Unresectable Cholangiocarcinoma Research Articles

Chemotherapy for hilar cholangiocarcinoma (HCCA): Outcomes in a tertiary referral centre

Background: Hilar cholangiocarcinoma (HCCA) is a malignant tumour arising from the bifurcation of the common hepatic duct. Most patients present with unresectable disease, and of those who are resected, recurrence rates remain high. Palliative chemotherapy may increase overall survival (OS) in patients with unresectable cholangiocarcinoma, with data conflicting regarding the role of adjuvant chemotherapy. No studies have investigated the role of palliative chemotherapy in the context of recurrent disease. We aimed to investigate the influence of chemotherapy on OS for non-resected patients and resected patients with disease recurrence for HCCA.

Discussion of: Is there a role for Ytrrium-90 in the treatment of unresectable and metastatic intrahepatic cholangiocarcinoma?

Discussion of: Is there a role for Ytrrium-90 in the treatment of unresectable and metastatic intrahepatic cholangiocarcinoma?

Safety and efficacy of nanoknife ablation for unresectable hilar cholangiocarcinoma

Objective To evaluate the safety and curative effect of nanoknife ablation in the treatment of unresectable hilar cholangiocarcinoma. Methods 15 patients with unresectable hilar cholangiocarcinoma received nanoknife ablation treatment from March 2016 to May 2017. The clinical variables of the patients before and after operation were analyzed. Results The operations in all the patients carred out successfully. Cardiac arrhythmia occurred in some patients during the operation accidentally.The level of CA19-9 increased significantly on postoperative day 1, 3 and then gradually decreased in 13 patients; one patient had no significant change of CA19-9, and the data for another patient was always in the normal range. The liver function of all patients gradually improved after operation, and the level of total bilirubin, AST and ALT showed a downward trend. The myocardial enzyme in all the patients increased on postoperative day 1, then returned to normal within the following 5 days. Postoperative complications included atrial fibrillation (1 case), upper gastrointestinal bleeding (1 case). The recanalization rates of the bile duct at 2 weeks, 1 month, and 2 months after surgery were 66.6%, 86.6%, and 93.3%, respectively. Conclusion Nanoknife ablation has superior safety, noteworthy efficacy and less complications in the treatment of the unresec-table hilar cholangiocarcinoma in the short term. Key words: Hilar cholangiocarcinoma, unresectable; Nanoknife ablation; Bile duct recanalization

Downstaging of unresectable intrahepatic or hilar cholangiocellular carcinoma by selective intra-arterial floxuridine and systemic cisplatin and gemcitabine. A dose finding single center phase IIa study.

478 Background: Patients with unresectable cholangiocarcinomas (CCC) have a poor prognosis even if palliative systemic chemotherapy is offered. A combined approach of systemic and intrahepatic chemotherapy may improve local control rates and allow downstaging. The aim of the study was to determine the maximum tolerated dose (MTD) of systemic intravenous gemcitabine in combination with intravenous cisplatin and hepatic arterial infusion with floxuridine in patients with unresectable intrahepatic or hilar CCC. Safety, toxicity, response rates and resectability rates after 3 months of combination treatment are reported. Methods: 12 patients were treated within a 3+3 dose escalation algorithm with 600, 800 or 1000 mg/m2 gemcitabine and a fixed dose of cisplatin 25 mg/m2 systemic chemotherapy on day 1, 8 every 3 weeks for 4 cycles and floxuridine 0,2 mg/kg on day 1-14 continous hepatic intra-arterial chemotherapy every 4 weeks for 3 cycles. PET/CT and/or CT scan was performed after 12 weeks. Results: The MTD of gemcitabine was 800 mg/m2 in this setting. Dose-limiting toxicities were recurrent biliary tract infections (n = 1) and neutropenic fever (n = 1). Response rates were: 27% partial remission and 73% stable disease. Although none of the patients achieved resectability after 3 months, 3-year-overall survival (OS) was 33%, median OS 21,9 months (1-49) and median progression-free survival 10,5 months (2-40). Conclusions: Combination of systemic gemcitabine and cisplatin plus intraarterial floxuridine is feasible and appears effective in disease control, but achievement of resectability seems challenging. Randomized trials comparing this combination to gemcitabine/cisplatin alone are warranted. Clinical trial information: NCT01692704.

