RESUMEN
In 2023, the NCCN Guidelines for Hepatobiliary Cancers were divided into 2 separate guidelines: Hepatocellular Carcinoma and Biliary Tract Cancers. The NCCN Guidelines for Biliary Tract Cancers provide recommendations for the evaluation and comprehensive care of patients with gallbladder cancer, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma. The multidisciplinary panel of experts meets at least on an annual basis to review requests from internal and external entities as well as to evaluate new data on current and emerging therapies. These Guidelines Insights focus on some of the recent updates to the NCCN Guidelines for Biliary Tract Cancers as well as the newly published section on principles of molecular testing.
Asunto(s)
Neoplasias de los Conductos Biliares , Neoplasias del Sistema Biliar , Colangiocarcinoma , Neoplasias de la Vesícula Biliar , Neoplasias Hepáticas , Humanos , Neoplasias del Sistema Biliar/diagnóstico , Neoplasias del Sistema Biliar/terapia , Neoplasias de la Vesícula Biliar/diagnóstico , Neoplasias de la Vesícula Biliar/terapia , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/terapia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Conductos Biliares IntrahepáticosRESUMEN
BACKGROUND: Cholangiocarcinoma (CCA) is a common and usually lethal liver cancer especially in Southeast Asia. Family caregivers (FCs) and their quality of life (QOL) is important for the care process to operate effectively. However, there are only few research articles about the QOL of CCA FCs. The goal of this study was to assess the QOL and its associated factors among CCA FCs. MATERIAL AND METHODS: This cross-sectional study was undertaken with 231 CCA FCs who were the primary FCs for CCA patients in a tertiary hospital in Northeastern Thailand. The QOL was measured using the Thai version of the World Health Organization's Quality of Life Questionnaire. Multivariate regression models were developed to investigate the predictors of the QOL, including the demographic characteristics, symptoms, anxiety and depression, and support care need. RESULTS: The CCA caregivers had moderate to high QOL for all of four domains: the mean score was 27.03 (SD=2.81) for physical, 23.13 (SD=2.81) for psychological, 11.32 (SD=1.08) for social relationships, and 28.08 (SD=2.81) for environment. Multivariable analysis shows that, symptoms, support care need, age and education level were significant predictors of FCs's QOL. Moreover. The QOL was lower in younger FCs (p<0.001). CONCLUSION: Symptoms, support care needs, age, and education level were associated with QOL among FCs for CCA patients. A holistic strategy that includes caregiver training, psychosocial therapies, and proper support may help these FCs for a better QOL.
Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Humanos , Calidad de Vida/psicología , Cuidadores/psicología , Tailandia , Estudios Transversales , Colangiocarcinoma/terapia , Encuestas y Cuestionarios , Neoplasias de los Conductos Biliares/terapia , Conductos Biliares IntrahepáticosRESUMEN
BACKGROUND AND AIMS: Limited data are available for tumor immune microenvironment (TIME) in Epstein-Barr virus (EBV)-associated lymphoepithelioma-like cholangiocarcinoma (EBV-LELCC), a rare subtype of intrahepatic cholangiocarcinoma (IHCC). We aimed to investigate TIME features in EBV-LELCC and the correlation between the components of TIME and the clinical outcomes. METHODS: Tumor tissues from five EBV-LELCC cases confirmed through EBER in situ hybridization and five stage-matched conventional IHCC (non-EBV IHCC) cases were collected. These samples were used to evaluate genetic alterations, TIME composition, and PD-L1 expression through ion AmpliSeq comprehensive cancer panel, PanCancer immune profiling panel, immunohistochemistry, and immunofluorescence staining. The correlation between clinical outcomes and TIME components was analyzed in the two EBV-LELCC cases receiving anti-PD-1 treatment. RESULTS: The genetic mutations identified in EBV-LELCC were BARD1, CD19, CD79B, EPHA5, KDM5A, MUC6, MUC16, PTEN, RECQL4, TET1, and TNFAIP3. Both CD79B and TNFAIP3 mutations were involved in the NF-κB signaling pathway. PD-L1 was highly expressed in tumor-infiltrating immune cells, especially the T cells and macrophages. The TIME of EBV-LELCC displayed abundant immune cell infiltration with a stronger adaptive immune response. Increased Th1 cells, NK CD56dim cells, and M1 macrophages, decreased M2 macrophages, exhausted CD8 T cell infiltration, and increased T cell activation signatures in TIME were associated with longer survival. Two patients with metastatic EBV-LELCC had good disease control after anti-PD-1 antibody treatment. A significantly larger TIME component made EBV-LELCCs more sensitive to immune checkpoint blockade (ICB). CONCLUSION: A better understanding of the composition of TIME in EBV-LELCC is critical for predicting the clinical outcomes of ICB treatment.
Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Infecciones por Virus de Epstein-Barr , Antígeno B7-H1 , Neoplasias de los Conductos Biliares/complicaciones , Conductos Biliares Intrahepáticos/patología , Colangiocarcinoma/complicaciones , Colangiocarcinoma/terapia , Infecciones por Virus de Epstein-Barr/complicaciones , Herpesvirus Humano 4/genética , Humanos , Inhibidores de Puntos de Control Inmunológico , Inmunoterapia , Oxigenasas de Función Mixta , FN-kappa B , Proteínas Proto-Oncogénicas , Proteína 2 de Unión a Retinoblastoma , Microambiente TumoralRESUMEN
OBJECTIVE: Prognosis of cholangiocarcinoma is poor, and palliative treatment options are limited in China. This study aimed to analyze prognostic factors affecting survival in patients with advanced cholangiocarcinoma. METHODS: Clinical data on 201 consecutive patients with cholangiocarcinoma who received treatment at a single center from May 2014 to December 2018 were analyzed retrospectively. Survival curves were plotted using the Kaplan-Meier method. Survival analyses were performed using a log-rank test. RESULTS: For first-line therapy, the disease control rate was 56% (85/152) and the overall response rate was 16% (24/152). The total disease control rate was 34% (23/67) for second-line therapy. The median progression-free survival was 7 months, and the median overall survival was 17 months. Next-generation sequencing was performed for 59 patients. The most frequently mutated genes were TP53 and PI3KCA. No significant association was found between gene mutations and treatment response or survival. Of 5 patients with high levels of microsatellite instability, 4 (80%) were sensitive to anti-programmed death 1 antibodies and remained in partial remission at last follow-up. CONCLUSIONS: Macroscopic tumor characteristics, rather than gene mutations, determine the prognosis of advanced cholangiocarcinoma. High microsatellite instability may be a favorable predictor of response to immunotherapy for cholangiocarcinoma.
Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Neoplasias de los Conductos Biliares/terapia , Conductos Biliares Intrahepáticos , Colangiocarcinoma/terapia , Humanos , Cuidados Paliativos , Pronóstico , Estudios RetrospectivosRESUMEN
BACKGROUND: The incidence of cholangiocarcinoma has doubled over the last 15 years with a similar rise in mortality, which provides the impetus for standardization of evidence-based care through the establishment of guidelines. METHODS: We compared available guidelines on the clinical management of cholangiocarcinoma in the United States and Europe, which included the National Comprehensive Cancer Network (NCCN), European Society for Medical Oncology (ESMO), British Society of Gastroenterology (BSG) and the International Liver Cancer Association (ILCA) guidelines. RESULTS: There is discordance in the recommendation for biopsy in patients with potentially resectable cholangiocarcinoma and in the recommendation for use of fluorodeoxyglucose positron emission tomography scans. Similarly, the recommendation for preoperative biliary drainage for extrahepatic and perihilar cholangiocarcinoma in the setting of jaundice is inconsistent across all four guidelines. The BILCAP (capecitabine) and ABC-02 trials (gemcitabine with cisplatin) have provided the strongest evidence for systemic therapy in the adjuvant and palliative settings, respectively, but all guidelines have refrained from setting them as standard of care, given heterogeneity in the study cohorts and ABC-02's negative intention-to-treat results. CONCLUSIONS: Future progress in enhancing survivorship of patients with cholangiocarcinoma would likely entail improvements in diagnostic biomarkers and novel systemic therapies. Based on recent results from studies of targeted therapy, future iterations of the guidelines will likely incorporate molecular profiling.
Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Tumor de Klatskin , Neoplasias de los Conductos Biliares/terapia , Conductos Biliares Intrahepáticos , Colangiocarcinoma/epidemiología , Colangiocarcinoma/terapia , Europa (Continente) , Humanos , Estados Unidos/epidemiologíaAsunto(s)
Neoplasias de los Conductos Biliares/terapia , Quimioradioterapia Adyuvante/métodos , Colangiocarcinoma/terapia , Hepatectomía/métodos , Recurrencia Local de Neoplasia/terapia , Anciano , Neoplasias de los Conductos Biliares/diagnóstico , Neoplasias de los Conductos Biliares/patología , Conductos Biliares Intrahepáticos/diagnóstico por imagen , Conductos Biliares Intrahepáticos/patología , Conductos Biliares Intrahepáticos/cirugía , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/patología , Colecistectomía , Resultado Fatal , Fluorouracilo/uso terapéutico , Humanos , Imagen por Resonancia Magnética , Masculino , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones , Reoperación , Factores de Tiempo , Radioisótopos de Itrio/administración & dosificaciónRESUMEN
Near-infrared photoimmunotherapy (NIR-PIT) is a novel therapy for cancers that uses NIR light and antibody-photosensitizer (IR700) conjugates. However, it is difficult to deliver NIR light into the bile duct for cholangiocarcinoma (CCA) from the conventional extracorporeal apparatus. Thus, in this study, we developed a dedicated catheter with light emitting diodes (LEDs) that supersedes conventional external irradiation devices; we investigated the therapeutic effect of NIR-PIT for CCA using the novel catheter. The new catheter was designed to be placed in the bile duct and a temperature sensor was attached to the tip of the catheter to avoid thermal burn. An anti-epidermal growth factor receptor (EGFR) antibody, Panitumumab-IR700 conjugate or anti-human epidermal growth factor receptor type 2 (HER2) antibody, Trastuzumab-IR700 conjugate, was used with EGFR- or HER2-expressing cell lines, respectively. The in vitro efficacy of NIR-PIT was confirmed in cultured cells; the capability of the new catheter for NIR-PIT was then tested in a mouse tumor model. NIR-PIT via the developed catheter treated CCA xenografts in mice. NIR-PIT had an effect in Panitumumab-IR700 conjugate- and Trastuzumab-IR700 conjugate-treated CCA cells that depended on the receptor expression level. Tumor growth was significantly suppressed in mice treated with NIR-PIT using the novel catheter compared with controls (P < .01). NIR-PIT was an effective treatment for EGFR- and HER2-expressing CCA cells, and the novel catheter with mounted LEDs was useful for NIR-PIT of CCA.
Asunto(s)
Neoplasias de los Conductos Biliares/terapia , Colangiocarcinoma/terapia , Inmunoterapia/instrumentación , Terapia por Luz de Baja Intensidad/instrumentación , Animales , Catéteres , Línea Celular Tumoral , Femenino , Humanos , Inmunoterapia/métodos , Rayos Infrarrojos/uso terapéutico , Terapia por Luz de Baja Intensidad/métodos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Panitumumab/farmacología , Fármacos Fotosensibilizantes/farmacología , Trastuzumab/farmacología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Cholangiocarcinoma is a highly lethal biliary epithelial tumor that is rare in the general population but has increased rates in patients with primary sclerosing cholangitis (PSC). It is heterogenous, and management varies by location. No effective prevention exists, and screening is likely only feasible in PSC. Patients often present in an advanced state with jaundice, weight loss, and cholestatic liver enzymes. Diagnosis requires imaging with magnetic resonance cholangiopancreatography, laboratory testing, and endoscopic retrograde cholangiopancreatography. Potentially curative options include resection and liver transplant with neoadjuvant or adjuvant chemoradiation. Chemotherapy, radiation, and locoregional therapy provide some survival benefit in unresectable disease.
