Photodynamic Therapy For Cholangiocarcinoma Research Articles

Photodynamic therapy for cholangiocarcinoma using low dose mTHPC (Foscan®)

Photodynamic therapy (PDT) combined with stenting is an effective treatment modality for palliation of nonresectable cholangiocarcinoma (CC). A drawback of standard PDT using Photofrin(®) as photosensitizer is the long lasting skin photosensitivity of up to 3 months. The aim of this study was to show the outcome of PDT of CC, potential side effects and to determine the best drug light interval (DLI) using mTHPC (Foscan(®)) at a low dose. 13 patients with nonresectable CC were treated with stenting and PDT (3mg Foscan(®) per treatment, 0.032-0.063 mg/kg body weight, 652 nm, 50 J/cm). Fluorescence measurements were performed with a single bare fiber for 5/13 patients prior to PDT at the tumor site to determine the fluorescence contrast. For another 7/13 patients, long-term fluorescence-kinetics were measured on the oral mucosa to determine the time of maximal relative fluorescence intensity. The results so far indicate a median survival time of 13 months. Side effects such as perforations or skin phototoxicity could not be observed. Foscan(®) fluorescence within the tumor site was clearly detectable but a significant fluorescence contrast of tumor to adjacent healthy tissue could not be found. The fluorescence kinetics measured in the oral mucosa showed a maximum at 3.85 days (median) after drug administration. Combined stenting and PDT performed with a low Foscan(®) dose results in equal and potentially longer survival times compared to standard Photofrin(®) PDT, while lowering the risk of side effects strongly. Thus it may improve the quality of life.

Photodynamic Therapy in Cholangiocarcinoma

Most patients with hilar cholangiocarcinoma have unresectable disease and require palliation with biliary stenting to alleviate symptoms. Although chemotherapy and radiotherapy have been ineffective, many studies have suggested that the use of photodynamic therapy (PDT) may improve quality of life and perhaps survival in these patients. The ability of PDT to transmit through bile makes it a unique platform for intervention in the biliary tree. This article addresses the clinical implications of endoscopic biliary drainage, explores past and present study findings with PDT for cholangiocarcinoma, and offers an introduction to the novel techniques for direct visualization.

Photodynamic therapy for unresectable cholangiocarcinoma: contribution of single operator cholangioscopy for targeted treatment

Photodynamic therapy (PDT) for unresectable cholangiocarcinoma is associated with improvement in cholestasis and survival. Single operator cholangioscopy (SOC) has been used for targeted laser illumination. We analyzed our growing experience of SOC with direct PDT. This is a retrospective analysis of a consecutive series of patients prospectively entered into a registry. Forty-five patients (24 male, aged 67.3 ± 10.6 years) were treated with PDT for cholangiocarcinoma during a five-year period. Thirty-two patients were treated with ERCP and PDT alone, and 13 were treated with ERCP and PDT using SOC. The two groups were then compared to observe any statistically significant difference in regards to age, gender, serum bilirubin, MELD score, adverse effects, or survival. An overall median of 1 PDT session per patient (range: 1-9) was performed. Twenty-six total sessions of PDT using SOC were performed in 13 patients with a median of 2.0 sessions per patient (range: 1-6). Median global survival was 168 days (range: 26-1353). Median survival for the PDT-only group was 200 days, and median survival for the PDT-with-SOC group was 386 days (p = 0.45). There was a statistically significant difference (p < 0.0001) between the two groups in regards to fluoroscopy time, with the PDT-only group having a median time of 21.1 min and the PDT-with-SOC group having a median time of 11.1 min. PDT related complications included 7 cases of mild phototoxicity and one case of moderate phototoxicity requiring hospitalization. SOC permits targeted therapy during PDT and can be successfully performed without adverse events while simultaneously reducing exposure to radiation.

Photodynamic therapy for cholangiocarcinoma by percutaneous transhepatic access

Photodynamic therapy for cholangiocarcinoma by percutaneous transhepatic access

Photodynamic therapy for cholangiocarcinoma.

Cholangiocarcinoma is the primary malignancy arising from the biliary epithelium, and it presents as jaundice, cholestasis, and cholangitis. Over 50 percent of patients present with advanced-stage disease, and the prognosis is poor with the survival measured in months even after biliary decompression. Palliative management has become the standard of care for unresectable disease, and this involves an endoscopic approach. Photodynamic therapy (PDT) involves the administration of a photosensitizer followed by local irradiation with laser therapy. The use of PDT for palliation of bile-duct tumors has produced promising results. Several studies conducted in Europe and the United States have shown that PDT produces a marked improvement in the symptoms of cholestasis, survival, and quality of life. This chapter summarizes the principle of PDT, the technique employed, and the published experience regarding PDT for cholangiocarcinoma.

