Phase I/II Study of Hepatic Arterial Infusion Chemotherapy With Gemcitabine in Patients With Unresectable Intrahepatic Cholangiocarcinoma (JIVROSG-0301) Preoperative biliary drainage for cancer of the head of the pancreas. Guidelines for the diagnosis and treatment of cholangiocarcinoma: an update Radiation therapy is associated with improved survival in the adjuvant and definitive treatment of intrahepatic cholangiocarcinoma. Hepatic Arterial Infusion with Oxaliplatin and 5-FU/Folinic Acid for Advanced Biliary Tract Cancer: A Phase II Study Transarterial chemoembolization with degradable starch microspheres (DSM-TACE): an alternative option for advanced HCC patients? Preliminary results. Modified response evaluation criteria in solid tumors and European Association for The Study of the Liver criteria using delayed-phase imaging at an early time point predict survival in patients with unresectable intrahepatic cholangiocarcinoma following yttrium-90 radioembolization. Overall survival peri-hilar cholangiocarcinoma: R1 resection with curative intent compared to primary endoscopic therapy. Targeted Therapy of Advanced Gallbladder Cancer and Cholangiocarcinoma with Aggressive Biology: Eliciting Early Response Signals from Phase 1 trials Gemcitabine-based versus fluoropyrimidine-based chemotherapy with or without platinum in unresectable biliary tract cancer: a retrospective study Perihilar Cholangiocarcinoma Postoperative Radiotherapy Does Not Improve Survival Long-term outcomes after hepatic resection combined with radiofrequency ablation for initially unresectable multiple and bilobar liver malignancies. Interventionally implanted port catheter systems for hepatic arterial infusion of chemotherapy in patients with primary liver cancer: A phase II-study (NCT00356161) Preoperative endoscopic versus percutaneous transhepatic biliary drainage in potentially resectable perihilar cholangiocarcinoma (DRAINAGE trial): design and rationale of a randomized controlled trial Extensive Use of Interventional Therapies Improves Survival in Unresectable or Recurrent Intrahepatic Cholangiocarcinoma Locoregional therapies in cholangiocarcinoma. Multi-Institutional Phase II Study of High-Dose Hypofractionated Proton Beam Therapy in Patients With Localized, Unresectable Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma. Radiofrequency Ablation of Intrahepatic Cholangiocarcinoma: Preliminary Experience Regional chemotherapy for unresectable primary liver cancer: results of a phase II clinical trial and assessment of DCE-MRI as a biomarker of survival. Multicenter phase II study of S-1 monotherapy as second-line chemotherapy for advanced biliary tract cancer refractory to gemcitabine Intraductal endoscopic radiofrequency ablation for the treatment of hilar non-resectable malignant bile duct obstruction. Intra-arterial Therapy for Advanced Intrahepatic Cholangiocarcinoma: A Multi-institutional Analysis Combination Chemotherapy With Gemcitabine and Cisplatin as First-Line Treatment for Immunohistochemically Proven Cholangiocarcinoma Phase II study of epirubicin, cisplatin, and capecitabine for advanced biliary tract adenocarcinoma Capecitabine plus hepatic intra-arterial epirubicin and cisplatin in unresectable biliary cancer: a phase II study. Treating Primary Liver Cancer with Hepatic Arterial Infusion of Floxuridine and Dexamethasone: Does the Addition of Systemic Bevacizumab Improve Results Comparison of external beam radiation and brachytherapy to external beam radiation alone for unresectable extrahepatic cholangiocarcinoma. Multimodal oncological therapy comprising stents, brachytherapy, and regional chemotherapy for cholangiocarcinoma. Treatment of unresectable cholangiocarcinoma: conventional transarterial chemoembolization compared with drug eluting bead-transarterial chemoembolization and systemic chemotherapy Yttrium-90 radioembolization for intrahepatic cholangiocarcinoma: safety, response, and survival analysis. Yttrium-90 microsphere radioembolization in unresectable intrahepatic cholangiocarcinoma. Treatment of unresectable cholangiocarcinoma using yttrium‐90 microspheres Radiotherapy is associated with improved survival in adjuvant and palliative treatment of extrahepatic cholangiocarcinomas. Brachytherapy and percutaneous stenting in the treatment of cholangiocarcinoma: a prospective randomised study. OEM-TACE: A New Therapeutic Approach in Unresectable Intrahepatic Cholangiocarcinoma Randomised controlled trial of temoporfin photodynamic therapy plus chemotherapy in nonresectable biliary carcinoma--PCS Nordic study. Phase II Study of Hepatic Arterial Infusion Chemotherapy with Oxaliplatin and 5-Fluorouracil for Advanced Perihilar Cholangiocarcinoma.
Objectives : No established therapy exists for unresectable intrahepatic cholangiocarcinoma ( ICC ) . We conducted a phase I/II study to ascertain the recommended dose ( RD ) of hepatic arterial infusion using gemcitabine ( GEM ) for ICC and to assess the efficacy and safety . Methods : For patients with unresectable ICC , GEM was administered through the hepatic artery via the port system as a 30-minute infusion on days 1 , 8 , and 15 every 4 weeks for 5 cycles . In phase I , dosage for levels 1 , 2 , and 3 was set at 600 , 800 , and 1000 mg/m2 , respectively , and was increased in 3 to 6 patients at a time . Maximum tolerated dose was defined as a dosage result ing in dose-limiting toxicity in 2 of 3 patients or 3 of 6 patients , and RD was estimated during the first cycle . In the phase II , more RD patients were added to assess tumor response and toxicity . Results : During the phase I , 16 patients were enrolled .  Maximum tolerated dose was not reached . Assuming RD at 1000 mg/m2 , the phase II enrolled a total of 13 patients . The following Grade 3 toxicities were observed : neutropenia 20 % , increased gamma-glutamyl transpeptidase 8 % , increased aspartate aminotransferase 4 % , increased alanine aminotransferase 4 % , increased bilirubin 4 % , nausea 4 % , and fatigue 4 % . The tumor response rate was 7.7 % ( complete response 0 , partial response 1 , stable disease 8 , and progressive disease 4 ) . Conclusion : Whereas the toxicity of hepatic arterial infusion with 1000 mg/m2 GEM for ICC was tolerable , expected efficacy could not be obtained , thus suggesting only minimal activity BACKGROUND The benefits of preoperative biliary drainage , which was introduced to improve the postoperative outcome in patients with obstructive jaundice caused by a tumor of the pancreatic head , are unclear . METHODS In this multicenter , r and omized trial , we compared preoperative biliary drainage with surgery alone for patients with cancer of the pancreatic head . Patients with obstructive jaundice and a bilirubin level of 40 to 250 micromol per liter ( 2.3 to 14.6 mg per deciliter ) were r and omly assigned to undergo either preoperative biliary drainage for 4 to 6 weeks , followed by surgery , or surgery alone within 1 week after diagnosis . Preoperative biliary drainage was attempted primarily with the placement of an endoprosthesis by means of endoscopic retro grade cholangiopancreatography . The primary outcome was the rate of serious complications within 120 days after r and omization . RESULTS We enrolled 202 patients ; 96 were assigned to undergo early surgery and 106 to undergo preoperative biliary drainage ; 6 patients were excluded from the analysis . The rates of serious complications were 39 % ( 37 patients ) in the early-surgery group and 74 % ( 75 patients ) in the biliary-drainage group ( relative risk in the early-surgery group , 0.54 ; 95 % confidence interval [ CI ] , 0.41 to 0.71 ; P<0.001 ) . Preoperative biliary drainage was successful in 96 patients ( 94 % ) after one or more attempts , with complications in 47 patients ( 46 % ) . Surgery-related complications occurred in 35 patients ( 37 % ) in the early-surgery group and in 48 patients ( 47 % ) in the biliary-drainage group ( relative risk , 0.79 ; 95 % CI , 0.57 to 1.11 ; P=0.14 ) . Mortality and the length of hospital stay did not differ significantly between the two groups . CONCLUSIONS Routine preoperative biliary drainage in patients undergoing surgery for cancer of the pancreatic head increases the rate of complications . ( Current Controlled Trials number , IS RCT N31939699 . The British Society of Gastroenterology guidelines on the management of cholangiocarcinoma were originally published in 2002 . This is the first up date since then and is based on a comprehensive review of the recent literature , including data from r and omised controlled trials , systematic review s , meta-analyses , cohort , prospect i ve and retrospective studies PURPOSE Intrahepatic cholangiocarcinomas ( IHC ) are rare tumors for which large r and omized studies regarding the use of radiation are not available . The purpose of this study was to examine the role of adjuvant and definitive radiation therapy in the treatment of IHC in a large group of patients . METHODS AND MATERIAL S This is a retrospective analysis of 3,839 patients with IHC collected from the Surveillance , Epidemiology , and End Results ( SEER ) data base . The primary endpoint was overall survival ( OS ) . RESULTS Patients received either surgery alone ( 25 % ) , radiation therapy alone ( 10 % ) , surgery and adjuvant radiation therapy ( 7 % ) or no treatment ( 58 % ) . The median age of the patient population was 73 years ( range , 22 - 102 years ) ; 52 % of patients were male and 81 % were Caucasian .  Median OS was 11 ( 95 % confidence interval [ CI ] , 9 - 13 ) , 6 ( 95 % CI , 5 - 6 ) , 7 ( 95 % CI , 6 - 8 ) , and 3 months for surgery and adjuvant radiation therapy , surgery alone , radiation therapy alone , and no treatment , respectively . The OS was significantly different between surgery alone and surgery and adjuvant radiation therapy ( p = 0.014 ) and radiation therapy alone and no treatment ( p < 0.0001 ) . Use of surgery and adjuvant radiation therapy conferred the greatest benefit on OS ( HR = 0.40 ; 95 % CI , 0.34 - 0.47 ) , followed by surgery alone ( hazard ratio [ HR ] , 0.49 ; 95 % CI , 0.44 - 0.54 ) and radiation therapy alone ( HR , 0.68 ; 95 % CI , 0.59 - 0.77 ) compared with no treatment , on multivariate analysis . Propensity score adjusted hazard ratios ( controlling for age , race/ethnicity , stage , and year of diagnosis ) were also significant ( surgery and adjuvant radiation therapy vs. surgery alone ( HR , 0.82 ; 95 % CI , 0.70 - 0.96 ) ; radiation therapy alone vs. no treatment ( HR , 0.67 ; 95 % CI , 0.58 - 0.76 ) ) . CONCLUSIONS The study results suggest that adjuvant and definitive radiation treatment prolong survival , although cure rates remain low . Future studies should evaluate the addition of chemotherapy and biologics to the treatment of IHC Background Effective and tolerable chemotherapy with gemcitabine and cisplatin for advanced biliary tract cancer ( BTC ) has been established recently . However , overall prognosis is still poor , and additional therapeutic approaches are needed for patients with locally advanced , irresectable and /or pretreated tumors .  Hepatic arterial infusion ( HAI ) of chemotherapy represents a safe and well-established treatment modality , but data on its use in patients with BTC are still sparse . Methods Patients with irresectable BTC predominant to the liver were included in a prospect i ve , open phase II study investigating HAI provided through interventionally implanted port catheters . Intraarterial chemotherapy consisted of biweekly oxaliplatin ( O ) 85 mg/m2 and folinic acid ( F ) 170 mg/m2 with 5-FU ( F ) 600 mg/m2 . Results Between 2004 and 2010 , 37 patients were enrolled . A total of 432 cycles of HAI were applied with a median of 9 ( range 1–46 ) cycles . Objective response rate was 16 % , and tumor control was achieved in 24 of 37 ( 65 % ) patients . Median progression-free survival was 6.5 months ( range 0.5–26.0 ; 95 % CI 4.3–8.7 ) , median overall survival was 13.5 ( range 0.9–50.7 ; 95 % CI 11.1–15.9 ) months . The most frequent adverse event was sensory neuropathy grade 1/2 in 10/14 patients . Conclusions Using a minimal invasive technique , repetitive HAI with OFF is feasible and results in clinical ly relevant tumor control with low toxicity in patients with liver predominant advanced BTC OBJECTIVE To assess safety , feasibility and effectiveness of transarterial chemoembolization with degradable-starch-microspheres ( DSM-TACE ) in the treatment of patients with advanced hepatocellular carcinoma ( HCC ) dismissing or ineligible for multikinase-inhibitor chemotherapy administration ( Sorafenib ) due to unbearable side effects or clinical contraindications . PATIENTS AND METHODS Six consecutive advanced HCC patients dismissing Sorafenib because of unbearable side effects or worsened clinical conditions were enrolled in our prospect i ve single-center pilot study . DSM-TACE was performed via a lobar approach , based on extent and distribution of the disease ( 1 treatment session for every lobe involved , with a 2-week interval in case of bilobar disease ) . Tumor response based on mRECIST criteria was evaluated on MD-CT performed at 1 month after " complete treatment " and every 3 months thereafter . RESULTS Eleven treatments were performed , and technical success was achieved in all patients . No intra/peri-procedural death/major complications occurred . No signs of liver failure or systemic toxicity were detected . At one month follow-up , 5 partial responses ( 83.3 % ) and 1 progression disease ( 16.6 % ) with an overall disease control ( ODC ) of 83.3 % were observed . In two patients with ODC and residual viable tumor higher than 50 % , a repeated DSM-TACE treatment was performed . During the mean follow-up of 11 months ( range : 4 - 14 months ) , an ODC of 66.6 % was obtained . Progression-free survival was 5.5 months with a cumulative 6-month and 1-year overall survival rates of 83.3 % and 66.6 % , respectively . CONCLUSIONS DSM-TACE seems to be a promising option for advanced HCC patients ineligible for Sorafenib administration or dismissing it due to progressive disease or unbearable side effects PURPOSE To investigate early imaging prognostic factors in unresectable intrahepatic cholangiocarcinoma ( ICC ) refractory to st and ard chemotherapy after yttrium-90 ( (90)Y ) radioembolization therapy .  MATERIAL S AND METHODS In an institutional review board-approved prospect i ve correlative study , 21 consecutive patients with ICC refractory to st and ard chemotherapy underwent (90)Y radioembolization therapy .  Target and overall Response Evaluation Criteria In Solid Tumors ( RECIST ) , modified RECIST ( mRECIST ) , and European Association for the Study of the Liver ( EASL ) treatment responses were assessed . The mRECIST and EASL criteria were modified for application on delayed phases of dynamic contrast-enhanced cross-sectional imaging studies . Conventional definitions for complete and partial response were applied ; these responses comprised objective response . Restaging imaging was obtained at 1- and 3-month intervals until patient death . Survival analyses by Kaplan-Meier and log-rank proportional models including application of the l and mark method to avoid lead-time bias were performed from the day of treatment . Significance was set at P < .05 . RESULTS Median overall survival ( OS ) from the time of (90)Y therapy was 16.3 months ( 95 % confidence interval , 7.2 - 25.4 mo ) . Significant differences between mRECIST and EASL versus RECIST were found when categorizing patients into responders and nonresponders ( P < .001 ) . Significantly prolonged OS was observed for patients with targeted objective response based on modified mRECIST and EASL criteria ( P = .005 and P = .001 , respectively ) at 3 months . RECIST was not found to correlate with survival at 1- or 3-month follow-up . CONCLUSIONS Modified target mRECIST and EASL criteria that employ delayed-phase contrast enhancement at 3 months after (90)Y radioembolization therapy for ICC predicted OS . RECIST did not correlate with survival BACKGROUND AND OBJECTIVES Patients with peri-hilar cholangiocarcinoma who undergo R1 resection with curative intent will have an improved survival compared to patients who were not resected . METHODS Review of a prospect i ve hepatobiliary data base identified 130 patients .  