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1.
Gene ; 806: 145935, 2022 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-34478821

RESUMEN

Soluble molecules of programmed death ligand 1 (sPD-L1) are known to modulate T-cell depletion, an important mechanism of hepatitis B virus (HBV) persistence and liver disease progression. In addition, PD-L1 polymorphisms in the 3'-UTR can influence PD-L1 expression and have been associated with cancer risk, although not definitively. The purpose of this study was to investigate the association of PD-L1 polymorphisms and circulating levels of sPD-L1 in HBV infection and live disease progression. In this study, five hundred fifty-one HBV infected patients of the three clinically well-defined subgroups chronic hepatitis B (CHB, n = 186), liver cirrhosis (LC, n = 142) and hepatocellular carcinoma (HCC, n = 223) and 240 healthy individuals (HC) were enrolled. PD-L1 polymorphisms (rs2297136 and rs4143815) were genotyped by in-house validated ARMS assays. Logistic regression models were applied in order to determine the association of PD-L1 polymorphisms with HBV infection as well as with progression of related liver diseases. Plasma sPD-L1 levels were quantified by ELISA assays. The PD-L1 rs2297136 AA genotype was associated with HBV infection susceptibility (HBV vs. HC: OR = 1.6; 95%CI = 1.1-2.3; p = 0.0087) and disease progression (LC vs. CHB: OR = 1.8; 95%CI = 1.1-2.9; p = 0.018). Whereas, the rs2297136 GG genotype was a protective factor for HCC development. Plasma sPD-L1 levels were significantly high in HBV patients (p < 0.0001) and higher in the LC followed by CHB and HCC groups. High sPD-L1 levels correlated with increased liver enzymes and with advanced liver disease progression (Child-pugh C > B > A, p < 0.0001) and BCLC classification (BCLC D > C > B > A, p = 0.031). We could, for the first time, conclude that PD-L1 rs2297136 polymorphism and plasma sPD-L1 protein levels associate with HBV infection and HBV-related liver disease progression.


Asunto(s)
Antígeno B7-H1/genética , Carcinoma Hepatocelular/genética , Virus de la Hepatitis B/patogenicidad , Hepatitis B Crónica/genética , Cirrosis Hepática/genética , Neoplasias Hepáticas/genética , Polimorfismo Genético , Regiones no Traducidas 3' , Adulto , Anciano , Antígeno B7-H1/sangre , Biomarcadores/sangre , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/virología , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Expresión Génica , Predisposición Genética a la Enfermedad , Virus de la Hepatitis B/crecimiento & desarrollo , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/virología , Humanos , Hígado/metabolismo , Hígado/patología , Hígado/virología , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/etiología , Cirrosis Hepática/virología , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas
2.
World J Surg Oncol ; 19(1): 293, 2021 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-34598689

RESUMEN

BACKGROUND: Transcatheter arterial chemoembolization has been widely used in patients with hepatocellular carcinoma. However, double blood supply and the existence of portal vein tumor thrombus influence the efficacy of transcatheter arterial chemoembolization. MAIN BODY: Theoretically, portal vein embolization combined with transcatheter arterial chemoembolization may bring a breakthrough in the therapeutic effect of hepatocellular carcinoma. The feasibility, efficacy, long-term survival benefits, and side effects of the combined treatment have been explored in previous studies. Chemotherapeutic agents may also be added in the portal vein embolization procedure to further improve the treatment response. CONCLUSION: In this study, we review the existing data and studies on the combined treatment in patients with hepatocellular carcinoma and provide an overall view of the strategy.


Asunto(s)
Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Carcinoma Hepatocelular/terapia , Humanos , Neoplasias Hepáticas/terapia , Vena Porta , Pronóstico
3.
Acta Gastroenterol Belg ; 84(3): 505-508, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34599577

RESUMEN

Hepatocellular adenoma (HCA) is an uncommon benign liver neoplasm usually solitary and identified incidentally on imaging. We report a case of a 50-year old female who was diagnosed with multiple hepatic adenomas of the inflammatory subtype. After discontinuation of oral contraception a decrease of both the number and size of the liver lesions was seen on magnetic resonance imaging (MRI) without the need of further intervention. The major challenge in the clinical management of patients with multiple HCAs resides in the risk assessment for future complications. In the case of multiple HCAs subtype seemed to be more relevant than the actual number of lesions. Because little is known about the natural evolution in patients with multiple HCAs, we performed a review of the current literature with focus on the different subtypes and their clinical relevance.


