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1.
Zhonghua Wai Ke Za Zhi ; 58(4): 289-294, 2020 Apr 01.
Artigo em Chinês | MEDLINE | ID: mdl-32241059

RESUMO

Intrahepatic cholangiocarcinoma(ICC) is the second most common primary liver cancer. The incidence of ICC has been significantly increased globally in recent years. The concealed onset of ICC usually results in late disease diagnosis. Liver resection is currently the only well-established treatment for ICC that may cure the disease, however, long-term survival rate is still unsatisfied due to the low resection rate and high recurrence rate. Local therapy combined with systemic chemotherapy is the main treatment for advanced or unresectable ICC, but the outcomes are still poor. With the in-depth understanding of the molecular mechanism of ICC and development of next-generation sequencing technology, multiple abnormal signaling pathways (RAS/MAPK, MET, EGFR) and gene mutations (FGFR2, IDH1/2) have been identified as potential therapeutic targets. Although there is still no approved targeted drugs for ICC, more than 100 clinical trials testing targeted therapy alone or in combination with chemotherapy are ongoing, among which some have shown promising application prospects. Molecular typing and personalized targeted therapy are important ways to improve the overall outcomes of ICC. This review summarized the recent advances in the targeted therapies for patients with ICC.


Assuntos
Neoplasias dos Ductos Biliares/terapia , Colangiocarcinoma/terapia , Neoplasias Hepáticas/terapia , Terapia de Alvo Molecular , Ductos Biliares Intra-Hepáticos , Humanos , Transdução de Sinais
2.
Medicine (Baltimore) ; 99(12): e19276, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32195932

RESUMO

This study aimed to investigate the efficacy and safety of drug-eluting beads (DEB) transarterial chemoembolization (TACE) treatment in Chinese intrahepatic cholangiocarcinoma (ICC) patients.37 ICC patients underwent DEB-TACE treatment in CTILC study (registered on clinicaltrials.gov with registry No. NCT03317483) were included in this present study. Treatment response was assessed according to modified Response Evaluation Criteria in Solid Tumors (mRECIST). Overall survival (OS) was calculated from the time of DEB-TACE operation until the date of death from any causes. Liver function change and adverse events (AEs) were recorded during and after DEB-TACE operation.3 (8.1%) patients achieved complete response (CR) and 22 (59.5%) patients achieved partial response (PR), with objective response rate (ORR) of 67.6%. After DEB-TACE treatment, mean OS was 376 days (95%CI: 341-412 days). Multivariate logistic regression analysis revealed that Bilobar disease (P = .040, OR: 0.105, 95% CI: 0.012-0.898) and portal vein invasion (P = .038, OR: 0.104, 95% CI: 0.012-0.881) could independently predict less possibility of ORR. Patients with ALB abnormal, TP abnormal, ALT abnormal and AST abnormal were increased at 1-week post DEB-TACE treatment (P = .034, P = .001, P < .001, P = .006, respectively), while returned to the levels at baseline after 1 to 3 months (all P > .050). Besides, most of the AEs were mild including pain, fever, vomiting, and nausea in this study.DEB-TACE was effective and well tolerated in treating ICC patients, and bilobar disease as well as portal vein invasion were independently correlated with less probability of ORR achievement.


Assuntos
Neoplasias dos Ductos Biliares/terapia , Quimioembolização Terapêutica/métodos , Colangiocarcinoma/terapia , Idoso , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/patologia , Doxorrubicina , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Neoplasias Hepáticas/secundário , Modelos Logísticos , Masculino , Microesferas , Pessoa de Meia-Idade , Invasividade Neoplásica , Veia Porta/patologia
3.
Einstein (Sao Paulo) ; 18: eRC4990, 2020.
Artigo em Inglês, Português | MEDLINE | ID: mdl-32130329

RESUMO

Transarterial radioembolization (TARE) with yttrium-90 microspheres is a palliative locoregional treatment, minimally invasive for liver tumors. The neoadjuvant aim of this treatment is still controversial, however, selected cases with lesions initially considered unresectable have been enframed as candidates for curative therapy after hepatic transarterial radioembolization. We report three cases in which the hepatic transarterial radioembolization was used as neoadjuvant therapy in an effective way, allowing posterior potentially curative therapies.


