- Email: [email protected]
Endoscopic stent placement combined with tumor ablation therapy
Gastrointest Interv 2015; 4:27–30
Contents lists available at ScienceDirect
Gastrointestinal Intervention journal homepage: www.gi-intervention.org
Invited Review Article
Endoscopic stent placement combined with tumor ablation therapy Rajesh Gupta, Duvvur Nageshwar Reddy* a b s t r a c t Palliative therapy of advanced pancreatobiliary cancers is focused primarily on biliary stenting in most patients. However, biliary stent occlusion or dysfunction is a main concern. Several types of stents are bleed designed and studied to improve stent function, but with limited success. Local ablative therapy, such as photodynamic therapy (PDT) and radiofrequency ablation (RFA) in combination with biliary stenting is a paradigm shift in the management of advanced pancreatobiliary malignancies. The current review analyzes the data on the role of combining either PDT or RFA with biliary stenting in inoperable pancreatobiliary malignancies. Copyright Ó 2015, Society of Gastrointestinal Intervention. Published by Elsevier. All rights reserved. Keywords: endoscopic stenting, pancreatobiliary cancers, photodynamic therapy, radiofrequency ablation
Introduction The management of pancreatobiliary cancers remains a formidable challenge.1 Surgery, if feasible, is the mainstay of treatment. However, the majority of patients present in an advanced stage of the disease, when only palliative therapy is feasible.2,3 In patients with unresectable disease, the main objective of palliative therapy is relief of biliary obstruction through endoscopic or radiological techniques, which include placement of plastic biliary stents, uncovered or covered self-expandable metallic stents (SEMS), or percutaneous transhepatic biliary drainage.4,5 These techniques have limited success, primarily due to stent occlusion or dysfunction. Two endoscopic modalities, photodynamic therapy (PDT) and radiofrequency ablation (RFA), have been used recently as palliative therapy, especially to improve stent patency.6 The main objective of this review is to discuss the role of PDT or RFA in combination with biliary stenting as palliative therapy for unresectable pancreatobiliary cancers. Photodynamic therapy PDT is a well-established therapeutic modality in oncology. It involves administration of a nontoxic photosensitizer that is preferentially retained by neoplastic tissue, which in turn, on activation by illuminating light of specific wavelength, causes ischemic necrosis of tumors.7 In an animal study, PDT was shown to reduce xenografted human cholangiocarcinoma tumor volume by more than 50%.8 These results generated further interest in PDT. Few uncontrolled human studies in unresectable cholangiocarcinoma
were carried out in which PDT was combined with biliary stenting.9–12 The results showed improvement in cholestasis and survival with few complications. Ortner et al13 published a first randomized prospective study comparing PDT in addition to biliary stenting with stenting alone. The results of this study were so impressive in favor of PDT with stenting, the study was terminated prematurely. However, this study has a major limitation because it included the majority of those patients in whom technically successful biliary stenting did not result in successful biliary drainage. Subsequently, Kahaleh et al14 compared efficacy of PDT with biliary stenting with biliary stenting alone in patients with unresectable cholangiocarcinoma. Their results were similar (median survival 16.2 months vs. 7.4 months, P < 0.04) to those of Ortner et al,13 in which significant median survival was observed after PDT (16.4 months vs. 3.3 months, P < 0.0001). However, patients in this study were different from those in the study of Ortner et al,13 because all patients who underwent both successful or unsuccessful biliary drainage were included. PDT has also been used as ablative therapy in inoperable pancreatic ductal adenocarcinoma. In a previous study of 16 patients with inoperable pancreatic carcinoma, substantial tumor necrosis was shown in all patients.15 Median survival after PDT was 9.5 months. Seven of 16 patients (44%) were alive 1 year after PDT. Significant gastrointestinal bleeding from the gastroduodenal artery developed in two patients and was managed endoscopically. Tumors of the head of the pancreas commonly cause distal biliary obstruction, which is managed by endoscopic biliary stenting using either plastic or SEMS in most cases. The patency of SEMS is a major challenge. Local ablative techniques such as PDT have
Department of Medical Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India Received 10 January 2015; Revised 30 April 2015; Accepted 8 May 2015 * Corresponding author. Chairman, Department of Medical Gastroenterology, Asian Institute of Gastroenterology, 6-3-661 Somajiguda, Hyderabad 500082, India. E-mail address: [email protected] (D.N. Reddy).
