Prophylactic use of a self-assembling peptide hydrogel for preventing delayed bleeding after endoscopic sphincterotomy: A propensity score-matched analysis.

BACKGROUND AND AIM: Delayed endoscopic sphincterotomy-related bleeding (ES bleeding) is an unavoidable adverse event (AE) that can have serious ramifications. Intraoperative ES bleeding, which stops spontaneously in most cases, is a known risk factor for delayed bleeding. This study aimed to examine the preventive effect of a novel self-assembling peptide (SAP) for delayed ES bleeding in patients who attained spontaneous hemostasis after intraoperative ES bleeding. METHODS: A total of 1507 patients met the eligibility criteria for inclusion in this study. The rates of delayed ES bleeding and AE besides bleeding were compared between patients administered the SAP (SAP group) and those who were simply observed after spontaneous hemostasis of intraoperative ES bleeding (control group). Propensity score matching was performed to adjust for differences between the groups. RESULTS: The rate of delayed ES bleeding was significantly lower in the SAP group than that in the control group (0.9% vs 3.8%, P = 0.044). The rates of AEs other than bleeding were 2.4% and 3.8% in the SAP and control groups, respectively, and the difference lacked statistical significance (P = 0.481). Multivariate analysis revealed that the use of SAP was significantly associated with a lower frequency of delayed ES bleeding (odds ratio, 0.35; 95% confidence interval, 0.13-0.98; P = 0.047). CONCLUSIONS: Self-assembling peptide may be a simple, safe, and useful way to reduce the risk of delayed ES bleeding in patients who experienced intraoperative ES bleeding and obtained subsequent spontaneous hemostasis.

Trisectoral Metal Stenting Using Combined Stent-by-Stent and Stent-in-Stent Method for Malignant Hilar Biliary Obstruction: A Prospective Pilot Study.

BACKGROUND: Endoscopic trisectoral metal stent (MS) placement for malignant hilar biliary obstruction (MHBO) poses technical challenges, although it may prolong survival and stent patency. Combined stent-by-stent and stent-in-stent (SBSIS) methods can reduce technical difficulty. This study aimed to examine the use of the SBSIS in patients with Bismuth type III or IV MHBO. METHODS: This prospective pilot study enrolled 30 eligible patients between January 2020 and October 2022. The study outcomes included technical and clinical success, recurrent biliary obstruction (RBO), and adverse events (AE) besides RBO associated with SBSIS for MHBO. RESULTS: The technical success rate was 93.3% (28/30 patients). Clinical success was achieved in all patients with technical success. The early and late AEs rates were 6.7% (2/30) and 7.1% (2/28), respectively. The incidence of RBO was 35.7% (10/28). RBO was treated with an endoscopic transpapillary approach in eight patients and an endoscopic ultrasound-guided transmural approach in two patients. The median time to RBO was 162 days, and the median overall survival was 148 days. CONCLUSIONS: This first prospective study investigating the SBSIS method demonstrated good technical feasibility with a low AE rate. Therefore, it can be considered a better option when contemplating trisectoral MS placement for high-grade MHBO.

Endoscopic radiofrequency ablation for ingrowth occlusion after bilateral metal stent placement for malignant hilar biliary obstruction: a prospective pilot study.

