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1.
Nihon Yakurigaku Zasshi ; 156(6): 392-402, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34719574

RESUMO

Pemigatinib (Pemazyre® Tablets 4.5 mg) is a novel fibroblast growth factor receptor (FGFR) inhibitor, created by Incyte Corporation. The product was approved in March 2021 and was launched in June 2021 for the treatment of patients with locally advanced or metastatic biliary tract cancer (BTC) with a fibroblast growth factor receptor 2 (FGFR2) fusion or rearrangement that has progressed after at least one prior line of systemic therapy. Pemigatinib was shown to selectively inhibit kinase activity of FGFR1~3 (IC50; 0.39~1.2 nM). In cultured cells, pemigatinib inhibited the phosphorylation of FGFR1 and its downstream signals, ERK1/2 and STAT5 in a concentration-dependent manner. Pemigatinib also potently inhibited the growth of various types of cell lines with FGFR 1~3 gene alteration. Pemigatinib was shown to induce concentration-dependent tumor regression in a tumor xenograft model mice in which tumor tissue sections from patients with cholangiocarcinoma (CCA) harboring FGFR2 gene fusions were transplanted. Pemigatinib was well tolerated in Japanese and overseas Phase1 studies (INCB 54828-101 and 202). In the global phase2 study (INCB 54828-202) conducted in CCA patients with FGFR2 gene fusions or rearrangements, significant improvement in the overall response rate was observed. Although several adverse reactions were observed which was based on the mechanism of action of pemigatinib, the safety profile and management of the adverse reactions were favorable. Pemigatinib is expected to contribute to second-line drug treatment after failure of standard therapies in biliary tract cancer.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Animais , Ductos Biliares Intra-Hepáticos , Humanos , Camundongos , Morfolinas , Pirimidinas , Pirróis , Comprimidos
2.
Cir Cir ; 89(S1): 87-92, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34762637

RESUMO

INTRODUCTION: Intrabiliary growth of colorectal liver metastasis determines their capability of dissemination and relapse. CASE REPORT: 65-year-old woman underwent sigmoidectomy (2011) and left hepatectomy due to liver metastases affecting the bile tract (2014). In 2020 she developed a 2cm tumour in the union of both hepatic ducts. Cholangiocarcinoma was suspected so resection of the main bile duct, the caudate lobe and lymphadenectomy were performed. On immunohistochemical examination, colorectal liver metastasis was confirmed. CONCLUSIONS: Liver metastases should be considered as the most likely diagnosis when bile duct dilatation or intrabiliary growth is seen in patients with a history of colorectal cancer.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Neoplasias Colorretais , Neoplasias Hepáticas , Idoso , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos , Feminino , Hepatectomia , Humanos , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia
3.
BMC Gastroenterol ; 21(1): 427, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34772340

RESUMO

BACKGROUND: In rare cases, intrahepatic cholangiocarcinoma can present as a pyogenic liver abscess and are often misdiagnosed. This study aimed to analyze the imaging features of intrahepatic cholangiocarcinoma mimicking a pyogenic liver abscess. METHODS: The clinical data and imaging results of eight patients with pathologically confirmed intrahepatic cholangiocarcinoma mimicking a liver abscess were retrospectively collected. RESULTS: The mean age was 58 years with a range of 46-68 years. Fever and leukocytosis were present in six patients. All the eight lesions were a single mass. Air-liquid levels were present in two patients. Only one patient showed hepatic lobar atrophy and hepatic capsule retraction. The double target sign of liver abscess was not noticed in the CT/MRI images of all eight patients. The inner wall of the lesion was rough and irregular, with multiple dot/patchy and wall nodule enhancements. The abscess wall and the marginal parenchyma were supplied by the hepatic artery in four patients, and the intralesional arteries were rough and disrupted. Bile duct dilatation was seen adjacent to the lesion. In seven patients, diffusion-weighted images showed irregular patchy restricted diffusion in the marginal parenchyma of the necrotic area in addition to the prominent restricted diffusion in the necrotic area. Two patients with cholangiolithiasis showed patchy slight CT hypodensity, slight T1 hypointensity, slight T2 hyperintensity, and patchy delayed enhancement. Multiple lymph nodes enlargement in the hepatic hilar area and the retroperitoneal space were seen in five patients. CONCLUSION: Intrahepatic cholangiocarcinoma mimicking a pyogenic liver abscess have unique imaging features and require careful image examination to avoid misdiagnosis.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Abscesso Hepático Piogênico , Idoso , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Ductos Biliares Intra-Hepáticos/diagnóstico por imagem , Colangiocarcinoma/diagnóstico por imagem , Diagnóstico Diferencial , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Estudos Retrospectivos
4.
Anticancer Res ; 41(10): 5249-5254, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34593478