Assuntos
Neoplasias dos Ductos Biliares/terapia , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Colangiocarcinoma/terapia , Neoplasias Hepáticas/terapia , Adulto , Idoso , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Resultado do Tratamento , Radioisótopos de Ítrio
4.
Internist (Berl) ; 61(2): 158-163, 2020 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-31919532

RESUMO

Interventional radiology offers a large variety of locoregional and local ablative treatment options for liver tumors. These can be applied as stand-alone minimally invasive procedures or in combination with other treatment options and with curative as well as palliative intent depending on the respective tumor stage. This review article presents the various locoregional and local ablative treatment techniques and describes the clinical value in the treatment of hepatocellular carcinoma and intrahepatic cholangiocarcinoma.


Assuntos
Neoplasias dos Ductos Biliares , Carcinoma Hepatocelular , Colangiocarcinoma , Neoplasias Hepáticas , Neoplasias dos Ductos Biliares/terapia , Ductos Biliares Intra-Hepáticos , Carcinoma Hepatocelular/terapia , Ablação por Cateter , Colangiocarcinoma/terapia , Humanos , Neoplasias Hepáticas/terapia
5.
Internist (Berl) ; 61(2): 170-174, 2020 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-31938815

RESUMO

Cholangiocellular carcinoma (CCA) is one of the primary liver tumors and overall represents a rare malignancy; however, in recent years the incidence, particularly of intrahepatic CCA (iCCA) has increased worldwide. Due to the high mortality, CCAs cause a significant proportion of cancer-related deaths also in Germany. Because the diagnosis is often made in advanced stages of the disease, in many cases a surgical approach with curative intention is not possible. For locally advanced or metastatic CCA the combination of gemcitabine and cisplatin currently remains the only approved systemic treatment. As the average survival time is only approximately 12 months even under first-line treatment with gemcitabine/cisplatin, research is focused on developing new molecularly targeted and immunological treatment options. Various studies are currently being carried out to investigate approval options for targeted treatment, which could be considered for genetically altered tumors, e.g. in fibroblast growth factor receptor (FGFR) fusion and isocitrate dehydrogenase (IDH) mutations. Additionally, initial clinical data on immune checkpoint inhibitors are available for CCA. Due to the complex selection and partially limited applicability of current treatment options in patients with CCA, an early collaboration with a gastroenterology and oncology center with the possibility of supervision by a tumor board consisting of gastroenterological oncologists, surgeons, radiologists and radio-oncologists or in advanced stages by a molecular tumor board is essential.


Assuntos
Neoplasias dos Ductos Biliares , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/terapia , Colangiocarcinoma/genética , Colangiocarcinoma/terapia , Alemanha , Humanos , Terapia de Alvo Molecular , Medicina de Precisão
6.
Medicine (Baltimore) ; 98(52): e18435, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31876723

RESUMO

INTRODUCTION: Intrahepatic cholangiocarcinoma (ICC) accounts for 10% to 15% of all primary hepatic carcinomas. However, there are no effective drug treatment strategies against ICC, and surgery is currently the only curative treatment. Here, we present a case of ICC successfully treated with anlotinib, a novel oral agent. PATIENT CONCERNS: The patient was a 66-year-old Han Chinese woman, and she was a retired worker. The patient had no history of hepatitis B infection or hypertension. Physical examination showed no abnormalities, and the patient showed no conscious discomfort. However, ultrasound revealed liver occupation. DIAGNOSIS: Liver ultrasound and enhanced computed tomography (CT) indicated liver cancer with intrahepatic metastasis. Serum carbohydrate antigen 199 and alpha fetoprotein levels were high at 4270 and 1561 ng/mL, respectively. Pathologic findings of CT-guided liver biopsy revealed an adenocarcinoma. Owing to further immunohistochemical staining and clinical results, a diagnosis of ICC was made. INTERVENTIONS: The patient had received 5 cycles of transhepatic arterial chemotherapy and embolization and 1 cycle of microwave ablation. Due to rapid tumor progression and loss of liver function, systemic chemotherapy was contraindicated. As second-line therapy, she received anlotinib, a novel tyrosine kinase inhibitor that inhibits tumor angiogenesis and proliferative signaling and has been used to treat refractory advanced non-small-cell lung cancer that shows progression despite treatment with ≥2 chemotherapy regimens. OUTCOMES: This patient showed a partial response after 2 cycles of treatment with anlotinib (12 mg daily, days 1-14 of a 21-day cycle). Drug-related side effects, such as hypertension and hand foot skin reaction, were observed. After 4 cycles of anlotinib, the efficacy appeared to be stable, and the patient showed a progression-free survival period of almost 4 months. However, the patient's condition worsened and she died of liver failure 6 months after treatment (overall survival, almost 6 months). CONCLUSION: Some cases of ICC may be responsive to the antiangiogenic drug, anlotinib, when combined with microwave ablation. Randomized clinical studies are required to further confirm the efficacy and safety of anlotinib in the clinical treatment of ICC.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias dos Ductos Biliares/terapia , Colangiocarcinoma/terapia , Indóis/uso terapêutico , Micro-Ondas/uso terapêutico , Quinolinas/uso terapêutico , Idoso , Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/diagnóstico por imagem , Terapia Combinada , Feminino , Humanos , Tomografia Computadorizada por Raios X , Ultrassonografia
7.
Medicine (Baltimore) ; 98(45): e17851, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702644