Asunto(s)
Adenoma de Células Hepáticas , Carcinoma Hepatocelular , Neoplasias Hepáticas , Adenoma de Células Hepáticas/inducido químicamente , Anticoncepción , Anticonceptivos Orales/efectos adversos , Femenino , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad
4.
J Coll Physicians Surg Pak ; 31(10): 1168-1173, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34601836

RESUMEN

OBJECTIVE: To describe the baseline characteristics and two-year outcomes of patients with Child-Pugh grades A and B cirrhosis; and evaluate the predictive value of liver stiffness for the development of adverse outcomes (AOs) in this patient population. STUDY DESIGN: A prospective cohort study. PLACE AND DURATION OF STUDY: The Second Hospital, Cheeloo College of Medicine, Shandong University, China between September 2018 and March 2021. METHODOLOGY: The present study consecutively included patients with Child-Pugh grades A and B cirrhosis. Patients were followed up every six months until two years. Baseline demographic characteristics and laboratory indexes were collected. Liver stiffness and controlled attenuation parameter were measured at baseline, month 6 and month 12. The observational endpoint was AOs, including liver-related patient death and hepatocellular carcinoma (HCC). RESULTS: A total of 174 patients were included in the final cohort. Hepatitis B virus (HBV)-induced liver cirrhosis accounted for the vast majority of enrolled cases (82.2%). AOs were observed in six patients. Multivariate logistic regression model was performed and liver stiffness was considered as the only independent predictor for AOs (OR 1.071, p = 0.006). Liver stiffness was also significantly improved at 12 months compared with the baseline data (median 10.6 vs. 13.3 kPa, p <0.001). CONCLUSION: Patients with Child-Pugh grades A and B cirrhosis had an acceptable short-term prognosis. Greater liver stiffness predicted two-year AOs in these patients with relatively mild cirrhosis. The prognostic value of changes in liver stiffness warrants further investigation. Key Words: Liver cirrhosis, Child-Pugh score, Liver stiffness, Asian population, Outcome.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Cirrosis Hepática/complicaciones , Estudios Prospectivos
5.
Zhonghua Nei Ke Za Zhi ; 60(7): 630-636, 2021 Jul 01.
Artículo en Chino | MEDLINE | ID: mdl-34619840

RESUMEN

Objective: To evaluate the efficacy and safety of anti-programmed cell death 1 (PD-1) receptor monoclonal antibody (MoAb) in patients with advanced hepatocellular carcinoma (HCC) after treatment of transcatheter arterial chemoembolization (TACE) combined with tyrosine kinase inhibitor (TKI). Methods: From February 2019 to February 2020, 56 HCC patients who relapsed after TACE-TKI treatment in Department of Interventional Radiology, The Second Affiliated Hospital of Guangzhou Medical University were enrolled. All patients received anti-PD-1 MoAb (sintilimab injection) and followed up every 6 weeks. According to mRECIST, the curative effect was evaluated as complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD). Objective response rate (ORR) and disease control rate (DCR), progression-free survival (PFS) and treatment-related adverse events (TRAEs) were recorded. Univariate analysis by Chi-square test and binary logistic regression model was used to determine the influencing factors of DCR. The Kaplan-Meier method and Cox proportional hazard regression model were used to analyze the survival data. Results: A total of 48 patients were enrolled in this study including 42 males and 6 females, with a median age of 55 years (29-71 years). ECOG scores comprised of 0 in 24 cases, 1-2 in 24 cases. Thirty-six patients were in Child-Pugh grade A of liver function and 12 cases were grade B. The median follow-up time was 4.5 months. There were 2 patients achieved CR, 12 patients with PR and 16 with SD. ORR was 29.2%, DCR was 62.5%. The independent influencing factors of DCR was ECOG score and AFP level (P=0.031, P=0.012). Median PFS was 4.1 months (95%CI 2.7-5.4 months), and ECOG score was the independent influencing factor of PFS (P=0.042). Treatment-related adverse events were reported in 70.8% (34/48) patients. Incidence of grade Ⅲ-Ⅳ TRAEs was 22.9% (11/48). Conclusion: In patients with HCC who relapse from TACE and TKI treatment, anti-PD-1 monoclonal antibody is efficacious safe especially in those with ECOG 0 score.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Carcinoma Hepatocelular , Quimioembolización Terapéutica , Inhibidores Enzimáticos/uso terapéutico , Neoplasias Hepáticas , Carcinoma Hepatocelular/tratamiento farmacológico , Femenino , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia
6.
Anticancer Res ; 41(10): 5241-5247, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34593477