Photodynamic therapy: Palliation and endoscopic technique in cholangiocarcinoma

Cholangiocarcinoma is the primary malignancy arising from the biliary epithelium. The disease is marked by jaundice, cholestasis, and cholangitis. Over 50 percent of patients present with advanced stage disease, precluding curative surgical resection as an option of treatment. Prognosis is poor, and survival has been limited even after biliary decompression. Palliative management has become the standard of care for unresectable disease and has evolved to include an endoscopic approach. Photodynamic therapy (PDT) consists of administration of a photosensitizer followed by local irradiation with laser therapy. Several studies conducted in Europe and the United States have shown a marked improvement in the symptoms of cholestasis, survival, and quality of life. This article summarizes the published experience regarding PDT for cholangiocarcinoma and the steps required to administer this therapy safely.

Photodynamic therapy for cholangiocarcinoma: overview and new developments

Photodynamic therapy (PDT) with hematoporphyrins has emerged as promising treatment for nonresectable cholangiocarcinoma in several prospective observational studies and two randomized studies. This review describes the mechanism of action of PDT, gives an overview of clinical experience in cholangiocarcinoma and summarizes the results published in 2007 and 2008. The mechanism of action of PDT has been further elucidated. PDT induces an apoptotic, antiangiogenic as well as an immunomodulatory response. Interleukin-6, a bile duct epithelium growth factor correlating with tumor burden, decreases after PDT. The efficacy of PDT was confirmed in a comparative study in the United States. Patients with no visible mass on imaging studies, high serum albumin levels and treatment immediately after diagnosis seem to benefit most from PDT. Although it is recommended to perform PDT in bile ducts without stents in place, illumination through metal stents is possible if the light dose is adjusted. Meso-tetrahydroxyphenyl chlorine is a new potent photosensitizer for PDT of cholangiocarcinoma. In advanced nonresectable cholangiocarcinoma, PDT is the only evidence-based treatment that improves survival when compared with stenting. Therefore, PDT should be offered to those who are unsuitable for surgery.

Factors Associated With Increased Survival After Photodynamic Therapy for Cholangiocarcinoma

Recent studies have shown a survival advantage using photodynamic therapy (PDT) in patients with unresectable cholangiocarcinoma. Factors associated with increased survival after PDT are unknown. Twenty-five patients with cholangiocarcinoma who were treated with PDT at the Mayo Clinic Rochester from 1991 to 2004 were studied. Porfimer sodium (2 mg/kg) was administered intravenously to patients with Bismuth type I (3 patients), type III a/b (13 patients), and type IV (9 patients) tumors. Forty-eight hours later, PDT was administered using a 1.5- to 2.5-cm diffusing fiber that was advanced across the tumor by either retrograde (20 patients) or percutaneous (5 patients) cholangiography. Laser light was applied for a total energy of 180 J/cm2 in 1-3 applications. Patients received PDT treatments every 3 months. Plastic biliary stents (10-11.5 F) were inserted to decompress the biliary system after PDT. Survival analysis was performed using Kaplan-Meier curves and Cox proportional hazards models. Patients were 64 (standard error of the mean, +/-2.6) years of age; 20 (80%) were men. The median overall survival period was 344 days. The median survival period after PDT was 214 days. The 1-year survival rate was 30%. On multivariate analysis, the presence of a visible mass on imaging studies (hazard ratio, 3.55; 95% confidence interval, 1.21-10.38), and increasing time between diagnosis and PDT (hazard ratio, 1.13; 95% confidence interval, 1.02-1.25) predicted a poorer survival rate after PDT. A higher serum albumin level (hazard ratio, 0.16; 95% confidence interval, 0.04-0.59) predicted a lower mortality rate after PDT. Patients with unresectable cholangiocarcinoma without a visible mass may benefit from earlier treatment with PDT.

Technology Insight: photodynamic therapy for cholangiocarcinoma

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.