RESUMO

To evaluate the safety and efficacy of the novel technique, transjugular portal vein embolization (TPVE).A single-center retrospective review of 18 patients (12 males and 6 females; mean age, 62 years) who underwent TPVE between January 2012 and January 2013 was conducted. The technical success rate, future liver remnant (FLR) volume, total liver volume (TLV) and FLR/TLV ratio after PVE were analyzed. Liver function, including total bilirubin (TB), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and International Normalized Ratio (INR), was assessed before and after PVE. Any complications of TPVE and liver resection after TPVE were recorded.TPVE was performed on 18 patients before right hepatic resection for both primary and secondary hepatic malignancies (10 hepatocellular carcinomas, 4 cases of colorectal liver metastasis, and 4 cholangiocarcinomas). Technical success was achieved in 100% of patients (18 of 18). The mean FRL significantly increased to 580 ±â€Š155 mL (P < .001) after PVE. The mean FLR/TLV ratio (%) significantly increased to 34 ±â€Š4 (P < .001) after PVE. One patient suffered septicemia after TPVE. A small number patients experienced mild to moderate abdominal pain during TPVE. No other major complications occurred after TPVE in our study. The patient who developed septicemia died 3 days after the surgery as a result of this complication and subsequent multiple organ dysfunction syndrome (MODS).Transjugular portal vein embolization is a safe, efficacious, and promising novel technique to induce hypertrophy of the FLR.


Assuntos
Neoplasias dos Ductos Biliares/terapia , Carcinoma Hepatocelular/terapia , Colangiocarcinoma/terapia , Embolização Terapêutica/métodos , Neoplasias Hepáticas/terapia , Idoso , Alanina Transaminase/metabolismo , Aspartato Aminotransferases/metabolismo , Neoplasias dos Ductos Biliares/metabolismo , Carcinoma Hepatocelular/metabolismo , Colangiocarcinoma/metabolismo , Embolização Terapêutica/efeitos adversos , Feminino , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
8.
J Surg Oncol ; 120(8): 1358-1364, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31614000

RESUMO

BACKGROUND: Little data regarding the selection of nonsurgical therapies for localized intrahepatic cholangiocarcinoma (ICC) are available. METHODS: A cohort of nonsurgically managed patients with American Joint Commission on Cancer clinical stage I/II ICC in the United States from 2004 to 2013 were identified in the National Cancer Database. Overall survival (OS) was compared according to treatment options (radiofrequency ablation [RFA] vs chemoradiotherapy) using propensity-score matching. RESULTS: Among 505 patients, 86 patients were treated with RFA and 419 patients were treated with chemoradiotherapy. After propensity matching (n = 84, each group), 5-year OS was 17.6% among patients who underwent RFA vs 3.8% among patients receiving chemoradiotherapy (P < .001). On bivariate analysis, RFA was related to an OS benefit (hazard ratio, 0.46; 95% confidence interval, 0.33-0.66; P < .001). Specifially, a stage-specific subgroup analysis revealed a survival benefit in favor of RFA among stage I patients (5-year OS; RFA: 20.1% vs chemoradiotherapy: 3.7%, P < .001), whereas no difference in OS was noted among patients with stage II disease. CONCLUSION: Among ICC patients with small (≤5 cm), solitary ICC without vascular invasion, RFA was associated with better survival compared with chemoradiotherapy.


Assuntos
Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/terapia , Colangiocarcinoma/mortalidade , Colangiocarcinoma/terapia , Ablação por Radiofrequência , Neoplasias dos Ductos Biliares/patologia , Quimiorradioterapia , Colangiocarcinoma/patologia , Estudos de Coortes , Feminino , Humanos , Masculino , Análise por Pareamento
9.
Cardiovasc Intervent Radiol ; 42(12): 1709-1717, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31578633

