Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Technology Insight: photodynamic therapy for cholangiocarcinoma

Nature Clinical Practice Gastroenterology & Hepatology volume 3, pages 459–467 (2006)Cite this article

Abstract

Cholangiocarcinoma is, in most cases, rapidly fatal. Curative resection can only be offered to approximately 10% of patients. Even after seemingly curative resection, recurrence frequently occurs. Adjuvant chemotherapy and/or radiotherapy do not reduce the recurrence rate after resection. In the palliative setting, endoscopic or percutaneous biliary drainage is performed to relieve jaundice; however, poor results have been obtained in patients with tumors involving the intrahepatic bile ducts. Biliary drainage alleviates jaundice, but there is no evidence that it prolongs life. Palliative chemotherapy and/or radiotherapy have not been proven to prolong life and relieve jaundice. Photodynamic therapy (PDT) is a relatively new local, minimally invasive procedure that can be used to treat cholangiocarcinoma. PDT uses the physical properties of light-absorbing molecules, so-called photosensitizers, which accumulate within proliferating cells. Activation of the photosensitizer by a non-thermal laser leads to selective photochemical destruction of tumors. In a randomized trial of patients with nonresectable cholangiocarcinoma, PDT prolonged survival time, improved cholestasis and quality of life considerably, and had a favorable side-effect profile. A second randomized trial confirmed the beneficial effect of PDT. For the time being, PDT is recommended for patients with nonresectable disease. The role of PDT before and after surgical resection needs to be assessed.

Key Points

  • Curative resection is possible for only ∼10% of all cholangiocarcinomas

  • Insertion of bilateral endoprostheses to improve jaundice is the gold standard of palliative treatment

  • Life expectancy after endoprosthesis insertion is short, particularly for patients with large tumors, bilateral intrahepatic extension and advanced tumor stage

  • Photodynamic therapy after insertion of bilateral endoprostheses is the first treatment that has been shown to prolong survival and improve quality of life for patients with nonresectable cholangiocarcinoma

  • In the absence of more-effective therapies, photodynamic therapy should be offered to all patients with nonresectable cholangiocarcinoma

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Possible mechanism for tumor destruction mediated by photodynamic therapy.
Figure 2: Endoscopic and cholangioscopic images before and after photodynamic therapy.
Figure 3: Kaplan–Meier survival curve of patients randomly allocated to either photodynamic therapy plus stenting (thick line), or stenting alone (dashed line).
Figure 4: Recommendations for photodynamic therapy in the bile duct.

Similar content being viewed by others

References

  1. Jemal A et al. (2005) Cancer Statistics 2005. CA Cancer J Clin 55: 10–30

    Article  Google Scholar 

  2. Jarnagin WR et al. (2001) Staging, resectability, and outcome in 225 patients with hilar cholangiocarcinoma. Ann Surg 234: 507–517

    Article  CAS  Google Scholar 

  3. Neuhaus P et al. (2003) Surgical management of proximal bile duct cancer: extended right lobe resection increases resectability and radicality. Langenbecks Arch Surg 388: 194–200

    Article  Google Scholar 

  4. Otto G et al. (2004) Hilar cholangiocarcinoma: resectability and radicality after routine diagnostic imaging. J Hepatobiliary Pancreat Surg 11: 310–318

    Article  Google Scholar 

  5. Jang JY et al. (2005) Actual long-term outcome of extrahepatic bile duct cancer after surgical resection. Ann Surg 241: 77–84

    PubMed  PubMed Central  Google Scholar 

  6. Weber SM et al. (2001) Intrahepatic cholangiocarcinoma: resectability, recurrence pattern, and outcomes. J Am Coll Surg 193: 384–391

    Article  CAS  Google Scholar 

  7. Todoroki T et al. (2001) Treatment strategy for patients with middle and lower third bile duct cancer. Br J Surg 88: 364–370

    Article  CAS  Google Scholar 

  8. Pitt HA et al. (1995) Perihilar cholangiocarcinoma. Postoperative radiotherapy does not improve survival. Ann Surg 221: 788–797

