Endoscopic Ultrasound and Endoscopic Retrograde Cholangiopancreatography for Malignant Distal Biliary Obstruction
Condition: Pancreatic Cancer; Pancreatic Neoplasms; Pancreatic Adenocarcinoma
MeSH terms: Pancreatic Neoplasms
Study type: Interventional

Summary: 
      The purpose of this study is to compare the rates of adverse events between patients
      undergoing Endoscopic Ultrasound- guided biliary drainage and Endoscopic Retrograde
      Cholangiopancreatography for distal malignant biliary obstruction.
    

Detailed description: 
      The current curative treatment for patients with occlusion of the distal common bile duct by
      pancreatic cancer is pancreaticoduodenectomy (Whipple procedure). Unfortunately, more than
      80% of patients have locally advanced or metastatic disease that requires neoadjuvant or
      palliative treatment. The goals of biliary drainage in the setting of locally advanced or
      metastatic pancreatic cancer are to palliate obstructive jaundice and lower serum bilirubin
      prior to systemic chemotherapy. In addition to resolving jaundice and associated pruritus,
      biliary drainage improves anorexia, indigestion and quality of life (1, 2). Endoscopic
      approach by means of retrograde cholangiopancreatography (ERCP) and biliary stent placement
      is the preferred treatment option for palliation of malignant obstructive jaundice.
      Endoscopic biliary drainage is safer than surgical bypass, with endoscopic placement of a
      plastic or metal stent having a lower relative risk of complications (3). When performed by
      experts, ERCP has favorable (80-90%) short-term (<90 days) success rates in the setting of
      malignant distal biliary obstruction (1-3). The rate of ERCP-associated adverse events (AEs)
      is 5-27% (4-7) and include pancreatitis, bleeding, infection, perforation and rarely death.

      In a recent audit of 524 consecutive patients with an intact papilla who underwent ERCP at a
      tertiary endoscopy unit, 49 (9.4%) had a previously failed attempt at an outside facility and
      more than 80% of these failures were in the setting of a distal malignant stricture (8).
      Cancer in the pancreatic head or uncinate process can cause extensive ampullary inflammation
      that precludes successful biliary cannulation using standard techniques. In such
      circumstances, advanced techniques such as needle-knife sphincterotomy, dual wire technique,
      trans-papillary pancreatic sphincterotomy and cannulation over a pancreatic duct stent are
      performed to access the bile duct (9, 10). While the technical success rate for advanced
      techniques in expert hands is more than 85%, the procedure is associated with an AE rate of
      about 10-20% (9-11).

      When ERCP is technically unsuccessful, patients are usually referred for interventional
      radiology-guided percutaneous transhepatic biliary drainage (PTBD). PTBD is usually a
      multi-step procedure that involves the initial placement of an external drainage catheter
      followed by internal trans-papillary stent placement. When the distal bile duct is severely
      strictured or when the intra-hepatic biliary system is non-dilated, PTBD is unsuccessful and
      is encountered in about 5-15% of patients with pancreatic cancer (12). The rate of short and
      long-term PTBD-related AEs is 5-10% and 20-30%, respectively (12-14). While most short-term
      AEs are due to infection and bleeding, the long-term AEs are due to stent dysfunction
      requiring frequent readmissions (12-14).

      More recently, EUS-guided biliary drainage (EUS-BD) has emerged as a novel alternative to
      PTBD and ERCP for biliary decompression when advanced cannulation techniques fail. EUS-BD is
      a minimally invasive technique where the extra-hepatic common bile duct
      (choledochoduodenostomy) or intrahepatic bile duct (hepatogastrostomy) is punctured under
      EUS-guidance and after transmural dilation a stent is deployed for biliary drainage.

      The potential advantages of EUS-BD are three-fold. Firstly, EUS-BD can be performed from
      multiple routes in the stomach and duodenum. Thus, duodenal stenosis is not a limitation to
      biliary access. Secondly, as biliary access is gained distant from the major duodenal
      papilla, the risk of post-procedure pancreatitis is low. Thirdly, as the deployed stent does
      not traverse the tumor, its patency could be longer. In a recent study of 95 patients with
      failed ERCP or inaccessible papilla, direct EUS-guided biliary drainage was successful in 86%
      of patients with an AE rate of 10.5% that included pancreatitis, bleeding, perforation, bile
      leak and infection (15). Most AEs were managed conservatively without the need for aggressive
      treatment measures. In another small, randomized trial of 25 patients with inoperable
      malignant biliary obstruction, there was no difference in clinical success, AEs, and costs
      between patients randomized to EUS-BD or PTBD (16). In a recent retrospective study of 208
      patients with malignant obstructive jaundice treated by ERCP or EUS-BD directed biliary metal
      stent placement, there was no difference in the rates of technical success (>90% in both
      cohorts) or AEs (8.65% in both cohorts) between groups (17). However, patients who underwent
      ERCP had a 5% incidence of post-procedure pancreatitis compared to 0% in the EUS-BD cohort.
      Given these promising outcomes, EUS-BD is currently practiced as a complimentary therapy that
      allows biliary drainage when technical failure is encountered at ERCP. EUS-BD and PTBD have
      been shown to be comparable in effectiveness after failed ERCP, however patients who
      underwent PTBD had higher rates of adverse events and required additional interventions (19).

      PTBD and EUS-BD have shown to be equally effective treatment options (16). The effectiveness
      of treatment outcomes between EUS-BD and ERCP needs to be evaluated. Since the treatment
      outcomes and safety profile of EUS-BD is comparable to ERCP and because EUS-BD is successful
      in more than 85% of patients with a failed ERCP, EUS-BD could be a first-line treatment
      option and not just a rescue measure for patients with malignant distal biliary obstruction.
    

Intervention name(s): EUS-BD; ERCP
Intervention type(s): Procedure; Procedure
Intervention description(s): EUS-BD is a minimally invasive technique where the common bile duct (choledochoduodenostomy) is punctured under EUS-guidance and after transmural dilation, a stent is deployed for biliary drainage.; During the ERCP, a small catheter and guidewire is inserted into the bile duct and the stent can be deployed into the duct.
Other intervention name(s): Endoscopic Ultrasound-guided biliary drainage; Endoscopic Retrograde Cholangiopancreatography
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment