Although endoscopic intervention is the mainstay for palliation of malignant biliary obstruction, a percutaneous approach has been preferred, particularly in patients with advanced high‐grade hilar ...malignant biliary obstruction, because of the technical difficulty and risk of complications. However, recently, primary endoscopic palliation using plastic or metal stents has had higher technical and clinical success with fewer adverse events than the percutaneous approach. Endoscopic interventions are being done more and more frequently because of advances in metal stents, accessories, and techniques. However, several concerns, such as optimal stent type, number, and deployment method, remain to be resolved. Therefore, we reviewed the literature in order to identify the optimal biliary stenting strategy for patients with hilar malignant biliary obstruction, focusing on stent type (plastic vs metal), number (unilateral single vs bilateral multiple), and deployment method (stent‐in‐stent vs stent‐by‐stent).
Background and Aims The efficacy of palliative biliary drainage by using bilateral or unilateral self-expandable metal stents (SEMSs) for a malignant hilar biliary stricture (MHS) remains ...controversial. This prospective, randomized, multicenter study investigated whether bilateral drainage by using SEMSs is superior to unilateral drainage in patients with inoperable MHSs. Methods Patients with inoperable high-grade MHSs who underwent palliative endoscopic insertion of bilateral or unilateral SEMSs were enrolled. The main outcome measurements were the rate of primary reintervention for malfunction after successful placement of SEMSs, stent patency, technical and clinical success rates, adverse events, and survival duration. Results A total of 133 pathology-diagnosed patients were randomized to the bilateral group (n = 67) or the unilateral group (n = 66). The primary technical success rates were 95.5% (64/67) and 100% (66/66) in the bilateral and unilateral groups, respectively ( P = .244). The clinical success rates were 95.3% (61/64) and 84.9% (56/66), respectively ( P = .047). The primary reintervention rates based on the per-protocol analysis were 42.6% (26/61) in the bilateral group and 60.3% (38/63) in the unilateral group ( P = .049). The median cumulative stent patency duration was 252 days in the bilateral group and 139 days in the unilateral group. The risk of stent patency failure was significantly higher in the unilateral group (log-rank test; P < .01). In a multivariate Cox proportional hazard model to assess stent patency, bilateral SEMS placement was a favorable factor (adjusted hazard ratio 0.30, 95% confidence interval, 0.172-0.521; P < .001). Survival probability and late adverse events were not different between the 2 groups. Conclusions Unilateral and bilateral drainage strategies by using SEMSs had similar technical success rates, but bilateral drainage resulted in fewer reinterventions and more durable stent patency in patients with inoperable high-grade MHSs. (Clinical trial registration number: NCT02166970.)
Background/Purpose
Compared with currently available duodenoscopy‐assisted systems, direct peroral cholangioscopy (DPOC) using an ultra‐slim endoscope is limited by technical difficulties. The ...multibending (MB) ultra‐slim endoscope was introduced as a dedicated cholangioscope for DPOC to challenge the technical problem. We retrospectively analyzed the clinical utility of DPOC using an MB endoscope with free‐hand insertion into the bile duct in patients with biliary diseases.
Methods
A total of 145 patients who underwent DPOC using an MB endoscope were analyzed. The primary outcome was the technical success rate of DPOC using the free‐hand insertion of the MB endoscope. The secondary outcomes were the technical success rates of DPOC‐guided diagnostic and therapeutic interventions, the diagnostic accuracy of DPOC‐guided target biopsy, and adverse events related to DPOC.
Results
Free‐hand biliary insertion of a MB endoscope for DPOC was technically successful in 133 patients (91.7%). DPOC‐guided target biopsy was successful in 36 of 38 patients (94.7%) and had a diagnostic accuracy of 91.7% (95% confidence interval, 82.6‐100). Sixty‐nine therapeutic interventions were performed; technical success was achieved in 65 (94.2%). No severe adverse events were observed.
Conclusions
The MB ultra‐slim endoscope was technically effective to perform a DPOC including various diagnosis and therapeutic interventions without device assistance. MB endoscope is considered to contribute to expanding a role of DPOC in diagnosis and treatment of diverse biliary tract diseases.