Asunto(s)
Neoplasias de los Conductos Biliares/diagnóstico , Neoplasias de los Conductos Biliares/terapia , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/terapia , Fosfatasa Alcalina/sangre , Neoplasias de los Conductos Biliares/patología , Conductos Biliares Extrahepáticos , Conductos Biliares Intrahepáticos , Bilirrubina/sangre , Quimioradioterapia Adyuvante , Colangiocarcinoma/patología , Pancreatocolangiografía por Resonancia Magnética , Colangitis Esclerosante/complicaciones , Humanos , Trasplante de Hígado , Factores de Riesgo , gamma-Glutamiltransferasa/sangreAsunto(s)
Neoplasias de los Conductos Biliares/diagnóstico , Colangiocarcinoma/secundario , Neoplasias de Cabeza y Cuello/secundario , Cuero Cabelludo/patología , Neoplasias Cutáneas/secundario , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/terapia , Conductos Biliares Intrahepáticos/diagnóstico por imagen , Conductos Biliares Intrahepáticos/patología , Biomarcadores de Tumor/análisis , Biopsia , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/terapia , Terapias Complementarias , Neoplasias de Cabeza y Cuello/diagnóstico , Neoplasias de Cabeza y Cuello/terapia , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/terapia , Tomografía Computarizada por Rayos XRESUMEN
Management of advanced intrahepatic cholangiocarcinoma (iCCA) is challenging and overall survival is poor. Progress in the development of new therapeutic options for metastatic cholangiocarcinoma (CCA) has been slow; hence, to date, there are no approved second-line agents in this setting. Although the development of immune checkpoint inhibitors has significantly improved overall survival in a variety of malignancies, there has not been a clinically important impact in CCA. This report presents a 66-year-old patient with chemotherapy-refractory iCCA who experienced a prolonged response to immunotherapy. Tumor genome profiling revealed a high tumor mutation burden of 17 mutations per megabase in the absence of microsatellite instability. He was started on immunotherapy with nivolumab and has experienced an ongoing response for 16 months without clinical symptoms and only minimal radiologic disease.
Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Neoplasias de los Conductos Biliares/terapia , Colangiocarcinoma/terapia , Neoplasias Hepáticas/terapia , Metástasis Linfática/terapia , Nivolumab/uso terapéutico , Anciano , Antineoplásicos Inmunológicos/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de los Conductos Biliares/genética , Neoplasias de los Conductos Biliares/inmunología , Neoplasias de los Conductos Biliares/patología , Conductos Biliares Intrahepáticos/patología , Conductos Biliares Intrahepáticos/cirugía , Capecitabina/farmacología , Capecitabina/uso terapéutico , Quimioradioterapia Adyuvante/métodos , Colangiocarcinoma/genética , Colangiocarcinoma/inmunología , Colangiocarcinoma/secundario , Análisis Mutacional de ADN , Resistencia a Antineoplásicos/genética , Fluorouracilo/farmacología , Fluorouracilo/uso terapéutico , Humanos , Conducto Inguinal/patología , Leucovorina/farmacología , Leucovorina/uso terapéutico , Hígado/diagnóstico por imagen , Hígado/patología , Neoplasias Hepáticas/secundario , Metástasis Linfática/diagnóstico por imagen , Masculino , Inestabilidad de Microsatélites , Neoplasia Residual , Nivolumab/farmacología , Compuestos Organoplatinos/farmacología , Compuestos Organoplatinos/uso terapéutico , Tomografía Computarizada por Tomografía de Emisión de Positrones , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Resultado del TratamientoRESUMEN
PURPOSE: Portal vein (PV) embolization (PVE) is traditionally performed via a PV sheath with selective embolization of PV branches. Here, the efficacy and safety of PVE with the use of only an 18-gauge needle is reported. MATERIALS AND METHODS: Consecutive patients who underwent PVE from 2009 through 2017 were retrospectively reviewed. Forty-five patients (mean age, 60 y ± 7.6; 38 men) underwent 45 PVE procedures. Hepatocellular carcinoma, cholangiocarcinoma, and metastases accounted for 26 (58%), 13 (29%), and 6 (13%) patients, respectively. PVE was performed by puncturing a branch of right PV with an 18-gauge needle under US guidance. Via the same needle, direct portography was performed, followed by PVE with an N-butyl cyanoacrylate/Lipiodol mixture. Percentage increase of future liver remnant (FLR) volume and increase in ratio of FLR to total liver volume were estimated as measures of efficacy. Complications were reported according to Society of Interventional Radiology classification. Fluoroscopy time, procedure time, and dose-area product (DAP) were recorded. RESULTS: Technical success rate was 100%. The median DAP, fluoroscopy time, and procedure time were 74,387 mGy·cm2 (IQR, 90,349 mGy·cm2), 3.5 min (IQR, 2.10 min), and 24 min (IQR, 10.5 min). Among the 23 patients with complete CT volumetry data, mean increase in the ratio of FLR to total liver volume and percentage increase of FLR volume were 12.5% ± 7.7 and 50% ± 33, respectively. There were 3 minor complications (asymptomatic nonocclusive emboli in FLR) and 3 major complications (1 hepatic vein emboli, 1 subphrenic collection, and 1 hepatic infarct). CONCLUSIONS: PVE via a sheathless 18-gauge needle approach is feasible, with satisfactory FLR hypertrophy.