RESUMO

BACKGROUND: Bile duct adenomas (BDA) may be precursor lesions of small duct-type, including mass-forming type intrahepatic cholangiocarcinoma (ICC). CASE REPORT: A 68-year-old woman was transferred to our facility for the treatment of a liver tumor, possibly metastasized from a pancreatic neuroendocrine tumor. Finally, two liver tumors were resected and histopathologically diagnosed as "BDA" and "ICC with a BDA-like component". In the BDA-like component, the MUC6 positive rate was notably lower and the Ki-67 positive rate was higher than the other BDAs and ICC component, respectively. The doubling time of the tumor volume in BDA was very long but was shortened (1,510 and 719 days). Distinct enlargement of the tumor and appearance of enhancement through diagnostic imaging was useful in diagnosing the transformation from a BDA to an ICC. CONCLUSION: An "adenoma-carcinoma sequence" may exist in the transformation process from a BDA to an ICC.


Assuntos
Adenoma/patologia , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/patologia , Neoplasias Hepáticas/secundário , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/patologia , Adenoma/complicações , Adenoma/cirurgia , Idoso , Neoplasias dos Ductos Biliares/complicações , Neoplasias dos Ductos Biliares/cirurgia , Colangiocarcinoma/complicações , Colangiocarcinoma/cirurgia , Diagnóstico Diferencial , Feminino , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/cirurgia , Tumores Neuroendócrinos/complicações , Tumores Neuroendócrinos/cirurgia , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/cirurgia , Prognóstico
5.
Zhonghua Nei Ke Za Zhi ; 60(7): 637-643, 2021 Jul 01.
Artigo em Chinês | MEDLINE | ID: mdl-34619841

RESUMO

Objective: Cholangiocarcinoma (CCA) is a malignant tumor derived from bile duct epithelial cells with extremely poor prognosis. The Hippo-Yes-associated protein (YAP)/transcription activator with PDZ binding motif (TAZ) signaling plays a critical role in cancer stem cell biology. Previous studies have shown that the positive expression of YAP/TAZ in CCA predicts larger tumor size and unfavorable clinical outcomes. We aim to evaluate the prognostic value of YAP/TAZ detection in CCA patients. Methods: CCA patients who underwent radical resection were retrospectively analyzed at our institution from January 2011 to June 2016. Postoperative pathological specimens were scored by YAP/TAZ immunohistochemical staining. The prognostic value of YAP/TAZ was analyzed by multivariate Cox-proportional hazards model. Results: A total of 91 CCA patients were enrolled. During a median follow-up time of 11.0 months, 69.2% patients relapsed and 45.1% died. The median OS and DFS were 10.7 months and 8.8 months respectively. The YAP/TAZ dual positive patients owned a worse TNM stage (P=0.015), poorer tissue differentiation (P=0.007), and a higher CA199 than those in negative patients. Multivariate Cox analysis identified that YAP/TAZ dual positivity as a significant factor predicted poorer OS (P=0.010) and DFS (P=0.028) in CCA patients after radical resection. In subgroup analysis, YAP/TAZ combination also significantly predicted OS (P=0.044) and DFS (P=0.043) in CCA patients with positive lymphatic metastasis and/or surgical margin who required adjuvant therapy. Conclusions: YAP/TAZ positivity is an independent predictive factor for survival in CCA patients after radical resectiony.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos/metabolismo , Colangiocarcinoma/cirurgia , Humanos , Prognóstico , Estudos Retrospectivos
6.
Zhonghua Wai Ke Za Zhi ; 59(10): 842-847, 2021 Oct 01.
Artigo em Chinês | MEDLINE | ID: mdl-34619910