2213-1795/$ – see front matter Copyright Ó 2015, Society of Gastrointestinal Intervention. Published by Elsevier. All rights reserved. http://dx.doi.org/10.1016/j.gii.2015.05.001
28
Gastrointestinal Intervention 2015 4(1), 27–30
been used to prolong stent patency or to unblock SEMS in situ with promising results. However, the results are still conflicting.
Radiofrequency ablation RFA is an effective local ablative therapy that has been used extensively in many solid organ malignancies, especially in hepatocellular carcinoma. It works by emitting heat energy via a bipolar probe by using high-frequency alternating current, which in turn causes localized tissue necrosis. Previous studies using percutaneous and intraoperative RFA in unresectable cholangiocarcinoma and pancreatic cancer have shown impressive results and significant survival advantage over both chemotherapy and supportive care.16 Recently, there is a growing interest in the role of RFA in palliation of pancreatobiliary cancers with the advent of endoscopic RFA catheters. There are two types of endobiliary RFA probes currently available; Habib Endo HPB (EMcision, London, UK) and Endobilary RFA catheter (Starmed, Seoul, Korea). Both are wire– guided, bipolar probes that can be passed through the working channel of a therapeutic duodenoscope. Steel et al17 published their experience of treating endobiliary RFA in 22 patients with malignant biliary obstruction (16 pancreatic patients and 6 cholangiocarcinoma patients). Deployment of the RFA catheter was successful in 21 patients. Biliary SEMS were placed in all patients after RFA. One patient failed to demonstrate successful biliary drainage after SEMS placement. All other patients maintained stent patency at 30 days. At 90 days follow up, stent occlusion developed in three patients and one more patient died. Since then, few other series have demonstrated the safety and efficacy of endobiliary RFA. Our own experience of endobiliary RFA in inoperable pancreatobiliary tumors has been promising.18 We performed cholangioscopic evaluation of bile ducts before and after endobiliary RFA in patients with inoperable cholangiocarcinoma (Figs. 1 and 2). Significant resolution of biliary stricture occured. The first application of RFA in an animal pancreas was reported in 1999 and was found to be safe.19 However, the results of early clinical applications of RFA in a human pancreas were disappointing and were associated with high morbidity (up to 40%) and mortality (up to 25%).20–25 Most of the complications arose as a result of inadvertent injury to adjacent structures. Subsequently, based on the thermal kinetics of RFA, the temperature settings of RFA were changed and reduced from 105 C to 90 C. This change significantly decreased RFA-related complications.26 Deployment of SEMS is the standard of care for patients with inoperable malignant biliary obstruction if life expectancy is >3 months. However, stent occlusion remains a problem that requires further interventions in >50% of patients. To maintain patency of SEMS, several therapeutic options have been studied, such as placements of another SEMS or plastic stent, PTD and RFA. Endoscopically applied RFA combined with biliary SEMS has been found to be well tolerated, safe, and appears to improve stent patency.16,21,22 We would further emphasize that endobiliary RFA has been applied in the management of inoperable cholangiocarcinoma and pancreatic cancer. Although RFA is a user-friendly technique, it has some limitations. Because RFA causes coagulative necrosis of tissue by direct contact, there is a possibility of incomplete contact of the lesion with the probe, which may affect the efficacy of the procedure. As demonstrated earlier, there is a linear relationship between energy delivered and depth of ablation. However, there is no standardized optimal dose of thermal energy and duration. Most of the studies have used RFA generator settings as recommended by the beneficiary. One interesting observation in these studies is improvement in survival.26,27
Fig. 1. Before radiofrequency ablation (A) Cholangiogram shows biliary stricture. (B) Cholangioscopic image also shows biliary stricture.