Phase I study of hepatic arterial infusion (HAI) therapy with floxuridine (FUDR) combined with systemic gemcitabine and oxaliplatin in patients with locally advanced intrahepatic cholangiocarcinoma (ICC).

417 Background: The standard of care for unresectable ICC is palliative systemic chemotherapy with cisplatin and gemcitabine. HAI therapy with FUDR in ICC resulted in high response rates [Kemeny 2011]. The use of HAI FUDR with systemic chemotherapy may improve outcomes. We conducted a phase 1 study of HAI FUDR with systemic gemcitabine and oxaliplatin. Methods: We enrolled patients in 3 cohorts: FUDR 0.16mg/kg/day x 14 days (Cohort 1), FUDR 0.12 mg/kg/day x 14 days with gemcitabine 1000mg/m2 on days 1, 8, 15 (Cohort 2), and FUDR 0.10 mg/kg/day x 14 days with gemcitabine 800mg/m2 days 1, 15 and oxaliplatin 85mg/m2 days 1, 15 (Cohort 3). The primary endpoint was the recommended phase 2 dose (RP2D) for Cohort 3. DLTs were assessed during cycle 1. Secondary objectives were response rate and survival. Results: We enrolled 24 patients, 6 male, age range 42-81 years (median 64). No DLTs were observed in Cohort 1 (FUDR). In Cohort 2 (FUDR + Gem), the addition of gemcitabine at 1000mg/m2 days 1, 8, 15 resulted in grade 3 LFT elevation in 2 patients; for subsequent patients, the gemcitabine dose was reduced to 800mg/m2, and no further DLT were noted. No DLT were observed in Cohort 3 (FUDR + GemOx). 10 patients experienced partial responses and conversion to resectable disease occurred in all cohorts. No other significant toxicities occurred. Conclusions: FUDR via HAI with systemic gemcitabine and oxaliplatin is well-tolerated in patients with unresectable cholangiocarcinoma, with a high rate of response and disease control, allowing for resection in some patients. Our RP2D is FUDR 0.10 mg/kg/day x 14 days, with gemcitabine 800mg/m2 days 1, 15 and oxaliplatin 85mg/m2 days 1, 15. Collaboration with MSKCC is ongoing. Clinical trial information: NCT01525069. [Table: see text]

Hepatic arterial infusion chemotherapy (HAIC) using 5-fluorouracil with systemic pegylated interferonα-2B for unresectable advanced intrahepatic cholangiocarcinoma.

428 Background: Cholangiocarcinoma is categorized into intrahepatic cholangiocarcinoma (ICC) and extrahepaticcholangiocarcinoma (ECC). The prognosis of ICC is far worse than that of ECC. In this study, the efficacy of hepatic arterial infusion chemotherapy (HAIC) using 5-fluorouracil (5-FU) combined with subcutaneous administration of pegylated interferon (PEG-IFN) α-2b for patients with unresectable advanced ICC was evaluated. Methods: The subjects were 21 unresectable advanced ICC patients treated using subcutaneous PEG-IFN α-2b (50-100 μg on day 1 of every week, for 4 weeks) and intra-arterial infusion of 5-FU (250 mg/day for 5 h on days 1-5 of every week, for 4 weeks). One treatment cycle lasted 4 weeks. Therapy was discontinued in patients with progressive disease (PD). For responses other than PD, treatment was repeated for ≥ 1 cycle. Results: The objective early response rate was 60.0 %. Cumulative survival rates were 71.6 % at 6 months, 53.7 % at 12 months, 28.6 % at 18 months, and 14.3 % at 24 months. Median survival time was 14.6 months. All adverse reactions were controllable by temporary suspension of treatment. Serious complications and treatment related deaths were not observed. Conclusions: The combination therapy of PEG-IFN α-2b and 5-FU for unresectable advanced ICC seems to be better than the results of the previous studies. In addition, most adverse effects are transient and well tolerated. Although a larger prospective study involving a larger population of patients with advanced ICC is needed to evaluate this combination therapy, this combination therapy may be useful for patients with unresectable advanced ICC as one of the therapeutic option.