Survival was compared using the log-rank test . RESULTS Seventy-nine patients ( 61 % ) were resected while 51 ( 49 % ) patients were not . Forty-two patients ( 54 % ) had an R0 resection . There was no difference in mean age ( 69 vs. 67 ; P = 0.8 ) , BMI ( 27.8 vs. 27.9 ; P = 1.0 ) , gender ( 73 % vs. 43 % male ; P = 0.1 ) , presence of jaundice ( 77 % vs. 64 % ; P = 0.5 ) , vascular involvement on pre operative imaging ( 77 % vs. 64 % ; P = 0.5 ) , stent ( 73.1 % vs. 64.3 % ; P = 0.72 ) , and lobar atrophy ( 27 % vs. 7 % , P = 0.2 ) in the resected versus non-resected patients . All patients underwent chemotherapy and /or radiation therapy . After a median follow up of 35.6 months the median OSl for all peri-hilar patients was 16.2 months ( 95 % CI = 11.2 - 23.4 ) . The median OS for resected patients was 18.9 months ( 95 % CI = 12.5 - 24.7 ) versus 5.0 months ( 95 % CI = 0 - 6.9 ) for patients not resected ( P < 0.001 ) . The only pre-operative predictor of OS was resection ( P = 0.041 ) . Vascular invasion , lobar atrophy , and stent placement were not statistically significant predictors . CONCLUSION Overall survival is improved in patients undergoing R1 resection and multi-modality therapy compared to patients not resected Purpose Patients with advanced cholangiocarcinoma ( CC ) and gallbladder carcinoma ( GC ) have few therapeutic options for relapsed disease . Methods Given the overall poor prognosis in this population and the availability of novel targeted therapies , we systematic ally analyzed the characteristics and outcomes for GC and CC patients treated on phase I trials with an emphasis on targeted agents and locoregional therapies . Results Of 40 treated patients ( GC=6 ; CC=34 ; median age , 60 years ) , 8 ( 20 % ) had stable disease (  SD ) > 6 months , 3 ( 8 % ) partial response ( PR ) , on protocol s with hepatic arterial drug infusion and anti-angiogenic , anti-HER-2/neu or novel MAPK/ERK kinase ( MEK ) inhibitors .  Median progression-free survival ( PFS ) on phase I trials was 2.0 months ( 95 % CI 1.7 , 2.8 ) versus 3.0 months ( 95 % CI 2.4 , 5.0 ) , 3.0 months ( 95 % CI 2.3 , 4.6 ) , and 3.0 months ( 95 % CI 2.4 , 3.9 ) for their first- , second- , and last-line FDA -approved therapy . In univariate analysis , > 3 metastatic sites , elevated alanine aminotransferase ( ALT ) ( > 56IU/L ) , serum creatinine ( > 1.6mg/dL ) , and CA19 - 9 ( > 35U/mL ) were associated with a shorter PFS . Mutational analysis revealed mutation in the KRAS oncogene in 2 of 11 patients ( 18 % ) . The SD > 6 months/PR rate of 28 % was seen with hepatic arterial infusion of oxaliplatin , and inhibitors of angiogenesis , HER-2/neu or MEK . Conclusions The PFS in phase I trials was similar to that of the first , second , and last-line therapy ( P=0.95 , 0.98 , 0.76 , respectively ) with FDA -approved agents given in the advanced setting , emphasizing a role for targeted agents in a clinical trials setting as potentially valuable therapeutic options for these patients Background There is no st and ard palliative chemotherapy regimen in biliary tract cancers ( BTC ) .  Fluoropyrimidine or gemcitabine , with or without platinum , are most frequently used . We conducted this study to clarify the efficacy of palliative chemotherapy in BTC . Methods Patients with unresectable BTC treated with palliative chemotherapy between Oct 2001 and Aug 2006 at Seoul National University Hospital were review ed retrospectively . Histologically confirmed cases of intrahepatic cholangiocarcinoma , gallbladder cancer , extrahepatic bile duct cancer , and ampulla of Vater carcinoma were enrolled . We analyzed the efficacy of regimens : gemcitabine ( G ) versus fluoropyrimidine ( F ) and with or without platinum ( P ) . Results A total of 243 patients were enrolled . 159 patients ( 65 % ) were male and the median age of the patients was 60 years ( range 26–81 ) . Intrahepatic cholangiocarcinoma , gallbladder cancer , extrahepatic bile duct cancer , and ampulla of Vater carcinoma were 92 , 72 , 58 , and 21 cases , respectively . The median progression free survival ( PFS ) was 4.3 months ( 95 % CI , 3.7–4.9 ) and median overall survival ( OS ) was 8.7 months ( 95 % CI , 7.4–10.0 ) . Ninety-nine patients received  G-based chemotherapy  ( 94 GP , 5 G alone ) , and 144 patients received F-based chemotherapy ( 83 FP , 61 F alone ) . The response rate ( RR ) , disease control rate ( DCR ) , PFS and OS of G-based chemotherapy versus F-based chemotherapy were 16.7 % vs. 19.5 % ( P = 0.591 ) , 52.8 % vs. 58.9 % ( P = 0.372 ) , 4.0 months vs. 4.3 months ( P = 0.816 ) , and 7.8 months vs. 9.1 months ( P = 0.848 ) , respectively . Sixty-six patients received F or G without P , and 177 patients received F or G with P. The RR , DCR , PFS and OS of chemotherapy without P versus chemotherapy including P were 12.7 % vs. 20.6 % ( P = 0.169 ) , 46.0 % vs. 60.6 % ( P = 0.049 ) , 3.3 months vs. 4.4 months ( P = 0.887 ) , and 10.6 months vs. 8.1 months ( P = 0.257 ) , respectively . Conclusion In unresectable BTC , F-based and G-based chemotherapy showed similar efficacy in terms of RR , DCR , PFS and OS . The benefit of adding P to F or G was not significant except for DCR . Further prospect i ve studies which define the efficacy of various chemotherapeutic regimens in BTC are warranted Objective The aims of this analysis were to determine prospect ively the effects of surgical resection and radiation therapy on the length and quality of survival as well as late toxicity in patients with perihilar cholangiocarcinoma . Background Retrospective analyses have suggested that adjuvant radiation therapy improves survival in patients with perihilar cholangiocarcinoma . However , in these reports , patients receiving radiotherapy  tended to have smaller , often resectable tumors , and were relatively fit . In comparison , patients who have not received radiotherapy  often had unresectable tumors , metastatic disease , or poor performance status . Methods From 1988 through 1993 , surgically staged patients with perihilar cholangiocarcinoma and 1 ) no evidence of metastatic disease , 2 ) Karnofsky score > 60,3 ) no prior malignancy or radiotherapy , and 4 ) a patent main portal vein were analyzed . Fifty patients were stratified by resection ( n = 31 ) versus operative palliation ( n = 19 ) and by radiation ( n = 23 ) versus no radiotherapy ( n = 27 ) . Results Patients undergoing resection had smaller tumors ( 1.9 ± 2.8 vs. 2.4 ± 2.1 cm , p < 0.01 ) that were less likely to invade the hepatic artery ( 3 % vs. 42 % , p < 0.05 ) or portal vein ( 6 % vs. 53 % , p < 0.05 ) . Multiple parameters that might have affected outcome were similar between patients who did and did not receive radiation therapy . Resection improved the length ( 24.2 ± 2.5 vs. 11.3 ± 1.0 months , p < 0.05 ) and quality of survival . Radiation had no effect on the length ( 18.4 ± 2.9 vs. 20.1 ± 2.4 months ) or quality of survival or on late toxicity . Conclusions This analysis suggests that in patients with localized perihilar cholangiocarcinoma , resection prolongs survival  whereas radiation has no effect on either survival or late toxicity . Thus , new agents or strategies to deliver adjuvant therapy are needed to improve survival in these patients BACKGROUND Hepatic resection ( HRE ) combined with radiofrequency ablation ( RFA ) offers a surgical option to a group of patients with multiple and bilobar liver malignancies who are traditionally unresectable for inadequate functional hepatic reserve . The aims of the present study were to assess the perioperative outcomes , recurrence , and long-term survival rates for patients treated with HRE plus RFA in the management of primary hepatocellular carcinoma ( HCC ) and metastatic liver cancer ( MLC ) . METHODS Data from all consecutive patients with primary and secondary hepatic malignancies who were treated with HRE combined with RFA between 2007 and 2013 were prospect ively collected and retrospectively review ed . RESULTS A total of 112 patients , with 368 hepatic tumors underwent HRE combined with ultrasound-guided RFA  , were included in the present study . There were 40 cases of HCC with 117 tumors and 72 cases of MLC with 251 metastases . Most cases of liver metastases originated from the gastrointestinal tract ( 44 , 61.1 % ) . Other uncommon lesions included breast cancer ( 5 , 6.9 % ) , pancreatic cancer ( 3 , 4.2 % ) , lung cancer ( 4 , 5.6 % ) , cholangiocarcinoma ( 4 , 5.6 % ) , and so on . The ablation success rates were 93.3 % for HCC and 96.7 % for MLC . The 1- , 2- , 3- , 4- , and 5-y overall recurrence rates were 52.5 % , 59.5 % , 72.3 % , 75 % , and 80 % for the HCC group and 44.4 % , 52.7 % , 56.1 % , 69.4 % , and 77.8 % for the MLC group , respectively . The 1- , 2- , 3- , 4- , and 5-y overall survival rates for the HCC patients were 67.5 % , 50 % , 32.5 % , 22.5 % , and 12.5 % and for the MLC patients were 66.5 % , 55.5 % , 50 % , 30.5 % , and 19.4 % , respectively . The corresponding recurrence-free survival rates for the HCC patients were 52.5 % , 35 % , 22.5 % , 15 % , and 10 % and for the MLC patients were 58.3 % , 41.6 % , 23.6 % , 16.9 % , and 12.5 % , respectively . CONCLUSIONS HRE combined with RFA provides an effective treatment approach for patients  with primary and secondary liver malignancies who are initially unsuitable for radical resection , with high local tumor control rates and promising survival data Background Hepatic arterial infusion ( HAI ) of chemotherapy requires the implantation of a transcatheter application system which is traditionally performed by surgery . This procedure , but particularly the adjacent drug application via pump or port is often hampered by specific complications and device failure . Interventionally implanted port catheter systems ( IIPCS ) facilitate the commencement of HAI without need for laparatomy , and are associated with favorable complication rates . We here present an evaluation of the most important technical endpoints associated with the use of IIPCS for HAI in patients with primary liver cancers . Methods 70 patients ( pts ) with hepatocellular ( HCC , n=33 ) and biliary tract cancer ( BTC , n=37 ) were enrolled into a phase II – study . Of those , n=43 had recurrent disease and n=31 suffered from liver-predominant UICC-stage IVb . All pts were provided with IIPCSs before being treated with biweekly , intraarterial chemotherapy ( oxaliplatin , 5-Flourouracil , folinic acid ) . The primary objective of the trial was defined as evaluation of device-related complications and port duration . Results Implantation of port catheters was successful in all patients . Mean treatment duration was 5.8 months , and median duration of port patency was not reached . Disease-progression was the most common reason for treatment discontinuation ( 44 pts . , 63 % ) , followed by chemotherapy-related toxicity ( 12 pts . , 17 % ) , and irreversible device failure ( 5 pts . , 7 % ) . A total of 28 port complications occurred in 21 pts ( 30 % ) . No unexpected complications were observed . Conclusions HAI via interventionally implanted port catheters can be safely applied to patients with primary liver tumors far advanced or/ and pretreated Background Liver surgery  in perihilar cholangiocarcinoma ( PHC ) is associated with high postoperative morbidity because the tumor typically causes biliary obstruction . Preoperative biliary drainage is used to create a safer environment prior to liver surgery , but biliary drainage may be harmful when severe drainage-related complications deteriorate the patients ’ condition or increase the risk of postoperative morbidity . Biliary drainage can cause cholangitis/cholecystitis , pancreatitis , hemorrhage , portal vein thrombosis , bowel wall perforation , or dehydration . Two methods of preoperative biliary drainage are mostly applied : endoscopic biliary drainage , which is currently used in most regional centers before referring patients for surgical treatment , and percutaneous transhepatic biliary drainage . Both methods are associated with severe drainage-related complications , but two small retrospective series found a lower incidence in the number of preoperative complications after percutaneous drainage compared to endoscopic drainage ( 18 - 25 % versus 38 - 60 % , respectively ) . The present study r and omizes patients with potentially resectable PHC and biliary obstruction between preoperative endoscopic or percutaneous transhepatic biliary drainage .  Methods / Design The study is a multi-center trial with an “ all-comers ” design , r and omizing patients between endoscopic or percutaneous transhepatic biliary drainage . All patients selected to potentially undergo a major liver resection for presumed PHC are eligible for inclusion in the study provided that the biliary system in the future liver remnant is obstructed ( even if they underwent previous inadequate endoscopic drainage ) . Primary outcome measure is the total number of severe preoperative complications between r and omization and exploratory laparotomy . The study is design ed to detect superiority of percutaneous drainage : a provisional sample size of 106 patients is required to detect a relative decrease of 50 % in the number of severe preoperative complications ( alpha = 0.95 ; beta = 0.8 ) . Interim analysis after inclusion of 53 patients ( 50 % ) will provide the definitive sample size . Secondary outcome measures encompass the success of biliary drainage , quality of life , and postoperative morbidity and mortality . Discussion The DRAINAGE trial is design ed to identify a difference in the number of severe drainage-related complications after endoscopic and percutaneous transhepatic biliary drainage in patients selected to undergo a major liver resection for perihilar cholangiocarcinoma . Trial registration Netherl and s Trial Register [ NTR4243 , 11 October 2013 ] Aim . To assess the outcomes of patients with unresectable intrahepatic cholangiocellular carcinoma ( ICC ) treated by a tailored therapeutic approach , combining systemic with advanced image-guided local or locoregional therapies . Material s and Methods . Treatment followed an algorithm established by a multidisciplinary GI-tumor team . Treatment options comprised ablation ( RFA , CT-guided brachytherapy ) or locoregional techniques ( TACE , radioembolization , i.a . chemotherapy ) . Results . Median survival was 33.1 months from time of diagnosis and 16.0 months from first therapy . UICC stage analysis showed a median survival of 15.9 months for stage I , 9 months for IIIa , 18.4 months for IIIc , and 13 months for IV . Only the number of lesions , baseline serum CEA and serum CA19 - 9 , and objective response ( RECIST ) were independently associated with survival . Extrahepatic metastases had no influence . Conclusion . Patients with unresectable ICC may benefit from hepatic tumor control provided by local or locoregional therapies . Future prospect i ve study formats should focus on supplementing systemic therapy by classes of interventions ( “ toolbox ” ) rather than specific techniques , that is , local ablation leading to complete tumor destruction ( such as RFA ) or locoregional treatment leading to partial remission ( such as radioembolization ) . This trial is registered with German Clinical Trials Registry ( Deutsche Register Klinischer Studien ) , DRKS-ID : DRKS00006237 Cholangiocarcinoma is a rare and aggressive malignancy of the biliary tract .  