RESUMO
BACKGROUND: A retrospective study was performed to characterize trends in centralization of care and compliance with National Comprehensive Cancer Network (NCCN) guidelines for resected cholangiocarcinoma (CCA), and their impact on overall survival (OS). METHODS: Using the National Cancer Database (NCDB) 2004-2015 we identified patients undergoing resection for CCA. Receiver Operating Characteristic (ROC) analyses identified time periods and hospital volume groups for comparison. Propensity score matching provided case-mix adjusted patient cohorts. Cox hazard analysis identified risk factors for OS. RESULTS: Among the 40,338 patients undergoing resection for CCA, the proportion of patients undergoing surgery at high volume hospitals increased over time (25%-44%, p < 0.001), while the proportion of patients undergoing surgery at low volume hospitals decreased (30%-15%, p < 0.001). Using ROC analyses, a hospital volume of 14 operations/year was the most sensitive and specific value associated with mortality. Surgery at high volume hospitals [HR] = 0.92, 95% CI: 0.88-0.97, p < 0.001) and receipt of care compliant with NCCN guidelines (HR = 0.87, 95% CI: 0.83-0.91, p < 0.001) were independently associated with improved OS. CONCLUSIONS: Both centralization of surgery for CCA to high volume hospitals and increased compliance with NCCN guidelines were associated with significant improvements in overall survival.
Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Serviços Centralizados no Hospital/normas , Colangiocarcinoma/cirurgia , Fidelidade a Diretrizes/estatística & dados numéricos , Guias de Prática Clínica como Assunto , Adulto , Idoso , Análise de Variância , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/patologia , Serviços Centralizados no Hospital/tendências , Colangiocarcinoma/mortalidade , Colangiocarcinoma/patologia , Bases de Dados Factuais , Feminino , Hospitais com Alto Volume de Atendimentos/estatística & dados numéricos , Hospitais com Baixo Volume de Atendimentos/estatística & dados numéricos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento , Estados UnidosRESUMO
BACKGROUND: Peritoneal metastasis from biliary carcinoma (PMC) is associated with poor prognosis when treated with chemotherapy. OBJECTIVE: To evaluate the impact on survival of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), and compare with conventional palliative chemotherapy for patients with PMC. MATERIAL AND METHODS: A prospective multicenter international database was retrospectively searched to identify all patients with PMC treated with a potentially curative CRS/HIPEC (CRS/HIPEC group). The overall survival (OS) was compared to patients with PMC treated with palliative chemotherapy (systemic chemotherapy group). Survival was analyzed using Kaplan-Meier method and compared with Log-Rank test. RESULTS: Between 1995 and 2015, 34 patients were included in the surgical group, and compared to 21 in the systemic chemotherapy group. In the surgical group, median peritoneal cancer index was 9 (range 3-26), macroscopically complete resection was obtained for 25 patients (73%). There was more gallbladder localization in the surgical group compared to the chemotherapy group (35% vs. 18%, p = 0.001). Median OS was 21.4 and 9.3 months for surgical and chemotherapy group, respectively (p=0.007). Three-year overall survival was 30% and 10% for surgical and chemotherapy group, respectively. CONCLUSION: Treatment with CRS and HIPEC for biliary carcinoma with peritoneal metastasis is feasible and may provide survival benefit when compared to palliative chemotherapy.