RESUMEN

AIM: To clarify the clinical and radiological features of isolated tumor thrombi in the inferior vena cava (IVC)/right atrium in patients with hepatocellular carcinoma (HCC) without hepatic vein invasion. PATIENTS AND METHODS: In this retrospective study, from January 2007 to December 2019, a total of 35,163 chemoembolization sessions were performed in 7,704 patients with HCC. Among them, 10 (0.13%) patients had tumor thrombi in the IVC/right atrium without definitive hepatic vein invasion. Computed tomographic (CT) scans, digital subtraction angiograms, and cone-beam CT images were retrospectively reviewed and interpreted. RESULTS: The tumor thrombi were supplied by the right inferior phrenic artery (n=8) or the right internal mammary artery (n=2). Follow-up CT scans in eight patients showed linear accumulation of iodized oil along the diaphragm, which was presumed to be a thrombosis of the phrenic vein. Retrospective review of formal radiological reports of pre-procedural CT scans revealed that a correct diagnosis of tumor thrombi of the IVC/right atrium was made in only three cases. CONCLUSION: HCC invading the phrenic vein may have tumor thrombi in the IVC/right atrium without hepatic vein invasion.


Asunto(s)
Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/mortalidad , Atrios Cardíacos/patología , Cardiopatías/terapia , Venas Hepáticas/patología , Trombosis/terapia , Vena Cava Inferior/patología , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/patología , Quimioembolización Terapéutica/métodos , Femenino , Estudios de Seguimiento , Cardiopatías/etiología , Cardiopatías/patología , Humanos , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Trombosis/etiología , Trombosis/patología
7.
Zhonghua Nei Ke Za Zhi ; 60(7): 599-614, 2021 Jul 01.
Artículo en Chino | MEDLINE | ID: mdl-34619836

RESUMEN

Hepatocellular carcinoma (HCC) is a malignancy originating from liver cells. Hepatitis B virus (HBV) is the major etiological factor contributed to the development of HCC in China. Pathologically, HCC is usually characterized of hypervascularity. The rationale of transarterial chemoembolization (TACE) is that the intraarterial infusion of cytotoxic agents followed by embolization of the tumor-feeding blood vessels causes a strong tumor killing effect. TACE is the most widely used primary treatment for unresectable HCC. In 2018, Chinese clinical practice guidelines for transarterial chemoembolization of hepatocellular carcinoma were published by Chinese College of Interventionalists. After several clinical and scientific advances are achieved, a new version of practice guidelines is updated in 2021.


Asunto(s)
Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Carcinoma Hepatocelular/terapia , China , Virus de la Hepatitis B , Humanos , Neoplasias Hepáticas/terapia
8.
Zhonghua Wai Ke Za Zhi ; 59(10): 801-806, 2021 Oct 01.
Artículo en Chino | MEDLINE | ID: mdl-34619903

RESUMEN

Tumor recurrence after curative resection of hepatocellular carcinoma(HCC) is a major challenge to patient survival. Postoperative adjuvant therapy has been proved to be an effective method in tackling tumor recurrence. However,its role in HCC remains unclear. First,there are many differences between Chinese and foreign guidelines in recommendations on adjuvant therapy of HCC. Chinese guidelines have made many recommendations on various modalities of adjuvant therapy of HCC,including anti-viral therapy,transarterial chemoembolization,and herbs. On the contrary,foreign guidelines don't make any recommendation on adjuvant therapy of HCC,except for anti-viral therapy. Second,clear definition of patients who have a higher risk of tumor recurrence is still unknown. In other words,patients who will benefit from adjuvant therapy is unclear. Although various kinds of adjuvant therapies have been proved to be efficient in preventing tumor recurrence and prolonging patient survival,a standard protocol is still lacking. There are many ongoing clinical trials investigating the value of adjuvant therapy in HCC. Emerging evidences will answer questions on the role of adjuvant therapy and how to perform it.