Complete surgical resection can be curative , but the majority of patients are diagnosed with advanced disease and usually die within a year of diagnosis . Most deaths are attributable to local disease progression rather than distant metastases , supporting the use of locoregional therapies . There is evidence that locoregional therapies can provide local tumor control result ing in increased survival while avoiding some of the side effects of systemic treatments , increasing potential treatment options for patients who may be unsuitable for systemic palliative treatments . This review considers the evidence for  locoregional therapies  in cholangiocarcinoma , which can be classified into endoscopic , vascular , percutaneous and radiation oncological therapies . Current guidelines do not recommend the routine use of locoregional therapies due to a lack of prospect i ve data , but the results of ongoing trials are likely to increase the evidence base and impact on clinical practice PURPOSE To evaluate the efficacy and safety of high-dose , hypofractionated proton beam therapy for hepatocellular carcinoma ( HCC ) and intrahepatic cholangiocarcinoma ( ICC ) . MATERIAL S AND METHODS In this single-arm , phase II , multi-institutional study , 92 patients with biopsy-confirmed HCC or ICC , determined to be unresectable by multidisciplinary review , with a Child-Turcotte-Pugh score ( CTP ) of A or B , ECOG performance status of 0 to 2 , no extrahepatic disease , and no prior radiation received 15 fractions of proton therapy to a maximum total dose  of 67.5 Gy  equivalent . Sample size was calculated to demonstrate > 80 % local control ( LC ) defined by Response Evaluation Criteria in Solid Tumors ( RECIST ) 1.0 criteria at 2 years for HCC patients , with the parallel goal of obtaining acceptable precision for estimating outcomes for ICC . RESULTS Eighty-three patients were evaluable : 44 with HCC , 37 with ICC , and two with mixed HCC/ICC . The CTP score was A for 79.5 % of patients and B for 15.7 % ; 4.8 % of patients had no cirrhosis . Prior treatment had been given to 31.8 % of HCC patients and 61.5 % of ICC patients . The median maximum dimension was 5.0 cm ( range , 1.9 to 12.0 cm ) for HCC patients and 6.0 cm ( range , 2.2 to 10.9 cm ) for ICC patients . Multiple tumors were present in 27.3 % of HCC patients and in 12.8 % of ICC patients . Tumor vascular thrombosis was present in 29.5 % of HCC patients and in 28.2 % of ICC patients . The median dose delivered to both HCC and ICC patients was 58.0 Gy . With a median follow-up among survivors of 19.5 months , the LC rate at 2 years was 94.8 % for HCC and 94.1 % for ICC . The overall survival rate at 2 years was 63.2 % for HCC and 46.5 % ICC . CONCLUSION High-dose hypofractionated proton therapy demonstrated high LC rates for HCC and ICC safely , supporting ongoing phase III trials of radiation in HCC and ICC The purpose of this study was to evaluate the safety and efficacy of percutaneous ultrasound (US)-guided radiofrequency ablation ( RFA ) in patients with intrahepatic cholangiocarcinoma ( ICCA ) in a small , nonr and omized series . From February 2004 to July 2008 , six patients ( four men and two women ; mean age 69.8 years [ range 48 to 83 ] ) with ICCA underwent percutaneous US-guided RFA . Preintervetional transarterial embolization was performed in two cases to decrease heat dispersion during RFA in order to increase the area of ablation . The efficacy of RFA was evaluated using contrast-enhanced dynamic computed tomography ( CT ) 1 month after treatment and then every 3 months thereafter . Nine RFA sessions were performed for six solid hepatic tumors in six patients . The duration of follow-up ranged from 13 to 21 months ( mean 17.5 ) . Posttreatment CT showed total necrosis in four of six tumors after one or two RFA sessions . Residual tumor was observed in two patients with larger tumors ( 5 and 5.8 cm in diameter ) . All patients tolerated the procedure , and there with no major complications . Only 1 patient developed post-RFA syndrome ( pain , fever , malaise , and leukocytosis ) , which resolved with oral administration of acetaminophen . Percutaneous RFA is a safe and effective treatment for patients with hepatic tumors : It is ideally suited for those who are not eligible for surgery . Long-term follow-up data regarding local and systemic recurrence and survival are still needed BACKGROUND This study reports the results of hepatic arterial infusion ( HAI ) with floxuridine ( FUDR ) and dexamethasone ( dex ) in patients with unresectable intrahepatic cholangiocarcinoma ( ICC ) or hepatocellular carcinoma ( HCC ) and investigates dynamic contrast-enhanced magnetic resonance imaging ( DCE-MRI ) assessment of tumor vascularity as a biomarker of outcome . PATIENTS AND METHODS Thirty-four unresectable patients ( 26 ICC and eight HCC ) were treated with HAI FUDR/dex . Radiologic dynamic and pharmacokinetic parameters related to tumor perfusion were analyzed and correlated with response and survival . RESULTS Partial responses were seen in 16 patients ( 47.1 % ) ; time to progression and response duration were 7.4 and 11.9 months , respectively . Median follow-up and median survival were 35 and 29.5 months , respectively ; 2-year survival was 67 % . DCE-MRI data showed that patients with pretreatment integrated area under the concentration curve of gadolinium contrast over 180 s ( AUC 180 ) > 34.2 mM.s had a longer median survival than those with AUC 180 < 34 mM.s ( 35.1 versus 19.1 months , P = 0.002 ) . Decreased volume transfer exchange between the vascular space and extracellular extravascular space ( -DeltaK(trans ) ) and the corresponding rate constant ( -Deltak(ep ) ) on the first post-treatment scan both predicted survival . CONCLUSIONS In patients with unresectable primary liver cancer , HAI therapy can be effective and safe . Pretreatment and early post-treatment changes in tumor perfusion characteristics may predict treatment outcome Summary Gemcitabine is widely used for the treatment of advanced biliary tract cancer ( BTC ) as first-line chemotherapy . However , there is no st and ard chemotherapy for patient with advanced BTC refractory to gemcitabine . We conducted a multicenter phase II study of S-1 monotherapy as second-line chemotherapy for patients with advanced BTC that were refractory to gemcitabine . S-1 was administered orally at a dose of 80 mg/m2 for 28 days , followed by 14 days of rest . This regimen was repeated every 6 weeks .  Tumor response was assessed every two cycles using the Response Evaluation Criteria in Solid Tumors version 1.0 . Twenty-two patients were enrolled between March 2007 and January 2010 , with 14 patients ( 64 % ) representing cases of recurrence after surgery . The overall response rate was 22.7 % , and the overall disease control rate was 50.0 % . The median overall survival time was 13.5 months ( 95 % CI , 7.1–23.1 months ) and the median time-to-progression was 5.4 months ( 95 % CI , 2.6–17.2 months ) . Grade 3/4 toxicities included neutropenia ( 5 % ) and anemia ( 5 % ) . The most common non-hematological toxicities were nausea ( 27 % ) , anorexia ( 55 % ) , and pigmentation ( 32 % ) . In conclusion , S-1 monotherapy is feasible and moderately efficacious second-line chemotherapy for advanced BTC AIM To evaluate the safety and technical success of endoscopic radiofrequency ablation ( RFA ) for palliative treatment of malignant hilar bile duct obstruction . METHODS In this study , a recently CE and FDA -approved endoscopic RFA catheter was first tested in an ex vivo pig liver model to study the effect of electrosurgical variables on the extent of the area of induced necrosis . Subsequently , a retrospective analysis was conducted of all patients treated with endoscopic RFA for malignant biliary obstruction at our center between February 2012 and April 2013 . All patients received an additional plastic stent implantation into the biliary tree following RFA . RESULTS In the pig model , ablation time of 60 - 90 seconds using the bipolar soft coagulation mode at 8 - 10 watts with an effect of 8 was found to be the most feasible setting . Twelve patients ( 5 females , 7 males ; mean age , 70 years ) underwent 19 endoscopic RFA ( range , 1 - 5 ) sessions . Deployment of RFA was successful in all patients . Systemic chemotherapy was administered in four patients . We observed biliary bleeding 4 - 6 wk after the intervention in three cases and two of these patients died : in one patient , spontaneous hemobilia occurred , whereas bleeding started during stent extraction in the other . In the third patient , bleeding was stopped by insertion of a non-covered self-exp and ing metal stent . Another three patients developed cholangitis during follow-up . Seven patients died during follow-up and median survival was 6.4 mo ( 95%CI : 0.05 - 12.7 ) from the time of the first RFA . CONCLUSION Endoscopic RFA is an easy to perform and technically highly successful procedure . However , hemobilia possibly associated with RFA occurred in three of our patients . Therefore , larger prospect i ve studies are needed to further evaluate the safety and efficacy of this promising new method Background Many patients with intrahepatic cholangiocarcinoma ( ICC ) present with advanced and inoperable disease . Data on the safety and efficacy of intra-arterial therapy ( IAT ) for ICC are limited . Methods Between 1992 and 2012 , a total of 198 patients with advanced ICC treated with IAT were retrospectively identified from the data bases of five major hepatobiliary institutions . Data on clinicopathological factors , morbidity , response rates , and overall survival were collected and analyzed . Results Median patient age was 61 years . Median tumor size was 8.1 cm , and 47.5 % patients had a solitary lesion . IAT consisted of conventional transarterial chemoembolization ( cTACE ) ( 64.7 % ) , drug-eluting beads ( DEB ) ( 5.6 % ) , bl and embolization ( TAE ) ( 6.6 % ) , or yttrium-90 radioembolization ( 23.2 % ) . Median number of IAT sessions was 2 ( range 1–8 ) . The median time between IAT sessions was 48 days . The periprocedural morbidity was 29.8 % ; most complications were minor ( n = 43 ) ; however , 16 patients had a grade 3–4 complication . Assessment of tumor response revealed complete or partial response in 25.5 % patients , while 61.5 % had stable disease ; 13.0 % had progressive disease . Median overall survival was 13.2 months and did not differ on the basis of the type of IAT ( cTACE , 13.4 months vs. DEB 10.5 months vs. TAE , 14.3 months vs. yttrium-90 , 11.3 months ; P = 0.46 ) .  