleeding was noted after the laceration of the left pulmonary ligament had been sutured. Ours is the first case of hemothorax reported in a patient following an uncomplicated procedure of sclerotherapy and ligation.

Simultaneous Versus Sequential Side-by-Side Bilateral Metal Stent Placement for Malignant Hilar Biliary Obstructions.

BACKGROUND: Endoscopic bilateral self-expandable metallic stent (SEMS) placement for malignant hilar biliary obstructions (MHBOs) is technically demanding, and a second SEMS insertion is particularly challenging. A simultaneous side-by-side (SBS) placement technique using a thinner delivery system may mitigate these issues. AIMS: We aimed to examine the feasibility and efficacy of simultaneous SBS SEMS placement for treating MHBOs using a novel SEMS that has a 5.7-Fr ultra-thin delivery system. METHODS: Thirty-four patients with MHBOs underwent SBS SEMS placement between 2010 and 2016. We divided the patient cohort into those who underwent sequential (conventional) SBS placement between 2010 and 2014 (sequential group) and those who underwent simultaneous SBS placement between 2015 and 2016 (simultaneous group), and compared the groups with respect to the clinical outcomes. RESULTS: The technical success rates were 71% (12/17) and 100% (17/17) in the sequential and simultaneous groups, respectively, a difference that was significant (P = .045). The median procedure time was significantly shorter in the simultaneous group (22 min) than in the sequential group (52 min) (P = .017). There were no significant group differences in the time to recurrent biliary obstruction (sequential group: 113 days; simultaneous group: 140 days) or other adverse event rates (sequential group: 12%; simultaneous group: 12%). CONCLUSIONS: Simultaneous SBS placement using the novel 5.7-Fr SEMS delivery system may be more straightforward and have a higher success rate compared to that with sequential SBS placement. This new method may be useful for bilateral stenting to treat MHBOs.

Influence of nicotine on choline-deficient, L-amino acid-defined diet-induced non-alcoholic steatohepatitis in rats.

Nicotine, a major compound in cigarette smoke, decreases food intake and body weight gain in mammals; however, the influence of nicotine on the progression of non-alcoholic steatohepatitis (NASH) remains controversial. This study aimed to investigate the effect of nicotine on NASH in rat models. Male Wistar rats were fed choline-deficient, l-amino acid-defined (CDAA) diet and treated with nicotine or saline. Food intake, body weight gain, presence of hepatic steatosis, inflammation, and fibrosis were assessed 6 weeks after the rats were fed CDAA diet. Hepatic branch vagotomy was performed to elucidate the mechanism through which nicotine affected steatohepatitis. CDAA diet induced hepatic steatosis, inflammation, and fibrosis, as well as increased the expression of inflammation-related genes. Conversely, nicotine significantly attenuated food intake, body weight gain, and inhibited the CDAA-diet-induced hepatic steatosis, inflammation, and fibrosis, together with increased expression of inflammation-related genes. Hepatic branch vagotomy by itself decreased food intake, body weight gain, and attenuated the CDAA-diet-induced hepatic steatosis, but not inflammation. However, nicotine did not change the food intake, body weight gain, and CDAA diet-induced hepatic steatosis and inflammation in vagotomized rats. These results suggest that nicotine attenuates the CDAA-diet-induced hepatic steatosis and inflammation through the hepatic branch of the vagus nerve in rats.

Conophylline inhibits non-alcoholic steatohepatitis in mice.

Conophylline (CnP), a vinca alkaloid extracted from the leaves of the tropical plant Ervatamia microphylla, attenuates hepatic fibrosis in mice. However, little is known about whether CnP inhibits steatosis, inflammation, and fibrosis in non-alcoholic steatohepatitis (NASH) in mice. A methionine-choline-deficient (MCD) diet was administered to male db/db mice as a NASH model, and CnP (1 µg/kg/d) was co-administered. Eight weeks after the commencement of the MCD diet, hepatic steatosis, inflammation, and fibrosis, and hepatic fat metabolism-, inflammation-, and fibrosis-related markers were examined. Feeding on an MCD for 8 weeks induced hepatic steatosis, inflammation, and fibrosis. CnP significantly attenuated the MCD-induced increases in hepatic steatosis, as well as hepatic inflammation and fibrosis. The MCD diet increased hepatic transforming growth factor-ß (TGF-ß) mRNA levels, which are correlated with hepatic steatosis, inflammation, and fibrosis. The diet also attenuated acyl-coenzyme A oxidase 1 (ACOX1) and carnitine palmitoyltransferase 1 (CPT1) mRNA levels, which are involved in ß-oxidation. The putative mechanism of the CnP effect involves reduced hepatic TGF-ß mRNA levels, and increased mRNA levels of hepatic peroxisome proliferator-activated receptor (PPAR) α and its target genes ACOX1 and CPT1. The results of this study indicate that CnP inhibits steatohepatitis, possibly through the inhibition of hepatic TGF-ß mRNA levels, and induces an increase in PPARα mRNA levels, resulting in the attenuation of hepatic steatosis, inflammation, and fibrosis in mice. CnP might accordingly be a suitable therapeutic option for NASH.