RESUMO

PURPOSE: To evaluate efficacy and complication rates of TACE with degradable starch microspheres (DSM-TACE) in patients with unresectable intrahepatic cholangiocarcinoma (ICC) with or without prior major liver resection (MLR). METHODS: This is a retrospective single-center study on 21 patients (age 63 ± 15 years) with either unresectable ICC progressive under systemic chemotherapy or unresectable intrahepatic tumor recurrence after prior MLR. Patients were treated by multi-agent (cisplatin/doxorubicin/mitomycin C) DSM-TACE between August 2012 and July 2016, repeated 3 times at 4-week intervals. Imaging response was evaluated using RECIST 1.1. Overall survival (OS) and complication rates, stratified by history of MLR, were investigated. RESULTS: Patients underwent a total 64 DSM-TACE sessions. Two patients (without MLR) were lost to follow-up after one uneventful DSM-TACE session. One patient underwent living-donor-liver transplantation after one DSM-TACE-session yielding partial remission. Of the remaining 18 patients, imaging response according to RECIST 1.1 was: complete remission in 2/18 (11.1%); PR in 9/18 (50%), and stable disease in 7/18 (38.9%), yielding an objective response rate of 61.1% and a disease control rate of 100%. Median OS of patients with objective response was significantly longer (18.0 months) than that of survival of patients with stable disease (4.8 months) (p = 0.001). Median OS of patients with MLR (12.5 months) was similar to that of patients without MLR (13.2 months). Of 21 patients, 2 (9.5%) developed post-interventional hepatobiliary abscesses, and one of these patients died due to subsequent sepsis. CONCLUSION: DSM-TACE is an effective treatment for unresectable and otherwise therapy-refractory intrahepatic cholangiocarcinoma, even in those patients with intrahepatic disease recurrence after prior MLR. LEVEL OF EVIDENCE: Level II, therapeutic study.


Assuntos
Neoplasias dos Ductos Biliares/terapia , Quimioembolização Terapêutica/métodos , Colangiocarcinoma/terapia , Amido/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos/cirurgia , Colangiocarcinoma/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Retrospectivos , Resultado do Tratamento
10.
World J Gastroenterol ; 25(31): 4343-4359, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31496617

RESUMO

the bile duct system and pancreas show many similarities due to their anatomical proximity and common embryological origin. Consequently, preneoplastic and neoplastic lesions of the bile duct and pancreas share analogies in terms of molecular, histological and pathophysiological features. Intraepithelial neoplasms are reported in biliary tract, as biliary intraepithelial neoplasm (BilIN), and in pancreas, as pancreatic intraepithelial neoplasm (PanIN). Both can evolve to invasive carcinomas, respectively cholangiocarcinoma (CCA) and pancreatic ductal adenocarcinoma (PDAC). Intraductal papillary neoplasms arise in biliary tract and pancreas. Intraductal papillary neoplasm of the biliary tract (IPNB) share common histologic and phenotypic features such as pancreatobiliary, gastric, intestinal and oncocytic types, and biological behavior with the pancreatic counterpart, the intraductal papillary mucinous neoplasm of the pancreas (IPMN). All these neoplastic lesions exhibit similar immunohistochemical phenotypes, suggesting a common carcinogenic process. Indeed, CCA and PDAC display similar clinic-pathological features as growth pattern, poor response to conventional chemotherapy and radiotherapy and, as a consequence, an unfavorable prognosis. The objective of this review is to discuss similarities and differences between the neoplastic lesions of the pancreas and biliary tract with potential implications on a common origin from similar stem/progenitor cells.


Assuntos
Neoplasias dos Ductos Biliares/etiologia , Carcinoma in Situ/etiologia , Carcinoma Ductal Pancreático/etiologia , Colangiocarcinoma/etiologia , Neoplasias Pancreáticas/etiologia , Lesões Pré-Cancerosas/etiologia , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/terapia , Sistema Biliar/patologia , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Carcinogênese/patologia , Carcinoma in Situ/patologia , Carcinoma in Situ/terapia , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/terapia , Colangiocarcinoma/patologia , Colangiocarcinoma/terapia , Progressão da Doença , Humanos , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/terapia , Células-Tronco/patologia
11.
World J Gastroenterol ; 25(29): 3941-3955, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31413529

RESUMO

BACKGROUND: Cholangiocarcinoma or biliary tract cancer has a high mortality rate resulting from late presentation and ineffective treatment strategy. Since immunotherapy by dendritic cells (DC) may be beneficial for cholangiocarcinoma treatment but their efficacy against cholangiocarcinoma was low. We suggest how such anti-tumor activity can be increased using cell lysates derived from an honokiol-treated cholangiocarcinoma cell line (KKU-213L5). AIM: To increase antitumour activity of DCs pulsed with cell lysates derived from honokiol-treated cholangiocarcinoma cell line (KKU-213L5). METHODS: The effect of honokiol, a phenolic compound isolated from Magnolia officinalis, on choangiocarcinoma cells was investigated in terms of the cytotoxicity and the expression of damage-associated molecular patterns (DAMPs). DCs were loaded with tumour cell lysates derived from honokiol-treated cholangiocarcinoma cells their efficacy including induction of T lymphocyte proliferation, proinflammatory cytokine production and cytotoxicity effect on target cholangiocarcinoma cells were evaluated. RESULTS: Honokiol can effectively activate cholangiocarcinoma apoptosis and increase the release of damage-associated molecular patterns. DCs loaded with cell lysates derived from honokiol-treated tumour cells enhanced priming and stimulated T lymphocyte proliferation and type I cytokine production. T lymphocytes stimulated with DCs pulsed with cell lysates of honokiol-treated tumour cells significantly increased specific killing of human cholangiocarcinoma cells compared to those associated with DCs pulsed with cell lysates of untreated cholangiocarcinoma cells. CONCLUSION: The present findings suggested that honokiol was able to enhance the immunogenicity of cholangiocarcinoma cells associated with increased effectiveness of DC-based vaccine formulation. Treatment of tumour cells with honokiol offers a promising approach as an ex vivo DC-based anticancer vaccine.


Assuntos
Neoplasias dos Ductos Biliares/terapia , Compostos de Bifenilo/farmacologia , Vacinas Anticâncer/imunologia , Colangiocarcinoma/terapia , Imunoterapia/métodos , Lignanas/farmacologia , Neoplasias dos Ductos Biliares/imunologia , Neoplasias dos Ductos Biliares/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Colangiocarcinoma/imunologia , Colangiocarcinoma/patologia , Células Dendríticas/imunologia , Células Dendríticas/transplante , Voluntários Saudáveis , Humanos , Imunogenicidade da Vacina , Ativação Linfocitária/efeitos dos fármacos , Linfócitos T Citotóxicos/efeitos dos fármacos , Linfócitos T Citotóxicos/imunologia , Transplante Autólogo/métodos
12.
BMJ Case Rep ; 12(8)2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31431431

RESUMO

Advanced cholangiocarcinoma especially those involving the vasculature have extremely limited options of cure. Ex situ liver resection entails performing a total hepatectomy, resecting the tumour on the back-table followed by reimplantation (autotransplantation) of the liver. Application of this technique for these tumours has rarely been done due to complexity of the procedure and the dismal prognosis of the lesions. We present our experience of two cases of advanced intrahepatic cholangiocarcinoma with limited extrahepatic disease who underwent ex situ resection with autotransplantation. They underwent preoperative therapy with a waiting period to assess the tumour biology. Both patients underwent ex situ resection with extended hepatectomy on the back table. Both patients remain well on follow-up 24 months and 20 months, respectively, with excellent quality of life. Despite its technical complexity, ex situ liver resection may offer prolonged overall survival in selected patients with advanced cholangiocarcinoma and limited extrahepatic disease.


Assuntos
Neoplasias dos Ductos Biliares/diagnóstico , Colangiocarcinoma/diagnóstico , Dor Abdominal/etiologia , Adulto , Neoplasias dos Ductos Biliares/complicações , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/terapia , Colangiocarcinoma/complicações , Colangiocarcinoma/diagnóstico por imagem , Colangiocarcinoma/terapia , Diagnóstico Diferencial , Feminino , Hepatectomia , Humanos , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Transplante Autólogo
13.
Int J Mol Sci ; 20(17)2019 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-31450710

RESUMO

Cholangiocarcinoma (CCA) is the second most common type of liver cancer, and is highly aggressive with very poor prognosis. CCA is classified into intrahepatic cholangiocarcinoma (iCCA) and extra-hepatic cholangiocarcinoma (eCCA), which is further stratified into perihilar (pCCA) and distal (dCCA). Cancer stem cells (CSCs) are a subpopulation of cancer cells capable of tumor initiation and malignant growth, and are also responsible for chemoresistance. Thus, CSCs play an important role in CCA carcinogenesis. Surface markers such as CD133, CD24, CD44, EpCAM, Sox2, CD49f, and CD117 are important for identifying and isolating CCA CSCs. CSCs are present in the tumor microenvironment (TME), termed 'CSC niche', where cellular components and soluble factors interact to promote tumor initiation. Epithelial-to-mesenchymal transition (EMT) is another important mechanism underlying carcinogenesis, involved in the invasiveness, metastasis and chemoresistance of cancer. It has been demonstrated that EMT plays a critical role in generating CSCs. Therapies targeting the surface markers and signaling pathways of CCA CSCs, proteins involved in TME, and immune checkpoint proteins are currently under investigation. Therefore, this review focuses on recent studies on the roles of CSCs in CCA; the possible therapeutic strategies targeting CSCs of CCA are also discussed.


Assuntos
Neoplasias dos Ductos Biliares/etiologia , Neoplasias dos Ductos Biliares/metabolismo , Colangiocarcinoma/etiologia , Colangiocarcinoma/metabolismo , Células-Tronco Neoplásicas/metabolismo , Animais , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/terapia , Biomarcadores , Colangiocarcinoma/patologia , Colangiocarcinoma/terapia , Terapia Combinada , Gerenciamento Clínico , Transição Epitelial-Mesenquimal , Humanos , Imunofenotipagem , Terapia de Alvo Molecular , Microambiente Tumoral
14.
BMJ Case Rep ; 12(7)2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31289161

RESUMO

Epstein-Barr virus (EBV) is implicated in the tumorigenesis of a variety of malignancies, including Burkitt's lymphoma, Hodgkin's disease and nasopharyngeal carcinoma (NPC). EBV+ lymphoepithelioma-like cholangiocarcinoma (LELCC) is a rare type of intrahepatic cholangiocarcinoma with a distinct pathology and poorly understood treatment options. Morphologically, this neoplasm resembles undifferentiated NPC, a commonly EBV+ tumour with a prominent lymphoid infiltrate. Almost all of the current literature regarding LELCC describes early stage tumours that are treated surgically and achieve good outcomes. In contrast, this report documents a late stage LELCC treated unsuccessfully with systemic chemotherapy.


Assuntos
Carcinoma/patologia , Colangiocarcinoma/patologia , Infecções por Vírus Epstein-Barr/complicações , Adulto , Carcinoma/terapia , Carcinoma/virologia , Colangiocarcinoma/terapia , Colangiocarcinoma/virologia , Diagnóstico Diferencial , Infecções por Vírus Epstein-Barr/virologia , Evolução Fatal , Feminino , Hepatite B Crônica/diagnóstico , Herpesvirus Humano 4/metabolismo , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Linfadenopatia/patologia , Recidiva Local de Neoplasia , Neoplasias Retroperitoneais/diagnóstico por imagem
15.
Cancer Radiother ; 23(5): 385-394, 2019 Sep.
Artigo em Francês | MEDLINE | ID: mdl-31300328

RESUMO

PURPOSE: The purpose of the study was to evaluate the outcomes of stereotactic radiation therapy for primary and secondary liver tumours in Jean-Perrin cancer centre (Clermont-Ferrand, France) in terms of efficacy and safety. MATERIALS AND METHODS: Between December 2013 and June 2016, 25 patients were included. Treatment was performed on a linear accelerator Novalis TX®. The prescription dose was 42 to 60Gy in three to five fractions. Local control at 1 year was evaluated with modified Response Evaluation Criteria in Solid Tumours (mRECIST) and RECIST criteria. Acute and late toxicity were evaluated with Common Terminology Criteria for Adverse Events (CTCAE) v4.0 criteria. RESULTS: Median follow-up was 10.5 months. Treatment tolerance was good with few side effects grade 3 or above, no acute toxicity and only one late toxicity. We have highlighted that hepatic artery haemorrhage was associated with the presence of a biliary prosthesis in contact with the artery (P=0.006) and in the irradiation field. There was no correlation with the dose delivered to the artery and hepatic artery haemorrhage. CONCLUSION: Stereotactic radiation therapy for liver tumours allows a good local control with few secondary effects. Caution should be exercised when treating patients with biliary prostheses in the vicinity of the target volume because there is a risk of haemorrhage of the hepatic artery in contact with the prosthesis.


Assuntos
Neoplasias Hepáticas/radioterapia , Hipofracionamento da Dose de Radiação , Lesões por Radiação/etiologia , Radiocirurgia/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Carcinoma/radioterapia , Carcinoma/secundário , Carcinoma/terapia , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/terapia , Colangiocarcinoma/radioterapia , Colangiocarcinoma/terapia , Terapia Combinada , Intervalo Livre de Doença , Embolização Terapêutica , Feminino , Seguimentos , França/epidemiologia , Hemorragia/etiologia , Hepatectomia , Artéria Hepática/efeitos da radiação , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Polietileno/efeitos da radiação , Polímeros/efeitos da radiação , Lesões por Radiação/epidemiologia , Planejamento da Radioterapia Assistida por Computador , Estudos Retrospectivos , Stents
16.
J Surg Oncol ; 120(4): 611-623, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31301148