Assuntos
Neoplasias dos Ductos Biliares/terapia , Procedimentos Cirúrgicos de Citorredução/métodos , Hipertermia Induzida/métodos , Neoplasias Peritoneais/terapia , Sistema de Registros , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/secundário , Feminino , Seguimentos , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/secundário , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida/tendênciasAssuntos
Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/cirurgia , Tumor de Klatskin/cirurgia , Neoplasias dos Ductos Biliares/classificação , Neoplasias dos Ductos Biliares/mortalidade , Bilirrubina/sangue , Quimioterapia Adjuvante , Colangiografia , Humanos , Tumor de Klatskin/classificação , Tumor de Klatskin/mortalidade , Tumor de Klatskin/patologia , Testes de Função Hepática , Estadiamento de Neoplasias , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/mortalidade , Estudos Retrospectivos , Taxa de Sobrevida , Tomografia Computadorizada por Raios X , UltrassonografiaRESUMO
INTRODUCTION: After liver transplantation for cholangiocarcinoma (CCC), patients have a poor prognosis without use of specific therapeutic strategies. Accordingly, recipients with incidental CCC might have the highest risk of recurrent disease; however, sparse data on the long-term outcome of unselected patients with incidental CCC have been published. The aim of this study was to evaluate the post-transplantation outcomes of patients with incidental CCC with special focus on tumor localization. MATERIAL AND METHODS: There were 11 primary liver transplantations in patients with incidental CCC of 1310 liver transplantation procedures performed between December 1994 and August 2013. All patients with incidental CCC received a chemotherapy regiment including gemcitabine/5 fluorouracil, doxorubicin, and mitomycin. The patients were switched from calcineurin inhibitors to mammalian target of rapamycin inhibitor-based immunosuppression shortly after CCC diagnosis. RESULTS: Intra- and extrahepatic tumors were found in 6 and 5 patients, respectively. At median follow-up examination of 26.3 months there were 8 CCC recurrences and 7 patient deaths. Overall survival after liver transplantation for incidental CCC was 88.9% at 1 year, 44.4% at 2 years, and 14.8% at 3 years. The corresponding rates of recurrence-free survival were 45.7%, 45.7%, and 0.0%, respectively. Post-transplantation CCC recurrences were universal with 0% 3-year recurrence-free survival both in patients with intra- and extrahepatic tumors (P = .475). CONCLUSIONS: Incidental CCC in liver transplantation is associated with poor outcomes irrespective of tumor localization. Introduction of new adjuvant multimodal treatment concepts is necessary to improve the prognosis for this subgroup of patients.
Assuntos
Neoplasias dos Ductos Biliares/mortalidade , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/mortalidade , Neoplasias Hepáticas/mortalidade , Transplante de Fígado/mortalidade , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/terapia , Ductos Biliares Intra-Hepáticos/patologia , Inibidores de Calcineurina/administração & dosagem , Colangiocarcinoma/patologia , Colangiocarcinoma/terapia , Terapia Combinada , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Doxorrubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Imunossupressores/administração & dosagem , Achados Incidentais , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Recidiva Local de Neoplasia/mortalidade , Prognóstico , Sirolimo/administração & dosagem , Análise de Sobrevida , Resultado do Tratamento , GencitabinaRESUMO
BACKGROUND: The purpose of the present study was to analyze the outcome of chemoradiotherapy for extrahepatic bile duct (EHBD) cancer patients with gross residual disease after surgical resection. PATIENTS AND METHODS: We retrospectively analyzed 30 patients with EHBD adenocarcinoma who underwent chemoradiotherapy after palliative resection (R2 resection). Postoperative radiotherapy was delivered to the tumor bed including residual tumor and regional lymph nodes (range=40-55.8 Gy). Most patients underwent chemoradiotherapy concurrently with 5-fluorouracil (5-FU) or gemcitabine. RESULTS: The 2-year locoregional progression-free, distant metastasis-free and overall survival rates were 33.3%, 42.4% and 44.5%, respectively. High radiation dose≥50 Gy had a marginally significant impact on superior locoregional progression-free survival compared to 40 Gy (p=0.081). One patient developed grade 3 late gastrointestinal toxicity. CONCLUSION: Adjuvant chemoradiotherapy for EHBD cancer patients with gross residual disease after surgery was well-tolerated. There could be a chance for durable locoregional control and even long-term survival in selected patients.
Assuntos
Neoplasias dos Ductos Biliares/terapia , Ductos Biliares Extra-Hepáticos/cirurgia , Quimiorradioterapia , Fluoruracila/uso terapêutico , Hepatectomia/efeitos adversos , Neoplasia Residual/terapia , Pancreaticoduodenectomia/efeitos adversos , Complicações Pós-Operatórias/terapia , Adulto , Idoso , Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Extra-Hepáticos/efeitos dos fármacos , Ductos Biliares Extra-Hepáticos/efeitos da radiação , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasia Residual/etiologia , Neoplasia Residual/mortalidade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/mortalidade , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: Gallbladder cancers and cholangiocarcinomas make up a heterogenous group of tumours with a poor prognosis in advanced stages. On the basis of evidence of dysregulation of the epidermal growth factor receptor, vascular endothelial growth factor and mitogen-activated protein kinase pathways in biliary cancers, we performed a phase 2 trial of sorafenib and erlotinib in patients with