Schwann cells (SCs) are known to produce myelin for saltatory nerve conduction in the peripheral nervous system (PNS). Schwann cell differentiation and myelination processes are controlled by several ...transcription factors including Sox10, Oct6/Pou3f1, and Krox20/Egr2. Chicken ovalbumin upstream promoter‐transcription factor II (COUP‐TFII/NR2F2) is an orphan receptor that plays a role in the development and differentiation. However, the role of COUP‐TFII in the transcriptional regulatory network of SC differentiation has not been fully identified yet. Thus, the objective of this study was to investigate the role and molecular hierarchy of COUP‐TFII during cAMP‐induced SC differentiation. Our results showed that dibutyryl‐cAMP (db‐cAMP) increased expression levels of COUP‐TFII along with the expressions of Oct6, Krox20, and myelin‐related genes known to be related to SC differentiation. Our mechanistic studies showed that COUP‐TFII acted downstream of Hsp90/ErbB2/Gab1/ERK‐AKT pathway during db‐cAMP‐induced SC differentiation. In addition, we found that COUP‐TFII induced Krox20 expression by directly binding to Krox20‐MSE8 as revealed by chromatin immunoprecipitation assay and promoter activity assay. In line with this, the expression of COUP‐TFII was increased before up‐regulation of Oct6, Krox20, and myelin‐related genes in the sciatic nerves during early postnatal myelination period. Finally, COUP‐TFII knockdown by COUP‐TFII siRNA or via AAV‐COUP‐TFII shRNA in SCs inhibited db‐cAMP‐induced SC differentiation and in vitro myelination of sensory axons, respectively. Taken together, these findings indicate that COUP‐TFII might be involved in postnatal myelination through induction of Krox20 in SCs. Our results present a new insight into the transcriptional regulatory mechanism in SC differentiation and myelination.
We proposed the hypothetical signal transduction network of COUP‐TFII expression in cAMP‐induced Schwann cell (SC) differentiation and in vitro myelination. COUP‐TFII expression is induced by activation of PKA/Hsp90/ErbB2/Gab1/ERK‐AKT pathway. It then exerts its function in cAMP‐induced SC differentiation and in vitro myelination by inducing Krox20 via up‐regulation of Oct6 or binding directly to the Krox20‐MSE8. These findings provide experimental evidence for a novel function and molecular mechanism of COUP‐TFII in SC differentiation and in vitro myelination.
Although the efficacy of palliative bilateral biliary drainage using self-expandable metal stents has been demonstrated, it is unclear which bilateral method is optimal for advanced malignant hilar ...biliary strictures (MHSs). This pilot study compared bilateral stent-in-stent (SIS) with stent-by-stent (SBS) deployment for advanced MHSs.
Patients with inoperable high-grade MHSs were enrolled in this prospective randomized multicenter study. The primary outcome was the rate of adverse events, whereas secondary outcomes were technical and clinical success, reintervention, therapeutic outcomes, stent patency, and survival duration.
This study randomized 69 of 74 pathologically diagnosed patients to the SIS (n = 34) or SBS (n = 35) groups. The total adverse event rate after stent deployment did not differ between the 2 groups (23.5% in the SIS group vs 28.6% in the SBS group, P = .633). The primary technical success rate was 100% (34/34) and 91.4% (32/35) in the SIS and SBS groups, respectively (P = .081). The clinical success rate was 94.1% (32/34) and 90.6% (29/32), respectively (P = .668). The stent patency rate at 3 months was 85.3% in the SIS group and 65.7% in the SBS group (P = .059). At 6 months, the stent patency rate was 47.1% and 31.4%, respectively (P = .184). The median cumulative stent patency and survival probability did not differ between the 2 groups.
Efficacy of bilateral SIS and SBS deployment may be similar in terms of total adverse events, technical and clinical success, stent patency, and survival. The stent patency rates at 3 and 6 months was higher in the SIS group without statistical difference. (Clinical trial registration number: NCT01141088.)
Background and Aim
Durable biliary drainage is essential in patients with pancreatic cancer in the era of effective neoadjuvant chemotherapy (NACT). Plastic stent (PS) tends to occlude easily, and ...current metal stents are designed for nonresectable cancer. We evaluated the efficacy of a modified non‐flared fully covered self‐expandable metal stent (M‐FCSEMS) during the perioperative period in patients with resectable or borderline resectable pancreatic cancer.
Methods
Consecutive patients with resectable or borderline resectable pancreatic ductal adenocarcinoma had a 12‐mm M‐FCSEMS (M‐FCSEMS group) or 7‐Fr PS (PS group) placed for biliary decompression before NACT or curative‐intent surgery. The primary outcome was the re‐intervention rate, and secondary outcomes were technical success, stent patency, and adverse events (AEs).
Results
Endoscopic stent placement was technically successful in all 60 patients. Twenty‐three patients underwent surgery and 37 NACT before surgery. Re‐intervention was performed in 10.0% (3/30) of patients in the M‐FCSEMS group and 36.7% (11/30) of patients in the PS group (P = 0.030). The stent patency at 180 days was 89.8% (95% confidence interval, 77.3–100.0%) in the M‐FCSEMS group and 30.2% (95% confidence interval, 11.4–80.0%) in the PS group (P < 0.0001). Stent‐related AEs occurred in 10.0% (3/30) in the M‐FCSEMS group and 40.0% (12/30) in the PS group (P = 0.015). Surgery‐related AEs occurred in 10.5% (2/19) and 14.3% (3/21) in the M‐FCSEMS and PS groups (P = 0.549).
Conclusions
Modified non‐flared fully covered self‐expandable metal stents are effective and safe for durable biliary drainage in patients with resectable or borderline resectable pancreatic cancer during the perioperative period.
Background
An electrocautery‐enhanced delivery system with a lumen‐apposing metal stent (LAMS) is available for one‐step endoscopic ultrasound‐guided transmural drainage (EUS‐TD). Bipolar ...electrosurgery has several potential clinical advantages, including reduced collateral thermal damage, enhanced hemostasis, and no requirement for a return electrode plate. In this study, we compared the technical feasibility and safety of a newly developed bipolar electrocautery‐enhanced delivery system with a conventional delivery system for EUS‐TD using a LAMS in a porcine model.
Method
Ten days before the study, 12 mini pigs underwent common bile duct ligation for EUS‐guided gallbladder drainage. Transenteric puncture was performed, followed by placement of a guidewire. In six pigs, a bipolar electrocautery‐enhanced delivery system with LAMS (Hot SPAXUS) was inserted over the guidewire and advanced into the gallbladder, without prior dilation of the tract, by applying a bipolar cut current. In the remaining six pigs, a conventional delivery system with LAMS (Cold SPAXUS) was inserted after tract dilatation using a cystotome. The stent was removed after 4 weeks.
Results
In all pigs, the stent was successfully inserted and deployed in the gallbladder without adverse events. The mean procedure time of EUS‐TD was significantly lower in the Hot SPAXUS group than that of the Cold SPAXUS group (mean ± standard deviation: 188.7 ± 5.2 vs 449.5 ± 97.5 s, P = .0019). Stent migration was not observed, and all stents were removed successfully.
Conclusions
Endoscopic ultrasound‐guided transmural drainage using a bipolar electrocautery‐enhanced LAMS is feasible for reducing the procedure time while maintaining the high success rate and safety of conventional LAMS.
Background and Aim
Endoscopic post‐papillectomy bleeding occurs in 3% to 20% of the cases, and delayed bleeding is also problematic. However, there is no consensus on how to reduce delayed ...post‐papillectomy bleeding. The aim of this study was to evaluate the efficacy of prophylactic argon plasma coagulation (APC) to minimize delayed bleeding and reduce the persistence of residual tumors after endoscopic papillectomy.
Methods
In a prospective pilot study of patients with benign ampullary tumors, the prophylactic APC group underwent APC at the resection margin following a conventional snaring papillectomy. Then, 24 h later after the papillectomy, all patients underwent a follow‐up duodenoscopy to identify post‐papillectomy bleeding and were followed up until 12 months. The main outcomes were the delayed (≥24 h) post‐papillectomy bleeding rate and the tumor persistence rate.
Results
The delayed post‐papillectomy bleeding rate was 30.8% (8/26) in the prophylactic APC group and 21.4% (6/28) in the non‐APC group (P = 0.434). The post‐procedure pancreatitis rates were 23.1% (6/26) and 35.7% (10/28), respectively (P = 0.310). The rate of tumor persistence did not differ between the two groups at 1 month (12.5% vs 7.4%, P = 0.656), 3 months (4.2% vs 3.7%, P = 1.00), 6 months (8.3% vs 3.7%, P = 0.595), and 12 months (0% vs 3.7%, P = 1.00). There were no procedure‐related mortalities or serious complications.
Conclusion
Prophylactic APC may not be effective in reducing delayed post‐papillectomy bleeding or remnant tumor ablation immediately after conventional papillectomy (Clinical trial registration—cris.nih.go.kr; KCT0001955).
Background and Aim
Endoscopic management of a benign biliary stricture (BBS) on the hilum is complicated and challenging. Although the placement of a fully covered self‐expandable metal stent ...(FCSEMS) is possible to increase effectiveness, stent migration and stent‐induced adverse events are problematic. We aimed to evaluate the usefulness of a modified short FCSEMS with a long lasso in patients with a difficult perihilar BBS.
Methods
Patients with perihilar BBS within 2 cm from the hilar confluence that failed initially with plastic stents were enrolled. A modified short FCSEMS was deployed and then removed 5–6 months later. The primary outcome was clinical success. Other technical success, adverse events, endoscopic success of stent removal, and recurrence of stricture during the follow‐up period were measured.
Results
Endoscopic intraductal placement was technically successful in all patients (n = 19). Combined contralateral plastic stent placement was performed in 13 patients (68.4%). The median duration of stent placement was 163 days (range, 138–196 days). Endoscopic stent removal was successful in all patients except one spontaneous distal migration. Stricture resolution without de novo focal stricture occurrence was 100%. Endoscopic stone removal after stricture improvement was successful in all 13 patients with bile duct stones above the stricture. During a follow‐up period (median 635 days) after stent removal, only one recurrence developed.
Conclusions
Temporary placement of a modified intraductal short FCSEMS with or without a contralateral plastic stent improved perihilar BBS in patients that primarily failed by plastic stents. Combined biliary stones were also successfully removed after stricture resolution.
Background and Aims Whether or not submucosal injection of a diluted epinephrine solution should be used to lift ampullary tumors during endoscopic snare papillectomy is unclear. This study aimed to ...investigate the clinical efficacy of a simple snaring method versus submucosal injection for papillectomy. Methods A prospective multicenter study was performed at 4 tertiary referral centers. Patients with papillary lesions were randomized to undergo either simple snare papillectomy (SSP) or submucosal injection papillectomy (SIP) using 1:10,000 diluted epinephrine. The main outcome measures were complete resection rate and post-papillectomy adverse events. Results A total of 50 patients with biopsy-proven papillary adenomas were enrolled. Complete resection rates in the SSP and SIP groups were 80.8% (21/26) and 50.0% (12/24), respectively ( P = .02). However, tumor persistence at 1 month (15.4% vs 8.3%, P = .62) and recurrence at 12 months (12.0% vs 9.5%, P = .58) did not differ despite initial differences in the prevalence of a positive resection margin. The mean tumor size was 12 mm in the SSP group and 9.29 mm in the SIP group. Post-papillectomy bleeding developed in 42.3% (11/26) and 45.8% (11/24) of patients, respectively ( P = .80). Delayed bleeding (>12 h) occurred in 27.3% (3/11) and 36.4% (4/11) of patients, respectively ( P = .50). Post-procedure pancreatitis occurred in 15.4% (4/26) and 25% (6/24) of patients, respectively ( P = .49). Pancreatitis severity did not differ between the groups, and there were no procedure-related mortalities. Conclusions Although the recurrence rate was similar between the SSP and SIP groups, SIP showed no advantage over SSP in terms of achieving complete resection or decreasing the frequency of post-papillectomy adverse events, such as bleeding. SSP may thus be a simpler and primarily recommendable technique. (Clinical trial registration number: NCT02165852 .)
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