RESUMO

Objective: To explore the feasibility and clinical value of a new classification for resectable intrahepatic cholangiocarcinoma (IHCC) according to the actual anatomy. Methods: The data of 135 patients with IHCC who were admitted to the Department of Hepatopancreatobiliary Surgery,Second Affiliated Hospital of Zhejiang University School of Medicine from November 2011 to November 2020 after discussion by a multidisciplinary team and planned to undergo radical resection were analyzed retrospectively. There were 77 males and 58 females,with a median age of 61 years (range:26 to 86 years),of which 38 cases had vascular invasion. This new classification was carried out independently by two hepatobiliary surgeons. First,a preliminary classification was made based on the location of the tumor,and then the final classification was based on vascular invasion. All patients were followed up by telephone,and the follow-up was as of November 2020. Survival time is defined as the time after surgery to follow-up or death. Log-rank test was used to compare patients' median recurrence-free survival and overall survival time. The Cox proportional hazard model was used to analyze the prognosis factors of the overall survival time of patients with IHCC. Results: Among the 135 patients,129 underwent R0 resection and 6 underwent R1 resection. According to the actual anatomy,28 cases (20.7%) belonged to segmental type, 43 cases (31.9%) belonged to branch type, 64 cases (47.4%). The median survival time of all patients was 35.2 months(95%CI:21.3 to 70.5 months),the 1-year cumulative survival rate was 75.1%,the 3-year cumulative survival rate was 45.8%,and the 5-year cumulative survival rate was 39.0%. After grouping according to the classification,the median survival time of segmental patients was 36.9 months (more than 50% of patients reached the median survival time),and the median survival time of branched patients was 33.8 months (95%CI:16.8 to 38.5);The median survival time of lobe patients was 25.0 months (95%CI:13.6 to 58.7). The result of Log-rank test between groups indicated that the median survival time of patients with segmental type was better than that of patients with branch and lobe type(HR=2.03,95%CI:1.24 to 3.64,P=0.006);There was no significant difference in survival time between patients with branch type and lobe type (P=0.685). The results of the multivariate analysis of the Cox risk ratio model suggested that the actual anatomical location classification (HR=2.32,95%CI:1.10 to 4.92,P=0.028) and the postoperative lymph node metastasis rate (HR=2.06,95%CI:1.24 to 3.45,P=0.005) were independent factors related to survival after radical resection of IHCC patients. Conclusion: It is simple and convenient to classify resectable IHCC by actual anatomy,which can be used to preliminarily judge the prognosis of patients and provide a feasible classification scheme for the clinic.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Neoplasias Hepáticas , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
7.
Zhonghua Yi Xue Za Zhi ; 101(38): 3134-3140, 2021 Oct 19.
Artigo em Chinês | MEDLINE | ID: mdl-34674423

RESUMO

Objective: To explore the value of preoperative neutrophil-to-lymphocyte ratio (NLR) and γ-glutamyl transpeptidase-to-platelet ratio index (GPRI) for predicting the prognosis of patients with HBV-related intrahepatic cholangiocarcinoma (ICC) after radical resection. Methods: The data of 79 patients who underwent radical resection for HBV-related ICC in the Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi'an Jiaotong University from January 2010 to December 2018 were retrospectively analyzed. Among them, 48(60.8%) patients were male and 31 (39.2%) patients were female, (56.9±11.2) years old. X-Tile statistical software was used to determine the best cut-off values of NLR and GPRI. The χ2 test was conducted to analyze the relationship between preoperative NLR and GPRI and the clinicopathological characteristics, and the Cox proportional hazard regression model was conducted for multivariate analysis. A nomogram prognostic prediction model was established based on independent risk factors screened by Cox regression model. Results: The best cut-off values of NLR and GPRI were 3.13 and 1.31 determined by the X-Tile software, respectively. With the best cut-off value, 79 patients were divided into NLR≤3.13 group (45 cases) and NLR>3.13 group (34 cases). GPRI≤1.31 group (54 cases) and GPRI>1.31 group (25 cases). Compared with the preoperative NLR ≤3.13 group, the proportion of patients with liver cirrhosis and atrophy, poor pathological differentiation, tumor diameter>5 cm and late TNM stage was significantly increased in the NLR>3.13 group (all P<0.05); Compared with preoperative GPRI ≤1.31 group, the proportion of patients with liver cirrhosis and atrophy was significantly increased in the GPRI>1.31 group (P=0.025). The postoperative overall survival time of the included patients was 2 to 126 months, with the median survival time being 18 months, and the 1, 3-year overall survival rates were 63.3%, 32.8%, respectively. Multivariate analysis showed that NLR, GPRI, liver cirrhosis and atrophy, and lymphatic metastasis were independent risk factors affecting the overall survival of patients with HBV-related ICC after radical resection (P<0.05). A nomogram prediction model was established based on independent risk factors, with the C-index of 0.750, and the prediction effect was close to the actual survival outcome of the patients. Conclusion: Preoperative peripheral blood NLR and GPRI can be used to predict the prognosis of patients with HBV-related ICC after radical resection.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Idoso , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/cirurgia , Feminino , Vírus da Hepatite B , Humanos , Linfócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos , Prognóstico , Estudos Retrospectivos , gama-Glutamiltransferase
8.
Se Pu ; 39(11): 1191-1202, 2021 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-34677014