This observation needs further validation. To understand the mechanism and effect of RFA as ablative therapy, one must look beyond local thermal injury. In this regard, the role of proinflammatory cytokines and immune modulation needs to be studied further. We would also like to emphasize that there is a need to generate more data. PDT versus RFA Both PDT and RFA have been used as ablative therapy with and without stent placement. Both modalities have advantages and limitations. PDT has been used more extensively and showed significant improvement in survival and relief from cholestasis. However, the high cost and photosensitivity are major limitations of PDT. By contract endobiliary RFA is evolving and many studies are underway as the more data are needed. The major advantages of RFA are its relatively low cost and user-friendly technique. In a recent study, Strand et al27 compared overall survival in 48 patients with unresectable cholangiocarcinoma who underwent palliative endoscopic retrograde cholangiopancreatography-directed RFA (16 patients) versus PDT (32 patients).27 Overall, survival of patients who underwent RFA was similar to that of those who underwent
Rajesh Gupta and Duvvur Nageshwar Reddy / Endoscopic stent placement
29
unresectable malignant biliary obstruction. Hence, combining local ablative therapy with biliary stenting is a rational approach. However, there is a need to generate more data. Conflicts of interest There is no conflict of interest.
References
Fig. 2. After radiofrequency ablation (A) Cholangiogram shows improvement of biliary stricture. (B) Cholangioscopic image also shows improvement of biliary stricture.
PDT (median 9.6 months vs. 7.5 months). However, there was huge difference in the cost of PDT and RFA. Though there were more episodes of stent occlusion and cholangitis in the RFA group, yet other adverse events were low and comparable in both groups. The major limitation of this study is retrospective analysis, single center experience, and small sample size. Currently, there is no randomized controlled prospective study in this area. Hence, there are still several unanswered questions. Should all patients of unresectable cholangiocarcinoma be offered local ablative therapy? Is ablative therapy combined with biliary stent superior to stenting alone? Does the site of cholangiocarcinoma affect the result of therapy? What are the predictors of response? We need more robust data to answer all these questions. In a recent editorial, we have argued that there is a need to go beyond biliary stenting in advanced cholangiocarcinoma.28 Conclusion Both PDT and endobiliary RFA are effective palliative therapy in advanced inoperable malignant biliary obstruction. The deployment of biliary plastic or SEMS is the standard of care for
1. de Groen PC, Gores GJ, LaRusso NF, Gunderson LL, Nagorney DM. Biliary tract cancers. N Engl J Med. 1999;341:1368–78. 2. Jarnagin WR, Fong Y, DeMatteo RP, Gonen M, Burke EC, Bodniewicz BSJ, et al. Staging, resectability, and outcome in 225 patients with hilar cholangiocarcinoma. Ann Surg. 2001;234:507–17. 3. Reed DN Jr, Vitale GC, Martin R, Bas H, Wieman TJ, Larson GM, et al. Bile duct carcinoma: trends in treatment in the nineties. Am Surg. 2000;66:711–4. 4. Farley DR, Weaver AL, Nagorney DM. “Natural history” of unresected cholangiocarcinoma: patient outcome after noncurative intervention. Mayo Clin Proc. 1995;70:425–9. 5. Deviere J, Baize M, de Toeuf J, Cremer M. Long-term follow-up of patients with hilar malignant stricture treated by endoscopic internal biliary drainage. Gastrointest Endosc. 1988;34:95–101. 6. Keane MG, Bramis K, Pereira SP, Fusa GK. Systematic review of novel ablative methods in locally advanced pancreatic cancer. World J Gastroenterol. 2014;7: 2267–78. 7. Webber J, Herman M, Kessel D, Fromm D. Current concepts in gastrointestinal photodynamic therapy. Ann Surg. 1999;230:12–23. 