Laser ablation of the biliary tree: in vivo proof of concept as potential treatment of unresectable cholangiocarcinoma

Objectives: The palliative treatment of cholangiocarcinoma is based on stent placement with well-known procedure-related complications. Consequently, alternative energy-based techniques were put forward with controversial long-term results. This study aims to evaluate the safety and effectiveness of biliary tree laser ablation (LA) in terms of: (i) absence of perforation, (ii) temperature increase, (iii) induced thermal damage in in vivo models.Materials and methods: The common bile duct and cystic ducts of two pigs were ablated with a diode laser (circumferential irradiation pattern) for 6 and 3 min at 7 W. Laser settings were chosen from previous ex vivo experiments. Local temperature was monitored through a fibre Bragg grating (FBG) sensor embedded into the laser delivery probe. Histopathological analysis of the ablated specimen was performed through in situ endomicroscopy, haematoxylin and eosin (H&E) and nicotinamide adenine dinucleotide (NADH) stains.Results: Temperature reached a plateau of 53 °C with consequent thermal damage on the application area, regardless of laser settings and application sites. No perforation was detected macroscopically or microscopically. At the H&E stain, wall integrity was always preserved. The NADH stain allowed to evaluate damage extension. It turned out that the ablation spreading width depended on application time and duct diameter. In situ endomicroscopy revealed a clear distinction between ablated and non-ablated areas.Conclusions: The temperature distribution obtained through LA proved to induce a safe and effective intraductal coagulative necrosis of biliary ducts. These results represent the basis for further experiments on tumour-bearing models for the treatment of obstructive cholangiocarcinoma.

Translating the ABC-02 trial into daily practice: outcome of palliative treatment in patients with unresectable biliary tract cancer treated with gemcitabine and cisplatin

Background: Biliary tract cancer (BTC) is an uncommon cancer with an unfavorable prognosis. Since 2010, the standard of care for patients with unresectable BTC is palliative treatment with gemcitabine plus cisplatin, based on the landmark phase III ABC-02 trial. This current study aims to evaluate the efficacy and safety of gemcitabine and cisplatin in patients with unresectable cholangiocarcinoma and gallbladder cancer in daily practice that meet the criteria for the ABC-02 trial in comparison to patients who did not.Methods: Patients diagnosed with unresectable BTC between 2010 and 2015 with an indication for gemcitabine and cisplatin were included. We divided these patients into three groups: (I) patients who received chemotherapy and met the criteria of the ABC-02 trial, (II) patients who received chemotherapy and did not meet these criteria and (III) patients who had an indication for chemotherapy, but received best supportive care without chemotherapy. Primary outcome was overall survival (OS) and secondary outcome was progression-free survival (PFS).Results: We collected data of 208 patients, of which 138 (66.3%) patients received first line chemotherapy with gemcitabine and cisplatin. Median OS of 69 patients in group I, 63 patients in group II and 65 patients in group III was 9.6 months (95%CI = 6.7–12.5), 9.5 months (95%CI = 7.7–11.3) and 7.6 months (95%CI = 5.0–10.2), respectively. Median PFS was 6.0 months (95%CI = 4.4–7.6) in group I and 5.1 months (95%CI = 3.7–6.5) in group II. Toxicity and number of dose reductions (p = .974) were comparable between the two chemotherapy groups.Conclusion: First-line gemcitabine and cisplatin is an effective and safe treatment for patients with unresectable BTC who do not meet the eligibility criteria for the ABC-02 trial. Median OS, PFS and treatment side effects were comparable between the patients who received chemotherapy (group I vs. group II).