advanced biliary cancers. METHODS: Eligible patients were previously untreated in the advanced setting with adequate hepatic and bone marrow function. Sorafenib and erlotinib were administered continuously at 400 mg BID and 100 mg daily, respectively. RESULTS: Thirty-four eligible patients were recruited. The study was terminated after the first stage of accrual owing to failure to meet the predetermined number of patients who were alive and progression free at 4 months. There were two unconfirmed partial responses (6%, 95% CI: 1-20%), with a median progression-free survival of 2 months (95% CI: 2-3), and median overall survival of 6 months (95% CI: 3-8 months). Grade 3 and 4 adverse events included hypertension, AST/ALT increase, bilirubin increase, diarrhoea, hypokalaemia, hypophosphatemia and rash. CONCLUSIONS: Despite compelling preclinical rationale, the combination of sorafenib and erlotinib does not have promising clinical activity in an unselected population of patients with biliary cancers. Improved patient selection based on tumour biology and molecular markers is critical for future evaluation of targeted therapies in this disease.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias dos Ductos Biliares/tratamento farmacológico , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/tratamento farmacológico , Neoplasias da Vesícula Biliar/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Quinazolinas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/mortalidade , Colangiocarcinoma/mortalidade , Intervalo Livre de Doença , Receptores ErbB/antagonistas & inibidores , Cloridrato de Erlotinib , Feminino , Neoplasias da Vesícula Biliar/mortalidade , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Niacinamida/efeitos adversos , Niacinamida/uso terapêutico , Compostos de Fenilureia/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Quinazolinas/efeitos adversos , Sorafenibe , Falha de Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidoresRESUMO
BACKGROUND: Unresectable cholangiocarcinoma (CCA) has a dismal prognosis. Initial studies of orthotopic liver transplantation (OLT) alone for CCA yielded disappointing outcomes. The Mayo Clinic demonstrated long-term survival using neoadjuvant chemoradiotherapy followed by OLT in selected patients with unresectable CCA. This study reports the Irish National Liver Transplant Programme experience of neoadjuvant therapy and OLT for unresectable CCA. MATERIALS AND METHODS: Twenty-seven patients with CCA were selected for neoadjuvant chemoradiotherapy in a single centre from October 2004 to September 2011. Patients were given brachytherapy, external beam radiotherapy and 5-fluorouracil (5-Fu), followed by liver transplantation if progression free (20 patients). RESULTS: Twenty progression-free patients after neoadjuvant therapy underwent OLT. Hospital mortality was 20%. Of the 16 patients who left hospital, survival rates were 94% and 61% at 1 and 4 years. Seven patients developed recurrent disease and died at intervals of 10-58 months after OLT, whereas 9 are disease free with a median follow-up of 37 months (18-76). Predictors of disease recurrence were a tumour in explant specimen and high CA 19.9 levels. DISCUSSION: In selected patients with unresectable CCA, long-term survival can be achieved using neoadjuvant chemoradiotherapy and OLT although short-term mortality is high. Prospective international registries may aid patient selection and refinement of neoadjuvant regimens.
Assuntos
Neoplasias dos Ductos Biliares/terapia , Ductos Biliares Intra-Hepáticos , Quimiorradioterapia Adjuvante , Colangiocarcinoma/terapia , Transplante de Fígado , Terapia Neoadjuvante , Adulto , Idoso , Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias dos Ductos Biliares/sangue , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/efeitos dos fármacos , Ductos Biliares Intra-Hepáticos/patologia , Ductos Biliares Intra-Hepáticos/efeitos da radiação , Ductos Biliares Intra-Hepáticos/cirurgia , Braquiterapia , Antígeno CA-19-9/sangue , Quimiorradioterapia Adjuvante/efeitos adversos , Quimiorradioterapia Adjuvante/mortalidade , Colangiocarcinoma/sangue , Colangiocarcinoma/mortalidade , Colangiocarcinoma/patologia , Intervalo Livre de Doença , Feminino , Fluoruracila/uso terapêutico , Mortalidade Hospitalar , Humanos , Irlanda , Estimativa de Kaplan-Meier , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/mortalidade , Projetos Piloto , Avaliação de Programas e Projetos de Saúde , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Cholangiocarcinomas (CCAs) are rare malignancies that originate from the epithelial cells of the bile ducts. It is the second most-common primary liver cancer after hepatocellular carcinoma. Recent epidemiologic studies have shown that the overall incidence and mortality rates of CCAs are increasing. Diagnosis is often challenging due to the difficulty in getting tissue/cytology for confirmation, and it comprises a combination of cross-imaging, tumor markers, histology, and cholangiography. Surgery involving major resections of liver, bile duct, pancreas, and at times adjacent vessels is the only chance for cure. Evaluation should be focused on the assessment of tumor resectability, hepatic reserve, and patient physiological fitness for major surgery. In patients not fit for major surgery, biliary drainage for jaundice is an appropriate intervention and if there is histologic confirmation of a CCA, palliative therapies focused on local and systemic disease control should be considered. The endeavor to expand the indications for liver transplantation reflects the efforts to provide an effective form of therapy for a previously untreatable disease. A multidisciplinary specialized approach should be the platform for providing the best comprehensive care for these patients.
Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos/cirurgia , Colangiocarcinoma/cirurgia , Hepatectomia , Transplante de Fígado , Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/mortalidade , Ductos Biliares Intra-Hepáticos/patologia , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/mortalidade , Diagnóstico por Imagem/métodos , Hepatectomia/efeitos adversos , Hepatectomia/mortalidade , Humanos , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Fatores de Risco , Resultado do TratamentoRESUMO
AIM: To evaluate the prognostic significance of CD24 expression in patients undergoing adjuvant chemoradiotherapy for extrahepatic bile duct (EHBD) cancer. METHODS: Eighty-four patients with EHBD cancer who underwent curative resection followed by adjuvant chemoradiotherapy were enrolled in this study. Postoperative radiotherapy was delivered to the tumor bed and regional lymph nodes up to a median of 40 Gy (range: 40-56 Gy). All patients also received fluoropyrimidine chemotherapy for radiosensitization during radiotherapy. CD24 expression was assessed with immunohistochemical staining on tissue microarray. Clinicopathologic factors as well as CD24 expression were evaluated in multivariate analysis for clinical outcomes including loco-regional recurrence, distant metastasis-free and overall survival. RESULTS: CD24 was expressed in 36 patients (42.9%). CD24 expression was associated with distant metastasis, but not with loco-regional recurrence nor with overall survival. The 5-year distant metastasis-free survival rates were 55.1% and 29.0% in patients with negative and positive expression, respectively (P = 0.0100). On multivariate analysis incorporating N stage, histologic differentiation and CD24 expression, N stage was the only significant factor predicting distant metastasis-free survival (P = 0.0089), while CD24 expression had borderline significance (P = 0.0733). In subgroup analysis, CD24 expression was significantly associated with 5-year distant metastasis-free survival in node-positive patients (38.4% with negative expression vs 0% with positive expression, P = 0.0110), but not in node-negative patients (62.0% with negative expression vs 64.0% with positive expression, P = 0.8599). CONCLUSION: CD24 expression was a significant predictor of distant metastasis for patients undergoing curative resection followed by adjuvant chemoradiotherapy especially for node-positive EHBD cancer.
Assuntos
Neoplasias dos Ductos Biliares/imunologia , Ductos Biliares Extra-Hepáticos/imunologia , Biomarcadores Tumorais/análise , Antígeno CD24/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/administração & dosagem , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/terapia , Ductos Biliares Extra-Hepáticos/patologia , Ductos Biliares Extra-Hepáticos/cirurgia , Procedimentos Cirúrgicos do Sistema Biliar , Quimiorradioterapia Adjuvante , Distribuição de Qui-Quadrado , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Dosagem Radioterapêutica , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Perihilar cholangiocarcinoma (PHCC) is a rare tumor with a poor prognosis. Outcomes may be optimized by centralization. Recent trends suggest further improvement by localization to transplant centers. This study examines outcomes from the management of PHCC in a nontransplant hepatopancreatobiliary center. METHODS: Data were collected prospectively from patients undergoing treatment for PHCC from October 1999 to May 2011. Twenty-four patients underwent surgery. A further 54 patients had inoperable PHCC. Outcome data are reported. RESULTS: Twenty-two of 24 patients required liver resection with histological R0 status in 12 (50%). In-hospital mortality occurred in two (8%). The mean survival of patients undergoing resection was 39 (95% CI: 16-61) months. The mean survival of nonresected patients was 5 (95% CI: 3-7) months (P<0.0001; log-rank; Mantel-Cox test). CONCLUSION: Currently acceptable standards of holistic care for patients with PHCC can be provided in a nontransplant regional hepatopancreatobiliary center. Further centralization may improve resection volumes and allow more patients to benefit from extended liver resection techniques.
Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos/cirurgia , Colangiocarcinoma/cirurgia , Hepatectomia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Quimioterapia Adjuvante , Colangiocarcinoma/mortalidade , Colangiocarcinoma/patologia , Estudos Transversais , Inglaterra , Feminino , Hepatectomia/efeitos adversos , Hepatectomia/mortalidade , Mortalidade Hospitalar , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
Cholangiocarcinoma (CC) is a rare primary malignancy of the biliary tract with a dismal prognosis. Curative resection can only be applied to a small proportion of early diagnosed patients. Palliative biliary drainage by either percutaneous or endoscopic insertion of endoprostheses improves quality-of-life by reducing pruritis, cholangitis, and pain, but has been reported to improve survival time only slightly. Photodynamic therapy (PDT) is a relatively new local, minimally invasive palliative strategy for unresectable CC. PDT uses a photosensitive molecule that accumulates in proliferating tissue such as tumors. Activation of the photosensitizer by use of light of a specific wavelength generates reactive oxygen species leading to selective tumor-cell death. After initial feasibility studies and promising prospective phase II studies, results from two prospective randomized controlled trials comparing PDT after endoprostheses insertion with endoprostheses alone for patients with unresectable CC have been published. One study resulted in dramatically prolonged median survival in the PDT group (493 days) compared with the non-PDT group (98 days) (P < 0.0001), and significantly improved performance status (PS) in the PDT group. A second study with high baseline patients' PS confirmed the benefit of PDT for survival (630 days in the PDT group compared with 210 days for endoprostheses alone, P < 0.01). The procedures were generally well tolerated. PDT has also been reported to have a favorable outcome as adjuvant and neoadjuvant therapy for CC. Although accumulated data and local expertise are limited, PDT can be regarded as a standard palliative therapy for unresectable CC.
Assuntos
Neoplasias dos Ductos Biliares/tratamento farmacológico , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/tratamento farmacológico , Neoplasias dos Ductos Biliares/sangue , Neoplasias dos Ductos Biliares/classificação , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/cirurgia , Bilirrubina/sangue , Colangiocarcinoma/sangue , Colangiocarcinoma/classificação , Colangiocarcinoma/mortalidade , Colangiocarcinoma/cirurgia , Éter de Diematoporfirina/uso terapêutico , Humanos , Cuidados Paliativos , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Stents , Resultado do TratamentoRESUMO
BACKGROUND: Extrahepatic biliary duct cancers (EBDC) are uncommon malignancies characterized by a poor prognosis with high rate of loco-regional recurrence. The purpose of the present study is to assess the feasibility and the potential impact of adjuvant radiotherapy (RT) in a series of patients treated in one institution. METHODS: Twenty three patients with non-metastatic bile duct cancer treated surgically with curative intent (4 gallbladder, 7 ampullary and 12 cholangiocarcinoma) received 3D conformal external beam RT to a median total dose of 50.4 Gy. Concurrent chemotherapy based on 5-FU was delivered to 21 patients (91%). Surgical margins were negative in 11 patients (48%), narrow in 2 (9%), and microscopically involved in 8 (35%). Eleven patients (55%) had metastatic nodal involvement. The average follow-up time for all patients was 30 months (ranging from 3-98). RESULTS: Acute gastrointestinal grade 2 toxicity (RTOG scale) was recorded in 2 patients (9%). Nausea or vomiting grade 1 and 2 was observed in 8 (35%) and 2 patients (9%) respectively. Only one patient developed a major late radiation-induced toxicity. The main pattern of recurrence was both loco-regional and distant (liver, peritoneum and/or lung). No difference was observed in loco-regional control according to the tumor location. The 5-year actuarial loco-regional control rate was 48.3% (67% and 30% for patients operated on with negative and positive/narrow/unknown margins respectively, p=0.04). The 5-year actuarial overall survival was of 35.9% for the entire group (61.4% in case of negative margins and 16.7% in case of positive/narrow/unknown margins, p=0.07). CONCLUSIONS: Postoperative RT with 50-60 Gy is feasible with acceptable acute and late toxicities. The potential benefit observed in our series may support the use of adjuvant RT in patients with locally advanced disease. Prospective randomized trials are warranted to confirm definitively the role of RT in this tumor location.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias dos Ductos Biliares/terapia , Ductos Biliares Extra-Hepáticos/patologia , Quimioterapia Adjuvante , Colangiocarcinoma/terapia , Radioterapia Adjuvante , Radioterapia Conformacional , Idoso , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/radioterapia , Neoplasias dos Ductos Biliares/cirurgia , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/mortalidade , Colangiocarcinoma/radioterapia , Colangiocarcinoma/cirurgia , Cisplatino/administração & dosagem , Terapia Combinada , Procedimentos Cirúrgicos do Sistema Digestório , Feminino , Fluoruracila/administração & dosagem , Humanos , Estimativa de Kaplan-Meier , Leucovorina/administração & dosagem , Irradiação Linfática , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Unresectable intrahepatic cholangiocarcinoma has a poor prognosis, with a median survival of 5 to 8 months without treatment. Response and survival after chemoembolization were evaluated. METHODS: Lobar or segmental chemoembolization with cisplatinum, doxorubicin, mitomycin-C, ethiodol, and polyvinyl alcohol particles was performed at monthly intervals for 1-4 sessions until the entire intrahepatic tumor burden was treated. Cross-sectional imaging and clinical and laboratory evaluation were performed before treatment, 1 month after treatment, and then every 3 months. A second cycle of treatment was performed for intrahepatic recurrence. Toxicity was assessed using NCI CTC v.3.0. Response was evaluated using RECIST criteria, and survival was estimated with Kaplan-Meier analysis. RESULTS: Sixty-two patients were treated. Thirty-seven had pathologically proven cholangiocarcinoma, and 25 had poorly differentiated adenocarcinoma of unknown primary, likely cholangiocarcinoma. One hundred and twenty-two total procedures were performed during the initial cycle of treatment (mean, 2.0 per patient). Twenty patients received a second cycle, for a total of 165 procedures. There were 5 major complications. Thirty-day disease-specific mortality was 0%. Forty-five of 62 patients were evaluable for morphologic response after completion of their initial cycle: 11% (n = 5) partial responses, 64% (n = 29) stable, and 24% (n = 11) progressed. Median time to progression from first chemoembolization was 8 months, with 28% free of progression at 12 months. Median survival from time of diagnosis was 20 months, with 1-, 2-, and 3-year survival of 75%, 39%, and 17%, respectively. Median survival from time of first chemoembolization was 15 months, with 1-, 2-, and 3-year survival of 61%, 27%, and 8%, respectively. There was no statistically significant difference in survival between patients with cholangiocarcinoma and those with poorly differentiated adenocarcinoma. Patients who also received systemic chemotherapy had improved overall survival (median 28 vs 16 months, P = .02; HR, 1.94; 95% CI, 1.13-3.33). CONCLUSIONS: Chemoembolization provided local disease control (PR + SD) of intrahepatic cholangiocarcinoma and adenocarcinoma of unknown primary in 76%. Overall survival after chemoembolization showed the best outcomes for those receiving multidisciplinary integrated liver-directed and systemic therapies.
Assuntos
Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioembolização Terapêutica/métodos , Neoplasias Primárias Desconhecidas/terapia , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/terapia , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/mortalidade , Colangiocarcinoma/terapia , Cisplatino/administração & dosagem , Doxorrubicina/administração & dosagem , Óleo Etiodado/administração & dosagem , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Álcool de Polivinil/administração & dosagemRESUMO
PURPOSE: To evaluate the effect of postoperative concurrent chemoradiotherapy using three-dimensional conformal radiotherapy and to identify the prognostic factors that influence survival in patients with extrahepatic bile duct cancer. METHODS AND MATERIALS: We retrospectively analyzed the data from 101 patients with extrahepatic bile duct cancer who had undergone postoperative concurrent chemoradiotherapy using three-dimensional conformal radiotherapy. Of the 101 patients, 52 (51%) had undergone complete resection (R0 resection) and 49 (49%) had microscopic or macroscopic residual tumors (R1 or R2 resection). The median radiation dose was 50 Gy. Also, 85 patients (84%) underwent concurrent chemotherapy with 5-fluorouracil. RESULTS: The median follow-up period was 47 months for the surviving patients. The 5-year overall survival rate was 34% for all patients. A comparison between patients with R0 and R1 resection indicated no significant difference in the 5-year overall survival (44% vs. 33%, p=.2779), progression-free survival (35% vs. 22%, p=.3107), or locoregional progression-free survival (75% vs. 63%, p=.2784) rates. An analysis of the first failure site in the 89 patients with R0 or R1 resection indicated isolated locoregional recurrence in 7 patients. Elevated postoperative carbohydrate antigen 19-9 level was an independent prognostic factor for overall survival (p=.001) and progression-free survival (p=.033). A total of 3 patients developed Grade 3 or greater late toxicity. CONCLUSION: Adjuvant concurrent chemoradiotherapy using three-dimensional conformal radiotherapy appears to improve locoregional control and survival in extrahepatic bile duct cancer patients with R1 resection. The postoperative carbohydrate antigen 19-9 level might be a useful prognostic marker to select patients for more intensified adjuvant therapy.