8. Wong Kee Song LM, Wang KK, Zinsmeister AR. Mono-L-aspartyl chlorin e6 (NPe6) and hematoporphyrin derivative (HpD) in photodynamic therapy administered to a human cholangiocarcinoma model. Cancer. 1998;82:421–7. 9. Berr F, Wiedmann M, Tannapfel A, Halm U, Kohlhaw KR, Schmidt F, et al. Photodynamic therapy for advanced bile duct cancer: evidence for improved palliation and extended survival. Hepatology. 2000;31:291–8. 10. Witzigmann H, Berr F, Ringel U, Caca K, Uhlmann D, Schoppmeyer K, 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. Ann Surg. 2006;244:230–9. 11. Zoepf T, Jakobs R, Arnold JC, Apel D, Riemann JF. Palliation of nonresectable bile duct cancer: improved survival after photodynamic therapy. Am J Gastroenterol. 2005;100:2426–30. 12. Leggett CL, Gorospe EC, Murad MH, Montori VM, Baron TH, Wang KK. Photodynamic therapy for unresectable cholangiocarcinoma: a comparative effectiveness systemic review and meta-analyses. Photodiagnosis Photodyn Ther. 2012;9:189–95. 13. Ortner ME, Caca K, Berr F, Liebetruth J, Mansmann U, Huster D, et al. Successful photodynamic therapy for non resectable cholangiocarcinoma: a randomized prospective study. Gastroenterology. 2003;125:1355–63. 14. Kahaleh M, Mishra R, Shami VM, Northup PG, Berg CL, Bashlor P, et al. Unresectable cholangiocarcinoma: comparison of survival in biliary stenting alone versus stenting with photodynamic therapy. Clin Gastroenterol Hepatol. 2008;6:290–7. 15. Bown SG, Rogowska AZ, Whitelaw DE, Lees WR, Lovat LB, Ripley P, et al. Photodynamic therapy for cancer of the pancreas. Gut. 2002;50:549–57. 16. Figueroa-Barojas P, Bakhru MR, Habib NA, Ellen K, Millman J, Jamal-Kabani A, et al. Safety and efficacy of radiofrequency ablation in the management of unresectable bile duct and pancreatic cancer: a novel palliation technique. J Oncol. 2013;2013:910897. 17. Steel AW, Postgate AJ, Khorsandi S, Nicholls J, Jiao L, Vlavianos P, et al. Endoscopically applied radiofrequency ablation appears to be safe in the treatment of malignant biliary obstruction. Gastrointest Endosc. 2011;73:149–53. 18. Monga A, Gupta R, Ramchandani M, Rao GV, Santosh D, Reddy DN. Endoscopic radiofrequency ablation of cholangiocarcinoma: new palliative treatment modality (with videos). Gastrointest Endosc. 2011;74:935–7. 19. Goldberg SN, Mallery S, Gazelle GS, Brugge WR. EUS-guided radiofrequency ablation in the pancreas: results in a porcine model. Gastrointest Endosc. 1999; 50:392–401. 20. Girelli R, Frigerio I, Salvia R, Barbi E, Tinazzi Martini P, Bassi C. Feasibility and safety of radiofrequency ablation for locally advanced pancreatic cancer. Br J Surg. 2010;97:220–5. 21. Matsui Y, Nakagawa A, Kamiyama Y, Yamamoto K, Kubo N, Nakase Y. Selective thermocoagulation of unresectable pancreatic cancers by using radiofrequency capacitive heating. Pancreas. 2000;20:14–20. 22. Hadjicostas P, Malakounides N, Varianos C, Kitiris E, Lerni F, Symeonides P. Radiofrequency ablation in pancreatic cancer. HPB (Oxford). 2006;8:61–4. 23. Gaidhane M, Smith I, Ellen K, Gatesman J, Habib N, Foley P, et al. Endoscopic ultrasound – guided radiofrequency ablation (EUS-RFA) of the pancreas in a porcine model. Gastoenterol Res Pract. 2012;2012:431451. 24. Daglilar ES, Yoon WJ, Mino-Kenudson M, Brugge WR. Controlled swine bile duct ablation with a bipolar radiofrequency catheter. Gastrointest Endosc. 2013; 77:815–9.
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25. Varshney S, Sewkani A, Sharma S, Kapoor S, Naik S, Sharma A, et al. Radiofrequency ablation of unresectable pancreatic carcinoma: feasibility, efficacy and safety. JOP. 2006;7:74–8. 26. Date RS, McMahon RF, Siriwardena AK. Radiofrequency ablation of the pancreas. I: Definition of optimal thermal kinetic parameters and the effect of simulated portal venous circulation in an ex-vivo porcine model. JOP. 2005;6: 581–7.
27. Strand DS, Cosgrove ND, Patrie JT, Cox DG, Bauer TW, Adams RB, et al. ERCPdirected radiofrequency ablation and photodynamic therapy are associated with comparable survival in the treatment of unresectable cholangiocarcinoma. Gastrointest Endosc. 2014;80:794–804. 28. Reddy DN, Ramachandani M. Endoscopic palliation of advanced Cholangiocarcinoma: can we go beyond stenting? Gastrointest Endosc. 2014;80: 805–6.
Contents lists available at ScienceDirect
Gastrointestinal Intervention journal homepage: www.gi-intervention.org
Invited Review Article
Endoscopic stent placement combined with tumor ablation therapy Rajesh Gupta, Duvvur Nageshwar Reddy* a b s t r a c t Palliative therapy of advanced pancreatobiliary cancers is focused primarily on biliary stenting in most patients. However, biliary stent occlusion or dysfunction is a main concern. Several types of stents are bleed designed and studied to improve stent function, but with limited success. Local ablative therapy, such as photodynamic therapy (PDT) and radiofrequency ablation (RFA) in combination with biliary stenting is a paradigm shift in the management of advanced pancreatobiliary malignancies. The current review analyzes the data on the role of combining either PDT or RFA with biliary stenting in inoperable pancreatobiliary malignancies. Copyright Ó 2015, Society of Gastrointestinal Intervention. Published by Elsevier. All rights reserved. Keywords: endoscopic stenting, pancreatobiliary cancers, photodynamic therapy, radiofrequency ablation
Introduction The management of pancreatobiliary cancers remains a formidable challenge.1 Surgery, if feasible, is the mainstay of treatment. However, the majority of patients present in an advanced stage of the disease, when only palliative therapy is feasible.2,3 In patients with unresectable disease, the main objective of palliative therapy is relief of biliary obstruction through endoscopic or radiological techniques, which include placement of plastic biliary stents, uncovered or covered self-expandable metallic stents (SEMS), or percutaneous transhepatic biliary drainage.4,5 These techniques have limited success, primarily due to stent occlusion or dysfunction. Two endoscopic modalities, photodynamic therapy (PDT) and radiofrequency ablation (RFA), have been used recently as palliative therapy, especially to improve stent patency.6 The main objective of this review is to discuss the role of PDT or RFA in combination with biliary stenting as palliative therapy for unresectable pancreatobiliary cancers. Photodynamic therapy PDT is a well-established therapeutic modality in oncology. It involves administration of a nontoxic photosensitizer that is preferentially retained by neoplastic tissue, which in turn, on activation by illuminating light of specific wavelength, causes ischemic necrosis of tumors.7 In an animal study, PDT was shown to reduce xenografted human cholangiocarcinoma tumor volume by more than 50%.8 These results generated further interest in PDT. Few uncontrolled human studies in unresectable cholangiocarcinoma
were carried out in which PDT was combined with biliary stenting.9–12 The results showed improvement in cholestasis and survival with few complications. Ortner et al13 published a first randomized prospective study comparing PDT in addition to biliary stenting with stenting alone. The results of this study were so impressive in favor of PDT with stenting, the study was terminated prematurely. However, this study has a major limitation because it included the majority of those patients in whom technically successful biliary stenting did not result in successful biliary drainage. Subsequently, Kahaleh et al14 compared efficacy of PDT with biliary stenting with biliary stenting alone in patients with unresectable cholangiocarcinoma. Their results were similar (median survival 16.2 months vs. 7.4 months, P < 0.04) to those of Ortner et al,13 in which significant median survival was observed after PDT (16.4 months vs. 3.3 months, P < 0.0001). However, patients in this study were different from those in the study of Ortner et al,13 because all patients who underwent both successful or unsuccessful biliary drainage were included. PDT has also been used as ablative therapy in inoperable pancreatic ductal adenocarcinoma. In a previous study of 16 patients with inoperable pancreatic carcinoma, substantial tumor necrosis was shown in all patients.15 Median survival after PDT was 9.5 months. Seven of 16 patients (44%) were alive 1 year after PDT. Significant gastrointestinal bleeding from the gastroduodenal artery developed in two patients and was managed endoscopically. Tumors of the head of the pancreas commonly cause distal biliary obstruction, which is managed by endoscopic biliary stenting using either plastic or SEMS in most cases. The patency of SEMS is a major challenge. Local ablative techniques such as PDT have
Department of Medical Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India Received 10 January 2015; Revised 30 April 2015; Accepted 8 May 2015 * Corresponding author. Chairman, Department of Medical Gastroenterology, Asian Institute of Gastroenterology, 6-3-661 Somajiguda, Hyderabad 500082, India. E-mail address: [email protected] (D.N. Reddy).
