Trial Information

Endoscopic Versus Percutaneous Biliary Drainage For Hilar Block Due to Carcinoma Gall Bladder: A Randomized Prospective Trial and Quality Of Life Assessment

Hypothesis: Percutaneous biliary stenting is superior to endoscopic stenting in providing
successful biliary drainage by 20% in patients with unresectable malignant hilar block due
to carcinoma of gall bladder.

Background: Malignant biliary obstruction at the liver hilum is caused by a heterogeneous
group of tumours that include cholangiocarcinoma, gallbladder cancer (CaGB) and metastatic
cancer. CaGB is the commonest cause of malignant hilar obstruction in India (1). Jaundice is
the second most common presentation and occurs in 30-60% of patients with CaGB (2-5). It is
obstructive in nature and frequently associated with pruritis, which is very disturbing for
the patients. Most patients with CaGB with surgical obstructive jaundice are not amenable to
a curative surgical resection (5) and hence effective palliation is the goal of treatment.
Although surgical bilioenteric bypass has been the traditional palliative approach (6), it
is associated with substantial morbidity and mortality. Non-operative alternatives in the
form of percutaneous and endoscopic drainage are available (7-8). Unilateral drainage of
single liver lobe may be sufficient to palliate the jaundice and, pruritis and improve the
quality of life (9-15). A few trials have shown that endoscopic drainage is better than
percutaneous drainage in patients with lower end bile duct obstruction due to pancreatic and
periampullary cancer. However, the scenario is quite different in patients with hilar
malignant obstruction. Endoscopic drainage is associated with a higher incidence of
cholangitis in patients with a block at the confluence (Bismuth types 2 and 3) and the
success rate varies from 40% to 80%, while percutaneous drainage may be associated with
complications such as biliary leak and bleeding. There has been no randomized trial
comparing endoscopic and percutaneous drainage in patients with malignant hilar obstruction
alone.

Objective: To compare unilateral PTBD and endoscopic stenting in patients with CaGB with
hilar block in terms of Successful drainage and Quality of life Patients and Methods
Consecutive patients with CaGB and jaundice will be enrolled in the study. The diagnosis of
CaGB and biliary obstruction will be established on the basis of an ultrasound of the
abdomen and a dual phase CT scan. Histological and/or cytological confirmation of the
malignancy will be established wherever possible by doing a FNAC/trucut biopsy. Hilar block
will be classified according to the Bismuth Corlette classification based on the
preprocedural investigations (16). Final differentiation between type 2 and 3 blocks will be
based on findings noted during intervention.

Inclusion criteria CaGB with hilar block not suitable for curative resection with one or
more of the following criteria: (i) Jaundice with serum bilirubin >10 mg/dl, (ii) Pruritus,
(iii) Cholangitis Exclusion criteria: Poor performance status: Karnofsky index < 60, Type
1 and 4 hilar block, Uncontrolled ascites, Duodenal obstruction, Patients who opted for
insertion of a metallic stent.

Sample size calculation: The number of patients to be included was calculated to be 91
patients in each group based on the assumption that percutaneous drainage will be better
than endoscopic drainage by 20 %. The sample size was calculated by the formula for a power
of 80% and alpha error of 0.05.

The patients will be randomly divided into two groups using random blocks generated by a
computer.

Group A - percutaneous biliary drainage (PTBD) Group B - Endoscopic stenting (ES)
Pre-procedural preparation(17) Patients will undergo detailed investigations and an informed
consent will be obtained.

The procedure will be performed under conscious sedation (midazolam and pentozocine) with a
liberal infiltration of local anesthetic at the site and the capsule of the liver for PTBD.

1. PTBD procedure (17) Either a right or left sided approach will be used for PTBD. Once
entry will be gained to a suitable duct the standard Seldinger technique will be used
to place a guidewire in the biliary system. The tract will be dilated and after
crossing the obstruction with a hydrophilic guidewire, a ring biliary catheter will be
placed to provide internal-external drainage. In a subsequent session, a 10 F, straight
plastic stent (polyurethane) will be placed into the system across the obstruction to
provide internal drainage.

2. Endoscopic stenting (18) A therapeutic duodenoscope and a standard sphincterotome will
be used for cannulation of the bile duct. A hydrophilic guidewire will be used to cross
the malignant stricture. After the stricture is crossed a guide catheter will be passed
over the guidewire and then a 10 F straight plastic stent will be inserted across the
stricture over the guidewire.

Primary outcome measures:

1. Successful drainage: A decrease in bilirubin to less than 75% of the pretreatment value
within 7 days

2. Early cholangitis: Occurring within 48 hours to 7 days of the procedure as evidenced by
fever, leukocytosis and worsening LFTs.

3. Quality of life

Secondary outcome measures:

1. Complications

2. Procedure-related and 30-day mortality

3. Stent patency time will be defined by time to stent occlusion.

Hematological and biochemical parameters will be assessed at days 2 and 7, 1 month after
stent placement and every 3 months thereafter. Patients will be re-evaluated 7 days, 1 month
after stent placement and 3 months thereafter.

Quality of life will be assessed using the WHO-QOL BREF26 and EORTC QLQ-30 questionnaires
pre-procedure, at 1 month and at 3 months.

World Health Organization-QOL BREF-26 (19) This has 26 items, which cover physical,
psychological, social and environmental domains. The daily activity is graded in accordance
with the 5 grade scale of performance status recommended by the WHO. WHO-QOL domain scores
will be calculated using the guidelines given in the WHO-QOL scoring manual. A high score
represents a high level of QOL.

EORTC QLQ-30 (20) The EORTC QLQ-30 consists of 30 generally applicable items. It
incorporates a functional scale (items 1-5), a role functioning scale (item 6,7), a general
symptom scale (item 8-19), scales on cognitive (item 20-25), emotional (items 21-24) and
social (items 26-27) functioning, financial strain scale (item 28) and global health status
scale (item 29,30). Scoring will be done using the EORTC scoring manual.

A high score for a functional scale will represent a high/healthy level of functioning, a
high score for global health status/QOL will represent high QOL but a high score for symptom
scale/item will represent a higher level of symptomatology/ problem.

All patients will be instructed to contact the department, if any symptom suggestive of a
complication appeared. Additional information regarding current status or death will be
obtained by direct contact with the referring physician or the patient by telephone/letter.

Statistical analysis Data will be analyzed according to both the intention-to-treat (ITT)
and per protocol (PP) methods. The baseline characteristics will be expressed in mean (SD).
The Pearson chi -square test and Fischer exact test will be used for comparison of
categorical data as appropriate. The t-test will be used for comparison of continuous
variables. Cumulative survival will be estimated using Kaplan-Meier life table analysis, and
the groups will be compared by log rank chi-square test.

The QOL score analysis will be done using Paired 't' test for comparison between baseline
and 1 month and baseline and 3 months within the groups. MANOVA will be used to assess the
trend of the scores.

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