Endoscopic Ultrasound and Endoscopic Retrograde Cholangiopancreatography for Malignant Distal Biliary Obstruction

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.

Inclusion Criteria:

1. ≥ 18 years of age.

2. Has jaundice due to malignant distal (more than 3cm distal to liver hilum) biliary
obstruction.

3. The subject (or when applicable the subject's LAR) is able to understand and willing
to sign an informed consent form prior to the initiation of any study procedures.

Exclusion Criteria:

1. Age <18 years

2. Females who are pregnant or lactating. Pregnancy in females of childbearing potential
will be determined by routine preoperative urine HCG testing.

3. Coagulopathy which cannot be corrected (INR >1.6, thrombocytopenia with platelet count
<50,000/ml)

4. Has surgically altered gastrointestinal anatomy such as but not limited to (Billroth
II/Roux en-Y, gastric bypass).

5. Liver metastasis involving >30% of liver volume.

6. Liver cirrhosis with portal hypertension and/or ascites.