Assuntos
Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/radioterapia , Ductos Biliares Extra-Hepáticos , Radioterapia Conformacional , Adulto , Idoso , Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias dos Ductos Biliares/sangue , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Extra-Hepáticos/cirurgia , Antígeno CA-19-9/sangue , Terapia Combinada/métodos , Feminino , Fluoruracila/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/mortalidade , Neoplasia Residual , Dosagem Radioterapêutica , República da Coreia , Estudos Retrospectivos , Análise de SobrevidaRESUMO
Gallbladder cancer is an aggressive tumor. Its incidence varies according to geography. Surgery is the standard treatment for localized stage but there is no standard treatment in metastatic or locally advanced disease. Because of the rarity of bile tract cancer (BTC) and gallblader carcinoma (GBC), most studies have grouped all BTC and GBC together, and there are very few GBC-specific studies. In addition, there is a paucity of randomized controlled studies in this disease with small numbers of patients and inclusion bias. One randomized trial ABC-02 was well conducted and showed a survival benefit in favor of gemcitabine (GEM)+cisplatin (CDDP), which can be regarded as the standard in locally advanced BTC. Adjuvant therapy after surgical resection is not validated. Understanding the molecular mechanisms of carcinogenesis of GBC has opened the way for the use of targeted therapies. This new treatment would improve survival and quality of life of our patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Vesícula Biliar/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/cirurgia , Capecitabina , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fluoruracila/análogos & derivados , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Mitomicina/administração & dosagem , Mitomicina/efeitos adversos , Invasividade Neoplásica , Estadiamento de Neoplasias , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxa de Sobrevida , Resultado do Tratamento , GencitabinaRESUMO
Cholangiocarcinoma (CCA) is a major cause of cancer deaths in northeast Thailand. It is aggressive, highly metastatic, and responds poorly to traditional chemotherapy. We demonstrated the potential for Cepharanthine (CEP), a biscoclaurine alkaloid extracted from Stephania cepharantha, to treat CCA. CEP significantly inhibited growth of human CCA cell lines in a dose- and time-dependent manner, regardless of the histologic type of tumor origin. Increasing cell apoptosis via caspase-3 and capase-9 activation was demonstrated in CEP-treated cells. We found that CEP controlled the growth of CCA cells through nuclear factor-kappa B (NF-kappaB) inactivation by inhibiting nuclear translocation. CEP treatment effectively reduced tumor size in CCA-inoculated mice without serious side effects. CEP also increased cell apoptosis in primary histocultures of CCA patients' tissues; this was demonstrated by immunohistochemistry using TUNEL staining. Our results suggest that CEP possesses therapeutic potential against human CCA.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Benzilisoquinolinas/uso terapêutico , Neoplasias dos Ductos Biliares/tratamento farmacológico , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/metabolismo , NF-kappa B/antagonistas & inibidores , Alcaloides/isolamento & purificação , Alcaloides/uso terapêutico , Apoptose/efeitos dos fármacos , Benzilisoquinolinas/isolamento & purificação , Neoplasias dos Ductos Biliares/metabolismo , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos , Ciclo Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Colangiocarcinoma/mortalidade , Colangiocarcinoma/patologia , Fragmentação do DNA/efeitos dos fármacos , Humanos , Fitoterapia , Stephania/química , Tailândia/epidemiologiaRESUMO
UNLABELLED: Intrahepatic cholangiocellular carcinoma after curative surgery was treated with pharmacokinetic modulation chemotherapy (PMC) as adjuvant chemotherapy. METHOD: PMC consists of medication with UFT and intravenous infusion of 5-FU. The dose of UFT is 300 mg/day and the infusion of 5-FU is performed with 500 mg/body once a week for one year. RESULTS: Twelve cases were treated with PMC (A-group) and eight cases were without PMC (B-group). The mean number of 5- FU infusions in all cases was 33.2 (6-48). The median survival time (MST) of A-group was 78.9 months, and of B-group was 74.3 months. Five-year cumulative survival rates of A-and B-group were 59.4%, 59%,and disease free survival rates were 37.5%, 25%,respectively. There was no significance between two groups. CONCLUSION: PMC as adjuvant chemotherapy for intrahepatic cholangiocellular carcinoma was not so effective in comparison with cases without adjuvant chemotherapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias dos Ductos Biliares/tratamento farmacológico , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/tratamento farmacológico , Administração Oral , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Neoplasias dos Ductos Biliares/mortalidade , Quimioterapia Adjuvante , Colangiocarcinoma/mortalidade , Feminino , Fluoruracila/administração & dosagem , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Tegafur/administração & dosagem , Uracila/administração & dosagemRESUMO
