Photodynamic therapy for unresectable cholangiocarcinoma: a comparative effectiveness systematic review and meta-analyses.

BACKGROUND Photodynamic therapy (PDT) with placement of a biliary stent may improve bile duct patency in patients with cholangiocarcinoma (CCA). We aimed to determine the effectiveness of biliary stenting with PDT compared to biliary stenting alone in the palliative treatment of CCA. MATERIALS AND METHODS Several databases were searched from inception to December 2011 for prospective studies comparing biliary stenting with PDT vs. biliary stenting only for CCA. Outcomes of interest included patient survival, quality of life (using Karnofsky score), and serum bilirubin levels. The relative risk (RR) for dichotomous outcomes and the weighted mean difference (WMD) for continuous outcomes were estimated using DerSimonian and Laird random-effects model. Inconsistency was quantified using I(2) statistics. The extent of publication bias was ascertained by visual inspection of funnel plots and Egger's test. RESULTS There were six studies that met inclusion criteria. A total of 170 participants received PDT and 157 had biliary stenting only. Compared with biliary stenting, PDT was associated with a statistically significant increase in the length of survival (WMD 265 days; 95% CI: 154-376; p = 0.01; I(2) = 65%), improvement in Karnofsky scores (WMD 7.74; 95% CI: 3.73-11.76; p = 0.01; I(2)= 14%), and a trend for decline in serum bilirubin (WMD -2.92 mg/dL; 95% CI: -7.54 to 1.71; p=0.22; I(2) = 94%). The pooled event rate for biliary sepsis was 15% and was similar between PDT and control groups. CONCLUSION Palliative treatment of CCA with PDT is associated with increased survival benefit, improved biliary drainage, and quality of life. However, the quality of this evidence is low.

[1]  D. Altman,et al.  Measuring inconsistency in meta-analyses , 2003, BMJ : British Medical Journal.

[2]  T. Sauerbruch,et al.  Feasibility and safety of long-term photodynamic therapy (PDT) in the palliative treatment of patients with hilar cholangiocarcinoma , 2011, European journal of medical research.

[3]  U. Mansmann,et al.  Successful photodynamic therapy for nonresectable cholangiocarcinoma: a randomized prospective study. , 2003, Gastroenterology.

[4]  A. Tannapfel,et al.  Photodynamic therapy for advanced bile duct cancer: Evidence for improved palliation and extended survival , 2000, Hepatology.

[5]  J. Regimbeau,et al.  Biliary drainage, photodynamic therapy and chemotherapy for unresectable cholangiocarcinoma with jaundice , 2009, Journal of gastroenterology and hepatology.

[6]  Kenneth K Wang,et al.  Factors associated with increased survival after photodynamic therapy for cholangiocarcinoma. , 2007, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[7]  P. Malfertheiner,et al.  Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer , 2010, Expert review of gastroenterology & hepatology.

[8]  T. Sauerbruch,et al.  Phase II study of photodynamic therapy and metal stent as palliative treatment for nonresectable hilar cholangiocarcinoma. , 2003, Gastrointestinal endoscopy.

[9]  N. Laird,et al.  Meta-analysis in clinical trials. , 1986, Controlled clinical trials.

[10]  G. Klatskin ADENOCARCINOMA OF THE HEPATIC DUCT AT ITS BIFURCATION WITHIN THE PORTA HEPATIS. AN UNUSUAL TUMOR WITH DISTINCTIVE CLINICAL AND PATHOLOGICAL FEATURES. , 1965, The American journal of medicine.

[11]  M. S. Lee,et al.  Prospective Study of the Effectiveness of Percutaneous Transhepatic Photodynamic Therapy for Advanced Bile Duct Cancer and the Role of Intraductal Ultrasonography in Response Assessment , 2005, Endoscopy.

[12]  T. Sauerbruch,et al.  Combination of bilateral metal stenting and trans-stent photodynamic therapy for palliative treatment of hilar cholangiocarcinoma. , 2010, Zeitschrift fur Gastroenterologie.

[13]  M. Ortner Photodynamic therapy for cholangiocarcinoma: overview and new developments , 2009, Current opinion in gastroenterology.

[14]  M. Ortner,et al.  Photodynamic therapy of nonresectable cholangiocarcinoma. , 1998, Gastroenterology.

[15]  D. Apel,et al.  Photodynamic therapy for palliation of nonresectable bile duct cancer—preliminary results with a new diode laser system , 2001, American Journal of Gastroenterology.

[16]  A. Weaver,et al.  "Natural history" of unresected cholangiocarcinoma: patient outcome after noncurative intervention. , 1995, Mayo Clinic proceedings.

[17]  G. Gores,et al.  Endoscopic application of photodynamic therapy for cholangiocarcinoma. , 2000, Gastrointestinal endoscopy.

[18]  D. Ziyaie,et al.  Photodynamic therapy is associated with an improvement in survival in patients with irresectable hilar cholangiocarcinoma. , 2009, HPB : the official journal of the International Hepato Pancreato Biliary Association.

[19]  T. Patel Increasing incidence and mortality of primary intrahepatic cholangiocarcinoma in the United States , 2001, Hepatology.

[20]  G. Weiss,et al.  Unresectable cholangiocarcinoma: comparison of survival in biliary stenting alone versus stenting with photodynamic therapy. , 2008, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[21]  G. Klatskin CONGENITAL HEMOLYTIC JAUNDICE CORRECTED BY SPLENECTOMY FOLLOWED TWENTY-SIX YEARS LATER BY BLEEDING TENDENCY, HEPATOMEGALY AND SUDDEN DEATH. , 1965, The American journal of medicine.

[22]  Thierry Ponchon,et al.  Plastic or metal stents for malignant stricture of the common bile duct? Results of a randomized prospective study. , 2003, Gastrointestinal endoscopy.

[23]  H. Thomas,et al.  Guidelines for the diagnosis and treatment of cholangiocarcinoma: consensus document , 2002, Gut.

[24]  G. Gores,et al.  Pilot study to assess patient outcomes following endoscopic application of photodynamic therapy for advanced cholangiocarcinoma , 2005, Journal of gastroenterology and hepatology.

[25]  F. Berr,et al.  Photodynamic therapy in patients with non-resectable hilar cholangiocarcinoma: 5-year follow-up of a prospective phase II study. , 2004, Gastrointestinal endoscopy.

[26]  J. Bridgewater,et al.  R0 but not R1/R2 resection is associated with better survival than palliative photodynamic therapy in biliary tract cancer , 2011, Liver international : official journal of the International Association for the Study of the Liver.

[27]  D. Apel,et al.  Palliation of Nonresectable Bile Duct Cancer: Improved Survival After Photodynamic Therapy , 2005, The American Journal of Gastroenterology.

[28]  A. Tannapfel,et al.  Surgical and Palliative Management and Outcome in 184 Patients With Hilar Cholangiocarcinoma: Palliative Photodynamic Therapy Plus Stenting Is Comparable to R1/R2 Resection , 2006, Annals of surgery.