BACKGROUND AND AIMS: Endoscopic biliary radiofrequency ablation (RFA) may be an option for the treatment of ingrowth occlusion after self-expandable metal stent (SEMS) deployment; however, its utility remains uncertain. This study aimed to examine the feasibility of RFA for the palliation of ingrowth after bilateral SEMS placement in patients with malignant hilar biliary obstruction. METHODS: This prospective, single-center, pilot study enrolled 30 patients who met the eligibility criteria between April 2020 and March 2022. Study outcomes were technical success, clinical success, recurrent biliary obstruction (RBO), and adverse events (AEs) besides RBO associated with RFA for ingrowth occlusion. Furthermore, factors predictive of clinical success were evaluated. RESULTS: Technical and clinical success rates were 93.3% (28/30) and 71.4% (20/28), respectively. The rates of early and late AEs were 6.7% (2/30) and 10.0% (2/20), respectively. The incidence rate of RBO after RFA was 45.0% (9/20), and the median time to RBO was 163 days. Multivariate analysis of the factors affecting clinical success revealed a positive association between the recanalization diameter on the ingrown part within the SEMS (odds ratio, 1.13; 95% confidence interval, 1.01-1.26; P = .038). The calculated optimal cutoff for the ratio of the recanalization diameter to the SEMS diameter for predicting clinical success was 51.1%. CONCLUSIONS: Endoscopic biliary RFA elicited promising results, with good long-term stent patency and without the requirement of any additional stent placement, for the palliation of ingrowth occlusion after bilateral SEMS placement. However, the clinical success rate was insufficient, necessitating improvements in the future. (Clinical trial registration number: UMIN000040154.).

Endoscopic Ultrasound-Guided Hepaticogastrostomy with Antegrade Stenting Without Dilation Device Application for Malignant Distal Biliary Obstruction in Pancreatic Cancer.

BACKGROUND: Endoscopic ultrasound-guided hepaticogastrostomy with antegrade stenting (EUS-HGAS) is a promising therapeutic option for malignant distal biliary obstruction (MDBO) in the event of transpapillary approach failure. Eliminating the fistula dilation step may further decrease the incidence of adverse events (AE) and simplify the procedure. AIMS: This study focused on MDBO associated with pancreatic cancer and aimed to examine the utility of EUS-HGAS without the use of any dilation devices. METHODS: This retrospective study investigated consecutive patients in whom the transpapillary approach had failed or was difficult, and who underwent EUS-HGAS without dilation device usage, using a tapered small-diameter catheter, ultrathin delivery system, and tapered dedicated plastic stent. The outcomes of this study included the technical success, clinical success, AE incidence, and recurrent biliary obstruction (RBO) associated with the procedure. RESULTS: During the study period, EUS-HGAS without dilation device usage was attempted for 57 patients with MDBO due to pancreatic cancer. The technical and clinical success rates were 91.2% (52/57) each. The median procedural time was 25 min. The rates of early and late AE besides RBO were 3.5% (2/57) and 1.9% (1/52), respectively. The incidence rate of RBO was 30.8% (16/52), and the median time to RBO was 245 days. The rate of successful endoscopic reintervention for RBO via the fistula was 100% (16/16). CONCLUSIONS: EUS-HGAS without the use of dilation devices showed good technical feasibility with a low AE rate. It may be a useful option for MDBO associated with pancreatic cancer when the transpapillary approach is difficult.

Endoscopic Ultrasound-Guided Naso-gallbladder Drainage Using a Dedicated Catheter for Acute Cholecystitis After Transpapillary Metal Stent Placement for Malignant Biliary Obstruction.

BACKGROUND: Acute cholecystitis is a significant adverse event after self-expandable metal stent (SEMS) placement for malignant biliary obstruction (MBO); however, no appropriate treatment strategy has been established for its management. AIMS: This study aimed to examine the feasibility and utility of endoscopic ultrasound-guided naso-gallbladder drainage (EUS-NGBD) for the management of acute cholecystitis occurring after SEMS placement. METHODS: This retrospective study investigated consecutive patients with acute cholecystitis after SEMS placement for unresectable MBO, in whom EUS-NGBD was attempted. The study outcomes included technical success, clinical success, procedure time, adverse event, and cholecystitis recurrence, associated with the procedure. RESULTS: During the study period, EUS-NGBD was performed for SEMS-related acute cholecystitis in 30 patients with MBO. The technical and clinical success rates were 96.7% (29/30) and 96.6% (28/29), respectively. The median procedure time was 15 min, and rate of procedure-related adverse event was 3.3% (1/30). The median duration from the procedure to tube removal was 9 days. No adverse events were observed after removal. The median hospitalization duration after the procedure was 14 days, and the median duration to the (re-)start of chemotherapy from cholecystitis onset was 13 days. The median overall survival after EUS-NGBD was 123 days, and the rate of cholecystitis recurrence until death was 4.2% (1/28). CONCLUSIONS: This study demonstrated that EUS-NGBD possesses good technical and clinical feasibility with an acceptable adverse event rates and short hospitalization and chemotherapy withdrawal period. Therefore, EUS-NGBD may be a good option for the treatment of SEMS-related cholecystitis in patients with MBO.