IAT response on modified response evaluation criteria in solid tumors ( mRECIST ; hazard ratio for complete – partial response 0.49 , 95 % confidence interval 0.30–0.81 ; P < 0.001 ) was independently associated with better survival . Conclusions IAT for ICC was safe and led to stable disease or partial to complete response in up to three-quarters of patients . Among patients with an  IAT response , overall survival was prolonged . The role of IAT therapy for ICC warrants further prospect i ve evaluation in clinical trials Objectives : The aim of this study was to determine the efficacy and safety profile of gemcitabine plus cisplatin in patients with immunohistochemically proven unresectable cholangiocarcinoma . Patients and Methods : Between March 2002 and December 2004 , a total of 24 patients with immunohistochemically proven cholangiocarcinoma were entered in this study . Treatment consisted of gemcitabine 1000 mg/m2 intravenous infusion on day 1 and 8 and cisplatin 70 mg/m2 intravenously on day 1 every 3 weeks . Results : Seventy-one cycles of treatment were given , with a median of 3 cycles ( range , 2–6 cycles ) . Five patients had a partial response ( PR ) , 12 patients had stable disease ( SD ) , and 7 patients progressed during treatment . A median survival of 9.30 months ( range , 6.43–12.17 ) was obtained hematologic and nonhematologic toxicities were generally acceptable . However , there was one treatment-related mortality caused by thrombotic thrombocytopenia purpura ( TTP ) associated with gemcitabine and cisplatin . Conclusions : The combination chemotherapy of gemcitabine and cisplatin had a modest effect and was a well tolerated treatment of patients with immunohistochemically proven metastatic or unresectable cholangiocarcinoma Advanced biliary tract carcinomas ( BTCs ) are associated with a very poor prognosis . New therapeutic strategies therefore are needed to improve efficacy and survival , and the current study was design ed with a new , effective drug combination UNLABELLED The aim of the present study was to evaluate the activity of hepatic intra-arterial infusion of epirubicin and cisplatin combined with oral capecitabine , in patients with unresectable biliary carcinomas . PATIENTS AND METHODS Twenty patients were treated by bolus infusion of epirubicin 50 mg/m2 and cisplatin 60 mg/m2 in the hepatic artery on day 1 , combined with oral capecitabine 1000 mg/m2 bid , from day 2 to day 15 . RESULTS Partial responses ( PR ) were observed in 6 patients ( 31.5 % ) , stable disease ( SD ) in 9 ( 47.5 % ) and progression ( PD ) in 4 ( 21 % ) . The median progression-free and overall survival periods were 11.6 and 18.0 months , respectively , and 1-year survival was 74 % . One patient died after the first cycle because of G4 diarrhea . The other patients had good tolerance , with minimal hematological toxicity and only 1 G3 vomiting . CONCLUSION This combined intra-arterial and oral approach to patients with biliary carcinomas was found to be active and safe and seems to produce an encouraging survival response Objectives : This study investigated the efficacy and safety of adding systemic ( IV ) bevacizumab ( Bev ) to hepatic arterial infusion ( HAI ) with floxuridine (FUDR)/dexamethasone ( Dex ) in unresectable primary liver cancer . Methods : Patients with unresectable intrahepatic cholangiocarcinoma ( ICC ) or hepatocellular carcinoma ( HCC ) were treated with HAI FUDR/Dex plus IV Bev . Results were compared to a recent study of HAI without Bev in a similar patient population . Results : Twenty-two patients ( 18 ICC , 4 HCC ) were treated with HAI FUDR/Dex plus Bev ; 7 ( 31.8 % ) had partial response and 15 ( 68.2 % ) had stable disease . Median survival was 31.1 months ( CI 14.14–33.59 ) , progression-free survival ( PFS ) 8.45 months ( CI 5.53–11.05 ) , and hepatic PFS 11.3 months ( CI 7.93–15.69 ) . In the previous trial with HAI alone ( no Bev ) , the response was 50 % ; median survival , PFS , and hepatic PFS were 29.5 , 7.3 , and 10.1 months . In the present trial , bilirubin elevation ( > 2 mg/dl ) was seen in 24 % of patients and biliary stents were placed in 13.6 % , versus 5.8 and 0 % , respectively , in the HAI trial without Bev . Due to increased biliary toxicity , the trial was prematurely terminated . Conclusion : Adding Bev to HAI FUDR/Dex appeared to increase biliary toxicity without clear improvement in outcome ( median PFS 8.45 vs. 7.3 months , and median survival 31.1 vs. 29.5 months , for HAI + Bev vs. HAI alone groups , respectively ) BACKGROUND Extrahepatic cholangiocarcinoma ( EHC ) is a rare malignancy with a relatively poor prognosis . There are no r and omized , prospect i ve data to help define the optimal method of radiation delivery for unresectable EHC . The purpose of this study was to evaluate the benefit of adding brachytherapy to external beam radiation therapy ( EBRT ) for unresectable EHC . METHODS A retrospective review of 1,326 patients with unresectable EHC using the Surveillance , Epidemiology , and End Results ( SEER ) data base was completed . Kaplan-Meier methods were used to analyze the primary endpoint , overall survival . Univariate and multivariate analysis was performed to identify and control for potential confounding variables , including age at diagnosis , sex , stage , grade , histology , race , year of diagnosis , and reason for no surgery . RESULTS Of the 1,326 patients with unresectable EHC , 1,188 ( 92.9 % ) received EBRT only , while 91 ( 7.1 % ) received both EBRT and brachytherapy . Patients receiving combined modality radiation therapy were more likely to be treated prior to the year 2000 . Median overall survival for patients receiving EBRT and EBRT plus brachytherapy was 9 and 11 months , respectively ( P=0.04 ) . Cause specific survival was 12 months for those receiving EBRT only , and 15 months for those who received EBRT + brachytherapy ( P=0.10 ) . Survival analysis performed on patients with locoregional disease only revealed a trend towards prolonged overall survival with those receiving EBRT + brachytherapy ( P=0.08 ) . Multivariate analysis revealed grade and stage of disease were correlated with both overall survival and cause specific survival ( P≤0.05 ) . CONCLUSIONS Among patients with unresectable EHC , the addition of brachytherapy to EBRT is associated with a prolonged median overall survival . However , the use of brachytherapy boost decreased in the last decade of the study BACKGROUND / AIMS To prospect ively evaluate our palliative management of unresectable cholangiocarcinoma ( CC ) treated with tailored multimodal oncological therapy . METHODS Between January 2005 and January 2010 , 50 consecutive patients with unresectable CC and jaundice were palliated with percutaneous drainage .  