Asunto(s)
Neoplasias de los Conductos Biliares/terapia , Carcinoma Hepatocelular/terapia , Colangiocarcinoma/terapia , Embolización Terapéutica/métodos , Enbucrilato/administración & dosificación , Aceite Etiodizado/administración & dosificación , Neoplasias Hepáticas/terapia , Vena Porta , Anciano , Angiografía de Substracción Digital , Neoplasias de los Conductos Biliares/diagnóstico por imagen , Neoplasias de los Conductos Biliares/patología , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/patología , Colangiocarcinoma/diagnóstico por imagen , Colangiocarcinoma/patología , Neoplasias Colorrectales/patología , Angiografía por Tomografía Computarizada , Embolización Terapéutica/efectos adversos , Embolización Terapéutica/instrumentación , Enbucrilato/efectos adversos , Diseño de Equipo , Aceite Etiodizado/efectos adversos , Estudios de Factibilidad , Femenino , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/secundario , Regeneración Hepática , Masculino , Persona de Mediana Edad , Agujas , Portografía/métodos , Punciones , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: The analysis of recent studies on plasmonic photothermal therapy (PPT) after intravenous administration of gold nanorods (GNRs) has demonstrated that the effectiveness of nanoparticle-assisted laser hyperthermia depends on a correct dosage strategy of nanoparticle administration. Accumulation of GNRs in tumor tissue dramatically increases the local heating of the tumor without damage to healthy tissues. However, the optimal doses of GNR intravenous injections (IVIs) for effective accumulation in tumors, and optimal protocols of PPT are not designed yet. The current study aims to improve the efficacy of PPT in tumor-bearing rats using multiple fractional intravenous administration of GNRs. MATERIALS AND METHODS: For PPT experiments, the GNRs with aspect ratio of 4.1 were functionalized with thiolated polyethylene glycol (PEG) and their suspensions were used for multiple fractional intravenous administration in outbred albino male rats with experimental model of rat liver cancer (cholangiocarcinoma line PC-1). Doppler ultrasonography was performed to characterize the vascularity of transplanted rat tumors before any treatment. After a final injection of GNRs, tumor was irradiated during 15 minutes by 808-nm NIR diode laser at a power density 2.3 W/cm2 . The animals were withdrawn from the experiment and sampling of tissues for morphological study and gold accumulation was performed 24 hours and 3 weeks after PPT. RESULTS: The multiple IVIs of gold nanorods and further PPT of transplanted cholangiocarcinoma provided significant damage to tumor tissue resulting in pronounced necrotic mass and retardation of the tumor growth. More importantly, the proposed PPT protocol had low toxicity as evidenced by histological examination of internal organs. The efficiency of PPT depends on the presence of newly formed vasculature as revealed by the Doppler ultrasound investigation. CONCLUSION: The repeatable IVIs promote greater of GNR accumulation within the tumor thus resulting in higher PPT efficacy. Accompanying ultrasonography can be useful for prognosis and monitoring of treatment. Lasers Surg. Med. 50:1025-1033, 2018. © 2018 Wiley Periodicals, Inc.