Transperitoneal laparoscopic umbilical resection of urachal remnants: a feasible surgical method.

BACKGROUND: To date, there is no standard established laparoscopic surgical method for managing urachal remnants because of their rarity, and several questions remain unanswered. Are there any problems for considering the operative indications about patients' factors for example, body mass index and so on? This study aimed to determine the feasible surgical method for managing urachal remnants and presents the operative outcomes of our cases in relation to the findings from the existing literature. METHODS: We analyzed the data of 16 patients (7 women and 9 men; age range, 19-48 years) who underwent surgery for urachal remnants between January 2013 and March 2019 at our institution. RESULTS: In our cases, all urachal remnants were urachal sinuses, and the primary complaints were umbilical pain and pus discharge. Most of these symptoms were controlled using umbilical drainage and oral antibiotic intake; however, incisional drainage was required in two cases. In all cases, we performed a laparoscopic resection of the urachal remnants; one patient underwent an open conversion due to a very thick abdominal wall. Therefore, "peri-umbilical distanse" was proposed as an index to verify the periumbilical abdominal wall thickness. This index may clear the difficulties of the laparoscopic resection of the urachal remnunts. A postoperative complication-local infection that was treated using re-suturing-was observed in one patient. No adverse events occurred in the other cases. Our method was appropriate because it allowed for complete urachal resection with good cosmetic results, i.e., a small and natural scar appearance. Additionally, if bladder injury occurred, bladder re-suturing was easily possible because of the laparoscopic port's position. CONCLUSIONS: We present an feasible method for laparoscopic urachal resection. This method may be recommended for young patients with an peri-umbilical distanse of < 2 cm.

Dual Agonist of Farnesoid X Receptor and Takeda G Protein-Coupled Receptor 5 Inhibits Hepatitis B Virus Infection In Vitro and In Vivo.

BACKGROUND AND AIMS: Chronic HBV infection is a major health problem worldwide. Currently, the first-line treatment for HBV is nucleos(t)ide analogs or interferons; however, efficient therapeutic approaches that enable cure are lacking. Therefore, anti-HBV agents with mechanisms distinct from those of current drugs are needed. Sodium taurocholate cotransporting polypeptide (NTCP) was previously identified as an HBV receptor that is inhibited by several compounds. Farnesoid X receptor (FXR) activation also inhibits NTCP function. APPROACH AND RESULTS: In this study, we investigated the inhibitory effect of bile acid (BA) derivatives-namely obeticholic acid (OCA), 6α-ethyl-24-nor-5ß-cholane-3α,7α,23-triol-23 sulfate sodium salt (INT-767; a dual agonist of FXR and Takeda G protein-coupled receptor [TGR5]), and 6α-ethyl-23(S)-methyl-cholic acid (INT-777; a TGR5 agonist)-3-(2,6-dichlorophenyl)-4-(3'-carboxy-2-chlorostilben-4-yl)oxymethyl-5-isopropylisoxazole (GW4064; a FXR agonist), cyclosporin A, and irbesartan. OCA and INT-777 suppressed HBV infection in HepG2-human NTCP-C4 cells. Interestingly, INT-767 showed potent inhibition by attaching to HBV particles rather than binding to NTCP. As an entry inhibitor, INT-767 was stronger than various natural BAs. Furthermore, in chimeric mice with humanized liver, INT-767 markedly delayed the initial rise of HBsAg, HBeAg, and HBV DNA and reduced covalently closed circular DNA. The strong inhibitory effect of INT-767 may be due to the cumulative effect of its ability to inhibit the entry of HBV and to stimulate FXR downstream signaling, which affects the postentry step. CONCLUSIONS: Our results suggest that BA derivatives, particularly INT-767, are prospective candidate anti-HBV agents. Clarifying the underlying mechanisms of BA derivatives would facilitate the development of anti-HBV agents.