A Case of Gastric Antral Vascular Ectasia Which Was Aggravated by Acid Reducer.

Gastric antral vascular ectasia (GAVE) is known to be characterized by red patches or spots in a diffuse or linear array in the antrum of the stomach. The precise etiology of GAVE remains to be elucidated. Argon plasma laser coagulation (APC) has been used to control oozing from GAVE; however, there is no satisfactory long-term effect of APC in the control of oozing from GAVE. An acid reducer is used after APC because even physiological acid exposure might delay post-APC ulcer healing. We describe the case of a patient who had used an acid reducer and experienced repeated gastrointestinal hemorrhage due to GAVE. After ceasing to administer the acid reducer, incidences of hospitalization due to oozing from GAVE stopped. After the administration of the acid reducer was restarted, the patient had tarry stool, and diffuse oozing of blood was seen again. We report a first case of GAVE which was aggravated by acid reducer.

Ezetimibe for the treatment of non-alcoholic fatty liver disease: A meta-analysis.

AIM: Several studies on the efficacy of ezetimibe, a potent inhibitor of cholesterol absorption, in treating non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) have been published; however, the results are inconsistent. We undertook a meta-analysis to evaluate the efficacy of ezetimibe in treating NAFLD and NASH. METHODS: PubMed, Medline, and Cochrane Library Full Text Database were searched until June 2016. The main inclusion criteria included original studies investigating the use of ezetimibe for the treatment of NAFLD and NASH. Identification of published work and data extraction were carried out by two reviewers based on the inclusion and exclusion criteria. All analyses were carried out using Comprehensive Meta-Analysis version 3 software. RESULTS: An initial search identified 103 peer-reviewed articles and abstracts. Six studies (two randomized controlled and four single-arm trials) involving 273 participants with NAFLD and NASH were identified. Ezetimibe significantly reduced serum aspartate aminotransferase, alanine aminotransferase, and γ-glutamyl transpeptidase levels, and hepatic steatosis and hepatocyte ballooning. However, hepatic inflammation and fibrosis did not improve by ezetimibe treatment in patients with NAFLD and NASH. In randomized controlled trials, only hepatocyte ballooning improved with ezetimibe treatment. CONCLUSIONS: Although ezetimibe attenuated serum liver enzymes and hepatic steatosis and ballooning in six studies, it improved only hepatocyte ballooning in randomized controlled trials. Larger studies and more randomized placebo-controlled trials are necessary to determine the effects of ezetimibe on NAFLD and NASH.

Bleeding risk of endoscopic ultrasound-guided fine-needle aspiration in patients undergoing antithrombotic therapy.

OBJECTIVES: Bleeding events related to endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) are rare. However, for patients treated with antithrombotic agents, the bleeding risk of EUS-FNA is uncertain. Hence, the aim of this study was to assess the bleeding event rate associated with EUS-FNA in patients receiving antithrombotic treatment. METHODS: A retrospective study was conducted in 742 consecutive patients who underwent EUS-FNA for solid lesions between 2008 and 2015. We compared the bleeding event rates among patients who were not administered antithrombotic agents, those whose agent use was discontinued, those who continued treatment with aspirin or cilostazol, and those who were administered heparin as a replacement. RESULTS: There were 131 patients (17.7 %) treated with antithrombotic agents. Seven experienced bleeding events, and the overall bleeding event rate was 0.9 % (7/742). All bleeding events were intraoperative; there were no postoperative bleeding episodes. Subgroup analysis by antithrombotic agent revealed bleeding event rates of 1.0 % (6/611), 0 % (0/62), 1.6 % (1/61), and 0 % (0/8) for the non-administration, discontinuation of agents, continuation of aspirin or cilostazol, and heparin replacement groups, respectively. Only one severe bleeding event necessitated hemostatic treatment (1/742; 0.1 %); this occurred in a patient in the non-administration group, and there were no severe bleeding events in patients receiving antithrombotic treatment. CONCLUSIONS: The present study found a low incidence of EUS-FNA-related bleeding in patients receiving antithrombotic treatment. The bleeding event rate was low even in patients who underwent EUS-FNA while continuing aspirin or cilostazol.

Δ40p53α suppresses tumor cell proliferation and induces cellular senescence in hepatocellular carcinoma cells.