Successful radical surgical resection of initially unresectable intrahepatic cholangiocarcinoma by downsizing chemotherapy with gemcitabine plus cisplatin: a case report

BackgroundIntrahepatic cholangiocarcinoma (ICC) is a subtype of biliary tract cancer (BTC). Recently, downsizing chemotherapy has been applied to initially unresectable BTCs, including ICC.Case presentationWe report a case of liver resection in a 23-year-old woman who was diagnosed with initially unresectable ICC attached to the inferior vena cava, with portal vein (PV) cavernous transformation. Positron emission tomography (PET) showed fluorodeoxyglucose (FDG) uptake in the para-aortic lymph nodes. Upon using downsizing chemotherapy (the combination of gemcitabine [GEM] and cisplatin [CDDP]), the size of tumor reduced by 55% and FDG uptake in the para-aortic lymph node metastases disappeared. A right hemihepatectomy was performed, along with dissection of lymph nodes, including the para-aortic lymph nodes. The PV cavernous transformation was preserved to maintain collateral flow as much as possible, as it was considered to originate from a congenital anomaly. Pathological examination revealed that R0 resection was performed and that there were no viable neoplastic cells remaining in the para-aortic lymph nodes. The patient is alive at 31 months after initial treatment, with a local recurrence.ConclusionDownsizing chemotherapy with GEM plus CDDP followed by radical surgical resection is an attractive treatment for initially unresectable BTC.

Clinical effects of endoscopic radiofrequency ablation for patients with advanced cholangiocarcinoma

Objective To investigate the efficacy and safety of endoscopic radiofrequency ablation on patients with advanced stage unresectable cholangiocarcinoma. Methods Clinical data of 45 cases with unresectable cholangiocarcinoma who underwent endoscopic retrograde cholangiopancreatography from October 2011 to October 2014 were collected. The patients were divided into two groups: the group A included 23 cases undergoing radiofrequency ablation, and the group B included 22 cases without ablation. The occurrence of complications, the postoperative levels of CA19-9 and total bilirubin (TBIL) in blood plasma, the patency of stents, and survival period were compared between the two groups. Results All of the 45 patients completed treatment, and no perforation, bleeding and bile leakage occurred. In the group A, 2 patients got fever and 5 patients got pancreatitis after operation, and the number in the group B was 3 and 4, respectively. Their symptoms disappeared after suitable treatment. The postoperative pain rate in group A (21.7%, 5/23) was significantly lower than that of group B (54.5%, 12/22, χ2=5.148, P=0.023). At 7th day of post-operation, the levels of CA19-9 in the two groups were 960.5±362.7 U/mL and 979.3±378.1 U/mL, respectively, and the levels of TBIL were 95.25±28.36 μmol/L and 98.75±20.76 μmol/L, respectively, which were not significantly different between the two groups(P>0.05), but were significantly decreased compared with the levels of pre-operation (P<0.05). The patency of self-expandable metal stent in group A (60.0%, 6/10) was significantly higher than that of group B (10.0%, 1/10, χ2=5.495, P=0.019) 9 months after operation. Kaplan-Meier analysis showed that the median survival time in the two groups had no statistical difference[271.0 days(95%CI: 168.4-373.4days) VS 245.0 days (95%CI: 200.3-289.7 days), χ2=1.380, P=0.258]. Conclusion For the patients with advanced unresectable cholangiocarcinoma, endoscopic radiofrequency ablation is able to relieve cancer pain, prolong the patency of stents, and improve the life quality, which deserves clinical applications. Key words: Biliary tract neoplasms; Cholangiopancreatography, endoscopic retrograde; Catheter ablation

Chemotherapy for hilar cholangiocarcinoma (HCCA): Outcomes in a tertiary referral centre

Background: Hilar cholangiocarcinoma (HCCA) is a malignant tumour arising from the bifurcation of the common hepatic duct. Most patients present with unresectable disease, and of those who are resected, recurrence rates remain high. Palliative chemotherapy may increase overall survival (OS) in patients with unresectable cholangiocarcinoma, with data conflicting regarding the role of adjuvant chemotherapy. No studies have investigated the role of palliative chemotherapy in the context of recurrent disease. We aimed to investigate the influence of chemotherapy on OS for non-resected patients and resected patients with disease recurrence for HCCA.