Scissor-type knife precut in balloon enteroscopy-assisted ERCP for patients with difficult biliary cannulation and surgically altered anatomy (with video).

BACKGROUND AND AIMS: Balloon enteroscopy-assisted ERCP (BE-ERCP) is useful for treating pancreatobiliary disease in patients with surgically altered anatomy (SAA); however, biliary cannulation, including the precut technique, is often challenging. This study aimed to examine the feasibility of scissor-type knife precutting (SKP) during BE-ERCP in patients with SAA. METHODS: This retrospective study investigated consecutive patients who underwent BE-ERCP and SKP for difficult biliary cannulation between 2016 and 2021. The study outcomes included the technical success and adverse event rates associated with SKP during BE-ERCP. RESULTS: During the study period, 125 patients with native duodenal papillae underwent BE-ERCP, and the papilla was reached in 116 patients. The success rate of biliary cannulation with the standard cannulation approach alone was 67.2% (78/116), which increased to 77.6% (90/116) with the inclusion of advanced cannulation techniques besides precutting and further improved to 87.9% (102/116) with the addition of needlife precutting. SKP was attempted in 12 patients in whom all other cannulation approaches were difficult or resulted in failure. The technical success rate of SKP was 66.7% (8/12); thus, SKP increased the final success rate of biliary cannulation to 94.8% (110/116). The rate of adverse events associated with SKP was 8.3% (1/12). CONCLUSIONS: This is the first study to report the use of the SKP technique for difficult biliary cannulation in patients with SAA, which may serve as a useful option for salvage cannulation during BE-ERCP.

Comparison of the removal ability of basket catheters for small bile duct stones impacted in the corner pocket of the lower bile duct.

BACKGROUND : Endoscopic stone extraction is often challenging in patients with a significant lower bile duct corner pocket, where small stones are likely to escape and become impacted. This study aimed to determine the utility of different types of baskets for retrieving corner pocket stones. METHODS : Seven types of retrieval baskets were evaluated on silicone models. The study outcomes included the characteristics of each basket and technical success rates associated with the retrieval of stones impacted in the corner pocket. RESULTS : The overall success rate was only 27.5 %, with significant differences between the baskets (P < 0.001). Only three baskets yielded successful removal. The success rates were 10 %, 25 %, and 70 % with the 8-wire Nitinol Basket, RASEN, and VorticCatch V, respectively, all of which are helical eight-wire baskets. RASEN and VorticCatch V share similar characteristics, including a strong spiral wire and smaller interwire spaces at their distal ends. The addition of rotation significantly increased the success rate to 80 % with the 8-wire Nitinol Basket (P < 0.001) and 90 % with RASEN (P < 0.001). CONCLUSIONS : Robust helical eight-wire baskets with smaller interwire spaces at the tip may be effective for extracting corner pocket stones, while the addition of rotational motion may improve the efficacy of retrieval.

Endobiliary Radiofrequency Ablation Using a Short-Type Balloon Enteroscope in Patients with Surgically Altered Anatomy.