2213-1795/$ – see front matter Copyright Ó 2015, Society of Gastrointestinal Intervention. Published by Elsevier. All rights reserved. http://dx.doi.org/10.1016/j.gii.2015.05.001
28
Gastrointestinal Intervention 2015 4(1), 27–30
been used to prolong stent patency or to unblock SEMS in situ with promising results. However, the results are still conflicting.
Radiofrequency ablation RFA is an effective local ablative therapy that has been used extensively in many solid organ malignancies, especially in hepatocellular carcinoma. It works by emitting heat energy via a bipolar probe by using high-frequency alternating current, which in turn causes localized tissue necrosis. Previous studies using percutaneous and intraoperative RFA in unresectable cholangiocarcinoma and pancreatic cancer have shown impressive results and significant survival advantage over both chemotherapy and supportive care.16 Recently, there is a growing interest in the role of RFA in palliation of pancreatobiliary cancers with the advent of endoscopic RFA catheters. There are two types of endobiliary RFA probes currently available; Habib Endo HPB (EMcision, London, UK) and Endobilary RFA catheter (Starmed, Seoul, Korea). Both are wire– guided, bipolar probes that can be passed through the working channel of a therapeutic duodenoscope. Steel et al17 published their experience of treating endobiliary RFA in 22 patients with malignant biliary obstruction (16 pancreatic patients and 6 cholangiocarcinoma patients). Deployment of the RFA catheter was successful in 21 patients. Biliary SEMS were placed in all patients after RFA. One patient failed to demonstrate successful biliary drainage after SEMS placement. All other patients maintained stent patency at 30 days. At 90 days follow up, stent occlusion developed in three patients and one more patient died. Since then, few other series have demonstrated the safety and efficacy of endobiliary RFA. Our own experience of endobiliary RFA in inoperable pancreatobiliary tumors has been promising.18 We performed cholangioscopic evaluation of bile ducts before and after endobiliary RFA in patients with inoperable cholangiocarcinoma (Figs. 1 and 2). Significant resolution of biliary stricture occured. The first application of RFA in an animal pancreas was reported in 1999 and was found to be safe.19 However, the results of early clinical applications of RFA in a human pancreas were disappointing and were associated with high morbidity (up to 40%) and mortality (up to 25%).20–25 Most of the complications arose as a result of inadvertent injury to adjacent structures. Subsequently, based on the thermal kinetics of RFA, the temperature settings of RFA were changed and reduced from 105 C to 90 C. This change significantly decreased RFA-related complications.26 Deployment of SEMS is the standard of care for patients with inoperable malignant biliary obstruction if life expectancy is >3 months. However, stent occlusion remains a problem that requires further interventions in >50% of patients. To maintain patency of SEMS, several therapeutic options have been studied, such as placements of another SEMS or plastic stent, PTD and RFA. Endoscopically applied RFA combined with biliary SEMS has been found to be well tolerated, safe, and appears to improve stent patency.16,21,22 We would further emphasize that endobiliary RFA has been applied in the management of inoperable cholangiocarcinoma and pancreatic cancer. Although RFA is a user-friendly technique, it has some limitations. Because RFA causes coagulative necrosis of tissue by direct contact, there is a possibility of incomplete contact of the lesion with the probe, which may affect the efficacy of the procedure. As demonstrated earlier, there is a linear relationship between energy delivered and depth of ablation. However, there is no standardized optimal dose of thermal energy and duration. Most of the studies have used RFA generator settings as recommended by the beneficiary. One interesting observation in these studies is improvement in survival.26,27
Fig. 1. Before radiofrequency ablation (A) Cholangiogram shows biliary stricture. (B) Cholangioscopic image also shows biliary stricture.
