Antibody array-based proteomic screening of novel biomarkers in malignant biliary stricture

BACKGROUND: Distinguishing between benign and malignant bile duct strictures has long been a diagnostic challenge in clinical practice. OBJECTIVE: This study aimed to discover novel biomarkers in bile to improve the diagnostic accuracy of malignant biliary strictures. METHODS: Bile samples were collected from 6 patients with malignant or benign biliary stricture, respectively. Protein profiles of the bile were analyzed with a semi-quantitative human antibody array of 440 proteins. Then the differential expressed proteins were screened by Venn diagram analysis. Following this, the accuracy of these potential biomarkers for discriminating between malignant and non-malignant biliary strictures was validated in a larger (n= 40) group of patients using lasso analysis. Results: Twenty proteins were found differentially expressed in malignant versus benign biliary strictures, 6 of which were identified by Venn diagram analysis to be up-regulated regardless of the location of biliary strictures. Among the 6 biomarkers, bile lipocalin-2, P-cadherin, and adipsin showed better diagnostic utility than that of bile CA19-9. Lasso analysis identified that lipocalin-2, P-cadherin and CA19-9 as a group of makers best distinguished malignant from benign strictures. CONCLUSIONS: Lipocalin-2 and P-cadherin measurements in bile could be clinically useful for the detection of malignant biliary strictures.

Endoscopic transpapillary gallbladder stenting to prevent acute cholecystitis in patients receiving FCEMS for benign biliary stricture

Background and study aims Fully covered self-expanding metal stents (FCSEMS) are being increasingly used for benign biliary strictures (BBS); however, they are associated with risk of acute cholecystitis. Prophylactic endoscopic transpapillary gallbladder stenting (ETPGBS) can facilitate continuous gallbladder drainage and prevent acute cholecystitis from occlusion of cystic duct orifice by the FCSEMS. The aim of this study was to assess the technical feasibility, efficacy, and safety of ETPGBS to prevent acute cholecystitis in patients receiving FCSEMS for BBS. Patients and methods This was a retrospective analysis of a prospectively collected database at a single center of all patients who underwent prophylactic ETPGBS with FCSEMS for BBS between December 1, 2016 and November 30, 2020. Results A total of 71 ETPGBS were placed during the study period. Sixteen patients (mean age: 66.4 ± 19.8 years; 81 % male) underwent ETPGBS prior to biliary FCSEMS during the same endoscopic session. FCSEMS were left in place (stent dwell time) for a median of 173 days (range: 69–473; mean 196 ± 121) with resolution of BBS and successful removal of ETPGBS and FCSEMS in 12 patients. There was significant improvement in total bilirubin level (5.25 ± 5.53 vs 0.94 ± 0.85 gm/dL; P = 0.008). No episodes of acute cholecystitis or any other post-procedural complications were noted during the median follow-up of 337 days (range: 150–856; mean 394 ± 236). Conclusions ETPGBS prevented stent-related acute cholecystitis with continued efficacy of FCSEMS for BBS.

Percutaneous Management of Benign Biliary Strictures

Benign biliary strictures are often due to a variety of etiologies, most of which are iatrogenic. Clinical presentation can vary from asymptomatic disease with elevated liver enzymes to obstructive jaundice and recurrent cholangitis. Diagnostic imaging methods, such as ultrasound, multidetector computed tomography, and magnetic resonance imaging (cholangiopancreatography), are used to identify stricture location, extent, and possible source of biliary obstruction. The management of benign biliary strictures requires a multidisciplinary team approach and include endoscopic, percutaneous, and surgical interventions. Percutaneous biliary interventions provide an alternative diagnostic and therapeutic approach, especially in patients who are not amenable to endoscopic evaluation. This review provides an overview of benign biliary strictures and percutaneous management by interventional radiologists. Diagnostic evaluation with percutaneous transhepatic cholangiography and treatment options, including biliary drainage, balloon dilation, retrievable/biodegradable stents, and other innovative minimally invasive options, are discussed.