Chemoradiation Therapy in Unresected Extrahepatic Cholangiocarcinoma is Associated with Improved Overall Survival Compared to Chemotherapy Alone: A Propensity Score Matched Analysis From the National Cancer Database

Chemoradiation Therapy in Unresected Extrahepatic Cholangiocarcinoma is Associated with Improved Overall Survival Compared to Chemotherapy Alone: A Propensity Score Matched Analysis From the National Cancer Database

Abstract CT063: Phase 2, open-label, multicenter study of the efficacy and safety of INCB054828 in patients (pts) with advanced, metastatic, or surgically unresectable cholangiocarcinoma (CCA) with inadequate response to prior therapy

Abstract Background: Dysregulation of fibroblast growth factor receptor (FGFR) signaling by FGFR translocations and activating mutations is implicated in many cancers, including CCA. FGFR2 translocations are the most common FGFR alterations, which occur in ~13% of pts with intrahepatic CCA and involve a variety of fusion partners/breakpoints. INCB054828 is a novel, orally available, selective inhibitor of FGFR1, FGFR2, and FGFR3 tyrosine kinase activities (AACR 2015; Abstract 771). Methods: This phase 2, open-label trial will evaluate INCB054828 monotherapy in pts with advanced/metastatic or surgically unresectable CCA (Table; NCT02924376). Pts will be prescreened centrally for FGF/FGFR status and enrolled in the following cohorts prior to start of treatment: FGFR2 translocations (Cohort A); other FGF/FGFR alterations (Cohort B); no FGF/FGFR alterations (Cohort C; negative control for effects of FGF/FGFR alterations on objective response rate [ORR]). Pts must be aged ≥18 years, with Eastern Cooperative Oncology Group performance status ≤2, disease progression after ≥1 prior systemic therapy, and no prior use of selective FGFR inhibitors. Pts will self-administer INCB054828 orally at a starting dose of 13.5 mg once-daily on a 21-day cycle (2 weeks on; 1 week off); treatment will continue until disease progression or unacceptable toxicity. The primary endpoint will be ORR (complete or partial response per independent radiologic review committee using Response Evaluation Criteria in Solid Tumors v1.1) in pts with FGFR2 translocations (Cohort A). Secondary endpoints will include ORR in pts positive or negative for any FGF/FGFR alterations and duration of response, progression-free survival, overall survival, and safety (all cohorts). The study is currently open for enrollment (estimated primary completion date, April, 2018). Study DesignPrescreen for FGF/FGFR Status• Adults with metastatic/surgically unresectable cholangiocarcinoma with disease progression after ≥1 previous systemic treatment- FGFR2 translocations → cohort A (n~60)- Other FGF/FGFR alterations → cohort B (n~20)- No FGF/FGFR alterations → cohort C (n~20)Screen for eligibility criteria and patient characteristics• Eastern Cooperative Oncology Group performance status ≤2• Adequate hepatic function (total bilirubin ≤1.5 × upper limit of normal [ULN; ≤2.5 × ULN for Gilbert syndrome or disease involving liver]; aminotransferases &amp;lt;2.5 × ULN [&amp;lt;5 × ULN with liver metastases])• Adequate renal function (creatinine clearance ≥30 mL/min; serum phosphate &amp;gt;institutional ULN; serum calcium &amp;gt;institutional normal range; potassium &amp;gt;institutional lower limit of normal)• Life expectancy ≥12 weeksEnroll and initiate INCB054828 treatment• Oral once daily dosing: 21-day (2-weeks-on/1-week-off) cycleStart response assessment after cycle 2• Stable disease/partial or complete response → continue treatment with restaging after cycle 4; imaging assessments increase to every 3 cycles after cycle 4• Disease progression → discontinue treatment; safety and survival follow-up Citation Format: Mitesh J. Borad, S. Lindsey Davis, Maeve A. Lowery, Ekaterine Asatiani, Christine F. Lihou, Huiling Zhen, Ghassan K. Abou-Alfa. Phase 2, open-label, multicenter study of the efficacy and safety of INCB054828 in patients (pts) with advanced, metastatic, or surgically unresectable cholangiocarcinoma (CCA) with inadequate response to prior therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT063. doi:10.1158/1538-7445.AM2017-CT063

