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.

Comparison of the long-term outcomes of EUS-guided gallbladder drainage and endoscopic transpapillary gallbladder drainage for calculous cholecystitis in poor surgical candidates: a multicenter propensity score-matched analysis.

BACKGROUND AND AIMS: Although long-term stent placement using endoscopic transpapillary gallbladder drainage (ETGBD) and EUS-guided gallbladder drainage (EUS-GBD) reportedly reduces cholecystitis recurrence, comparative evidence of their safety and efficacy is scarce. This study aimed to examine and compare the long-term utility of EUS-GBD versus that of ETGBD in poor surgical candidates. METHODS: A total of 379 high-risk surgical patients with acute calculous cholecystitis met the eligibility criteria for enrollment in this study. The technical success and adverse events (AEs) were compared between the EUS-GBD and ETGBD groups, and propensity score matching was performed to adjust for differences between the groups. Both groups underwent plastic stent placement, and scheduled stent exchange and removal were not performed in either group. RESULTS: The technical success rate of EUS-GBD was significantly higher than that of ETGBD (96.7% vs 78.9%, P < .001), whereas the early AE rate did not differ significantly between the 2 methods (7.8% vs 8.9%, P = 1.000). The rate of recurrent cholecystitis did not differ significantly (3.8% vs 3.0%, P = 1.000), but the rate of symptomatic late AEs, in addition to cholecystitis, was significantly lower with EUS-GBD than with ETGBD (1.3% vs 13.4%, P = .006). Consequently, the overall late AE rate was significantly lower with EUS-GBD (5.0% vs 16.4%, P = .029). Multivariate analysis revealed that EUS-GBD was associated with a significantly longer time to late AE (hazard ratio, .26; 95% confidence interval, .10-.67; P = .005). CONCLUSIONS: Long-term stent placement via EUS-GBD is a promising potential option for limiting late AEs, including recurrence, in poor surgical candidates with calculous cholecystitis.

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.

Long-Term Impact of Endoscopic Gallbladder Stenting for Calculous Cholecystitis in Poor Surgical Candidates: A Multi-center Comparative Study.

BACKGROUND: Although long-term stent placement using endoscopic gallbladder stenting (EGBS) reportedly reduces cholecystitis recurrence in patients unfit to undergo cholecystectomy, its efficacy and safety remain uncertain. AIMS: This study aimed to examine the long-term effect of EGBS in poor surgical candidates of cholecystectomy. METHODS: A total of 528 high-risk surgical patients with acute calculous cholecystitis met this study's eligibility criteria. The technical success and adverse events (AE) were compared between patients who underwent EGBS and those who underwent percutaneous transhepatic gallbladder drainage (PTGBD). Elective stent exchange and removal were not performed after EGBS. The external tube was removed after improvement of cholecystitis following PTGBD. RESULTS: The technical success rate was significantly lower with EGBS compared to PTGBD (75.4% versus 98.7%, P < 0.001), while the early-AE rate did not differ significantly between the two methods (7.7% versus 4.3%, P = 0.146). The 1-, 3-, and 5-year cumulative incidence rates of cholecystitis were 3.8%, 7.2%, and 7.2% with EGBS, and 11.7%, 17.6%, and 30.2% with PTGBD, respectively (P = 0.001). Conversely, those of symptomatic late-AE (except cholecystitis) were 8.2%, 22.7%, and 31.4% with EGBS, and 7.5%, 10.9%, and 13.1% with PTGBD, respectively (P = 0.035). Thus, the 1-, 3-, and 5-year cumulative incidence of overall late-AE was 12.0%, 30.4%, and 40.4% with EGBS, and 19.2%, 28.3%, and 42.5% with PTGBD, respectively (P = 0.649). CONCLUSIONS: Long-term stent placement via EGBS is useful for preventing the recurrence of cholecystitis, but the success rate is low and the frequency of other late-AE increases with the prolongation of the indwelling period.

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.

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.

Safety and Efficacy of Endoscopic Retrograde Cholangiopancreatography in Patients with Performance Status 4.

BACKGROUND: The risk related to endoscopic retrograde cholangiopancreatography (ERCP) in patients with Eastern Cooperative Oncology Group performance status (PS) 4 is uncertain and remains a concern. AIMS: We aimed to examine the safety and efficacy of ERCP in patients with PS4 compared to those in patients with PS0-3. METHODS: A total of 1845 patients met the eligibility criteria for study inclusion between 2014 and 2018. The patients were divided into two groups: PS0-3 and PS4 groups. The adverse event and therapeutic success rates in each group were compared. Propensity score matching was performed to adjust for differences between the groups. RESULTS: The therapeutic success rate was 96% in both groups. The overall adverse event rate was 6% and 10% in the PS0-3 and PS4 groups, respectively, showing no significant difference (P = 0.272). Although the rates of pancreatitis, bleeding, perforation, and cholangitis were equivalent in both groups, the pulmonary adverse event rate was significantly higher in the PS4 group (5% vs. 0.4%; P = 0.006). Severe adverse events were also significantly more frequent in the PS4 group (8% vs. 2%; P = 0.012). Multivariate analyses showed that long procedure time was a significant risk factor for adverse events in patients with PS4 (odds ratio, 10.70; 95% CI 1.30-87.70; P = 0.028). CONCLUSIONS: Although ERCP can be performed effectively in patients with PS4, the risk of pulmonary and severe adverse events is high. Prolonged procedures should be avoided in patients with PS4.