RESUMO

Exosomes are extracellular vesicles with a diameter in the range of 50-200 nm and a double-layer lipid membrane structure that are released by various types of cells under normal or abnormal physiological conditions. At present, according to their extensive biological functions, exosomes have been used in a wide range of research fields and applications, including as potential biomarkers and drug delivery vehicles. Intrahepatic cholangiocarcinoma is a malignant tumor of the biliary epithelium with the characteristics of cholangiocellular differentiation, which accounts for 10%-15% of all types of primary liver cancer. Intrahepatic cholangiocarcinoma has no obvious clinical symptoms in the early stages, which results in a low survival rate. Imaging equipment dependent diagnostic methods and currently commonly used diagnostic markers with low sensitivity/specificity have necessitated the development of new specific markers for intrahepatic cholangiocarcinoma. In this study, exosomes were isolated from serum using a commercial kit and characterized through nanoparticle tracking analysis, Western blotting analysis, and transmission electron microscopic analysis to prove the successful isolation of exosomes. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that the protein profiles of the serum and serum exosome samples were significantly different. In particular, some high-abundance proteins in the serum samples were significantly reduced or disappeared in the serum exosome sample. Meanwhile, some protein bands (which may belong to exosomes) that did not appear in the serum samples appeared in the serum exosome samples, leading to the conduciveness of subsequent mass spectrometry analysis. The serum and serum exosome samples of the healthy control and intrahepatic cholangiocarcinoma groups were analyzed by liquid chromatography-mass spectrometry for label-free quantitative proteomics. In total, 547 proteins were identified in the serum exosome samples, of which 341 (more than 60%) could be found in the exosomal protein database. In addition, 271 and 430 credible proteins were screened from the serum and serum exosome samples for multi-dimensional statistical analysis and differential protein discovery. Unsupervised principal component analysis and supervised orthogonal partial least squares discriminant analysis based on the quantitative proteome of the serum and serum exosome samples could distinguish the healthy control and intrahepatic cholangiocarcinoma groups well, which illustrates that the two types of samples both have potential in the diagnosis of intrahepatic cholangiocarcinoma. There were 15 upregulated and 8 downregulated proteins screened in the intrahepatic cholangiocarcinoma group compared to the healthy control group based on the serum samples, while 33 upregulated and 18 downregulated proteins were screened in the intrahepatic cholangiocarcinoma group compared to the healthy control group based on the serum exosome samples, and only four of the differential proteins screened based on the two types of samples were duplicates. At the same time, 35 of the 51 differentially expressed proteins screened based on serum exosome samples belonged to the exosomal protein database. Finally, biological information analysis was performed according to these differential proteins. The molecular functions, biological processes, and signal pathways enriched by these differential proteins mainly involved the innate immune responses, inflammatory responses, and blood coagulation. This study provides a reference value for potential biomarker discovery and exploration of the process of occurrence, development, and metastasis of intrahepatic cholangiocarcinoma. Moreover, compared with proteomic analysis based on serum samples, proteomic analysis based on serum exosome samples can be used to identify more differential proteins and biological information, and although these differential proteins and biological information may show big differences, the specificity and sensitivity of exosome-based diagnosis and the superiority of exosomes as samples for proteomic analysis has proven the application value of exosomes.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Exossomos , Neoplasias Hepáticas , Ductos Biliares Intra-Hepáticos , Humanos , Proteômica
9.
Anticancer Res ; 41(10): 4917-4928, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34593439

RESUMO

BACKGROUND/AIM: The functions of interleukin 33 (IL-33) in cholangiocarcinoma (CCA) are unclear. This study aimed to evaluate the roles of IL-33 in CCA progression. MATERIALS AND METHODS: The effect of intracellular IL-33 using shIL-33 knocked down KKU-055 (IL-33KD-KKU-055) compared to parental (Pa) KKU-055 and extracellular IL-33 using recombinant human IL-33 (rhIL-33) treatment on the proliferation and invasion of CCA cells grown in 3D cultures was studied. Relevant markers were determined by western blot or ELISA. RESULTS: IL-33KD-KKU-055 cells showed increased proliferation and invasion in 3D cultures compared to Pa-KKU-055 cells, with NF-κB and IL-6 up-regulation. Treatment with 2 ng/ml rhIL-33 promoted Pa-KKU-055 cell proliferation by inducing NF-κB and IL-6 expressions. Upon GSK-3ß inactivation and increased nuclear full-length IL-33 (flIL-33), 20 ng/ml rhIL-33 had no effect on proliferation. Both 2 and 20 ng/ml rhIL-33 induced proliferation and invasion of IL-33-negative KKU-213 cells in 3D cultures, as well as NF-κB and IL-6 up-regulation. CONCLUSION: Intracellular and extracellular IL-33 have distinct roles in the mechanisms of CCA progression.


Assuntos
Neoplasias dos Ductos Biliares/prevenção & controle , Biomarcadores Tumorais/metabolismo , Colangiocarcinoma/prevenção & controle , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glicogênio Sintase Quinase 3 beta/metabolismo , Interleucina-33/farmacologia , NF-kappa B/metabolismo , Apoptose , Neoplasias dos Ductos Biliares/metabolismo , Neoplasias dos Ductos Biliares/patologia , Biomarcadores Tumorais/genética , Proliferação de Células , Colangiocarcinoma/metabolismo , Colangiocarcinoma/patologia , Glicogênio Sintase Quinase 3 beta/genética , Humanos , NF-kappa B/genética , Invasividade Neoplásica , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
10.
J Int Med Res ; 49(10): 3000605211050539, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34637352