Asunto(s)
Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Carcinoma Hepatocelular/cirugía , Hepatectomía , Humanos , Neoplasias Hepáticas/cirugía , Recurrencia Local de Neoplasia
9.
Zhonghua Wai Ke Za Zhi ; 59(10): 812-815, 2021 Oct 01.
Artículo en Chino | MEDLINE | ID: mdl-34619905

RESUMEN

Hepatocellular carcinoma is a serious disease that threatens the health of Chinese people. At present,various treatments for hepatocellular carcinoma have their own advantages and disadvantages,which are suitable for its specific individual patient. This article makes a brief review about the importance of standardized treatment for hepatocellular carcinoma. Meanwhile,it should be noticed that standardized staging system is the prerequisite for making a reasonable treatment plan,standardized pathological diagnosis is the basis of comprehensive treatment,standardized treatment is the key to the efficacy,and the multidisciplinary team is the organizational basis for standardized treatment.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Trasplante de Hígado , Carcinoma Hepatocelular/terapia , Humanos , Neoplasias Hepáticas/terapia
10.
Zhonghua Wai Ke Za Zhi ; 59(10): 821-828, 2021 Oct 01.
Artículo en Chino | MEDLINE | ID: mdl-34619907

RESUMEN

Objective: To identify whether splenectomy for treatment of hypersplenism has any impact on development of hepatocellular carcinoma(HCC) among patients with liver cirrhosis and hepatitis. Methods: Patients who underwent splenectomy for hypersplenism secondary to liver cirrhosis and portal hypertension between January 2008 and December 2012 were included from seven hospitals in China, whereas patients receiving medication treatments for liver cirrhosis and portal hypertension (non-splenectomy) at the same time period among the seven hospitals were included as control groups. In the splenectomy group, all the patients received open or laparoscopic splenectomy with or without pericardial devascularization. In contrast, patients in the control group were treated conservatively for liver cirrhosis and portal hypertension with medicines (non-splenectomy) with no invasive treatments, such as transjugular intrahepatic portosystemic shunt, splenectomy or liver transplantation before HCC development. All the patients were routinely screened for HCC development with abdominal ultrasound, liver function and alpha-fetoprotein every 3 to 6 months. To minimize the selection bias, propensity score matching (PSM) was used to match the baseline data of patients among splenectomy versus non-splenectomy groups. The Kaplan-Meier method was used to calculate the overall survival and cumulative incidence of HCC development, and the Log-rank test was used to compare the survival or disease rates between the two groups. Univariate and Cox proportional hazard regression models were used to analyze the potential risk factors associated with development of HCC. Results: A total of 871 patients with liver cirrhosis and hypertension were included synchronously from 7 tertiary hospitals. Among them, 407 patients had a history of splenectomy for hypersplenism (splenectomy group), whereas 464 patients who received medical treatment but not splenectomy (non-splenectomy group). After PSM,233 pairs of patients were matched in adjusted cohorts. The cumulative incidence of HCC diagnosis at 1,3,5 and 7 years were 1%,6%,7% and 15% in the splenectomy group, which was significantly lower than 1%,6%,15% and 23% in the non-splenectomy group (HR=0.53,95%CI:0.31 to 0.91,P=0.028). On multivariable analysis, splenectomy was independently associated with decreased risk of HCC development (HR=0.55,95%CI:0.32 to 0.95,P=0.031). The cumulative survival rates of all the patients at 1,3,5,and 7 years were 100%,97%,91%,86% in the splenectomy group,which was similar with that of 100%,97%,92%,84% in the non-splenectomy group (P=0.899). In total,49 patients (12.0%) among splenectomy group and 75 patients (16.2%) in non-splenectomy group developed HCC during the study period, respectively. Compared to patients in non-splenectomy group, patients who developed HCC after splenectomy were unlikely to receive curative resection for HCC (12.2% vs. 33.3%,χ²=7.029, P=0.008). Conclusion: Splenectomy for treatment of hypersplenism may decrease the risk of HCC development among patients with liver cirrhosis and portal hypertension.


Asunto(s)
Carcinoma Hepatocelular , Hipertensión Portal , Neoplasias Hepáticas , Estudios de Cohortes , Humanos , Hipertensión Portal/complicaciones , Cirrosis Hepática/complicaciones , Neoplasias Hepáticas/cirugía , Esplenectomía
11.
Zhonghua Wai Ke Za Zhi ; 59(10): 829-835, 2021 Oct 01.
Artículo en Chino | MEDLINE | ID: mdl-34619908