Asunto(s)
Colangiocarcinoma/terapia , Oro/farmacología , Hipertermia Inducida/métodos , Fototerapia/métodos , Animales , Colangiocarcinoma/irrigación sanguínea , Colangiocarcinoma/diagnóstico por imagen , Modelos Animales de Enfermedad , Láseres de Semiconductores , Masculino , Nanotubos , Polietilenglicoles/farmacología , Ratas , Ultrasonografía DopplerRESUMEN
Hyperthermia, which is a noninvasive treatment that causes tumor cells to become heated and that works in synergy with anticancer drugs and radiation therapy, is emerging as a promising treatment for patients with cancer. The purpose of this study is to report the efficacy of hyperthermia combined with chemotherapy (gemcitabine/cisplatin) for the treatment of a patient with unresectable cholangiocarcinoma. A 54-year-old man was diagnosed as hilar cholangiocarcinoma (Klatskin tumor) and was administered neoadjuvant and preoperative radiation with chemotherapy. However, because the treatment with radiation and chemotherapy was not successful, he decided to undergo hyperthermia combined with chemotherapy as a second treatment option. He was suffering from fatigue, dyspepsia, epigastralgia, and jaundice. Hyperthermia combined with chemotherapy was administered 32 times over a period of 4 months. The patient experienced no critical complications, and the patient's condition improved, with the carbohydrate antigen 19-9 (CA 19-9) and the total bilirubin levels being relatively lowered. In addition, the computed tomography scan showed that the cholangiocarcinoma had not progressed. In conclusion, this case report suggests radiofrequency hyperthermia combined with chemotherapy may be a promising treatment option for patients with unresectable cholangiocarcinoma.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/terapia , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/terapia , Fiebre/fisiopatología , Terapia Combinada/métodos , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVES: The aim of this was to determine survival after starting neoadjuvant therapy for patients who became ineligible for orthotopic liver transplantation (OLT). METHODS AND MATERIALS: Since January 1993, 215 patients with unresectable cholangiocarcinoma began treatment with planned OLT. Treatment included external-beam radiation therapy (EBRT) with fluorouracil, bile duct brachytherapy, and postradiotherapy fluorouracil or capecitabine before OLT. Adverse findings at the staging operation, death, and other factors precluded OLT in 63 patients (29%), of whom 61 completed neoadjuvant chemoradiation. RESULTS: By October 2012, 56 (89%) of the 63 patients unable to undergo OLT had died. Twenty-two patients (35%) became ineligible for OLT before the staging operation, 38 (60%) at the staging operation, and 3 (5%) after staging. From the date of diagnosis, median overall survival was 12.3 months. Survival was 17% at 18 months and 7% at 24 months. Median survival after fallout was 6.8 months. Median survival after the staging operation was 6 months. Two patients lived for 3.7 and 8.7 years before dying of cancer or liver failure caused by persistent biliary stricture at the site of the original cancer, respectively. Univariate analysis showed that time from diagnosis to fallout correlated with overall survival (P=0.04). CONCLUSIONS: In highly selected patients initially suitable for OLT, the mortality rate for cholangiocarcinoma was high in patients who became ineligible for OLT. Their survival, however, was comparable to expected survival for patients with locally advanced or metastatic disease treated with nontransplant therapies. The most common reason for patient fallout was adverse findings at the staging operation.
Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Neoplasias de los Conductos Biliares/terapia , Braquiterapia , Capecitabina/uso terapéutico , Colangiocarcinoma/terapia , Fluorouracilo/uso terapéutico , Adulto , Anciano , Neoplasias de los Conductos Biliares/patología , Quimioradioterapia Adyuvante , Colangiocarcinoma/patología , Técnicas de Diagnóstico Quirúrgico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Tasa de SupervivenciaRESUMEN
We reported a case of hilar cholangiocellularcarcinoma with complete obstruction of the portal vein. The patient, who was a 65-year-old woman, suffered from fever and general fatigue as a result of acute cholangitis after insertion of a tube stent into the right bile duct. The main tumor was present on the right side of S1 and spread to both sides of the bile duct. S1 lobe was swollen and diffuse intrahepatic invasion was noted in the right lobe and S1. The portal vein was completely obstructed at the porta hepatis with a coronary vein-left renal vein shunt. We immediately administered a high-dose hepatic arterialinfusion( 5-FU 1 g×3 days: one day off 1 g×3 days)(HDHAI)to the right hepatic artery using a transient catheter insertion method. After 2 courses of HDHAI, the intrahepatic invasion decreased. However, after 4 courses of HDHAI(2 on the right side and 2 on the left side), the invasion on the left side of the IVC had increased. We then chose radiation therapy. Subsequently, transient cystic changes were observed; however, 4 months after radiation, the invasion on the left side of the IVC had regrown into the cardia. The patient suffered from vomiting as a result of the narrowing of the esophagus. We chose HDHAI and dilation of the esophagus using a balloon. Finally, the invasion on the left side of the IVC and S1 swelling decreased, and she could eat again. Thirteen months later, she remains an outpatient. We recommend HDHAI and radiation therapy to hilar cholangiocellularcarcinoma even if the portal vein is completely obstructed.
Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Neoplasias de los Conductos Biliares/terapia , Quimioradioterapia , Colangiocarcinoma/terapia , Drenaje , Fluorouracilo/uso terapéutico , Arteria Hepática , Vena Porta/diagnóstico por imagen , Anciano , Antimetabolitos Antineoplásicos/administración & dosificación , Neoplasias de los Conductos Biliares/diagnóstico por imagen , Colangiocarcinoma/diagnóstico por imagen , Femenino , Fluorouracilo/administración & dosificación , Humanos , Infusiones Intraarteriales , Tomografía Computarizada por Rayos XRESUMEN
Synergy between yttrium-90 (90Y) and antineoplastic drugs was investigated. Viability of HepaRG (hepatocellular carcinoma) and HuCCT1 (cholangiocarcinoma) cells was studied through a tetrazolium dye reduction assay. A combination index (CI) was calculated, with CI < 1 denoting synergy and CI > 1 denoting antagonism. In HepaRG cells, gemcitabine showed synergy with 90Y (CI = 0.70 [95% confidence interval = 0.65-0.75]), whereas oxaliplatin (CI = 1.15 [1.08-1.21]), paclitaxel (CI = 1.26 [1.15-1.37]), and sorafenib (CI = 1.77 [1.65-1.89]) showed antagonism. In HuCCT1 cells, gemcitabine (CI = 0.54 [0.50-0.58]) and oxaliplatin (CI = 0.86 [0.82-0.90]) showed synergy with 90Y, whereas paclitaxel (CI = 1.18 [1.09-1.27]) and sorafenib (CI = 1.21 [1.12-1.30]) showed antagonism. These results suggest that gemcitabine and oxaliplatin should be tested in combination with 90Y radioembolization for treatment of liver cancer.
Asunto(s)
Carcinoma Hepatocelular/terapia , Colangiocarcinoma/terapia , Desoxicitidina/análogos & derivados , Niacinamida/análogos & derivados , Compuestos Organoplatinos/administración & dosificación , Paclitaxel/administración & dosificación , Compuestos de Fenilurea/administración & dosificación , Piridinas/administración & dosificación , Radioisótopos de Itrio/uso terapéutico , Antineoplásicos/administración & dosificación , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Quimioradioterapia/métodos , Colangiocarcinoma/patología , Desoxicitidina/administración & dosificación , Relación Dosis-Respuesta a Droga , Relación Dosis-Respuesta en la Radiación , Sinergismo Farmacológico , Humanos , Niacinamida/administración & dosificación , Tolerancia a Radiación/efectos de los fármacos , Radiofármacos/administración & dosificación , Sorafenib , GemcitabinaRESUMEN
BACKGROUND: Cholangiocarcinoma (CCA) remains a major health problem and causes high mortality in Northeastern Thailand. Patients with CCA have a poor prognosis, and little is known about their health-related quality of life (HRQOL) and its determinants. OBJECTIVE: The objective of this study was to investigate factors affecting HRQOL and its changes over time among CCA patients. METHODS: Two hundred thirty-seven patients with CCA were recruited during a 6-month period in 2011 in 5 tertiary hospitals in 4 provinces of northeastern Thailand. Health-related quality of life after diagnosis of CCA was measured by the Functional Assessment of Cancer Therapy-Hepatobiliary questionnaire (Thai version 4). The HRQOL score of CCA patients at different times after diagnosis was compared by repeated-measures analysis of variance. Generalized estimating equation was used to identify factors affecting HRQOL among CCA patients. RESULTS: Of 237 eligible patients registered, 99 confirmed cases completed follow-up at 2 months. Overall HRQOL varied over time, with the score at baseline being significantly lower than 1 and 2 months later. An adjusted analysis showed that patients who were 60 to 69 years old had higher HRQOL scores than did younger patients. Patients using alternative medicine had lower HRQOL scores than did those who did not. CONCLUSIONS: Health-related quality-of-life scores among CCA patients changed over time and were related to age at recruitment and use of alternative medicine. IMPLICATIONS FOR PRACTICE: Healthcare providers should carefully communicate about the diagnosis and its implications. Patients with CCA, especially younger patients and those who have used traditional medicine, may benefit from counseling and help with mobilizing family and social support.
Asunto(s)
Colangiocarcinoma/terapia , Calidad de Vida , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Terapias Complementarias/estadística & datos numéricos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , TailandiaRESUMEN
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.