RESUMO

BACKGROUND AND OBJECTIVES: Race/ethnicity and socioeconomic factors are associated with worse cancer outcomes. Our aim was to determine the association of these factors with receipt of surgery and multimodality therapy for cholangiocarcinoma. METHODS: Patients with cholangiocarcincoma in the National Cancer Database were identified. Racial/ethnic groups were defined as non-Hispanic White, non-Hispanic Black, Asian, and Hispanic. Socioeconomic factors were insurance status, income, and education. RESULTS: Of 12 095 patients with non-metastatic cholangiocarcinoma, 42% received surgery. Black race was associated with decreased odds of receiving surgery (odds ratio [OR]: 0.66l; P < .001) compared to White patients. Socioeconomic factors accounted for 21% of this disparity. Accounting for socioeconomic and clinicopathologic variables, Black race (OR: 0.73; P < .001), uninsured status (OR: 0.43; P < .001), and Medicaid insurance (OR: 0.63; P < .001) were all associated with decreased receipt of surgery. Of 4808 patients who received surgery, 47% received multimodality therapy. There were no racial/ethnic or socioeconomic differences in receipt of multimodality therapy once patients accessed surgical care. Similar results were seen in patients with advanced disease who received chemotherapy as primary treatment. CONCLUSION: Racial/ethnic and socioeconomic disparities exist in treatment for cholangiocarcinoma, however only for primary treatment. In patients who received surgery or chemotherapy, there were no disparities in receipt of multimodality therapy. This emphasizes the need to improve initial access to health care for minority and socioeconomical disadvantaged patients.


Assuntos
Neoplasias dos Ductos Biliares/etnologia , Colangiocarcinoma/etnologia , Grupos Étnicos/estatística & dados numéricos , Acesso aos Serviços de Saúde , Disparidades em Assistência à Saúde/estatística & dados numéricos , Fatores Socioeconômicos , Idoso , Neoplasias dos Ductos Biliares/economia , Neoplasias dos Ductos Biliares/terapia , Colangiocarcinoma/economia , Colangiocarcinoma/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Cobertura do Seguro , Masculino , Prognóstico , Estados Unidos
17.
Oncology ; 97(4): 191-201, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31266042

RESUMO

Endoscopic decompression of bile duct stenosis in unresectable cholangiocarcinoma (CC) may be difficult due to localization of the tumor, but it is important for pursuing oncologic treatment afterwards. Besides the initial diagnosis, jaundice and cholangitis are the most important indications for immediate endoscopic treatment. Endoscopic retrograde cholangiopancreatography is the favored approach for biliary access and stent placement. Hilar tumors are more difficult to treat and sometimes need higher endoscopic or radiologic expertise. In general, biliary decompression is accompanied by antibiotic treatment. Oncologic treatment of CC remains difficult, as it has to be interrupted when -infectious complications occur. For chemotherapy, a gemcitabine/cisplatin-based regime is favored. A validated -second-line treatment does not exist. Several therapeutic options are therefore offered to patients, including photodynamic therapy, selective internal radiotherapy, and high-dose radiotherapy. Exact treatment recommendations do not exist due to tumor rarity and lack of randomized controlled trials. In the present article, we take a look at current endoscopic, medical, and oncologic challenges from the endoscopist's point of view.


Assuntos
Neoplasias dos Ductos Biliares/terapia , Colangiocarcinoma/terapia , Endoscopia , Oncologia/tendências , Antibacterianos/uso terapêutico , Antineoplásicos/farmacologia , Colangiopancreatografia Retrógrada Endoscópica , Colangite/terapia , Constrição Patológica , Humanos , Fotoquimioterapia , Radioterapia
18.
Cancer Treat Rev ; 78: 1-7, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31255945

RESUMO

Cholangiocarcinoma is the most common aggressive biliary tract malignancy with dismal prognosis. Though surgical resection of the primary tumors yields better prognosis, majority of patients present at advanced, inoperable stages rendering systemic therapy as the only option. A significant progress has been made in understanding the cholangiocarcinoma tumorigenesis and molecular markers over the last decade, which opens doors to precision medicine in this dismal cancer. Intrahepatic cholangiocarcinomas are most likely to harbor mutations in isocitrate dehydrogenase genes (IDH1, IDH2), fibroblast growth factor receptors (FGFR1, FGFR2, FGFR3), Eph receptor 2 (EPHA2), and BAP1 (gene involved in chromatin remodeling) genes, whereas ARID1B, ELF3, PBRM1, cAMP dependent protein kinase (PRKACA, and PRKACB) genetic mutations were implicated more commonly in distal and perihilar subtypes. Genomic studies have shown that FGFR2 aberrations are implicated in approximately 15% of intrahepatic cholangiocarcinomas, which make FGFR2 aberrations (Achilles heel) as potential novel targets in the management of cholangiocarcinoma. The current review comprehensively focuses on the role of FGFR2 inhibition either alone or in combination with other targeted therapy that act on down-stream and alternate kinase pathways in cholangiocarcinoma.