PURPOSE: Extrahepatic cholangiocarcinoma is a rare malignancy. Despite radical resection, survival remains poor, with high rates of local and distant failure. To clarify the role of radiotherapy with chemotherapy, we performed a retrospective analysis of resected patients who had undergone chemoradiotherapy. METHODS AND MATERIALS: A total of 45 patients (13 with proximal and 32 with distal disease) underwent resection plus radiotherapy (median dose, 50.4 Gy). All but 1 patient received concurrent fluoropyrimidine-based chemotherapy. The median follow-up was 30 months for all patients and 40 months for survivors. RESULTS: Of the 45 patients, 33 underwent adjuvant radiotherapy, and 12 were treated neoadjuvantly. The 5-year actuarial overall survival, disease-free survival, metastasis-free survival, and locoregional control rates were 33%, 37%, 42%, and 78%, respectively. The median survival was 34 months. No patient died perioperatively. Patient age =60 years and perineural involvement adversely affected survival on univariate analysis. Patients undergoing R0 resection had a significantly improved rate of local control but no survival advantage. Despite having more advanced disease at presentation, patients treated neoadjuvantly had a longer survival (5-year survival 53% vs. 23%, p = 0.16) and similar rates of Grade 2-3 surgical morbidity (16% vs. 33%, p = 0.24) compared with those treated in the postoperative setting. CONCLUSION: These study results suggest a possible local control benefit from chemoradiotherapy combined with surgery in patients with advanced, resected biliary cancer. Furthermore, our results suggest that a treatment strategy that includes preoperative chemoradiotherapy might result in improved tumor resectability with similar surgical morbidity compared with patients treated postoperatively, as well as potentially improved survival outcomes. Distant failure remains a significant failure pattern, suggesting the need for more effective systemic therapy.
Assuntos
Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/terapia , Ductos Biliares Extra-Hepáticos , Colangiocarcinoma/mortalidade , Colangiocarcinoma/terapia , Fluoruracila/uso terapêutico , Hepatectomia/estatística & dados numéricos , Radioterapia Conformacional/estatística & dados numéricos , Adulto , Idoso , Antineoplásicos/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , North Carolina/epidemiologia , Prevalência , Estudos Retrospectivos , Análise de Sobrevida , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Cholangiocarcinoma is a therapeutically challenging malignancy. This report describes a case where the patient received multimodal therapy, including surgery, adjuvant chemoradiation therapy, and combination chemotherapy and successfully achieved long-term survival. Specifically, the patient achieved an extended complete response after combination chemotherapy with TS-1 (an orally administered drug that is a combination of tegafur, 5-chloro-2, 4-dihydroxypyridine [CDHP], and oteracil potassium [Oxo]) and cisplatin for recurrence. This result suggests that chemoradiation or combination chemotherapy regimens using oral 5-fluorouracil (5-FU) analogues might therefore be helpful in patients with this malignancy. However, further clinical trials are required.
Assuntos
Neoplasias dos Ductos Biliares/terapia , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/terapia , Neoplasias Hepáticas/secundário , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias dos Ductos Biliares/mortalidade , Colangiocarcinoma/mortalidade , Colangiocarcinoma/secundário , Cisplatino/administração & dosagem , Terapia Combinada , Intervalo Livre de Doença , Combinação de Medicamentos , Humanos , Metástase Linfática , Masculino , Ácido Oxônico/administração & dosagem , Tegafur/administração & dosagemRESUMO
AIM: To study the factors that may affect survival of cholangiocarcinoma in Lebanon. METHODS: A retrospective review of the medical records of 55 patients diagnosed with cholangio-carcinoma at the American University of Beirut between 1990 and 2005 was conducted. Univariate and multivariate analyses were performed to determine the impact of surgery, chemotherapy, body mass index, bilirubin level and other factors on survival. RESULTS: The median survival of all patients was 8.57 mo (0.03-105.2). Univariate analysis showed that low bilirubin level (< 10 mg/dL), radical surgery and chemotherapy administration were significantly associated with better survival (P = 0.012, 0.038 and 0.038, respectively). In subgroup analysis on patients who had no surgery, chemotherapy administration prolonged median survival significantly (17.0 mo vs 3.5 mo, P = 0.001). Multivariate analysis identified only low bilirubin level < 10 mg/dL and chemotherapy administration as independent predictors associated with better survival (P < 0.05). CONCLUSION: Our data show that palliative and postoperative chemotherapy as well as a bilirubin level < 10 mg/dL are independent predictors of a significant increase in survival in patients with cholangiocarcinoma.