RESUMEN

Objectives: To examine the efficacy of terminal branches portal vein embolization(TBPVE) for the increment of FLR in hepatocellular carcinoma (HCC) patients and to introduce its clinical value with transcatheter chemoembolization(TACE) in the treatment of HCC patients without surgery. Methods: One hundred and fifty HCC patients from three clinical centers of china underwent TBPVE technique from December 2016 to May 2021,including 89 males and 61 females. The average age was 51.9 years(range:18 to 79 years).One hundred and one patients were diagnosed with a background of HBV infection,including 27 patients with portal venous hypertension.TACE was performed simultaneously with TBPVE in 102 patients.Fifty-three patients underwent hepatectomy,who were subdivided into HBV positive and HBV negative groups,with TACE and without TACE groups to analyze the increment of future liver remnant (FLR), complications and survival data.These data were also analyzed in other 97 patients without hepatectomy. Results: All the patients reached adequate FLR successfully in 14 days after TBPVE including patients with portal venous hypertension.The average increment rates of FLR was 56.2% in 7 days and 57.8% in 14 days after TBPVE. There was no significant difference neither between HBV positive and HBV negative groups(7 days:(55.0±27.3)% vs.(57.8±20.9)%,t=0.885,P=0.373; 14 days:(57.3±24.6)% vs.(58.3±23.7)%;t=0.801,P=0.447),or between with TACE and without TACE groups(7 days:(62.3±26.3)% vs. (48.8±20.6)%;t=1.788,P=0.077;14 days:(64.4±25.0)% vs.(55.2±23.1)%;t=1.097,P=0.257).The morbidity and mortality rates were 20.8% and 1.9% in patients with hepatectomy.The 1-,3-year overall survival(OS) and disease-free(DFS) rates were 87.5%,64.5% and 64.7%,40.6% for patients underwent surgery.There was no significant difference of 1-,3-year OS and DFS between HBV positive and negative groups,but there were different between TACE and without TACE groups.The 1-,3-year OS for patients underwent TBPVE and TACE but without surgery were 80.1%, 53.7%. Conclusion: TBPVE is a good alternative technique for modulation of FLR for staged hepatectomy even in HBV positive HCC patients and can be applied with TACE procedure simultaneously as an option treatment for patients with no intend to surgery.


Asunto(s)
Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Carcinoma Hepatocelular/terapia , Femenino , Humanos , Neoplasias Hepáticas/terapia , Masculino , Persona de Mediana Edad , Vena Porta , Resultado del Tratamiento
12.
Zhonghua Wai Ke Za Zhi ; 59(10): 836-841, 2021 Oct 01.
Artículo en Chino | MEDLINE | ID: mdl-34619909

RESUMEN

Objective: To investigate the feasibility and oncological efficacy of structuring process approach to laparoscopic anatomical liver central lobectomy for hepatocellular carcinoma. Methods: The clinical data of 65 patients with hepatocellular carcinoma who underwent laparoscopic anatomical liver central lobectomy at the Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital from April 2017 to April 2021 was retrospectively analyzed. There were 39 males and 26 females,aged (M(QR)) 61.2 (29.5) years (range:25 to 80 years).The body mass index was (24.2±3.8) kg/m2 (range:19.5 to 26.1 kg/m2) and the tumor diameter was (6.7±2.9)cm(range:3.4 to 10.5 cm).This structuring process approach was designed using a series of main vessels as the plane markers, along which liver transection was carried out. The perioperative indicators and early oncological efficacy were then analyzed. Results: All the procedures were successfully carried out laparoscopically. The operative time was (190.5±70.4) minutes (range:90 to 280 minutes). The blood loss was (370.6±120.8)ml(range:100 to 1 050 ml). No patient received blood transfusion or converted to laparotomy. Postoperative complications occurred in 8 cases(12.3%). Postoperative hospital stay was (7.5±2.5) days(range:5 to 18 days).There was no perioperative death and rehospitalization within 30 days. Pathological study showed all the operations to be R0 resections, the average surgical margin was (2.4±1.9)cm(range:0.5 to 3.1 cm).The tumor recurrence rate was 12.3% after 1 year follow-up. Conclusion: Structuring process approach to laparoscopic anatomical liver central lobectomy could be used to treat patients with hepatocellular carcinoma.


Asunto(s)
Carcinoma Hepatocelular , Laparoscopía , Neoplasias Hepáticas , Carcinoma Hepatocelular/cirugía , Femenino , Humanos , Neoplasias Hepáticas/cirugía , Masculino , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Resultado del Tratamiento
13.
Zhonghua Wai Ke Za Zhi ; 59(10): 875-880, 2021 Oct 01.
Artículo en Chino | MEDLINE | ID: mdl-34619915