Splice variants of certain genes impact on genetic biodiversity in mammals. The tumor suppressor TP53 gene (encoding p53) plays an important role in the regulation of tumorigenesis in hepatocellular carcinoma (HCC). Δ40p53α is a naturally occurring p53 isoform that lacks the N-terminal transactivation domain, yet little is known about the role of Δ40p53α in the development of HCC. Here, we first report on the role of Δ40p53α in HCC cell lines. In the TP53+/Δ40 cell clones, clonogenic activity and cell survival dramatically decreased, whereas the percentage of senescence-associated ß-galactosidase (SA-ß-gal)-positive cells and p21 (also known as WAF1, CIP1 and CDKN1A) expression significantly increased. These observations were clearly attenuated in the TP53+/Δ40 cell clones after Δ40p53α knockdown. In addition, exogenous Δ40p53 expression significantly suppressed cell growth in HCC cells with wild-type TP53, and in those that were mutant or null for TP53 Notably, Δ40p53α-induced tumor suppressor activity was markedly attenuated in cells expressing the hot-spot mutant Δ40p53α-R175H, which lacks the transcription factor activity of p53. Moreover, Δ40p53α expression was associated with increased full-length p53 protein expression. These findings enhance the understanding of the molecular pathogenesis of HCC and show that Δ40p53α acts as an important tumor suppressor in HCC cells.

Associations between polymorphisms in folate-metabolizing genes and pancreatic cancer risk in Japanese subjects.

BACKGROUND: Evidence supporting the associations between folate metabolizing gene polymorphisms and pancreatic cancer has been inconclusive. We examined their associations in a case-control study of Japanese subjects. METHODS: Our case-control study involved 360 newly diagnosed pancreatic cancer cases and 400 frequency-matched, non-cancer control subjects. We genotyped four folate metabolizing gene polymorphisms, including two polymorphisms (rs1801133 and rs1801131) in the methylenetetrahydrofolate (MTHFR) gene, one polymorphism (rs1801394) in the 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) gene and one polymorphism (rs1805087) in the 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR) gene. Genotyping was performed using Fluidigm SNPtype assays. Unconditional logistic regression methods were used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for the associations between folate metabolizing gene variants and pancreatic cancer risk. RESULTS: Overall we did not observe a significant association between these four genotypes and pancreatic cancer risk. For rs1801133, compared with individuals with the CC genotype of MTHFR C677T, the OR for those with the CT genotype and TT genotype was 0.87 (0.62-1.22) and 0.99 (0.65-1.51), respectively. For rs1801131, individuals with the CC genotype had approximately 1.2-fold increased risk compared with those with the AA genotype, but the association was not statistically significant. In analyses stratified by smoking and drinking status, no significant associations were noted for C677T genotypes. No significant interactions were observed with smoking and drinking with respect to pancreatic cancer risk. CONCLUSIONS: Our data did not support the hypothesis that MTHFR polymorphisms or other polymorphisms in the folate metabolizing pathway are associated with pancreatic cancer risk.

Feasibility of the placement of a novel 6-mm diameter threaded fully covered self-expandable metal stent for malignant hilar biliary obstructions (with videos).

BACKGROUND AND AIMS: Uncovered self-expandable metal stents (USEMSs) are used to treat unresectable malignant hilar biliary obstructions (MHBOs). However, ingrowth is not prevented, and reintervention is often troublesome. A novel 6-mm threaded fully covered self-expandable metal stent (T-FCSEMS) is available that may mitigate these issues. We aimed to clarify the safety and efficacy of T-FCSEMS placement for MHBO. METHODS: Thirty patients underwent T-FCSEMS placements for MHBOs between 2014 and 2015. T-FCSEMSs were used for initial stenting in 17 patients (initial group) and for reinterventions for USEMS occlusions caused by ingrowth in 13 patients (reintervention group). The technical success rates, times to recurrent biliary obstruction, and the reintervention success rates were evaluated. RESULTS: The technical success rates were 94% (16/17) and 92% (12/13) in the initial group and reintervention group, respectively. Intrahepatic bile duct occlusions caused liver abscesses 8 days and 22 days after T-FCSEMS placements in 2 cases (7%) in the initial group, in which T-FCSEMSs were placed across the intrahepatic bile duct bifurcation. The median times to recurrent biliary obstruction were 210 days in the initial group after bilateral placement and 112 days and 152 days in the reintervention group after bilateral and unilateral placements, respectively. During reintervention, T-FCSEMS removal was successful in all patients in whom it was attempted, and the success rate of endoscopic reintervention was 100% in both groups. CONCLUSIONS: T-FCSEMS placement is a promising option for both initial stenting and reintervention for MHBO. However, we should consider the possibility of intrahepatic bile duct occlusion.