Forty-three patients underwent  metallic-stent implantation followed by brachytherapy . Patients were divided into two arms : the intra-arterial chemotherapy arm ( IA arm , n=17 ) consisted of patients treated with locoregional treatment ( IA admission of Cisplatin and 5-fluorouracil , or chemoembolization with Lipiodol ) and /or systemic chemotherapy , while the systemic chemotherapy arm ( IV arm , n=23 ) included all the other patients , who were treated only with systemic chemotherapy . RESULTS In total , 78 metal self-exp and able stents were placed . Hilar involvement with mass-forming and periductal infiltrating types of CC ( 84 % ) was predominant . The average number of percutaneous interventional procedures was 11.61 per patient ( range , 4 - 35 ) . The median overall survival from diagnosis of disease for all patients was 13.5 months ( range , 11.0 - 18.8 months ) . The median overall survival times were 25.2 months ( range , 15.2 - 31.3 months ) and 11.5 months ( range , 8.5 - 12.6 months ) in the IA and IV arms , respectively ( p<0.05 ) . The 1- , 2- , and 3-year survival rates in the IA and IV arms were 88.2 % , 52.9 % , and 10.1 % and 43.5 % , 25.4 , and 0 % , respectively . There were no major complications ( WHO III/IV ) due to interventional procedures . CONCLUSIONS We could reach acceptable prognosis in patients with unresectable CC using complex tailored oncological therapy . However , the main limitations of prolonging survival are performance status , patient compliance and the maintaining of biliary tract patency Background Unresectable cholangiocarcinoma ( CCC ) has a poor prognosis . Patients with intrahepatic CCC have a very limited benefit from systemic chemotherapy ( ChT ) . The aim of this prospect i ve study was to evaluate the feasibility , safety , and efficacy of conventional transarterial chemoembolization ( cTACE ) with mitomycin-C and of irinotecan-eluting beads ( iDEB-TACE ) , and to retrospectively compare them with ChT with oxaliplatin and gemcitabine . Material s and methods Between June 2002 and June 2010 , three independent prospect i ve trials were carried out and compared retrospectively . Following predefined study protocol s , 26 patients with histologically proven intrahepatic CCC were treated with iDEB-TACE ( 200 mg irinotecan ) , 10 patients were treated with cTACE using 15 mg mitomycin-C mixed with 5–10 ml of ionized oil ( lipiodol ) , followed by embolization with gelfoam , and 31 patients received systemic ChT with gemcitabine and oxaliplatin .  Treatment response and progression-free survival ( PFS ) were assessed by computer tomography or MRI every 2 months according to Response Evaluation Criteria in Solid Tumors . Clinical and laboratory data were assessed for side-effects according to National Cancer Institute-Common Toxicity Criteria . Results iDEB-TACE result ed in PFS of 3.9 months and overall survival ( OS ) of 11.7 months , compared with a PFS of 1.8 months and OS of 5.7 months , respectively , in patients treated with cTACE , and a PFS of 6.2 months and OS of 11.0 months , respectively , in patients treated with oxaliplatin and gemcitabine . The medium follow-up of patients treated with iDEB-TACE was 12 months ; 2 months after treatment , 13 patients ( 50 % ) had progressive disease , 11 patients ( 42 % ) had stable disease , and one patient had a partial response and became eligible for secondary liver resection . Local tumor control was achieved in 66 % of patients ; 4 % had a partial response , 62 % had stable disease , and 27 % progressive disease . Common Toxicity Criteria grade III or IV toxicities for iDEB-TACE were abdominal pain ( n=7 ) , hepatic abscess ( n=1 ) , pleural empyema due to biliary leakage ( n=1 ) , and one death due to cholangitis with hepatic failure in a patient with liver cirrhosis .  No hematological side-effects were observed . Almost every patient experienced a ‘ postembolization syndrome ’ with low- grade fever , nausea , and abdominal pain for up to 2 weeks . Conclusion This is the first study demonstrating that treatment of patients suffering from intrahepatic CCC with iDEB-TACE is safe in patients with normal liver function , and results in a prolongation of PFS and OS . Local tumor control , PFS and OS seem similar to systemic ChT with oxaliplatin and gemcitabine , but superior to cTACE PURPOSE To present data on safety , antitumoral response , and survival following yttrium-90 ( (90)Y ) radioembolization for patients with unresectable intrahepatic cholangiocarcinoma ( ICC ) . MATERIAL S AND METHODS The present study exp and s on the cohort of 24 patients with ICC described in a pilot study , and includes 46 patients treated with (90)Y radioembolization at a single institution during an 8-year period . Via retrospective review of a prospect ively collected data base , patients were stratified by performance status , tumor distribution ( solitary or multifocal ) , tumor morphology ( infiltrative or peripheral ) , and presence/absence of portal vein thrombosis . Primary endpoints included biochemical and clinical toxicities , and secondary endpoints included imaging response ( World Health Organization [ WHO ] and European Association for the Study of Liver Disease [ EASL ] criteria ) and survival . Uni-/multivariate analyses were performed . RESULTS Ninety-two treatments were performed , with a mean of two per patient . Fatigue and transient abdominal pain occurred in 25 patients ( 54 % ) and 13 patients ( 28 % ) , respectively . Treatment-related gastroduodenal ulcer developed in one patient ( 2 % ) . WHO imaging findings included partial response ( n = 11 ; 25 % ) , stable disease ( n = 33 ; 73 % ) , and progressive disease ( n = 1 ; 2 % ) . EASL imaging findings included partial/complete response ( n = 33 ; 73 % ) and stable disease ( n = 12 ; 27 % ) . Survival varied based on presence of multifocal ( 5.7 mo vs 14.6 mo ) , infiltrative ( 6.1 mo vs 15.6 mo ) , and bilobar disease ( 10.9 mo vs 11.7 mo ) . Disease was converted to resectable status in five patients , who successfully underwent curative ( ie , R0 ) resection . CONCLUSIONS Radioembolization with (90)Y is safe and demonstrates antitumoral response and survival benefit in select patients with ICC . Results are most pronounced in patients with solitary tumors , for whom conversion to curative resection is possible Intrahepatic cholangiocarcinoma is increasing in frequency worldwide , but radical surgical treatment is practicable in 30 - 40 % of cases . The median survival without therapy is about 8 months , increased to 12 months in combination with systemic chemotherapy . Therefore , locoregional therapies , such as , radiofrequency ablation or transarterial chemoembolization have been employed . Radioembolization with yttrium-90 microspheres ( 90Y-TARE ) is a novel intrarterial treatment which could be included in the armamentarium of treatment options , having shown higher median survival ( up to 22 months ) and low complication rates . Evidence -based algorithms for staging and allocation to treatment should be defined in the future , after robust results obtained through r and omized controlled trials , thus establishing the exact role and timing of 90Y-TARE in the treatment protocol of unresectable intrahepatic cholangiocarcinoma The objective of this report was to present data from an open‐label cohort study in which patients with intrahepatic cholangiocarcinoma ( ICC ) underwent radioembolization with yttrium‐90 ( 90Y ) microspheres PURPOSE Extrahepatic cholangiocarcinomas ( EHC ) are rare tumors of the biliary tree because of their low incidence , large r and omized studies examining radiotherapy ( RT ) for EHC have not been performed . The purpose of this study was to examine the role of adjuvant and palliative RT in the treatment of EHC in a large patient population . METHODS AND MATERIAL S This was a retrospective analysis of 4,758 patients with EHC collected from the Surveillance , Epidemiology , and End Results data base . The primary endpoint was overall survival . RESULTS Patients underwent surgery ( 28.8 % ) , RT ( 10.0 % ) , surgery and RT ( 14.7 % ) , or no RT or surgery ( 46.4 % ) . The median age of the patient population was 73 years ( range , 23 - 104 ) , 52.5 % were men , and 80.7 % were white . The median overall survival time was 16 months ( 95 % confidence interval [ CI ] 15 - 17 ) , 9 months ( 95 % CI 9 - 11 ) , 9 months ( 95 % CI 9 - 10 ) , and 4 months ( 95 % CI 3 - 4 ) for surgery and RT , surgery , RT , and no RT or surgery , respectively . The overall survival was significantly different between the surgery and surgery and RT groups ( p < .0001 ) and RT and no RT or surgery groups ( p < .0001 ) on the log-rank test . The propensity score-adjusted analyses of surgery and RT vs. surgery ( hazard ratio , 0.94 ; 95 % CI , 0.84 - 1.05 ) were not significantly different , but that for RT vs. no RT or surgery ( hazard ratio , 0.61 ; 95 % CI , 0.54 - 0.70 ) was significantly different . CONCLUSION These results suggest that palliative RT prolongs survival in patients with EHC . The benefit associated with surgery and RT was significant on univariate analysis but not after controlling for potential confounders using the propensity score . Future studies should evaluate the addition of chemotherapy and biologic agents for the treatment of EHC PURPOSE To evaluate the effect of radiation therapy including intraluminal brachytherapy with iridium-192 on survival of patients with malignant biliary strictures ( cholangiocarcinoma , histologically improved ) treated with metallic stent  in a prospect i ve r and omised study . METHOD AND MATERIAL S In the prospect i ve r and omised study , 21 patients with cholangiocarcinoma were treated with implantation of percutaneous stents followed with intraluminal Ir-192 brachytherapy ( mean dose 30 Gy ) and external radiotherapy ( mean dose 50 Gy ) and 21 patients were treated only with stents insertion . We did not find any statistically significant differences in age and tumor localization between these two groups of patients . RESULTS All the patients died . In the group of patients treated with brachytherapy and with stent implantation , the mean survival time was 387.9 days . In the group of patients treated only with stent insertion the mean survival was 298 days . In effort to eliminate possible effect of external radiotherapy we treated the control group of eight patients with cholangiocarcinoma by stent insertion and brachytherapy only . CONCLUSION Our results show that combined radiation therapy could extend the survival in the patients with cholangiocarcinoma obstruction Intrahepatic cholangiocarcinoma ( ICC ) is a rare life-threatening disease , whose only treatment with potential for cure is surgical resection . However , only 27 % of patients at most are suitable for surgery when first diagnosed . For patients with unresectable disease , therapeutic options are chemotherapy or chemoradiation . We evaluated the feasibilty and safety of oxaliplatin-eluting microspheres transarterial chemoembolization ( OEM-TACE ) associated with chemotherapy ( ChT ) in patients affected by unresectable ICC . Between December 2005 and May 2008 we treated nine patients ( six female and three male ) with unresectable ICC . All patients had undergone OEM-TACE associated with chemotherapy with oxaliplatin and gemcitabine .  A retrospective comparison was carried out with a historical group of 11 patients treated with ChT only , estimating the prevalence of adverse effects and the median survival of the two groups . A total of 30 TACEs were performed during the observational time ( ranging from one to seven procedures per patient ) . OEM-TACEs were followed by few adverse effects ( AEs ) , without G4 AEs , according to CTACAE 3.0 . According to RECIST criteria , 44 % ( 4/9 ) of patients achieved partial responses and 56 % ( 5/9 ) stabililization of disease . Overall survival analysis in the two groups showed a significantly increased survival in patients treated with ChT and OEM-TACE , with respect to those treated with ChT ( 30 vs. 12.7 months ; p = 0.004 ) . In conclusion , in our experience OEM-TACE associated with ChT in the treatment of advanced unresectable ICC is a safe and feasible treatment causing no major adverse events . Although RECIST criteria can underestimate the rate of responses in patients treated with locoregional therapies , we achieved very encouraging results . A r and omized multicentric trial is warranted to assess the actual superiority of OEM-TACE associated with ChT compared to conventional chemotherapy BACKGROUND Photodynamic therapy ( PDT ) in combination with stent have shown promising results in the treatment of biliary tract cancer ( BTC ) in patients not suitable for surgery . Chemotherapy has been shown to improve survival in patients with local advanced and metastatic BTC . MATERIAL AND METHODS In the current r and omized trial the combination of chemotherapy and stent with and without temoporfin ( Foscan ) photodynamic therapy ( PDT ) , with a primary endpoint on feasibility and safety , has been performed . Ten patients in each group . RESULTS No serious , acute procedure-related complication related to PDT or the treatment combination was seen . The number of patients with cholangitis was equal in both groups . In the PDT group -- arm A -- two patients had cutaneous erythema after sun exposition , one of them with a localized blister . No neutropenic infection was seen . Quality of Life ( QoL ) was similar in both treatment groups . Progression free survival was numerically longer in the PDT group . CONCLUSION The treatment combination was feasible . There was no serious complication related to PDT or the treatment combination . Number of cholangitis was equal in both groups , two abscesses were observed in the PDT group . Progression free survival was numerically longer in the PDT group Purpose To evaluate the efficacy and safety of hepatic arterial infusion ( HAI ) of oxaliplatin and 5-fluorouracil for advanced perihilar cholangiocarcinoma ( PCC ) in this prospect i ve phase II study . Material s and Methods The protocol was approved by the local ethics committee , and all patients gave informed consent . Patients with nonresectable PCC were included in a prospect i ve , open phase II study investigating HAI through interventionally implanted port catheters . HAI consisted of infusions of oxaliplatin 40 mg/m2 for 2 hours , followed by 5-fluorouracil 800 mg/m2 for 22 hours on days 1 - 3 every 3 - 4 weeks . A maximum of six cycles of HAI were applied for tumor control patients followed by maintenance with oral capecitabine until tumor progression . The primary end points were tumor response and progression-free survival ( PFS ) . The secondary end points were local PFS , overall survival , and adverse events . Kaplan-Meier methodology and Cox regression analysis were used to evaluate the risk factors for survival . Results Between 2012 and 2015 , 37 patients were enrolled . The overall response rate was 67.6 % ( 25 of 37 ) , and the disease control rate was 89.2 % ( 33 of 37 ) . Median PFS , local PFS , and overall survival were 12.2 , 25.0 , and 20.5 months , respectively . All three survival lengths in patients with periductal infiltrating pattern were found to be significantly longer than those in patients with mass-forming pattern ( P < .001 , hazard ratio < 0.2 ) . Macroscopic growth patterns ( P = .018 ) and number of HAI cycles ( P < .001 ) were independent risk factors of survival . The most frequent adverse events were grade s 1 and 2 gastrointestinal side effects and sensory neuropathy in 31 ( 83.8 % ) and 28 ( 75.7 % ) patients , respectively . Conclusion HAI with oxaliplatin and 5-fluorouracil may be an encouraging treatment choice for advanced PCC due to its high tumor control , survival benefit , and low toxicity , especially in patients with periductal infiltrating pattern . © RSNA , 2016
Background : Cholangiocarcinoma ( CC ) is the second most primary liver malignancy with increasing incidence in Western countries .
Currently , surgical R0 resection is regarded as the only potentially curative treatment .
The results of systemic chemotherapy and best supportive care ( BSC ) in patients with metastatic disease are often disappointing in regard to toxicity , oncologic efficacy , and overall survival .
In current practice , the use of different locoregional therapies is increasingly more accepted .
For localized ICC , either primary or recurrent , radiofrequency ablation ( RFA ) is by far the most commonly used thermal ablation modality .
Conclusion : Dedicated locoregional therapies are commonly used for primary and recurrent ICC as well as liver-only and liver-dominant extrahepatic metastatic disease .