Multi-center study of endoscopic revision after side-by-side metal stent placement for malignant hilar biliary obstruction.

BACKGROUND: The recent development of ultra-thin delivery systems, which enable simultaneous insertion of two metal stents, has encouraged wider adoption of side-by-side (SBS) stent placement for malignant hilar biliary obstruction (MHBO). However, the management of stent occlusion after SBS placement has not been well-characterized. This study aimed to examine the outcomes of endoscopic reintervention (E-RI) after SBS placement in patients with MHBO. METHODS: Sixty-seven patients who underwent E-RI for stent occlusion after SBS placement between 2013 and 2020 at three tertiary-care referral centers were investigated. We evaluated the technical success, clinical success, recurrent biliary obstruction (RBO), and adverse events other than RBO rates associated with E-RI. Furthermore, the factors associated with successful E-RI were also evaluated. RESULTS: The technical success and clinical success rates were 79.1% (53/67) and 76.1% (51/67), respectively. Early adverse events other than RBO occurred in 4.5% (3/67) and late events in 3.9% (2/51). The RBO rate after E-RI was 52.9% (27/51), and the median time to RBO after E-RI was 85 days. Common bile duct (CBD) diameter (odds ratio 2.62; 95% confidence interval, 1.37-5.01; P = 0.003) and metastatic disease (odds ratio, 0.11; 95% confidence interval, 0.02-0.64; P = 0.015) were independently correlated with E-RI success in the multivariate analysis. CONCLUSIONS: This study demonstrated that E-RI after SBS placement is technically feasible and safe, but the success rate was significantly lower in patients with narrow CBDs and metastatic diseases. These factors may be useful for the selection of the initial stenting method.

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.

Endobiliary radiofrequency ablation combined with bilateral metal stent placement for malignant hilar biliary obstruction.

BACKGROUND: The effectiveness of endobiliary radiofrequency ablation (RFA) is still uncertain, especially in patients with malignant hilar biliary obstruction (MHBO). We examined the efficacy of endobiliary RFA followed by bilateral self-expandable metal stent (SEMS) placement for unresectable MHBO. METHODS: 41 patients met the eligibility criteria for study inclusion. We evaluated the technical success, functional success, and recurrent biliary obstruction (RBO) associated with RFA with bilateral SEMS placement. RESULTS: The technical and functional success rates were both 95.1 % (39/41). The RBO rate was 38.5 % (15/39), and the median time to RBO was 230 days. Stricture length was positively correlated with time to RBO in the multivariate analysis (P = 0.03). The median time to RBO was significantly longer in patients with strictures > 15 mm in length than in those with strictures ≤ 15 mm (314 vs. 156 days; P = 0.02). CONCLUSIONS: The present study showed that endobiliary RFA with bilateral SEMS placement achieved good results, but selection of patients with an appropriate stricture length may be needed to obtain a sufficient ablative effect.

Early Covered Self-Expandable Metal Stent Placement Is Effective for Massive Post-endoscopic Sphincterotomy Bleeding.

BACKGROUND: Placement of covered self-expandable metallic stent (CSEMS) for post-endoscopic sphincterotomy (ES) bleeding achieves excellent hemostasis results. Although CSEMS placement is typically performed after failure of conventional endoscopic combination therapy, its excellent outcomes may justify earlier placement. AIMS: We aimed to examine the efficacy of "early" CSEMS placement for massive post-ES bleeding. METHODS: The medical records of 2750 patients who underwent ES between 2005 and 2019 were reviewed retrospectively, and 61 patients who developed massive post-ES bleeding were enrolled. These patients were divided into those who underwent early CSEMS placement (E-CSEMS group) and those who underwent conventional endoscopic combination therapy (Conventional group). The outcomes of hemostasis procedures were compared between the groups. RESULTS: The primary success rates of endoscopic hemostasis were 100% (21/21) and 98% (39/40) in the E-CSEMS group and Conventional group, respectively, without significant differences (P = 1.000). However, in the E-CSEMS group, re-bleeding was significantly less frequent (5% vs. 31%; P = 0.023), the median hemostasis procedure time was significantly shorter (14 min vs. 26 min; P < 0.001), and transfusion after initial hemostasis treatment was less commonly required (10% vs. 38%; P = 0.034). Multivariate analyses showed that hemodialysis was associated with a significantly higher re-bleeding rate (P = 0.029), while CSEMS placement was associated with a significantly lower re-bleeding rate (P = 0.039). CONCLUSIONS: Early CSEMS placement may be effective for improving the clinical outcomes of massive post-ES bleeding by decreasing re-bleeding and the extent of bleeding.