Phase 2, open-label, multicenter study of the efficacy and safety of INCB054828 in patients (pts) with advanced, metastatic, or surgically unresectable cholangiocarcinoma (CCA) with inadequate response to prior therapy.

TPS4145 Background: Dysregulation of fibroblast growth factor receptor (FGFR) signaling by FGFR translocations and activating mutations is implicated in many cancers, including CCA. FGFR2 translocation, the most common FGFRalteration, occurs in ~13% of pts with intrahepatic CCA. INCB054828 is a novel, orally available, selective inhibitor of FGFR1, FGFR2, and FGFR3 tyrosine kinase activity (AACR 2015; Abstract 771). Methods: This phase 2, open-label trial will evaluate INCB054828 monotherapy in pts with advanced/metastatic or unresectable CCA (NCT02924376). Pts will be prescreened locally or centrally for FGF/FGFR status prior to enrollment (Table): FGFR2 translocation (Cohort A); other FGF/FGFR alteration (Cohort B); no FGF/FGFR alteration (Cohort C; negative control for effects of FGF/FGFR alteration on objective response rate [ORR]). Eligibility criteria include: age ≥18 years; ECOG performance status ≤2; adequate liver and renal function; life expectancy ≥12 wks; disease progression after ≥1 prior systemic therapy; no prior use of selective FGFR inhibitors. Pts will self-administer INCB054828 orally at a starting dose of 13.5 mg QD on a 21-day cycle (2 wks on; 1 wk off); treatment will continue until disease progression or unacceptable toxicity. The primary endpoint will be ORR (complete or partial response, independent radiologic review committee, RECIST v1.1) in pts with FGFR2 translocation (Cohort A). Secondary endpoints include ORR in pts positive or negative for any FGF/FGFRalteration and duration of response, PFS, OS, and safety (all cohorts). The study has currently enrolled 2 pts (recruitment ongoing; estimated primary completion, April 2018). Clinical trial information: NCT02924376. [Table: see text]

The oral VEGF receptor tyrosine kinase inhibitor pazopanib in combination with the MEK inhibitor trametinib in advanced cholangiocarcinoma

Background:Cholangiocarcinoma is an aggressive malignancy with limited therapeutic options. MEK inhibition and antiangiogenic therapies have individually shown modest activity in advanced cholangiocarcinoma, whereas dual inhibition of these pathways has not been previously evaluated. We evaluated the safety and efficacy of combination therapy with the oral VEGF receptor tyrosine kinase inhibitor pazopanib plus the MEK inhibitor trametinib in patients with advanced cholangiocarcinoma.Methods:In this open-label, multicentre, single-arm trial, adults with advanced unresectable cholangiocarcinoma received pazopanib 800 mg daily and trametinib 2 mg daily until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS) with secondary end points including overall survival (OS), response rate, and disease control rate (DCR).Results:A total of 25 patients were enrolled and had received a median of 2 prior systemic therapies (range 1–7). Median PFS was 3.6 months (95% CI: 2.7–5.1) and the 4-month PFS was 40% (95% CI: 24.7–64.6%). There was a trend towards increased 4-month PFS as compared with the prespecified null hypothesised 4-month PFS of 25%, but this difference did not reach statistical significance (P=0.063). The median survival was 6.4 months (95% CI: 4.3–10.2). The objective response rate was 5% (95% CI: 0.13–24.9%) and the DCR was 75% (95% CI: 51%, 91%). Grade 3/4 adverse events attributable to study drugs were observed in 14 (56%) and included thrombocytopenia, abnormal liver enzymes, rash, and hypertension.Conclusions:Although the combination of pazopanib plus trametinib had acceptable toxicity with evidence of clinical activity, it did not achieve a statistically significant improvement in 4-month PFS over the prespecified null hypothesised 4-month PFS.