    Article  CAS  Google Scholar 

  9. Sagawa N et al. (2005) Effectiveness of radiation therapy after surgery for hilar cholangiocarcinoma. Surg Today 35: 548–552

    Article  Google Scholar 

  10. Todoroki T (2000) Chemotherapy for bile duct carcinoma in the light of adjuvant chemotherapy to surgery. Hepatogastroenterology 47: 644–649

    CAS  PubMed  Google Scholar 

  11. Takada T et al. (2002) Is postoperative adjuvant chemotherapy useful for gallbladder carcinoma? A phase III multicenter prospective randomized controlled trial in patients with resected pancreaticobiliary carcinoma. Cancer 95: 1685–1695

    Article  Google Scholar 

  12. Figueras J et al. (2000) Changing strategies in diagnosis and management of hilar cholangiocarcinoma. Liver Transpl 6: 786–794

    Article  CAS  Google Scholar 

  13. Rea DJ et al. (2005) Liver transplantation with neoadjuvant chemoradiation is more effective than resection for hilar cholangiocarcinoma. Ann Surg 242: 451–458

    PubMed  PubMed Central  Google Scholar 

  14. Sudan D et al. (2002) Radio chemotherapy and transplantation allow long-term survival for nonresectable hilar cholangiocarcinoma. Am J Transplant 2: 774–779

    Article  Google Scholar 

  15. Prat F et al. (1998) Predictive factors for survival of patients with inoperable malignant distal biliary strictures: a practical management guideline. Gut 42: 76–80

    Article  CAS  Google Scholar 

  16. Chang WH et al. (1998) Outcome in patients with bifurcation tumors who undergo unilateral versus bilateral hepatic duct drainage. Gastrointest Endosc 47: 354–362

    Article  CAS  Google Scholar 

  17. Kaasis M et al. (2002) Plastic or metal stents for malignant stricture of the common bile duct? Results of a randomized prospective study. Gastrointest Endosc 57: 178–182

    Article  Google Scholar 

  18. Bowling TE et al. (1996) A retrospective comparison of endoscopic stenting alone with stenting and radiotherapy in non-resectable cholangiocarcinoma. Gut 39: 852–855

    Article  CAS  Google Scholar 

  19. Shinchi H et al. (2000) Length and quality of survival following external beam radiotherapy combined with expandable metallic stent for unresectable hilar cholangiocarcinoma. J Surg Oncol 75: 89–94

    Article  CAS  Google Scholar 

  20. Glimelius B et al. (1996) Chemotherapy improves survival and quality of life in advanced biliary and pancreatic cancer. Ann Oncol 7: 593–600

    Article  CAS  Google Scholar 

  21. Rao S et al. (2005) Phase III study of 5FU, etoposide and leucoverin (FELV) compared to epirubicin, cisplatin and 5FU (ECF) in previously untreated patients with advanced biliary cancer. Br J Cancer 92: 1650–1654

    Article  CAS  Google Scholar 

  22. Roelandts R (1991) The history of photochemotherapy. Photodermatol Photoimmunol Photomed 5: 184–189

    Google Scholar 

  23. Daniell MD et al. (1991) A history of photodynamic therapy. Aust NZ J Surg 5: 340–348

    Article  Google Scholar 

  24. Finsen NF (1901) Phototherapy. London: Arnold

    Google Scholar 

  25. Hayata Y et al. (1985) Photodynamic therapy with hematoporphyrin derivate in cancer of the upper gastrointestinal tract. Semin Surg Oncol 1: 1–11

    Article  CAS  Google Scholar 

  26. Kessel D (2004) Photodynamic therapy: from the beginning. Photodiagn Photodyn Ther 1: 3–7

    Article  CAS  Google Scholar 

  27. Fingar VH and Wiemann TJ (1990) Studies on the mechanism of photodynamic therapy induced tumor destruction. Proc SPIE: Photodyn Ther Mech II 1203: 168–177