BACKGROUND: Endoscopic radiofrequency ablation (RFA) is expected to prolong stent patency for malignant biliary obstruction (MBO). However, its feasibility when used in conjunction with a balloon enteroscope (BE) in patients with surgically altered anatomy (SAA) remains unknown. AIMS: This study aimed to investigate the feasibility of RFA combined with metal stent insertion under BE guidance for MBO in patients with SAA. METHODS: Thirty-seven patients who underwent treatment between October 2016 and January 2021 and met the eligibility criteria were investigated retrospectively. Study outcomes included technical and clinical success, recurrent biliary obstruction (RBO), and other adverse events besides RBO associated with RFA with metal stent placement using BE. RESULTS: Technical and clinical success rates were 100% (37/37) each. The rates of early and late adverse events were 8.1% (3/37) and 8.1% (3/37), respectively. RBO occurred in 32.4% (12/37) of the patients, and the median time to RBO was 296 days. The cause of RBO was ingrowth in eight patients, overgrowth in three patients, and indeterminate in one patient. All reinterventions for RBO were successful using the BE approach; all ingrowths, except one, were recanalized using additional RFA without additional stent placement. The frequency of reintervention-related adverse events was 9.1% (1/11). The median time to RBO after reintervention was 166 days. CONCLUSIONS: This study demonstrated the technical safety and feasibility as well as good long-term outcomes of endobiliary RFA combined with metal stent placement under BE guidance. This approach may be a useful option for treating MBO in patients with SAA.

Safety and Efficacy of Gemcitabine Plus Nab-Paclitaxel for Metastatic Pancreatic Cancer Patients Undergoing Biliary Stent Placement.

BACKGROUND: Gemcitabine plus nab-paclitaxel (GnP) is the first-line chemotherapeutic regimen for metastatic pancreatic cancer (MPC); however, there are concerns regarding its safety in patients undergoing biliary stent placement. This study aimed to examine the tolerability and efficacy of GnP in MPC patients who underwent biliary stent placement. METHODS: A total of 105 MPC patients who had received GnP treatment between 2015 and 2020 were included and investigated. The patients were divided into two groups: those undergoing biliary stent placement for symptomatic biliary obstruction (BO) (With-BO group) and those without biliary stent placement (Without-BO group). The best tumor response, overall survival (OS), and adverse events in each group were compared. RESULTS: The partial response, stable disease, and progressive disease rates were 22%, 61%, and 14.6% in the With-BO group, and 26.6%, 46.9%, and 21.9% in the Without-BO group, respectively, with no significant differences. The median OS was 12.2 months and 14.6 months in the With-BO and Without-BO groups, respectively (P = 0.483). Grade 3 or higher biliary tract-related events were significantly more common in the With-BO group (41.5%) than in the Without-BO group (1.6%) (P < 0.001), but all events were managed successfully by urgent intervention. The rates of any treatment-related toxicities, including febrile neutropenia, were not significantly different, and there were no chemotherapy-related deaths in either group. CONCLUSIONS: GnP can be as tolerable and effective in MPC patients with biliary stents as in those without biliary stents. However, careful management and appropriate reintervention to treat biliary tract-related adverse events are required.

Who Can Avoid Biopsy of Magnetic Resonance Imaging-Negative Lobes without Compromising Significant Cancer Detection among Men with Unilateral Magnetic Resonance Imaging-Positive Lobes?