RESUMO

Primary hepatic carcinosarcoma (HCS) is an extremely rare malignant tumor of the liver that contains carcinomatous and sarcomatous components. The diagnosis, treatment, and prognosis of HCS pose great challenges to clinicians. Herein, we present a case of HCS in a 67-year-old man with unique pathological manifestation. Preoperative magnetic resonance imaging showed a malignant lesion in the right liver and a small sub-focus in the left liver. Radical treatment was performed, including excision of the right posterior lobe of the liver, thrombectomy of the right posterior portal vein, and radiofrequency ablation of lesions in the left liver. The specimens were confirmed to be HCS by pathological examinations, which revealed a combination of poorly differentiated hepatocellular carcinoma, moderately differentiated cholangiocellular carcinoma, and spindle cell sarcoma. Transhepatic arterial chemotherapy and embolization was performed after surgery. Unfortunately, pulmonary metastasis occurred 1.5 months later, which meant a poor prognosis. In this report, we discuss the clinicopathological characteristics of this case and factors that affected surgical outcomes, which may add some ideas for the future diagnosis and treatment of HCS patients.


Assuntos
Neoplasias dos Ductos Biliares , Carcinoma Hepatocelular , Carcinossarcoma , Colangiocarcinoma , Neoplasias Hepáticas , Idoso , Ductos Biliares Intra-Hepáticos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinossarcoma/diagnóstico por imagem , Carcinossarcoma/cirurgia , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Masculino
11.
Artigo em Inglês | MEDLINE | ID: mdl-34639305

RESUMO

Background-Extrahepatic cholangiocarcinoma (ECC) is a rare, morbid, fatal cancer with distressing symptoms. Maintaining a high quality of life while reducing hospital charges and length of stay (LOS) for the end-of-life period remains a major challenge for the healthcare system. Palliative care utilization has been shown to address these challenges; moreover, its use has increased in recent years among cancer patients. However, the utilization of palliative care in rare cancers, such as ECC, has not yet been explored. Objectives-To investigate palliative care utilization among ECC patients admitted to US hospitals between 2007 and 2016 and its association with patient demographics, clinical characteristics, hospital charges, and LOS. Methods-De-identified patient data of each hospitalization were retrieved from the National Inpatient Sample (NIS) database. Codes V66.7 (ICD-9-CM) or Z51.5 (ICD-10-CM) were used to find palliative care utilization. Multivariate adjusted logistic regression analyses were conducted to assess factors associated with palliative care use, LOS, hospital charges, and in-hospital death. Results-Of 4426 hospitalizations, only 6.7% received palliative care services. Palliative care utilization did not significantly increase over time (p = 0.06); it reduced hospital charges by USD 25,937 (p < 0.0001) and LOS by 1.3 days (p = 0.0004) per hospitalization. Palliative care was positively associated with female gender, severe disease, and age group ≥80 (p ≤ 0.05). The average LOS was 8.5 days for each admission. Conclusions-Hospital admissions with palliative care utilization had lower hospital charges and LOS in ECC. However, ECC patients received less palliative care compared with more common cancers sharing similar symptoms (e.g., pancreatic cancer). ECC patients also had longer LOS compared with the national average. Further research is warranted to develop interventions to increase palliative care utilization among ECC hospital patients.


Assuntos
Colangiocarcinoma , Cuidados Paliativos , Colangiocarcinoma/epidemiologia , Colangiocarcinoma/terapia , Feminino , Mortalidade Hospitalar , Hospitalização , Humanos , Pacientes Internados , Tempo de Internação , Qualidade de Vida , Estudos Retrospectivos , Estados Unidos/epidemiologia
12.
BMC Surg ; 21(1): 359, 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34627199

RESUMO

BACKGROUND: Lymph node dissection (LND) is of great significance in intrahepatic cholangiocarcinoma (ICC). Although the National Comprehensive Cancer Network (NCCN) guidelines recommend routine LND in ICC, the effects of LND remains controversial. This study aimed to explore the role of LND and some related issues and of in ICC. METHODS: Patients were identified in two Chinese academic centers. Inverse probability of treatment weighting (IPTW) was used to reduce bias. Kaplan-Meier curves and Cox proportional hazards models were used to compare overall survival (OS) and disease-free survival (DFS). RESULTS: Of 232 patients, 177 (76.3%) underwent LND, and 71 (40.1%) had metastatic lymph nodes. A minimum of 6 lymph nodes were dissected in 66 patients (37.3%). LND did not improve the prognosis of ICC. LNM > 3 may have worse OS and DFS than LNM 1-3, especially in the LND > = 6 group. For patients who did not underwent LND, the adjuvant treatment group had better OS and DFS. CONCLUSIONS: The proportions of patients who underwent LND and removed > = 6 lymph nodes were not high enough. LND has no definite predictive effect on prognosis. Patients with 4 or more LNMs may have a worse prognosis than patients with 1-3 LNMs. Adjuvant therapy may benefit patients of nLND.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/cirurgia , Humanos , Excisão de Linfonodo , Estudos Retrospectivos
13.
BMC Gastroenterol ; 21(1): 375, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34645392