RESUMEN

Hepatocellular carcinoma(HCC) is one of the most common malignant tumors of the digestive system in the clinic. In recent years, the proposal and development of immunotherapy have set off a worldwide anticancer upsurge. In particular, programmed death receptor 1(PD-1) and programmed death receptor ligand 1(PD-L1) inhibitor have been used in a wide variety of tumor diseases and achieved good curative effect. However, the application of PD-1 or PD-L1 inhibitors in HCC is mostly still at the stage of clinical trials, and some clinical trials have shown gratifying results in patients with advanced HCC and postoperative recurrence. More studies have shown that PD-1 or PD-L1 inhibitors combined with radiofrequency, chemoradiotherapy, and molecular targeted drugs can bring greater benefits to patients.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/tratamiento farmacológico , Humanos , Inhibidores de Puntos de Control Inmunológico , Neoplasias Hepáticas/tratamiento farmacológico , Recurrencia Local de Neoplasia , Receptor de Muerte Celular Programada 1
14.
Sheng Wu Gong Cheng Xue Bao ; 37(9): 3042-3060, 2021 Sep 25.
Artículo en Chino | MEDLINE | ID: mdl-34622616

RESUMEN

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths and the fifth most common cancer worldwide. Clinically therapeutic options for HCC are very limited, and the overall survival rate of patients is very low. Therefore, early diagnosis and treatment of HCC have important impact on overall survival of patients. At present, alpha-fetoprotein (AFP) is one of the most widely used serological markers for HCC. Many evidences have shown that as a specific onco-protein, AFP has great research value in the occurrence, development, diagnosis and treatment of HCC. Here, we briefly introduce the molecular mechanism of AFP in the regulation of HCC occurrence and development, and its role in tumor escape from immune surveillance. We focus on the application of AFP as an important HCC target or carcino-embryonic antigen (CEA) in HCC clinical diagnosis and treatment.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Detección Precoz del Cáncer , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , alfa-Fetoproteínas
15.
Anticancer Res ; 41(10): 4937-4946, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34593441

RESUMEN

BACKGROUND/AIM: Dysregulation of the c-Myc gene is frequently found in human hepatocellular carcinoma (HCC), often accompanied by genetic and epigenetic alterations in other cancer-related genes. Here, we investigated the tumorigenic potential of c-Myc in diverse genetic environments in which the Ras, Wnt/ß-catenin, Sonic hedgehog, or P53 pathways were either activated or inactivated. MATERIALS AND METHODS: Hydrodynamic tail vein injection was employed to administer expression transposons and generate transgenic livers expressing c-Myc together with a constitutively active form of RAS (HRASG12V), ß-catenin (ß-cateninS33Y), Smo (SmoM2), or short hairpin RNA targeting P53 (shp53). RESULTS: c-Myc was most tumorigenic when the RAS signaling pathway was activated, whereas no tumors were found in mice when either ß-cateninS33Y or SmoM2 was co-expressed with c-Myc. Approximately 40% of mice had HCC when c-Myc was over-expressed under P53 inactivation. Furthermore, we investigated the effect of mutation in c-Myc on hepatocarcinogenesis. CONCLUSION: No significant differences in tumorigenic potential were found between wild type c-Myc and c-MycT58A, minimizing the role of the mutation in hepatocarcinogenesis.


Asunto(s)
Carcinogénesis/patología , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas Experimentales/patología , Neoplasias Hepáticas/patología , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Animales , Apoptosis , Carcinogénesis/genética , Carcinogénesis/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Proliferación Celular , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas Experimentales/genética , Neoplasias Hepáticas Experimentales/metabolismo , Ratones , Ratones Endogámicos C57BL , Proteínas Proto-Oncogénicas c-myc/genética , Células Tumorales Cultivadas , Proteína p53 Supresora de Tumor/genética
16.
Medicine (Baltimore) ; 100(39): e27332, 2021 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-34596136

RESUMEN

ABSTRACT: Growing evidence supports that the tumor microenvironment plays a key role in the development and progression of tumors. But immune microenvironment of hepatocellular carcinoma (HCC) has not yet been fully explored. In the present investigation, the clinical value and prognostic significance of immune-related genes in HCC were investigated.The immune and stromal scores of HCC were calculated through the application of Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data Algorithm based on the Cancer Genome Atlas database. Differentially expressed genes were identified using the "edgeR" package of the R software. Functional annotation and pathway enrichment were performed using "ggplots2" and "clusterProfiler" packages in R software. Protein-protein interaction network was constructed using STRING, and the hub genes were identified through the Cytoscape. Survival analysis was performed using Kaplan-Meier methods. Tumor Immune Estimation Resource algorithm was used to view the immune landscape of the microenvironment in HCC.Firstly, the immune and stromal scores of HCC were calculated and we found that the immune and stromal scores of HCC were closely related to the patients' prognosis. Then the differentially expressed genes were identified respectively stratified by the median value of the immune and stromal scores, and the immune-related genes that related to the prognosis in HCC patients were further identified. Functional enrichment analysis and protein-protein interaction networks further showed that these genes mainly participated in immune-related biological process. In addition, dendritic cells were found to be the most abundant in the microenvironment of HCC through Tumor Immune Estimation Resource algorithm and were significantly associated with the patients' prognosis. To robust the results, the immune-related genes were validated in an independent dataset from the Gene Expression Omnibus database.We arrived at a more comprehensive understanding of the microenvironment of HCC and extracted 7 immune-related genes that were significantly associated with the recurrence survival of HCC.