OBJECTIVES: To assess whether biopsy of multiparametric magnetic resonance imaging (MRI)-negative lobes can be avoided without compromising significant cancer (SC) detection among men with unilateral MRI-positive lobes. METHODS: From April 2013 to April 2019, 322 men with elevated prostate-specific antigen (PSA <20 ng/mL) and unilateral MRI-positive lobes underwent targeted 4-core and systematic 14-core biopsy. MRI findings were prospectively collected and evaluated according to the Prostate Imaging-Reporting and Data System (PI-RADS) version 2, and scores ≥3 were considered positive. SC was defined as Gleason score ≥3 + 4 or maximal cancer length ≥5 mm. We developed predictive models of overall cancer and SC in MRI-negative lobes and evaluated the performance of these models. RESULTS: Detection rates of overall cancer/SC were 69%/61% for the overall cohort, 58%/48% for MRI-positive lobes, and 36%/20% for MRI-negative lobes. Age ≥75 years, PSA density ≥0.3, and PI-RADS ≥4 were independently predictive of both overall cancer and SC in MRI-negative lobes; 1 point was assigned for each risk factor, and the predictive score was defined as the sum of points (0-3) for both overall cancer and SC. Areas under the curve of the model for overall cancer/SC were 0.67/0.71. In the decision curve analysis, the model was of value above the threshold probability of 13%/6% for detecting overall cancer/SC in MRI-negative lobes. Of 40 men with score 0, overall cancer/SC was detected in the MRI-negative lobe in 4 (10%)/1 (2.5%). CONCLUSION: Biopsies of MRI-negative lobes may be avoided without compromising SC detection using our predictive model.

Effect of Central Corticotropin-Releasing Factor on Hepatic Lipid Metabolism and Inflammation-Related Gene Expression in Rats.

Corticotropin-releasing factor (CRF) in the brain acts on physiological and pathophysiological modulation of the hepatobiliary system. Central CRF administration aggravates experimental acute liver injury by decreasing hepatic blood flow. Conversely, minimal evidence is available regarding the effect of centrally acting CRF on hepatic lipid metabolism and inflammation. We examined whether central CRF affects hepatic lipid metabolism and inflammation-related gene expression in rats. Male Long Evans rats were intracisternally injected with CRF (10 µg) or saline. Rats were sacrificed 2 h, 6 h, and 24 h after the CRF injection, the liver was isolated, and mRNA was extracted. Next, hepatic lipid metabolism and inflammation-related gene expression were examined. Hepatic SREBF1 (sterol regulatory element-binding transcription factor 1) mRNA levels were significantly increased 6 h and 24 h after intracisternal CRF administration when compared with those in the control group. Hepatic TNFα and IL1ß mRNA levels increased significantly 6 h after intracisternal CRF administration. Hepatic sympathectomy or guanethidine treatment, not hepatic branch vagotomy or atropine treatment, inhibited central CRF-induced increase in hepatic SREBF1, TNFα and IL1ß mRNA levels. These results indicated that central CRF affects hepatic de novo lipogenesis and inflammation-related gene expression through the sympathetic-noradrenergic nervous system in rats.

Virological Factors Associated With the Occurrence of Hepatitis B Virus (HBV) Reactivation in Patients With Resolved HBV Infection Analyzed Through Ultradeep Sequencing.

BACKGROUND: Hepatitis B virus reactivation (HBVr) is an important complication of immunosuppressive drug therapy. It can occur via both virological and host factors; however, the underlying mechanisms remain largely unknown. METHODS: We examined serum samples derived from patients with HBVr and those with acute hepatitis B (AHB). The targeted nucleic acid molecule in hepatitis B virus deoxyribonucleic acid was amplified and analyzed by next-generation sequencing. RESULTS: The percentage of patients infected with genotype Bj among the HBVr patients was significantly higher than that in the AHB patients. The frequency of mutation sites in the whole HBV genome, especially in the envelope region, in the HBVr was significantly higher than that in the AHB. The prevalence of the S3N amino acid substitution in the envelope protein and mutations at positions G1896A and G1899A in the precore region were significantly higher in the HBVr compared with AHB. The population of S3N amino acid substitution and nucleotide G1896A and G1899A mutations in each individual showed a similar percentage of occurrence. CONCLUSIONS: We identified specific virological factors in patients with HBVr through ultradeep sequencing. Our findings could be beneficial for the elucidation of mechanisms underlying HBVr development and for disease control.

Screening siRNAs against host glycosylation pathways to develop novel antiviral agents against hepatitis B virus.

AIM: Hepatitis B virus (HBV) relies on glycosylation for crucial functions, such as entry into host cells, proteolytic processing and protein trafficking. The aim of this study was to identify candidate molecules for the development of novel antiviral agents against HBV using an siRNA screening system targeting the host glycosylation pathway. METHODS: HepG2.2.15.7 cells that consistently produce HBV were employed for our in vitro study. We investigated the effects of siRNAs that target 88 different host glycogenes on hepatitis B surface antigen (HBsAg) and HBV DNA secretion using the siRNA screening system. RESULTS: We identified four glycogenes that reduced HBsAg and/or HBV DNA secretion; however, the observed results for two of them may be due to siRNA off-target effects. Knocking down ST8SIA3, a member of the sialyltransferase family, significantly reduced both HBsAg and HBV DNA secretion. Knocking down GALNT7, which transfers N-acetylgalactosamine to initiate O-linked glycosylation in the Golgi apparatus, also significantly reduced both HBsAg and HBV DNA levels. CONCLUSIONS: These results showed that knocking down the ST8SIA3 and GALNT7 glycogenes inhibited HBsAg and HBV DNA secretion in HepG2.2.15.7 cells, indicating that the host glycosylation pathway is important for the HBV life cycle and could be a potential target for the development of novel anti-HBV agents.

Effect of Adrenergic Agonists on High-Fat Diet-Induced Hepatic Steatosis in Mice.

The autonomic nervous system, consisting of sympathetic and parasympathetic branches, plays an important role in regulating metabolic homeostasis. The sympathetic nervous system (SNS) regulates hepatic lipid metabolism by regulating adrenergic receptor activation, resulting in the stimulation of hepatic very-low-density lipoprotein-triglyceride (TG) production in vivo. However, only a few studies on the relationship between SNS and hepatic steatosis have been reported. Here, we investigate the effect of adrenergic receptor agonists on hepatic steatosis in mice fed a high-fat diet (HFD). The α-adrenergic receptor agonist phenylephrine (10 mg/kg/d) or the ß-adrenergic receptor agonist isoproterenol (30 mg/kg/d) was coadministered with HFD to male mice. After five weeks, hepatic steatosis, TG levels, and hepatic fat metabolism-related biomarkers were examined. HFD treatment induced hepatic steatosis, and cotreatment with phenylephrine, but not isoproterenol, attenuated this effect. Phenylephrine administration upregulated the mRNA levels of hepatic peroxisome proliferator-activated receptor alpha and its target genes (such as carnitine palmitoyltransferase 1) and increased hepatic ß-hydroxybutyrate levels. Additionally, phenylephrine treatment increased the expression of the autophagosomal marker LC3-II but decreased that of p62, which is selectively degraded during autophagy. These results indicate that phenylephrine inhibits hepatic steatosis through stimulation of ß-oxidation and autophagy in the liver.

RBM10-TFE3 renal cell carcinoma characterised by paracentric inversion with consistent closely split signals in break-apart fluorescence in-situ hybridisation: study of 10 cases and a literature review.

AIMS: Xp11 rearrangement in renal cell carcinoma (RCC) typically involves gene fusion to the gene encoding transcription factor E3 (TFE3), a member of the microphthalmia-associated transcription factor family on chromosome Xp11.2. Dual-colour break-apart fluorescence in-situ hybridisation (FISH) is recommended to confirm histological diagnoses. Recently, RNA-binding motif protein 10 (RBM10), encoded by a gene on chromosome Xp11.3, was identified as a chimeric partner of TFE3; thus, RBM10-TFE3 fusion results from paracentric inversion. RBM10-TFE3 RCC may yield a false-negative result in FISH analysis of TFE3 expression. The aim of the present study was to investigate the clinicopathological features of RBM10-TFE3 RCC. METHODS AND RESULTS: Ten patients with RBM10-TFE3 RCC aged 31-71 years were investigated. Histological analysis, immunostaining, dual-colour break-apart FISH for TFE3, reverse transcription polymerase chain reaction and sequencing analysis were performed. No patient had a history of exposure to chemotherapy. Two of these patients died of RCC, and three were alive but developed metastases. Microscopically, the tumours were composed of a mixed architecture of tubulocystic and papillary patterns with scattered psammoma bodies. The tumours showed strong nuclear immunoreactivity for TFE3. FISH showed consistent closely spaced split signals in the RCCs of four patients, and polysomic signals with occasional closely spaced split signals in the RCCs of six patients. Of the latter six patients, five had renal failure, and four developed tumours in kidneys subjected to haemodialysis. CONCLUSIONS: The present study suggests that the carcinogenesis of RBM10-TFE3 RCC in some, but not all, patients may be associated with chronic kidney disease. The aggressive nature of RBM10-TFE3 RCC should be considered, as five patients experienced metastases.