RESUMO

BACKGROUND: The prognostic nutritional index, a marker of nutritional status and systemic inflammation, is a known biomarker for various cancers. However, few studies have evaluated the predictive value of the prognostic nutritional index in patients with biliary tract cancer. Therefore, we investigated the prognostic significance of the prognostic nutritional index, and developed a risk-stratification system to identify prognostic factors in patients with biliary tract cancer. METHODS: Between July 2010 and March 2021, 117 patients with biliary tract cancer were recruited to this single-center, retrospective study. The relationship between clinicopathological variables, including the prognostic nutritional index, and overall survival was analyzed using univariate and multivariate analyses. A P < 0.05 was considered statistically significant. RESULTS: The median age was 75 (range 38-92) years. Thirty patients had intrahepatic cholangiocarcinoma; 29, gallbladder carcinoma; 27, distal cholangiocarcinoma; 17, ampullary carcinoma; and 13, perihilar cholangiocarcinoma. Curative (R0) resection was achieved in 99 patients. In univariate analysis, the prognostic nutritional index (< 42), lymph node metastasis, carbohydrate antigen 19-9 level (> 20 U/mL), preoperative cholangitis, tumor differentiation, operation time (≥ 360 min), and R1-2 resection were significant risk factors for overall survival. The prognostic nutritional index (P = 0.027), lymph node metastasis (P = 0.040), and tumor differentiation (P = 0.006) were independent prognostic factors in multivariate analysis. A combined score of the prognostic nutritional index and pathological findings outperformed each marker alone, in terms of discriminatory power. CONCLUSIONS: The prognostic nutritional index, lymph node metastasis, and tumor differentiation were independent prognostic factors after surgical resection in patients with biliary tract cancer. A combined prediction model using the prognostic nutritional index and pathological findings accurately predicted prognosis, and can be used as a novel prognostic factor in patients with biliary tract cancer.


Assuntos
Neoplasias dos Ductos Biliares , Neoplasias do Sistema Biliar , Colangiocarcinoma , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias do Sistema Biliar/patologia , Colangiocarcinoma/patologia , Colangiocarcinoma/cirurgia , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Avaliação Nutricional , Prognóstico , Estudos Retrospectivos
15.
Lancet Gastroenterol Hepatol ; 6(11): 956-969, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34626563

RESUMO

Biliary tract cancers (cholangiocarcinomas and gallbladder cancers) are increasing in incidence and have a poor prognosis. Most patients present with advanced disease, for which the treatment is palliative chemotherapy. Over the past few years, the genomic landscape of biliary tract cancers has been examined and several targeted therapies have been developed. Molecular targets with clinically meaningful activity include fibroblast growth factor receptor (FGFR), isocitrate dehydrogenase (IDH), RAS-RAF-MEK (MAP2K1)-ERK (MAPK3), HER2 (also known as ERBB2), DNA mismatch repair, and NTRK. Pemigatinib, a FGFR1-3 inhibitor, showed encouraging response rates and survival data as second-line treatment and received US Food and Drug Administration (FDA) approval in April, 2020, for previously treated advanced or metastatic cholangiocarcinoma with FGFR2 gene fusion or rearrangements. Ivosidenib, an IDH1 inhibitor, showed improved progression-free survival versus placebo in second-line treatment in the phase 3 ClarIDHy trial. Early phase trials of dabrafenib plus trametinib (BRAF and MEK inhibition) and zanidatamab (a bispecific HER2-antibody) have yielded encouraging response rates. Immunotherapy has mainly produced responses in tumours with deficient mismatch repair or high microsatellite instability (also known as dMMR or MSI-H) or higher PD-L1 score, or both. However, early phase trials of immunotherapy plus chemotherapy in unselected patient populations appear promising. NTRK inhibitors have also shown promise in early phase trials of NTRK-fusion positive solid tumours, including cholangiocarcinoma. In this Review, we discuss current and emerging therapies for advanced biliary tract cancers, with a focus on molecularly targeted therapy.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias do Sistema Biliar/tratamento farmacológico , Colangiocarcinoma/tratamento farmacológico , Terapia de Alvo Molecular/métodos , Cuidados Paliativos/métodos , Neoplasias do Sistema Biliar/genética , Neoplasias do Sistema Biliar/metabolismo , Neoplasias do Sistema Biliar/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Colangiocarcinoma/genética , Colangiocarcinoma/metabolismo , Colangiocarcinoma/patologia , Humanos , Fatores Imunológicos/uso terapêutico , Estadiamento de Neoplasias
16.
World J Surg Oncol ; 19(1): 316, 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34715880