A novel agent to potentiate photodynamic therapy of cholangiocarcinoma

A novel agent to potentiate photodynamic therapy of cholangiocarcinoma

4613 Endoscopic application of photodynamic therapy for cholangiocarcinoma.

Background: Preliminary evidence from Europe indicates that photodynamic therapy (PDT) provides effective relief from biliary obstruction in advanced cholangiocarcinoma.We developed an effective method of applying PDT in the biliary tract using equipment available in the U.S. Methods: Endoscopic retrograde cholangiography was performed to define the proximal and distal extent of intraductal tumor. Tumor length was determined by using the endoscope diameter as reference. A laser fiber used for PDT in esophageal carcinoma (Optiguide 200, QLT PhotoTherapeutics Inc., Vancouver, B.C.) was inserted into an 8 FR. biliary catheter (Glo-Tip, Wilson-Cook Medical, Inc., Winston-Salem, NC) equipped with a.038-in side-hole at its distal tip. Either a 1 cm or 2.5 cm diffuser tip could be applied depending upon the estimated stricture length. Following positioning of a.035-in guidewire proximal to the biliary stricture, the preloaded catheter (catheter plus laser fiber) was advanced over the guidewire using the monorail technique. The guidewire was then withdrawn from the catheter, and the laser diffuser tip advanced and positioned across the stricture. Radioopaque markers on the diffuser tip facilitated accurate positioning with a 3-5 mm proximal and distal overlap with normal tissue. Laser light was applied at a wavelength of 630 nm with a total energy of 180 joules/cm2. Following PDT, 10 FR. or 11.5 FR. plastic stents were inserted. Results: Eight PDT sessions were performed on six patients (age 38-73) over a six-month period. Bismuth type was as follows: type IV (n=2), type III (n=3), and type II (n=1). Using the pre-loaded biliary catheter, adequate positioning of the laser fiber was achieved in all patients. A fracture of the diffuser tip occurred during one of the treatments. Skin phototoxicity or other procedure-related complications were not identified during the mean follow-up of 13 weeks. Conclusions: 1. PDT for cholangiocarcinoma is technically feasible using a preloaded biliary catheter (catheter plus a standard laser fiber) and a monorail technique for catheter positioning. 2.Fracture of the laser diffuser tip with resulting reduction in power output is the main technical problem associated with this therapy. Judicious use of the elevator function of the duodenoscope may prevent this complication. 3. These techniques are being utilized in a randomized clinical trial at our institution comparing PDT and stenting with stenting alone for the palliation of unresectable cholangiocarcinoma. Background: Preliminary evidence from Europe indicates that photodynamic therapy (PDT) provides effective relief from biliary obstruction in advanced cholangiocarcinoma.We developed an effective method of applying PDT in the biliary tract using equipment available in the U.S. Methods: Endoscopic retrograde cholangiography was performed to define the proximal and distal extent of intraductal tumor. Tumor length was determined by using the endoscope diameter as reference. A laser fiber used for PDT in esophageal carcinoma (Optiguide 200, QLT PhotoTherapeutics Inc., Vancouver, B.C.) was inserted into an 8 FR. biliary catheter (Glo-Tip, Wilson-Cook Medical, Inc., Winston-Salem, NC) equipped with a.038-in side-hole at its distal tip. Either a 1 cm or 2.5 cm diffuser tip could be applied depending upon the estimated stricture length. Following positioning of a.035-in guidewire proximal to the biliary stricture, the preloaded catheter (catheter plus laser fiber) was advanced over the guidewire using the monorail technique. The guidewire was then withdrawn from the catheter, and the laser diffuser tip advanced and positioned across the stricture. Radioopaque markers on the diffuser tip facilitated accurate positioning with a 3-5 mm proximal and distal overlap with normal tissue. Laser light was applied at a wavelength of 630 nm with a total energy of 180 joules/cm2. Following PDT, 10 FR. or 11.5 FR. plastic stents were inserted. Results: Eight PDT sessions were performed on six patients (age 38-73) over a six-month period. Bismuth type was as follows: type IV (n=2), type III (n=3), and type II (n=1). Using the pre-loaded biliary catheter, adequate positioning of the laser fiber was achieved in all patients. A fracture of the diffuser tip occurred during one of the treatments. Skin phototoxicity or other procedure-related complications were not identified during the mean follow-up of 13 weeks. Conclusions: 1. PDT for cholangiocarcinoma is technically feasible using a preloaded biliary catheter (catheter plus a standard laser fiber) and a monorail technique for catheter positioning. 2.Fracture of the laser diffuser tip with resulting reduction in power output is the main technical problem associated with this therapy. Judicious use of the elevator function of the duodenoscope may prevent this complication. 3. These techniques are being utilized in a randomized clinical trial at our institution comparing PDT and stenting with stenting alone for the palliation of unresectable cholangiocarcinoma.