Hepatic intra-arterial and systemic chemotherapy followed by maintenance therapy for the treatment of cholangiocarcinoma.

The aim is to report clinical outcomes of hepatic intra-arterial (IACHT) and systemic chemotherapy (SCHT), followed by gemcitabine-based maintenance therapy (maintenance), for the treatment of relapsed or unresectable cholangiocarcinoma. In this retrospective observational study, 145 cholangiocarcinoma patients were treated with Epirubicin-Cisplatin as IACHT associated with Capecitabine or 5-fluorouracil as SCHT. Maintenance was performed with gemcitabine-based schedule. Toxicity was assessed with NCI-CTCAE and tumor response with RECIST 1.1. Tumor response was complete in 1%, partial in 20%, stable disease in 48% and progression in 31% of patients (3months after therapy). The most frequent adverse events were: anemia (24%), nausea and vomiting (33%), alopecia (60%). Cholangiocarcinoma patients may benefit from IAHCT-SCHT. Maintenance may prolong clinical benefits. ClinicalTrials.gov registry Identifier: NCT01920503.

Percutaneous stenting for transhepatic cholangiojejunostomy

Objective: To describe a new technique that can be used for palliative treatment for unresectable cholangiocarcinoma. Methods: The procedure was performed on a patient with recurrence of IC after two years of a left hepatectomy. Since it was a case of advanced disease with no possibility of resection, we performed a modified Longmire procedure (intrahepatic cholangiojejunostomy). Levels of bilirubin remained elevated after the surgical procedure, we decided to associate an internal drainage using a stent promoting jaundice relief using the preview modified Longmire procedure. Results: Patient remained jaundice free until she died of other complications of the disease after 04 months. During this period of time patients presented normal levels of bilirubin. Did not present acute cholangitis and referred better quality of life since she did not have external drains. Conclusion: We conclude that this technique can be an alternative palliative treatment for patients with advanced cholangiocarcinoma or even in cases of complex benign strictures of the biliary tree.

Liver Transplant for Nonhepatocellular Carcinoma Malignancy.

Liver transplant is now an acceptable and effective treatment for specific nonhepatocellular malignancies. Worldwide, hilar cholangiocarcinoma accounts for 3% of all primary gastrointestinal malignancies and for 10% of primary hepatobiliary malignancies. For patients who have early-stage, unresectable cholangiocarcinoma, liver transplant preceded by neoadjuvant radiotherapy can result in tumor-free margins, accomplish a radical resection, and treat the underlying primary sclerosing cholangitis when present. Hepatic epithelioid hemangioendothelioma is a rare tumor of vascular origin with a variable malignant potential. Excellent results have been reported with liver transplant for patients with unresectable hepatic epithelioid hemangioendothelioma, with 1-year and 10-year survival rates of 96% and 72%. Hepatoblastoma is the most common primary hepatic malignancy in children. The long-term survival rate after transplant ranges from 66% to 77% in patients with unresectable tumors and good response to chemotherapy. Metastatic liver disease is not an indication for liver transplant, with the exception of cases in which the primary tumor is a neuroendocrine tumor. Indication for liver transplant for hepatic metastasis from neuroendocrine tumors is mainly for patients with unresectable tumors and for palliation of medically uncontrollable symptoms. Posttransplant survival in those patients with low tumor activity index is excellent, despite recurrence of the tumor. Some recent data on liver transplant for unresectable hepatic metastases from colorectal cancer have reported limited survival benefits compared with previous reports. However, due to the high rate of tumor recurrence in a very short time after liver transplant, especially in the era of organ shortage, this indication has not been favored by the transplant community. The indications for liver transplant for nonhepatocellular carcinoma malignancy and its limitations have evolved dramatically over the past decades and will continue to be redefined through future research and investigations.

Effectiveness and safety of sorafenib for unresectable and advanced intrahepatic cholangiocarcinoma: A pilot study.

405 Background: Patients with unresectable and advanced intrahepatic cholangiocarcinoma (ICC) usually have short survival due to a lack of effective treatment. This multicenter, single arm, open labeled, prospective study was conducted to evaluate the effectiveness and safety of the multikinase inhibitor, sorafenib, combined with best supportive care (BSC) in these patients. Methods: Forty-four patients with unresectable and advanced ICC were treated with sorafenib (400 mg, twice daily) and BSC. The primary endpoint was disease control rate (DCR) at week 12; secondary endpoints included time to progression (TTP), progression-free survival (PFS), overall survival (OS), duration of therapy (DOT), and adverse events (AEs). Results: The DCR at week 12 was 15.9%. The median TTP was 5.6 months, and the median PFS and OS were 3.2 and 5.7 months (95% confidence interval [CI]: 2.4-4.1 months; 3.7-8.5 months), respectively. The median DOT was 1.8 months (95% CI: 1.9-3.9 months). Grades 1 and 2 AEs occurred in 75% of patients, and one grade 4 AE (hand and foot skin reaction) was observed in one patient. Conclusions: This is the first and only prospective pilot study to examine the use of sorafenib specifically for ICC. Sorafenib with BSC had an acceptable DCR and safety profile in patients with unresectable and advanced ICC. [Table: see text]

Phase II study of first-line radioembolization with yttrium-90 glass microspheres for intrahepatic cholangiocarcinoma.

482 Background: The standard of care for unresectable intrahepatic cholangiocarcinoma (ICC) is systemic chemotherapy. The role of liver directed therapy for ICC is controversial given the lack of level I data. We conducted a phase II study to determine the safety and effectiveness of first-line liver directed therapy with radioembolization with yttrium-90 (Y90) glass microspheres for ICC. Methods: Eligible patients were enrolled on an IRB-approved phase II study (NCT01253148). Patients were included if they had no evidence of extrahepatic metastases, Childs-Pugh A, without main portal vein thrombus, bilirubin &lt; 2 mg/dL, ECOG performance status of 0-2, and no prior chemotherapy, liver embolization, or radiation therapy for ICC. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS) and toxicity. Results: Twenty-five patients were enrolled between 2010 and 2013 with a median followup of 13 months (9-20 months). The median age was 76 years. Twenty patients came off study due to progression or death. The overall response rate was 56%. Median PFS was 6 months (95% CI: 4-12 months). This was likely due to tumors appearing larger after treatment due to tumor inflammation despite a decrease in CA19-9 levels. Univariate (UVA) and multivariate analysis (MVA) failed to identify any prognostic factors associated with PFS. Despite the low median PFS, median OS was 22 months (95% CI: 10 months to upper limit not reached). However, UVA and MVA failed to identify and prognostic factors for OS. Treatment was well tolerated with no reported grade 3 gastrointestinal or general disorder toxicities. Grade 3 ALT, AST, and alkaline phosphatase increase were reported in 4%, 4%, and 8%, respectively. Grade 4 hyperbilirubinemia and thrombocytopenia were reported in 4% and 4%, respectively. There were 2 patient who developed sepsis one patient who died within 30 days of treatment. Conclusions: First-line liver directed therapy with radioembolization with Y90 glass microspheres is a safe and effective treatment for ICC. Further prospective clinical trials are needed to identify the proper sequencing of liver directed therapy and systemic chemotherapy. Clinical trial information: NCT01253148.