    Article  Google Scholar 

  28. Abels C (2004) Targeting of the vascular system of solid tumors by photodynamic therapy (PDT). Photochem Photobiol Sci 3: 765–771

    Article  CAS  Google Scholar 

  29. Korbelik M and Doughtery GJ (1999) Photodynamic therapy-mediated immune response against subcutaneous mouse tumors. Cancer Res 59: 1941–1946

    CAS  PubMed  Google Scholar 

  30. Gollnick SO et al. (1997) Altered expression of interleukin 6 and interleukin 10 as a result of photodynamic therapy in vivo. Cancer Res 57: 3904–3909

    CAS  PubMed  Google Scholar 

  31. Casas A et al. (2002) Photodynamic therapy of activated and resting lymphocytes and its antioxidant response. Lasers Med Sci 17: 42–50

    Article  CAS  Google Scholar 

  32. Marcus SL and McIntyre WR (2002) Photodynamic therapy systems and applications. Expert Opin Emerg Drugs 7: 321–324

    Article  CAS  Google Scholar 

  33. Dougherty TJ (1987) Studies on the structure of porphyrins contained in Photofrin II. Photochem Photobiol 46: 569–573

    Article  CAS  Google Scholar 

  34. Kennedy JC and Pottier RH (1992) Endogenous protoporpyhrin IX: a clinical useful photosensitizer for photodynamic therapy. J Photochem Photobiol B 14: 275–292

    Article  CAS  Google Scholar 

  35. Hinnen P et al. (2000) Porphyrin biosynthesis in human Barrett's esophagus and adenocarcinoma after ingestion of 5-aminolaevulinic acid. Br J Cancer 83: 539–543

    Article  CAS  Google Scholar 

  36. Gossner L et al. (1998) Photodynamic therapy of high-grade dysplasia and early stage carcinomas by means of 5-aminolevulinic acid. Gastroenterology 114: 447–445

    Article  Google Scholar 

  37. Kelty CJ et al. (2002) The use of 5-aminolevulinic acid as a photosensitizer in photodynamic therapy and photodiagnosis. Photochem Photobiol Sci 3: 158–167

    Article  Google Scholar 

  38. Webber J et al. (1997) Side effects and photosensitization of human tissue after aminolevulinic acid. J Surg Res 68: 31–37

    Article  CAS  Google Scholar 

  39. Wong Kee Song LM et al. (1998) Mono-L-aspartyl chlorin e6 (NPe6) and hematoporphyrin derivate (HpD) in photodynamic therapy administered to a human cholangiocarcinoma model. Cancer 82: 421–427

    Article  CAS  Google Scholar 

  40. Neumann J and Brandsch M (2003) δ-aminolevulinic acid transport in cancer cells of the human extrahepatic biliary duct. J Pharmacol Exp Ther 305: 219–224

    Article  CAS  Google Scholar 

  41. Ortner MA et al. (1998) Photodynamic therapy of nonresectable cholangiocarcinoma. Gastroenterology 114: 536–542

    Article  CAS  Google Scholar 

  42. Ortner MA (2000) Photodynamic therapy of nonresectable cholangiocellular carcinoma. Gastrointest Endosc Clin North Am 10: 481–486

    Article  CAS  Google Scholar 

  43. Berr F et al. (2000) Photodynamic therapy for advanced bile duct cancer: evidence for improved palliation and extended survival. Hepatology 31: 291–298

    Article  CAS  Google Scholar 

  44. Rumalla A et al. (2001) Endoscopic application of photodynamic therapy for cholangiocarcinoma. Gastrointest Endosc 53: 500–504

    Article  CAS  Google Scholar 

  45. Dumoulin FL et al. (2003) Phase II study of photodynamic therapy and metal stent as palliative treatment for nonresectable hilar cholangiocarcinoma. Gastrointest Endosc 57: 860–867