This observation needs further validation. To understand the mechanism and effect of RFA as ablative therapy, one must look beyond local thermal injury. In this regard, the role of proinflammatory cytokines and immune modulation needs to be studied further. We would also like to emphasize that there is a need to generate more data. PDT versus RFA Both PDT and RFA have been used as ablative therapy with and without stent placement. Both modalities have advantages and limitations. PDT has been used more extensively and showed significant improvement in survival and relief from cholestasis. However, the high cost and photosensitivity are major limitations of PDT. By contract endobiliary RFA is evolving and many studies are underway as the more data are needed. The major advantages of RFA are its relatively low cost and user-friendly technique. In a recent study, Strand et al27 compared overall survival in 48 patients with unresectable cholangiocarcinoma who underwent palliative endoscopic retrograde cholangiopancreatography-directed RFA (16 patients) versus PDT (32 patients).27 Overall, survival of patients who underwent RFA was similar to that of those who underwent
Rajesh Gupta and Duvvur Nageshwar Reddy / Endoscopic stent placement
29
unresectable malignant biliary obstruction. Hence, combining local ablative therapy with biliary stenting is a rational approach. However, there is a need to generate more data. Conflicts of interest There is no conflict of interest.
References
Fig. 2. After radiofrequency ablation (A) Cholangiogram shows improvement of biliary stricture. (B) Cholangioscopic image also shows improvement of biliary stricture.
PDT (median 9.6 months vs. 7.5 months). However, there was huge difference in the cost of PDT and RFA. Though there were more episodes of stent occlusion and cholangitis in the RFA group, yet other adverse events were low and comparable in both groups. The major limitation of this study is retrospective analysis, single center experience, and small sample size. Currently, there is no randomized controlled prospective study in this area. Hence, there are still several unanswered questions. Should all patients of unresectable cholangiocarcinoma be offered local ablative therapy? Is ablative therapy combined with biliary stent superior to stenting alone? Does the site of cholangiocarcinoma affect the result of therapy? What are the predictors of response? We need more robust data to answer all these questions. In a recent editorial, we have argued that there is a need to go beyond biliary stenting in advanced cholangiocarcinoma.28 Conclusion Both PDT and endobiliary RFA are effective palliative therapy in advanced inoperable malignant biliary obstruction. The deployment of biliary plastic or SEMS is the standard of care for
1. de Groen PC, Gores GJ, LaRusso NF, Gunderson LL, Nagorney DM. Biliary tract cancers. N Engl J Med. 1999;341:1368–78. 2. Jarnagin WR, Fong Y, DeMatteo RP, Gonen M, Burke EC, Bodniewicz BSJ, et al. Staging, resectability, and outcome in 225 patients with hilar cholangiocarcinoma. Ann Surg. 2001;234:507–17. 3. Reed DN Jr, Vitale GC, Martin R, Bas H, Wieman TJ, Larson GM, et al. Bile duct carcinoma: trends in treatment in the nineties. Am Surg. 2000;66:711–4. 4. Farley DR, Weaver AL, Nagorney DM. “Natural history” of unresected cholangiocarcinoma: patient outcome after noncurative intervention. Mayo Clin Proc. 1995;70:425–9. 5. Deviere J, Baize M, de Toeuf J, Cremer M. Long-term follow-up of patients with hilar malignant stricture treated by endoscopic internal biliary drainage. Gastrointest Endosc. 1988;34:95–101. 