RESUMO

BACKGROUND: The aim of this study was to investigate the prognostic value of arginase-1 (Arg-1) and glypican-3 (GPC-3) in patients with intrahepatic cholangiocarcinoma (ICC). METHODS: Two hundred and thirty-seven patients with ICC were included in this study. All patients had undergone radical surgery and had complete clinical information. Immunohistochemistry was used to assess the levels of Arg-1 and GPC-3 in ICC tissues. Univariate and multivariate analyses were conducted to identify independent risk factors in ICC. The relationship between Arg-1 and GPC-3 levels and patient survival was determined using the Kaplan-Meier method. RESULTS: High Arg-1 and GPC-3 expression levels were associated with poor prognosis in patients with ICC, and they could be as new prognostic biomarkers in ICC. CONCLUSION: Arg-1 and GPC-3 can serve as independent prognostic biomarkers in ICC.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Arginase , Neoplasias dos Ductos Biliares/cirurgia , Colangiocarcinoma/cirurgia , Glipicanas , Humanos , Prognóstico
17.
BMC Cancer ; 21(1): 1079, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34615513

RESUMO

BACKGROUND: Activation of the oncogene yes-associated protein (YAP) is frequently detected in intrahepatic cholangiocarcinoma (iCCA); however, the expression pattern and the functional impact of its paralogue WW domain-containing transcription regulator 1 (WWTR1; synonym: TAZ) are not well described in different CCA subtypes. METHODS: Immunohistochemical analysis of YAP and TAZ in iCCA and extrahepatic CCA (eCCA) cohorts was performed. YAP/TAZ shuttling and their functional impact on CCA cell lines were investigated. Target genes expression after combined YAP/TAZ inhibition was analyzed. RESULTS: Immunohistochemical analysis of iCCA and eCCA revealed YAP or TAZ positivity in up to 49.2%; however, oncogene co-expression was less frequent (up to 23%). In contrast, both proteins were jointly detectable in most CCA cell lines and showed nuclear/cytoplasmic shuttling in a cell density-dependent manner. Next to the pro-proliferative function of YAP/TAZ, both transcriptional co-activators cooperated in the regulation of a gene signature that indicated the presence of chromosomal instability (CIN). A correlation between YAP and the CIN marker phospho-H2A histone family member X (pH2AX) was particularly observed in tissues from iCCA and distal CCA (dCCA). The presence of the CIN genes in about 25% of iCCA was statistically associated with worse prognosis. CONCLUSIONS: YAP and TAZ activation is not uncoupled from cell density in CCA cells and both factors cooperatively contribute to proliferation and expression of CIN-associated genes. The corresponding group of CCA patients is characterized by CIN and may benefit from YAP/TAZ-directed therapies.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neoplasias dos Ductos Biliares/genética , Colangiocarcinoma/genética , Instabilidade Cromossômica/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Fatores de Transcrição/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Ductos Biliares Extra-Hepáticos , Ductos Biliares Intra-Hepáticos , Contagem de Células , Linhagem Celular Tumoral , Colangiocarcinoma/metabolismo , Colangiocarcinoma/patologia , Histonas/metabolismo , Humanos , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Prognóstico , Análise Serial de Tecidos , Fatores de Transcrição/antagonistas & inibidores
18.
Mymensingh Med J ; 30(4): 1079-1085, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34605480