Percutaneous Transhepatic Biodegradable Biliary Stent Placement for Benign Biliary Strictures

This article aimed to assess the safety and effectiveness of biodegradable stents in the management of benign biliary strictures. This is a retrospective observational study that included all adult patients who had biodegradable stent placement for a benign cause of biliary stricture between July 2016 and August 2019. Nineteen patients were included. Seventeen patients had liver transplant. One patient had hepaticojejunostomy due to primary sclerosing cholangitis and one patient had iatrogenic left main bile duct occlusion. Stents were successfully deployed in all 19 patients (technical success: 100%). Patency rate was 90% (17/19) at 6 months and 80% (12/15) at 12 months. Seven patients in the study had stricture recurrence and needed reintervention with mean time to reintervention of 418 days (range: 8–1,155 days). There was one major complication due to cholangitis and sepsis, which required a treatment course with piperacillin/tazobactam for 10 days. No procedure-related pancreatitis or deaths occurred. Biodegradable stents are a safe and effective treatment option for benign biliary strictures and can achieve long-term patency without the need for reinterventions.

A Prospective Multicenter Study of “Inside Stents” for Biliary Stricture: Multicenter Evolving Inside Stent Registry (MEISteR)

Background: Endoscopic biliary stent placement is the standard of care for biliary strictures, but stents across the papilla are prone to duodenobiliary reflux, which can cause stent occlusion. Preliminary studies of “inside stents” placed above the papilla showed encouraging outcomes, but prospective data with a large cohort were not reported. Methods: This was a prospective multicenter registry of commercially available inside stents for benign and malignant biliary strictures. Primary endpoint was recurrent biliary obstruction (RBO). Secondary endpoints were technical success of stent placement and removal, adverse events, and stricture resolution. Results: A total of 209 inside stents were placed in 132 (51 benign and 81 malignant) cases with biliary strictures in 10 Japanese centers. During the follow-up period of 8.4 months, RBO was observed in 19% of benign strictures. The RBO rate was 49% in malignant strictures, with the median time to RBO of 4.7 months. Technical success rates of stent placement and removal were both 100%. The adverse event rate was 8%. Conclusion: This prospective multicenter study demonstrated that inside stents above the papilla were feasible in malignant and benign biliary strictures, but a randomized controlled trial is warranted to confirm its superiority to conventional stents across the papilla.

Evaluation of the Feasibility and Effectiveness of Placement of Fully Covered Self-Expandable Metallic Stents via Various Insertion Routes for Benign Biliary Strictures

Background and aims: The goals of the management of benign biliary stricture (BBS) are to relieve symptoms and resolve short-/long-term stricture. We performed fully covered self-expandable metallic stent (hereafter, FCSEMS) placement for BBS using various methods and investigated the treatment outcomes and adverse events (AEs). Methods: We retrospectively studied patients who underwent FCSEMS placement for refractory BBS through various approaches between January 2017 and February 2020. FCSEMS were placed for 6 months, and an additional FCSEMS was placed if the stricture had not improved. Technical success rate, stricture resolution rate, and AE were measured. Results: A total of 26 patients with BBSs that were difficult to manage with plastic stents were included. The mean overall follow-up period was 43.3 ± 30.7 months. The cause of stricture was postoperative (46%), inflammatory (31%), and chronic pancreatitis (23%). There were four insertion methods: endoscopic with duodenoscopy, with enteroscopy, EUS-guided transmural, and percutaneous transhepatic. The technical success rate was 100%, without any AE. Stricture resolution was obtained in 19 (83%) of 23 cases, except for three cases of death due to other causes. Stent migration and cholangitis occurred in 23% and 6.3%, respectively. Stent fracture occurred in two cases in which FCSEMSs were placed for more than 6 months (7.2 and 10.3 months). Conclusion: FCSEMS placement for refractory BBS via various insertion routes was feasible and effective. FCSEMSs should be exchanged every 6 months until stricture resolution because of stent durability. Further prospective study for confirmation is required, particularly regarding EUS-guided FCSEMS placement.

A bile duct stent broken during repeat pregnancy in a post-liver transplant patient

A young female patient who developed anastomotic biliary stricture following an orthotopic liver transplantation was observed. A self-expandable metallic stent was placed to correct the stricture. At the 8th month of her repeat pregnancy, the stent broke asymptomatically into half. Fortunately, the second childbirth, like the first one, had no complications. Eighteen months later, due to obstruction of fragments by sludge and gallstones, re-stenting was performed with a coated biliary stent. Four years and five months later, recurrent jaundice occurred due to occlusion of the second stent. This was addressed by surgical removal of both stents. Two years after surgery, the bile ducts remain completely patent. We found only two cases in literature on a similar extremely rare biliary stenting complication. It has been suggested that stent deformation may be related to pregnancy. The feasibility of using stenting in benign biliary strictures in some clinical situations is discussed.