6. Keane MG, Bramis K, Pereira SP, Fusa GK. Systematic review of novel ablative methods in locally advanced pancreatic cancer. World J Gastroenterol. 2014;7: 2267–78. 7. Webber J, Herman M, Kessel D, Fromm D. Current concepts in gastrointestinal photodynamic therapy. Ann Surg. 1999;230:12–23. 8. Wong Kee Song LM, Wang KK, Zinsmeister AR. Mono-L-aspartyl chlorin e6 (NPe6) and hematoporphyrin derivative (HpD) in photodynamic therapy administered to a human cholangiocarcinoma model. Cancer. 1998;82:421–7. 9. Berr F, Wiedmann M, Tannapfel A, Halm U, Kohlhaw KR, Schmidt F, et al. Photodynamic therapy for advanced bile duct cancer: evidence for improved palliation and extended survival. Hepatology. 2000;31:291–8. 10. Witzigmann H, Berr F, Ringel U, Caca K, Uhlmann D, Schoppmeyer K, 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. Ann Surg. 2006;244:230–9. 11. Zoepf T, Jakobs R, Arnold JC, Apel D, Riemann JF. Palliation of nonresectable bile duct cancer: improved survival after photodynamic therapy. Am J Gastroenterol. 2005;100:2426–30. 12. Leggett CL, Gorospe EC, Murad MH, Montori VM, Baron TH, Wang KK. Photodynamic therapy for unresectable cholangiocarcinoma: a comparative effectiveness systemic review and meta-analyses. Photodiagnosis Photodyn Ther. 2012;9:189–95. 13. Ortner ME, Caca K, Berr F, Liebetruth J, Mansmann U, Huster D, et al. Successful photodynamic therapy for non resectable cholangiocarcinoma: a randomized prospective study. Gastroenterology. 2003;125:1355–63. 14. Kahaleh M, Mishra R, Shami VM, Northup PG, Berg CL, Bashlor P, et al. Unresectable cholangiocarcinoma: comparison of survival in biliary stenting alone versus stenting with photodynamic therapy. Clin Gastroenterol Hepatol. 2008;6:290–7. 15. Bown SG, Rogowska AZ, Whitelaw DE, Lees WR, Lovat LB, Ripley P, et al. Photodynamic therapy for cancer of the pancreas. Gut. 2002;50:549–57. 16. Figueroa-Barojas P, Bakhru MR, Habib NA, Ellen K, Millman J, Jamal-Kabani A, et al. Safety and efficacy of radiofrequency ablation in the management of unresectable bile duct and pancreatic cancer: a novel palliation technique. J Oncol. 2013;2013:910897. 17. Steel AW, Postgate AJ, Khorsandi S, Nicholls J, Jiao L, Vlavianos P, et al. Endoscopically applied radiofrequency ablation appears to be safe in the treatment of malignant biliary obstruction. Gastrointest Endosc. 2011;73:149–53. 18. Monga A, Gupta R, Ramchandani M, Rao GV, Santosh D, Reddy DN. Endoscopic radiofrequency ablation of cholangiocarcinoma: new palliative treatment modality (with videos). Gastrointest Endosc. 2011;74:935–7. 19. Goldberg SN, Mallery S, Gazelle GS, Brugge WR. EUS-guided radiofrequency ablation in the pancreas: results in a porcine model. Gastrointest Endosc. 1999; 50:392–401. 20. Girelli R, Frigerio I, Salvia R, Barbi E, Tinazzi Martini P, Bassi C. Feasibility and safety of radiofrequency ablation for locally advanced pancreatic cancer. Br J Surg. 2010;97:220–5. 21. Matsui Y, Nakagawa A, Kamiyama Y, Yamamoto K, Kubo N, Nakase Y. Selective thermocoagulation of unresectable pancreatic cancers by using radiofrequency capacitive heating. Pancreas. 2000;20:14–20. 22. Hadjicostas P, Malakounides N, Varianos C, Kitiris E, Lerni F, Symeonides P. Radiofrequency ablation in pancreatic cancer. HPB (Oxford). 2006;8:61–4. 23. Gaidhane M, Smith I, Ellen K, Gatesman J, Habib N, Foley P, et al. Endoscopic ultrasound – guided radiofrequency ablation (EUS-RFA) of the pancreas in a porcine model. Gastoenterol Res Pract. 2012;2012:431451. 24. Daglilar ES, Yoon WJ, Mino-Kenudson M, Brugge WR. Controlled swine bile duct ablation with a bipolar radiofrequency catheter. Gastrointest Endosc. 2013; 77:815–9.
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