RESUMO

Complete assessment of obstructive jaundice requires the use of various imaging modalities that are required to detect the cause and level of obstruction thus helping in treatment planning. Magnetic Resonance Cholangio Pancreatography (MRCP) is a current available technology which is a non-invasive technique that visualizes the gallbladder, biliary tree and pancreatic duct and also provides information about surrounding structures. This study was done to correlate the MRCP findings with post-operative result and thereby demonstrate the specificity, sensitivity and efficacy of MRCP as an accurate investigatory tool for biliary obstruction. Total of fifty (50) patients of clinically diagnosed obstructive jaundice were studied from March 2017 to August 2017 in the Department of Radiology and Imaging, Combined Military Hospital, Dhaka, Bangladesh. In all these cases, USG was the initial screening investigation followed by MRCP. Cause and level of obstruction were evaluated using MRCP findings. MRCP results were correlated with surgical findings and few cases also with direct ERCP findings. Statistical analysis was done to see the sensitivity, specificity, accuracy, positive and negative predictive values of MRCP in diagnosis of biliary obstruction. In this study, USG detected level of obstruction in 56% (28 out of 50) cases. USG could detect causes of obstruction in 100% (02 out of 02) cases of choledocal cyst and 66.67% (02 out of 03) benign stricture, 60% (03 out of 05) cases of periampullary carcinoma, 57.70% (06 out of 14) cases of choledocholithiasis, and 42.86% (15 out of 26) cases of cholangiocarcinoma. On the other hand, MRCP detected level of obstruction in 98% (49 out of 50) cases. MRCP could detect causes of obstruction in 100% cases of cholangiocarcinoma, choledocholithiasis, benign stricture and choledocal cyst and 80% (04 out of 05) cases of periampullary carcinoma. In this study, ERCP could detect causes of obstruction in 32 cases of choledocholithiasis and benign stricture, but in case of cholangiocarcinoma ERCP was failed in 3 cases. In this study, for detection of cause of obstruction, ERCP had the highest sensitivity (97.79%); followed by MRCP (96.65%) and USG (60.25%). The overall diagnostic accuracy for detection of cause of obstruction was the highest for ERCP (95.50%); followed by MRCP (94.50%) and USG (64.50%). MRCP can be done in a short duration and is a noninvasive diagnostic modality compared to ERCP. MRCP needs to be advocated as a viable and non-invasive alternative with compararable sensitivity and specificity to ERCP.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Colestase , Bangladesh , Ductos Biliares Intra-Hepáticos , Colangiopancreatografia por Ressonância Magnética , Colestase/diagnóstico por imagem , Colestase/etiologia , Humanos
19.
Curr Oncol ; 28(5): 4067-4079, 2021 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-34677263

RESUMO

The therapeutic and diagnostic modalities of light are well known, and derivative photodynamic reactions with photosensitizers (PSs), specific wavelengths of light exposure and the existence of tissue oxygen have been developed since the 20th century. Photodynamic therapy (PDT) is an effective local treatment for cancer-specific laser ablation in malignancies of some organs, including the bile duct. Although curability for extrahepatic cholangiocarcinoma is expected with surgery alone, patients with unresectable or remnant biliary cancer need other effective palliative therapies, including PDT. The effectiveness of PDT for cholangiocarcinoma has been reported experimentally or clinically, but it is not the standard option now due to problems with accompanied photosensitivity, limited access routes of irradiation, tumor hypoxia, etc. Novel derivative treatments such as photoimmunotherapy have not been applied in the field hepatobiliary system. Photodynamic diagnosis (PDD) has been more widely applied in the clinical diagnoses of liver malignancies or liver vascularization. At present, 5-aminolevulinic acid (ALA) and indocyanine green (ICG) dyes are mainly used as PSs in PDD, and ICG has been applied for detecting liver malignancies or vascularization. However, no ideal tools for combining both PDD and PDT for solid tumors, including hepatobiliary malignancies, have been clinically developed. To proceed with experimental and clinical trials, it is necessary to clarify the effective photosensitive drugs that are feasible for photochemical diagnosis and local treatment.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Ácido Aminolevulínico , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/tratamento farmacológico , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/diagnóstico por imagem , Colangiocarcinoma/tratamento farmacológico , Humanos , Fármacos Fotossensibilizantes/uso terapêutico
20.
Molecules ; 26(19)2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34641520

RESUMO

Immunotherapy harnessing immune functions is a promising strategy for cancer treatment. Tumor sensitization is one approach to enhance tumor cell susceptibility to immune cell cytotoxicity that can be used in combination with immunotherapy to achieve therapeutic efficiency. Cordycepin, a bioactive compound that can be extracted from some Cordyceps spp. has been reported to effectively inhibit tumor growth, however, the mechanism of its tumor sensitization activity that enhances immune cell cytotoxicity is unknown. In the present study, we investigated the potency of cordycepin to sensitize a lethal cancer, cholangiocarcinoma (CCA), to natural killer (NK) cells. Treatment with cordycepin prior to and during co-culturing with NK-92 cells significantly increased cell death of KKU-213A as compared to solitary cordycepin or NK treatment. Moreover, sensitization activity was also observed in the combination of NK-92 cells and Cordyceps militaris extract that contained cordycepin as a major component. The cordycepin treatment remarkably caused an increase in TRAIL receptor (DR4 and DR5) expression in KKU-213A, suggesting the possible involvement of TRAIL signaling in KKU-213A sensitization to NK-92 cells. In conclusion, this is the first report on the sensitization activity of cordycepin on CCA cells to NK cytotoxicity, which supports that cordycepin can be further developed as an alternate immunomodulating agent.


Assuntos
Neoplasias dos Ductos Biliares/tratamento farmacológico , Colangiocarcinoma/tratamento farmacológico , Cordyceps/química , Desoxiadenosinas/farmacologia , Células Matadoras Naturais/imunologia , Antineoplásicos Fitogênicos/farmacologia , Neoplasias dos Ductos Biliares/patologia , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Colangiocarcinoma/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Células Matadoras Naturais/efeitos dos fármacos , Extratos Vegetais/farmacologia , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/genética , Receptor fas/genética
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