Asunto(s)
Neoplasias de los Conductos Biliares/mortalidad , Conductos Biliares Intrahepáticos , Colangiocarcinoma/mortalidad , Neoplasias Hepáticas/mortalidad , Trasplante de Hígado/mortalidad , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/terapia , Conductos Biliares Intrahepáticos/patología , Inhibidores de la Calcineurina/administración & dosificación , Colangiocarcinoma/patología , Colangiocarcinoma/terapia , Terapia Combinada , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Doxorrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Inmunosupresores/administración & dosificación , Hallazgos Incidentales , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Mitomicina/administración & dosificación , Recurrencia Local de Neoplasia/mortalidad , Pronóstico , Sirolimus/administración & dosificación , Análisis de Supervivencia , Resultado del Tratamiento , GemcitabinaRESUMEN
In this basic research study, Zhang et al created and report on a clever magnetic resonance (MR)-guided radiofrequency (RF) system that enables focal hyperthermic heating, targeting, and visualization for the treatment of cholangiocarcinoma. The key novelty is creating localized MR-induced heating around a metallic guidewire, which they subsequently demonstrate can be successfully combined with chemotherapy to (a) reduce cell proliferation in vitro, (b) decrease tumor growth in mouse xenografts, and (c) increase biliary uptake of chemotherapeutic drugs in swine. An added benefit of the system is using the wire as an intraluminal receiver antenna to improve the resolution of intraprocedural imaging guidance.
Asunto(s)
Neoplasias de los Conductos Biliares/terapia , Colangiocarcinoma/terapia , Desoxicitidina/análogos & derivados , Fluorouracilo/farmacología , Hipertermia Inducida , Imagen por Resonancia Magnética/métodos , Animales , Desoxicitidina/farmacología , Humanos , GemcitabinaRESUMEN
PURPOSE: To determine whether magnetic resonance (MR) imaging heating guidewire-mediated radiofrequency (RF) hyperthermia could enhance the therapeutic effect of gemcitabine and 5-fluorouracil (5-FU) in a cholangiocarcinoma cell line and local deposit doses of chemotherapeutic drugs in swine common bile duct (CBD) walls. MATERIALS AND METHODS: The animal protocol was approved by the institutional animal care and use committee. Green fluorescent protein-labeled human cholangiocarcinoma cells and cholangiocarcinomas in 24 mice were treated with (a) combination therapy with chemotherapy (gemcitabine and 5-FU) plus RF hyperthermia, (b) chemotherapy only, (c) RF hyperthermia only, or (d) phosphate-buffered saline. Cell proliferation was quantified, and tumor changes over time were monitored with 14.0-T MR imaging and optical imaging. To enable further validation of technical feasibility, intrabiliary local delivery of gemcitabine and 5-FU was performed by using a microporous balloon with (eight pigs) or without (eight pigs) RF hyperthermia. Chemotherapy deposit doses in the bile duct walls were quantified by means of high-pressure liquid chromatography. The nonparametric Mann-Whitney U test and the paired-sample Wilcoxon signed rank test were used for data analysis. RESULTS: Combination therapy induced lower mean levels of cell proliferation than chemotherapy only and RF hyperthermia only (0.39 ± 0.13 [standard deviation] vs 0.87 ± 0.10 and 1.03 ± 0.13, P < .001). Combination therapy resulted in smaller relative tumor volume than chemotherapy only and RF hyperthermia only (0.65 ± 0.03 vs 1.30 ± 0.021 and 1.37 ± 0.05, P = .001). Only in the combination therapy group did both MR imaging and optical imaging show substantial decreases in apparent diffusion coefficients and fluorescent signals in tumor masses immediately after the treatments. Chemotherapy quantification showed a higher average drug deposit dose in swine CBD walls with intrabiliary RF hyperthermia than without it (gemcitabine: 0.32 mg/g of tissue ± 0.033 vs 0.260 mg/g ± 0.030 and 5-FU: 0.660 mg/g ± 0.060 vs 0.52 mg/g ± 0.050, P < .05). CONCLUSION: The use of intrabiliary MR imaging heating guidewire-mediated RF hyperthermia can enhance the chemotherapeutic effect on a human cholangiocarcinoma cell line and local drug deposition in swine CBD tissues.