Endoscopic Versus Percutaneous Drainage For Hilar Block in Gall Bladder Cancer
Condition: Gallbladder Cancer; Obstructive Jaundice
MeSH terms: Gallbladder Neoplasms; Jaundice; Jaundice, Obstructive
Study type: Interventional

Summary: 
      Cancer of the gallbladder (CaGB) is one of the most common causes of malignant obstructive
      jaundice. Jaundice is the second most common presentation and occurs in 30-60% of patients
      with CaGB. It is obstructive in nature and frequently associated with pruritus, which is very
      disturbing for the patients. The usual mechanism of obstruction is direct infiltration of the
      bile duct by the tumour. Most patients with CaGB with obstructive jaundice are not amenable
      to a curative surgical resection and hence effective palliation is the goal of treatment.
      Although surgical bypass has been the traditional palliative approach, it is associated with
      substantial morbidity and mortality. Non-operative alternatives in the form of percutaneous
      and endoscopic drainage are available. 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 peri-ampullary cancer. However, the scenario is quite different in patients
      with upper end of bile duct obstruction as occurs due to CaGB. Endoscopic drainage is
      associated with a higher incidence of cholangitis in patients with a block at the upper end
      of the bile duct 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
      obstruction due to CaGB. The objective of the present study is to carry out a randomized
      prospective trial comparing percutaneous and endoscopic biliary drainage in patients with
      CaGB with obstructive jaundice and to assess their quality of life.
    

Detailed description: 
      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.

      References

        1. Malkan G, Mohandas KM. Epidemiology of digestive cancers in India. I. General principles
           and esophageal cancer. Indian J Gastroenterol 1997;16(3):98-102

        2. Wanebo HJ, Castle WN, Fechner RE. Is carcinoma of the gall bladder a curable lesion? Ann
           Surg 1982;195:624-31.

        3. Kelly TR, Chamberlain TR. Carcinoma of the gall bladder. Am J Surg 1982; 143:737-41

        4. Morrow CF, Sutherland DE, Florack G, Eisenberg MM, Grage TB. Primary carcinoma gall
           bladder: Significance of subserosal lesions and results of aggressive surgical treatment
           and adjuvant chemotherapy. Surgery 1983;94:709-14

        5. Kumaran V, Gulati MS, Paul SB, Pande GK, Sahni P, Chattopadhyay TK. The role of dual
           phase helical CT in assessing respectability of carinoma of the gall bladder. Eur Radiol
           2002;12:1993-99.

        6. Bismuth H, Castaing D, Traynor O. Resection or palliation; priority of surgery in the
           treatment of hilar cancer. World J Surg 1988; 12:39-47.

        7. Huibregtse K, Tytgat GNJ. Palliative treatment of jaundice by transpapillary
           introduction of biliary endoprosthesis. Gut 1982; 23:371-5.

        8. Cotton PB. Endoscopic methods for relief of malignant obstructive jaundice. World J Surg
           1984;8:854-61.

        9. Dowsett JF, Vaira D, Hatfield AR, Cairns SR, Polydorou AA, Frost R, et al. Endoscopic
           biliary therapy using the combined percutaneous and endosopic route. Gastroenterology
           1989;96:1180-6.

       10. Polydorou AA, Cairns SR, Dowsett JF, Hatfield AR, Salmon PR, Cotton PB, et al.
           Palliation of proximal malignant biliary obstruction by endoscopic endoprosthesis
           insertion. Gut 1991;32:685-9.

       11. De Palma GD, Galloro G, Sicilliano S, Ivonini P, Catanzano C. Unilateral versus
           bilateral endoscopic hepatic duct drainage in patients with malignant hilar biliary
           obstruction: results of a prospective, randomized and controlled study. Gastrointest
           Endosc 2001;53:547-53

       12. Sherman S. Endoscopic drainage of malignant hilar obstruction: is one biliary stent
           enough or should we place two? Gastrointest Endosc 2001;53:681-4.

       13. Chang WH, Kortan P, Haber GB. Outcome in patients with bifurcation tumors who undergo
           unilateral versus bilateral hepatic duct drainage. Gastrointest Endosc 1998;47:354-62

       14. Mehta S, Ozden ZS, Dhanireddy S, Pleskow DP, Chutanni R. Endoscopic single versus double
           (bilateral) Wallstents for palliation of malignant Bismuth type III/IV hilar strictures:
           comparison of clinical outcomes and costs (abstract). Gastrointest Endosc 1999;49:AB234.

       15. De Palma, Angelo Pezzullo, Maria Rega, Unilateral placement of metallic stents for
           malignant hilar obstruction: a prospective study. Gastrointest Endosc 2003;55:50-5.

       16. Bismuth H, Castaing D, Traynor O. Resection or palliation :priority of surgery in the
           treatment of hilar cancer. World j Surg 1988;12:39-47.

       17. Gulati MS, Srinivasan A, Agarwal PP. Percutaneous Management of Malignant Biliary
           Obstruction: The Indian Perspective. Tropical Gastroenterology 2003;24:47-58.

       18. Ahuja V, Garg PK, Kumar D, Goindi G, Tandon RK. Presence of white bile associated with
           lower survival in malignant biliary obstruction. Gastrointest Endosc 2002;55:186-91.

       19. World Health Organization Handbook for Reporting Results of cancer Treatment. World
           Health Organization Publication No .48 Geneva World Health Organization 1979.

       20. Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ et al. The European
           Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument
           for use in international clinical trials in oncology. J Natl Cancer Inst 1993;85:365-76.
    

Intervention name(s): Endoscopic biliary stenting, Percutaneous biliary stenting
Intervention type(s): Procedure
Intervention description(s): percutaneous 10 F stent, endoscopic 10 F stent insertion
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Gallbaldder Cancer; Endoscopic stenting; Percutaneous biliary drainage