    Article  Google Scholar 

  46. Harewood GC et al. (2005) Pilot study to assess patient outcomes following endoscopic application of photodynamic therapy for advanced cholangiocarcinoma. J Gastroenterol Hepatol 20: 415–420

    Article  Google Scholar 

  47. Shim CS et al. (2005) Prospective study of the effectiveness of percutaneous transhepatic photodynamic therapy for advanced bile duct cancer and the role of intraductal ultrasonography in response assessment. Endoscopy 37: 425–433

    Article  CAS  Google Scholar 

  48. Bismuth H et al. (1992) Management strategies in resection for hilar cholangiocarcinoma. Ann Surg 215: 31–37

    Article  CAS  Google Scholar 

  49. Wiedmann M et al. (2004) Photodynamic therapy in patients with non-resectable hilar cholangiocarcinoma: 5-year follow-up of a prospective phase II study. Gastrointest Endosc 60: 68–75

    Article  Google Scholar 

  50. Zoepf T et al. (1999) Photodynamic therapy (PDT) for palliation of nonresectable bile duct cancer—first results with a new diode laser system. Am J Gastroenterol 96: 2093–2097

    Article  Google Scholar 

  51. Zoepf T et al. (2001) Photodynamic therapy with 5-aminolevulinic acid is not effective in bile duct cancer. Gastrointest Endosc 54: 763–764

    Article  CAS  Google Scholar 

  52. Ortner MA et al. (2003) Successful photodynamic therapy for nonresectable cholangiocarcinoma: a randomized prospective study. Gastroenterology 125: 1355–1363

    Article  Google Scholar 

  53. Zoepf T et al. (2005) Palliation of nonresectable bile duct cancer: improved survival after photodynamic therapy. Am J Gastroenterol 100: 2426–2430

    Article  CAS  Google Scholar 

  54. McCaughan JS Jr et al. (1991) Photodynamic therapy to treat tumors of the extrahepatic biliary ducts. A case report. Arch Surg 126: 111–113

    Article  Google Scholar 

  55. Nanashima A et al. (2004) Adjuvant photodynamic therapy for bile duct carcinoma after surgery: a preliminary study. J Gastroenterol 39: 1095–1101

    Article  Google Scholar 

  56. Wiedmann M et al. (2003) Neoadjuvant photodynamic therapy as a new approach to treating hilar cholangiocarcinoma. Cancer 97: 2783–2790

    Article  Google Scholar 

  57. Vauthey JN et al. (1994) Recent advances in the management of cholangiocarcinomas. Semin Liver Dis 14: 109–114

    Article  CAS  Google Scholar 

  58. Bisland SK et al. (2004) Metronomic photodynamic therapy as a new paradigm for photodynamic therapy: rationale and preclinical evaluation of technical feasibility for treating malignant brain tumors. Photochem Photobiol 80: 22–30

    Article  CAS  Google Scholar 

  59. Sylantiev C et al. (2005) Acute neuropathy mimicking prophyria induced by aminolevulinic acid during photodynamic therapy. Muscle Nerve 31: 390–393

    Article  Google Scholar 

  60. Frank J et al. (2006) Ascorbic acid suppresses cell death in rat DS-sarcoma cancer cells induced by 5-aminolevulinic acid-based photodynamic therapy. Free Radic Biol Med 40: 827–836

    Article  CAS  Google Scholar 

  61. Jakus J et al. (2005) Photosensitizers and antioxidants: a way to new drugs? Photochem Photobiol Sci 4: 694–69855

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors thank Professor André Blum for his helpful criticisms.

Author information

Authors and Affiliations

  1. chief (head) physicians in the Department for Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland

    Maria-Anna Ortner & Gian Dorta

Authors
  1. Maria-Anna Ortner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gian Dorta
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Maria-Anna Ortner.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ortner, MA., Dorta, G. Technology Insight: photodynamic therapy for cholangiocarcinoma. Nat Rev Gastroenterol Hepatol 3, 459–467 (2006). https://doi.org/10.1038/ncpgasthep0543

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncpgasthep0543

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing