Clinical treatment of cholangiocarcinoma: an updated comprehensive review.

Cholangiocarcinoma (CCA) is a heterogeneous group of neoplasms of the bile ducts and represents the second most common hepatic cancer after hepatocellular carcinoma; it is sub-classified as intrahepatic cholangiocarcinoma (iCCA) and extrahepatic cholangiocarcinoma (eCCA), the latter comprising both perihilar cholangiocarcinoma (pCCA or Klatskin tumor), and distal cholangiocarcinoma (dCCA). The global incidence of CCA has increased worldwide in recent decades. Chronic inflammation of biliary epithelium and bile stasis represent the main risk factors shared by all CCA sub-types. When feasible, liver resection is the treatment of choice for CCA, followed by systemic chemotherapy with capecitabine. Liver transplants represent a treatment option in patients with very early iCCA, in referral centers only. CCA diagnosis is often performed at an advanced stage when CCA is unresectable. In this setting, systemic chemotherapy with gemcitabine and cisplatin represents the first treatment option, but the prognosis remains poor. In order to ameliorate patients' survival, new drugs have been studied in the last few years. Target therapies are directed against different molecules, which are altered in CCA cells. These therapies have been studied as second-line therapy, alone or in combination with chemotherapy. In the same setting, the immune checkpoints inhibitors targeting programmed death 1 (PD-1), programmed death-ligand 1 (PD-L1), cytotoxic T-lymphocyte antigen-4 (CTLA-4), have been proposed, as well as cancer vaccines and adoptive cell therapy (ACT). These experimental treatments showed promising results and have been proposed as second- or third-line treatment, alone or in combination with chemotherapy or target therapies.

Factors associated with survival in patients operated on for hilar cholangiocarcinoma with curative intention.

OBJECTIVE: To determine the long-term survival and to analyze the factors associated with it in the patients operated on for hilar cholangiocarcinoma (HC) with curative intention. METHOD: Non concurrent cohort study. We included all patients who underwent surgery with curative intent for HC between 2002 and 2016. An analysis of factors associated with survival using Kaplan Meier, log-rank test and Cox regression was performed. A p-value less than 0.05 was considered significant. RESULTS: Thirty patients were operated on. The median age was 65.5 years (range: 33-84); 24 patients (80%) were male. The surgical margin was negative in 27 patients (90%). Twenty-one patients (70%) presented complications and three patients (10%) died postoperatively. Survival at the year, 5 years and 10 years were 65.7%, 37.3% and 16.6%, respectively. In multivariable analysis, the only factor associated with survival was the T stage (hazard ratio: 0.309; 95% confidence interval: 0.101-0.942; p = 0.03). DISCUSSION: Patients operated on for HC with curative intent in our center have adequate long-term survival, with high postoperative morbidity and mortality. The only factor that was associated with survival was T stage.

OBJETIVO: Determinar la sobrevida a largo plazo y analizar los factores asociados a esta en pacientes operados por colangiocarcinoma hiliar (CH) con intención curativa. MÉTODO: Estudio de cohorte no concurrente. Se incluyeron todos los pacientes sometidos a cirugía con intención curativa por CH entre 2002 y 2016. Se realizó un análisis de los factores asociados a la sobrevida mediante Kaplan Meier, test de log-rank y regresión de Cox. Se consideró significativo un valor de p < 0.05. RESULTADOS: Se operaron 30 pacientes. La mediana de edad fue de 65.5 años (rango: 33-84); 24 (80%) fueron de sexo masculino. El margen quirúrgico resultó negativo en 27 (90%) pacientes. Veintiún (70%) pacientes presentaron complicaciones y 3 (10%) fallecieron en el posoperatorio. Las sobrevidas al año, a 5 años y a 10 años fueron del 65.7%, el 37.3% y el 16.6%, respectivamente. En el análisis multivariable, el único factor asociado a la sobrevida fue el estadio T (hazard ratio: 0.309; intervalo de confianza del 95%: 0.101-0.942; p = 0.03). DISCUSIÓN: Los pacientes operados por CH con intención curativa en nuestro centro presentan una adecuada sobrevida a largo plazo, con una elevada morbimortalidad posoperatoria. El único factor que se asoció a la sobrevida fue el estadio T.

Intrahepatic, Perihilar and Distal Cholangiocarcinoma: Management and Outcomes

Abstract: Introduction and aims. Cholangiocarcinomas are a heterogeneous group of tumors that can be classified into three clinically distinct types of cancers, intrahepatic, perihilar and distal cholangiocarcinoma. The inconsistent use of nomenclature for these cancers has obscured a true knowledge of the epidemiology, natural history and response to therapy of these cancers. Our aims were to define demographic characteristics, management and outcomes of these three distinct cancer types. Materials and methods. A retrospective study of patients enrolled in an institutional cancer registry from 1992 to 2010. Median survival was compared between different treatment modalities over three time periods for the three types of cholangiocarcinoma at different stages of the disease using Kaplan Meyer analysis. Results. 242 patients were identified. All cases were reviewed and classified into intrahepatic (90 patients), distal (48 patients) or perihilar (104 patients) cholangiocarcinomas. These cancers differed in median age of onset, gender distribution, median survival and stage. 13.8% of patients presented with stage I, 5.8% with stage II, 9.6% with stage III, 28% with stage IV, with 41.8% having unknown stage. The overall median survival was 15.8 months, and was 23, 25, 14, and 4.5 months for stages I, II, III, and IV respectively. Surgery improved survival in both early and advanced stages. Multimodality therapies further improved outcomes, particularly for perihilar cholangiocarcinoma. Conclusion. Perihilar, distal and intrahepatic cholangiocarcinoma vary in their presentation, natural history and therapeutic approach to management. A consistently applied classification is essential for meaningful interpretation of studies of these cancers.

Intrahepatic, perihilar and distal cholangiocarcinoma: Management and outcomes.

 Introduction and aims. Cholangiocarcinomas are a heterogeneous group of tumors that can be classified into three clinically distinct types of cancers, intrahepatic, perihilar and distal cholangiocarcinoma. The inconsistent use of nomenclature for these cancers has obscured a true knowledge of the epidemiology, natural history and response to therapy of these cancers. Our aims were to define demographic characteristics, management and outcomes of these three distinct cancer types. MATERIALS AND METHODS: A retrospective study of patients enrolled in an institutional cancer registry from 1992 to 2010. Median survival was compared between different treatment modalities over three time periods for the three types of cholangiocarcinoma at different stages of the disease using Kaplan Meyer analysis. RESULTS: 242 patients were identified. All cases were reviewed and classified into intrahepatic (90 patients), distal (48 patients) or perihilar (104 patients) cholangiocarcinomas. These cancers differed in median age of onset, gender distribution, median survival and stage. 13.8% of patients presented with stage I, 5.8% with stage II, 9.6% with stage III, 28% with stage IV, with 41.8% having unknown stage. The overall median survival was 15.8 months, and was 23, 25, 14, and 4.5 months for stages I, II, III, and IV respectively. Surgery improved survival in both early and advanced stages. Multimodality therapies further improved outcomes, particularly for perihilar cholangiocarcinoma. CONCLUSION: Perihilar, distal and intrahepatic cholangiocarcinoma vary in their presentation, natural history and therapeutic approach to management. A consistently applied classification is essential for meaningful interpretation of studies of these cancers.

Tratamiento quirúrgico de los tumores de Klatskin / Surgical treatment of Klatskin tumors (Hilar Cholangiocarcinoma)

Cholangiocarcinomas are relatively rare tumors, even that in recent years it was observed a worldwide increase of its incidence. Approximately between 60-70% of cholangiocarcinomas arise from the hilus of the liver, between 20 to 30 % in the extrahepatic biliary tree, and 5 to 10 % are intrahepatic. The hilar cholangiocarcinoma was first described by Gerard Klatskin in 1965, and that is the reason for which it is termed in such eay. The prognosis is usually discouraging. The authors comment the clinical features, etiologic, factors, diagnosis and treatment. The role of staging laparoscopy in this malignancy is described: laparoscopy is a powerful diagnostic tool in patients with intrahepatic carcinoma. Staging, resectability and outcome of patients with irresecable tumors, but at present, this therapy is reserved for selected patients and in very specialized centers.(AU)

Tratamiento quirúrgico de los tumores de Klatskin / Surgical treatment of Klatskin tumors (Hilar Cholangiocarcinoma)

Cholangiocarcinomas are relatively rare tumors, even that in recent years it was observed a worldwide increase of its incidence. Approximately between 60-70% of cholangiocarcinomas arise from the hilus of the liver, between 20 to 30 % in the extrahepatic biliary tree, and 5 to 10 % are intrahepatic. The hilar cholangiocarcinoma was first described by Gerard Klatskin in 1965, and that is the reason for which it is termed in such eay. The prognosis is usually discouraging. The authors comment the clinical features, etiologic, factors, diagnosis and treatment. The role of staging laparoscopy in this malignancy is described: laparoscopy is a powerful diagnostic tool in patients with intrahepatic carcinoma. Staging, resectability and outcome of patients with irresecable tumors, but at present, this therapy is reserved for selected patients and in very specialized centers.

Tumor de Klatskin / Klatskin tumor

Epidemiología, factores de riesgo, clasificación, clínica, diagnóstico, y tratamiento de este tumor maligno de la confluencia biliar. En cuanto a su diagnóstico, se describen los signos directos e indirectos que deben tenerse en cuenta al realizar una ecografía, así como algunos aspectos del diagnóstico diferencial.

Colangiocarcinoma hilar / Cholangiocarcinoma

Os autores fazem revisão sobre o tumor de Klatskin, abordando, principalmente, aspectos diagnósticos e terapêutica