Intraductal placement of a fully covered metal stent with a long string for distal malignant biliary obstruction without endoscopic sphincterotomy: Prospective multi-center feasibility study.

BACKGROUND: Stent migration and sludge clogging are characteristic problems in biliary covered self-expandable metal stent (SEMS) placement. Intraductal placement without endoscopic sphincterotomy (ES) may help reduce their occurrence. We examined the feasibility of intraductal placement of a covered SEMS with a long string without ES in patients with unresectable distal malignant biliary obstruction (MBO). METHODS: This was a prospective multi-center observational study. Forty patients with distal MBO were enrolled between July 2016 and August 2018. We evaluated recurrent biliary obstruction (RBO), adverse events other than RBO, and reintervention associated with intraductal placement without ES. RESULTS: Both technical and functional success rates were 100% (40/40). The rate of adverse events other than RBO was 5% (2/40). The RBO rate was 33% (13/40), and the median time to RBO was 339 days. RBO was mainly caused by overgrowth on the papillary side, occurring in six patients; all such patients had pancreatic cancer and a distance between the papilla and the stricture of ≤20 mm. Other causes were overgrowth at the hepatic side in two patients and sludge in five patients. No instances of stent migration occurred. Success rates of endoscopic transpapillary reintervention and stent removal using the string were 92% (12/13) and 77% (10/13), respectively. CONCLUSIONS: Intraductal placement without ES using a long-stringed covered SEMS is a promising option for distal MBO. Since overgrowth on the papillary side is frequent, the procedure should be avoided in patients with short distances between the stricture and the papilla. (Clinical Trial Registry: UMIN000023370).

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.

Balloon enteroscopy-assisted radial incision and cutting method for refractory hepaticojejunostomy anastomotic strictures.

BACKGROUND: Balloon enteroscopy-assisted balloon dilation and temporary biliary stent placement are effective for hepaticojejunostomy anastomotic strictures (HJAS), but the re-stenosis rates are relatively high. We examined the feasibility and efficacy of a novel treatment technique for refractory HJAS, called balloon enteroscopy-assisted radial incision and cutting (BE-RIC). METHODS: Between January 2016 and June 2018, 11 patients with refractory HJAS that recurred after balloon dilation and/or stent placement, underwent BE-RIC. We evaluated the technical success, clinical success, adverse events, and re-stenosis rates associated with BE-RIC. RESULTS: The technical success rate of BE-RIC was 91 % (10/11). Clinical success was achieved in all patients who underwent technically successful procedures. The procedure-related adverse event rate was 9 % (1/11). No re-stenosis was observed during the follow-up period; 9 patients were followed up for more than 6 months, and of these, 5, 4, and 2 patients were followed up for more than 12, 18, and 24 months, respectively, without re-stenosis. CONCLUSIONS: BE-RIC for refractory HJAS showed favorable results. BE-RIC might be a useful option for treating refractory HJAS.

Combined side-by-side and stent-in-stent method for triple metal stenting in patients with malignant hilar biliary obstruction.

BACKGROUND AND AIM: Endoscopic placement of three branched self-expandable metallic stents (SEMS) for high-grade malignant hilar biliary obstruction (MHBO) is technically challenging. We examined the feasibility and efficacy of a novel stenting method combining side-by-side and stent-in-stent (SBSIS) placement for MHBO. METHODS: Between January 2015 and December 2018, 27 consecutive patients with high-grade MHBO underwent SBSIS placement. We evaluated the technical success, functional success, recurrent biliary obstruction (RBO), adverse events other than RBO, and reintervention success rates associated with SBSIS placement. RESULTS: Technical success rate was 85% (23/27). Insertion of the third SEMS failed in four patients, and median diameter of the common bile duct (CBD) was significantly smaller in patients in whom technical failure occurred (5 mm vs 8 mm; P = 0.004). Functional success was achieved in all patients in whom the procedure was a technical success. Rate of adverse events other than RBO was 15% (4/27). RBO rate was 43% (10/23), and median time to RBO was 157 days. Success rate of endoscopic reintervention for RBO was 89% (8/9). CONCLUSION: SBSIS placement showed favorable results and is a promising option in patients with high-grade MHBO requiring triple metal stenting. However, it might be preferable to avoid SBSIS in patients with a narrow CBD. Clinical Trial Registry: UMIN000035721.