Asunto(s)
Carcinoma Hepatocelular/inmunología , Neoplasias Hepáticas/inmunología , Microambiente Tumoral/inmunología , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Perfilación de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Pronóstico , Mapas de Interacción de Proteínas , Células del Estroma , Microambiente Tumoral/genética
17.
Ann Palliat Med ; 10(9): 9702-9714, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34628896

RESUMEN

BACKGROUND: Metabolic-associated fatty liver disease (MAFLD) is highly prevalent in type 2 diabetes mellitus (T2DM) patients and can rapidly progress to steatohepatitis, liver fibrosis, and hepatocellular carcinoma (HCC). Accurate evaluation and proper management of MAFLD can help prevent adverse liver outcomes. Here we evaluated the precision of the FibroTouch (FT) in the staging of liver steatosis and fibrosis in patients with MAFLD combined with T2DM using two indicators: controlled attenuation parameter (CAP) and liver stiffness measurement (LSM). METHODS: Eighty-five adult MAFLD combined with T2DM patients were selected at our center from July 2016 to July 2019 and underwent liver puncture biopsy for histopathology and the FT assay simultaneously. Two blinded pathologists independently reviewed the samples. The severity of fatty liver was classified using two scoring systems: the nonalcoholic fatty liver disease activity score (NAS) and the fibrosis score. Scores were then assessed following the Pathology Working Group of the NASH Clinical Research Network of the National Institutes of Health. Similarly, the severity of nonalcoholic steatohepatitis (NASH) was classified using the European Steatosis Activity Fibrosis (SAF) system. The FT assay was applied to obtain the LSM and the CAP. FT accuracy in diagnosing steatosis and fibrosis was determined by the receiver operating characteristic (ROC) curve and the area under the ROC curve (AUROC). RESULTS: Using biopsy analysis as the gold standard, the AUROCs and cutoff values of CAP in diagnosing liver steatosis were as follows: 0.84 (95% CI: 0.67-1.01) and 278 dB/m for S ≥ S1, 0.88 (95% CI: 0.81-0.95) and 305 dB/m for S ≥ S2, 0.89 (95% CI: 0.82-0.95) and 307 dB/m for S ≥ S3. The AUROCs and cutoff values of LSM in diagnosing liver fibrosis were as follows: 0.76 (95% CI: 0.66-0.86) for F ≥ F2, 0.81 (95% CI: 0.71-0.91) and 13.8 kPa for F ≥ F3, 0.92 (95% CI: 0.85-1.00) and 20.1 kPa for F ≥ F4. CONCLUSIONS: In patients of MAFLD with T2DM, CAP and LSM obtained by FT are highly accurate in assess liver steatosis and fibrosis, respectively, with AUROC values ranging from 0.76 to 0.92.


Asunto(s)
Carcinoma Hepatocelular , Diabetes Mellitus Tipo 2 , Diagnóstico por Imagen de Elasticidad , Neoplasias Hepáticas , Enfermedad del Hígado Graso no Alcohólico , Adulto , Humanos , Cirrosis Hepática , Estados Unidos
18.
World J Gastroenterol ; 27(34): 5715-5726, 2021 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-34629796

RESUMEN

Recently, increasing attention has been paid to the application of artificial intelligence (AI) to the diagnosis of diverse hepatic diseases, which comprises traditional machine learning and deep learning. Recent studies have shown the possible value of AI based data mining in predicting the incidence of hepatitis, classifying the different stages of hepatitis, diagnosing or screening for hepatitis, forecasting the progression of hepatitis, and predicting response to antiviral drugs in chronic hepatitis C patients. More importantly, AI based on radiology has been proven to be useful in predicting hepatitis and liver fibrosis as well as grading hepatocellular carcinoma (HCC) and differentiating it from benign liver tumors. It can predict the risk of vascular invasion of HCC, the risk of hepatic encephalopathy secondary to hepatitis B related cirrhosis, and the risk of liver failure after hepatectomy in HCC patients. In this review, we summarize the application of AI in hepatitis, and identify the challenges and future perspectives.