Assuntos
Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/terapia , Colangiocarcinoma/genética , Colangiocarcinoma/terapia , Aberrações Cromossômicas , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Animais , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/patologia , Gerenciamento Clínico , Humanos , Prognóstico
19.
Future Oncol ; 15(18): 2125-2137, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31161810

RESUMO

Aim: Limited data exist on impact of the metastatic sites on survival in patients with metastatic intrahepatic cholangiocarcinoma (ICC). Methods: Patients with metastatic ICC were identified in the SEER from 2010 to 2015. Results: A total of 981 patients were identified, of this population, liver (57.9%) is the most common site of ICC metastases, followed by lung, bone and brain. Respective median overall survival and cancer-specific survival were 6 and 9 months in entire population. Further analysis suggested that patients treated by surgery to primary and/or metastatic lesions had a better survival outcome than patients had no surgery (p ≤ 0.001). Conclusion: Liver is the most common site for ICC metastases, local treatment such as surgery to primary or metastatic lesions obviously benefit patients.


Assuntos
Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/mortalidade , Colangiocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/epidemiologia , Neoplasias dos Ductos Biliares/terapia , Colangiocarcinoma/epidemiologia , Colangiocarcinoma/terapia , Terapia Combinada , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Especificidade de Órgãos , Vigilância da População , Prognóstico , Programa de SEER , Estados Unidos/epidemiologia
20.
Anticancer Res ; 39(6): 3095-3100, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31177154

RESUMO

BACKGROUND/AIM: To retrospectively evaluate the outcome of patients with unresectable biliary cholangiocarcinoma (CC) treated with radiotherapy (RT) plus/minus chemotherapy (CHT). MATERIALS AND METHODS: Data of patients with intrahepatic CC (ICC), Klatskin's tumor (KT), distal extrahepatic CC (ECC), and gallbladder cancer (GBC) diagnosed from 1991 to 2017 were retrospectively analyzed. The treatment was mainly based on RT plus concurrent CHT +/- brachytherapy (BRT) boost. The Kaplan-Meier method was used to calculate survival curves that were compared using the log-rank test. RESULTS: Seventy-six patients were included in this analysis (males: 59%; females: 41%; median age: 66.5 years). A minority of patients (7.9%) were treated for disease recurrence after surgery. According to TNM, 78.5% of patients had T stage >3 and 77.6% of patients were treated with concurrent CHT-RT while 22.3% received RT followed by sequential CHT. Median RT dose was 50 Gy (range: 16-75 Gy) delivered with conventional fractionation. CHT was based on Gemcitabine or 5-fluorouracil. BRT was prescribed to 51.3% of patient with a median dose of 14 Gy. Reported Grade ≥3 acute GI and hematological toxicity were 13.2% and 8.1%, respectively. No other severe acute toxicities were reported. One- and 2-year overall survival (OS) were 58.1% and 25.8%, respectively (median: 13.5 months), while 1- and 2-year progression-free survival (PFS) were 43.4% and 9.4%, respectively. None of the following variables had a significant impact on OS and PFS: BRT boost, tumor site, concurrent CHT, and the drugs used in concurrent CHT. In contrast, patients receiving RT with 2D technique showed a PFS significantly higher compared to patients treated with the 3D technique (median: 15.5 vs. 8.5 months; p=0.02). CONCLUSION: Combined modality treatment (RT+CHT±BRT) in unresectable biliary cancer was associated with acceptable toxicity and OS comparable to the actual standard treatment (CHT). The significantly improved PFS in patients undergoing 2D-RT raises doubts regarding the adequacy of target delineation in these neoplasms.


Assuntos
Neoplasias dos Ductos Biliares/terapia , Braquiterapia , Quimiorradioterapia , Colangiocarcinoma/terapia , Neoplasias da Vesícula Biliar/terapia , Tumor de Klatskin/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/administração & dosagem , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/patologia , Braquiterapia/efeitos adversos , Braquiterapia/mortalidade , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/mortalidade , Colangiocarcinoma/mortalidade , Colangiocarcinoma/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Fracionamento da Dose de Radiação , Feminino , Fluoruracila/administração & dosagem , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/patologia , Humanos , Tumor de Klatskin/mortalidade , Tumor de Klatskin/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
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