Immunohistochemical expressionof sodium-dependent glucose transporter - 2 (SGLT-2) in clear cell renal carcinoma: possible prognostic implications.

PURPOSE: Glucose is a major energy resource for tumor cell survival and growth, and its influx into cells is mainly carried out by facilitative glucose transporters (GLUTs). Sodium - dependent glucose transporters (SGLTs) have been highlighted as playing important roles in diabetic treatment. However, their potential roles in cancer remain unclear. We examined expression patterns of SGLTs in tumor tissues together with conventional pathological variables to determine prognostic significance in patients with renal cell carcinoma (RCC). MATERIALS AND METHODS: Nephrectomy specimens were obtained from 68 patients. GLUT - 1, - 2 and SGLT - 1, - 2 expression in tumor and adjacent normal tissues were analyzed by immunohistochemical staining, and intensity was quantified using an image analyzer. RESULTS: The four glucose transporters evaluated were broadly distributed in tumor tissues as well as throughout the normal parenchyma. There was no significant correlation between transporter expression and conventional pathological variables. However, increased SGLT - 2 expression was significantly associated with shorter overall survival (p < 0.01), regardless of metastatic status. CONCLUSIONS: We propose possible prognostic significance of SGLT - 2 expression in human RCC. Given that glucose is a major energy resource for tumor cells and that glucose transport is largely mediated by SGLT, SGLT - 2 may serve as a possible therapeutic target in RCC.

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.

Significance of sarcopenia as a prognostic factor for metastatic urothelial carcinoma patients treated with systemic chemotherapy.

BACKGROUND: Recently, numerous studies have reported an association between sarcopenia and poor outcomes in various kinds of malignancies. We investigated whether sarcopenia predicts the survival of patients with metastatic urothelial carcinoma who underwent systemic chemotherapy. METHODS: We reviewed 87 metastatic urothelial carcinoma patients who underwent chemotherapy (gemcitabine plus cisplatin or gemcitabine plus carboplatin for cisplatin-unfit patients) between 2007 and 2015. A computed tomography scan prior to chemotherapy was used for evaluating sarcopenia, and we measured three cross-sectional areas of skeletal muscle at the third lumbar vertebra and calculated the skeletal muscle index (SMI), the paraspinal muscle index (PSMI), and the total psoas area (TPA) of each patient. Predictive values of survival were assessed using Cox regression analysis. RESULTS: The median overall survival (OS) was 16 months (95% CI 13.5-18). Although SMI alone was not a significant predictor of shorter OS (P = 0.117) in univariate analysis, SMI stratified by the value of the body mass index (BMI) was a significant predictor of shorter OS in univariate analysis (P = 0.037) and was also an independent predictor of shorter OS in multivariate analysis (P = 0.026). PSMI and TPA were not significant prognostic factors even when stratified by BMI (P = 0.294 and 0.448), respectively. CONCLUSION: Neither PSMI nor TPA could substitute SMI as a predictor for poor outcomes in metastatic urothelial carcinoma patients treated with systemic chemotherapy in our study. SMI stratified by BMI is a useful predictor of prognosis in these patients.