Asunto(s)
Carcinoma Hepatocelular , Hepatitis A , Neoplasias Hepáticas , Inteligencia Artificial , Humanos , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/epidemiología , Neoplasias Hepáticas/epidemiología
19.
World J Gastroenterol ; 27(35): 5803-5821, 2021 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-34629804

RESUMEN

Nonalcoholic fatty liver disease (NAFLD) is becoming a frequent liver disease, especially in patients with metabolic syndrome and especially in Western countries. Complications of NAFLD comprise progressive fibrosis, cirrhosis and hepatocellular carcinoma. NAFLD also represents an independent risk factor for cardiovascular disease, extrahepatic neoplasia and other organ damage, such as renal insufficiency. Given the epidemiological importance of the disease, new developments in specific treatment of the disease and the wide availability of noninvasive techniques in estimating steatosis and fibrosis, NAFLD should be subject to screening programs, at least in countries with a high prevalence of the disease. The review discusses prerequisites for screening, cost-effectiveness, current guideline recommendations, suitability of techniques for screening and propositions for the following questions: Who should be screened? Who should perform screening? How should screening be performed? It is time for a screening program in patients at risk for NAFLD.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Síndrome Metabólico , Enfermedad del Hígado Graso no Alcohólico , Humanos , Cirrosis Hepática , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiología , Síndrome Metabólico/complicaciones , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/epidemiología
20.
World J Gastroenterol ; 27(35): 5978-5988, 2021 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-34629814

RESUMEN

BACKGROUND: The nature of input data is an essential factor when training neural networks. Research concerning magnetic resonance imaging (MRI)-based diagnosis of liver tumors using deep learning has been rapidly advancing. Still, evidence to support the utilization of multi-dimensional and multi-parametric image data is lacking. Due to higher information content, three-dimensional input should presumably result in higher classification precision. Also, the differentiation between focal liver lesions (FLLs) can only be plausible with simultaneous analysis of multi-sequence MRI images. AIM: To compare diagnostic efficiency of two-dimensional (2D) and three-dimensional (3D)-densely connected convolutional neural networks (DenseNet) for FLLs on multi-sequence MRI. METHODS: We retrospectively collected T2-weighted, gadoxetate disodium-enhanced arterial phase, portal venous phase, and hepatobiliary phase MRI scans from patients with focal nodular hyperplasia (FNH), hepatocellular carcinomas (HCC) or liver metastases (MET). Our search identified 71 FNH, 69 HCC and 76 MET. After volume registration, the same three most representative axial slices from all sequences were combined into four-channel images to train the 2D-DenseNet264 network. Identical bounding boxes were selected on all scans and stacked into 4D volumes to train the 3D-DenseNet264 model. The test set consisted of 10-10-10 tumors. The performance of the models was compared using area under the receiver operating characteristic curve (AUROC), specificity, sensitivity, positive predictive values (PPV), negative predictive values (NPV), and f1 scores. RESULTS: The average AUC value of the 2D model (0.98) was slightly higher than that of the 3D model (0.94). Mean PPV, sensitivity, NPV, specificity and f1 scores (0.94, 0.93, 0.97, 0.97, and 0.93) of the 2D model were also superior to metrics of the 3D model (0.84, 0.83, 0.92, 0.92, and 0.83). The classification metrics of FNH were 0.91, 1.00, 1.00, 0.95, and 0.95 using the 2D and 0.90, 0.90, 0.95, 0.95, and 0.90 using the 3D models. The 2D and 3D networks' performance in the diagnosis of HCC were 1.00, 0.80, 0.91, 1.00, and 0.89 and 0.88, 0.70, 0.86, 0.95, and 0.78, respectively; while the evaluation of MET lesions resulted in 0.91, 1.00, 1.00, 0.95, and 0.95 and 0.75, 0.90, 0.94, 0.85, and 0.82 using the 2D and 3D networks, respectively. CONCLUSION: Both 2D and 3D-DenseNets can differentiate FNH, HCC and MET with good accuracy when trained on hepatocyte-specific contrast-enhanced multi-sequence MRI volumes.


Asunto(s)
Carcinoma Hepatocelular , Aprendizaje Profundo , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico por imagen , Medios de Contraste , Hepatocitos , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Imagen por Resonancia Magnética , Estudios Retrospectivos
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