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1.
HPB (Oxford) ; 24(3): 342-352, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34400051

RESUMO

BACKGROUND: This study aimed to investigate the work status of clinicians in China and their management strategy alteration for patients with hepatocellular carcinoma (HCC) during the COVID-19 pandemic. METHODS: A nationwide online questionnaire survey was conducted in 42 class-A tertiary hospitals across China. Experienced clinicians of HCC-related specialties responded with their work status and management suggestions for HCC patients during the pandemic. RESULTS: 716 doctors responded effectively with a response rate of 60.1%, and 664 were included in the final analysis. Overall, 51.4% (341/664) of clinicians reported more than a 60% reduction of the regular workload and surgeons declared the highest proportion of workload reduction. 92.5% (614/664) of the respondents have been using online medical consultation to substitute for the "face-to-face" visits. Adaptive adjustment for the treatment strategy for HCC was made, including the recommendations of noninvasive and minimally invasive treatments such as transcatheter arterial chemoembolization for early and intermediate stage. Targeted therapy has been the mainstay for advanced stage and also as a bridge therapy for resectable HCC. DISCUSSION: During the COVID-19 pandemic, online medical consultation is recommended to avoid social contact. Targeted therapy as a bridge therapy is recommended for resectable HCC considering the possibility of delayed surgery.


Assuntos
COVID-19 , Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/terapia , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/terapia , Pandemias , SARS-CoV-2 , Inquéritos e Questionários
2.
BMC Cancer ; 19(1): 1037, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31684910

RESUMO

BACKGROUND: SMAD4 is frequently inactivated and associated with a poor prognosis in pancreatic ductal adenocarcinoma (PDAC). Abnormal SMAD4 expression also plays an important role in the malignant progression of PDAC. METHODS: We investigated SMAD4 status in PDAC by immunohistochemical methods to explore the relationships between SMAD4 expression and clinicopathological features and then detected SMAD4 mutations by Sanger sequencing in 95 patients with PDAC to identify new mutation sites in PDAC. We further evaluated the effects of a missense mutation, Y353C, in the SMAD4 MH2 domain, on cell proliferation and migration in vitro. RESULTS: Immunohistochemistry showed that the expression of SMAD4 in PDAC carcinoma tissue was significantly lower than that in normal pancreatic tissue, and negative SMAD4 expression was closely related to tumour diameter, staging, lymph node metastasis and differentiation. Sanger sequencing analysis showed that the rate of SMAD4 mutation was 11.8% in 85 PDAC cases, and the novel SMAD4 Y353C missense mutation identified in this study promoted cell migration and invasion without affecting cell proliferation in vitro. Furthermore, SMAD4 Y353C resulted in reduced expression of E-cadherin and increased expression of Vimentin compared with wild-type SMAD4 overexpression. CONCLUSION: This study supports the key role of SMAD4 as a tumour suppressor gene in PDAC and shows that SMAD4 Y353C is associated with poor progression of PDAC.


Assuntos
Carcinoma Ductal Pancreático/genética , Mutação de Sentido Incorreto/genética , Neoplasias Pancreáticas/genética , Proteína Smad4/genética , Caderinas/metabolismo , Carcinogênese , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Proteína Smad4/metabolismo , Vimentina/metabolismo
3.
Hepatobiliary Pancreat Dis Int ; 15(6): 626-632, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27919852

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT) is rare. The present study aimed to determine post-surgical prognoses in HCC patients with BDTT, as outcomes are currently unclear. METHODS: We compared the prognoses of 110 HCC patients without BDTT (group A) to 22 cases with BDTT (group B). The two groups were matched in age, gender, tumor etiology, size, number, portal vascular invasion, and TNM stage. Additionally, 28 HCC patients with BDTT were analyzed to identify prognostic risk factors. RESULTS: The 1-, 3-, and 5-year overall survival rates were 90.9%, 66.9%, and 55.9% for group A and 81.8%, 50.0%, and 37.5% for group B, respectively. The median survival time in groups A and B was 68.8 and 31.4 months, respectively (P=0.043). The patients for group B showed higher levels of serum total bilirubin, alanine aminotransferase and gamma-glutamyl transferase, a larger hepatectomy range, and a higher rate of anatomical resection. In subgroup analyses of patients with BDTT who underwent R0 resection, TNM stage III-IV was an independent risk factor for overall survival; these patients had worse prognoses than those with TNM stage I-II after R0 resection (hazard ratio=6.056, P=0.014). Besides, univariate and multivariate analyses revealed that non-R0 resection and TNM stage III-IV were independent risk factors for both disease-free survival and overall survival of 28 HCC patients with BDTT. The median overall survival time of patients with BDTT who underwent R0 resection was longer than that of patients who did not undergo R0 resection (31.0 vs 4.0 months, P=0.007). CONCLUSIONS: R0 resection prolonged survival time in HCC patients with BDTT, although prognosis remains poor. For such patients, R0 resection is an important treatment that determines long-term survival.


Assuntos
Carcinoma Hepatocelular/cirurgia , Colestase/cirurgia , Hepatectomia , Neoplasias Hepáticas/cirurgia , Células Neoplásicas Circulantes/patologia , Adulto , Idoso , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , China , Colestase/sangue , Colestase/mortalidade , Colestase/patologia , Feminino , Hepatectomia/efeitos adversos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Duração da Cirurgia , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Carga Tumoral
4.
BMC Surg ; 16: 22, 2016 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-27094483

RESUMO

BACKGROUND: Although the Barcelona Clinic Liver Cancer (BCLC) staging system suggests that patients with stage B hepatocellular carcinoma (HCC) should be treated with transcatheter arterial chemoembolization instead of surgical treatment, recent studies indicated that the prognosis of surgical resection for patients with BCLC stage B HCC was better than that of TACE. However, the portion of patients with stage B that will achieve better outcomes from surgical treatment remains unclear. In this study, we identified risk factors that influence the prognosis of BCLC stage B HCC after R0 surgical resection to determine whether some patients with stage B HCC may benefit more from R0 resection than other patients and to provide a guideline to estimate the tendency. METHODS: The clinical data of 78 patients with BCLC stage B HCC after R0 surgical treatment within 11 years were analyzed retrospectively, using relapse or death as the endpoint. Kaplan-Meier survival and Cox regression analyses were used to study prognosis (disease-free survival, DFS and overall survival, OS) and independent risk factors. RESULTS: For all stage B patients, 1-, 2-, and 5-year DFS rates were 62.5, 36.4, and 16.6%, respectively. Cumulative tumor size >5.0 cm and tumor number ≥4 were independent prognostic risk factors for DFS. The 1-, 2-, and 5- year DFS rates and OS rates of patients with at least one of these two factors were 49.0, 17.2, and 7.4% (for DFS), and 78.6, 54.8, and 13.4% (for OS), respectively, which were significantly lower than patients without these two factors (77.8, 58.3, and 27.2% for DFS, and 94.4, 83.3,and 51.8% for OS, respectively, P < 0.01). CONCLUSIONS: The analyses indicated that the outcomes of R0 resection were much better for patients with BCLC stage B HCC with two or three tumors and cumulative tumor sizes of ≤5.0 but >3.0 cm than other patients with stage B.


Assuntos
Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida
5.
BMC Cancer ; 15: 1004, 2015 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-26698563

RESUMO

BACKGROUND: The objective of the study was to explore the clinical expression, radiological and pathological features, differential diagnosis, and biological behavior of a clear cell myomelanocytic tumor. In a case involving a clear cell myomelanocytic tumor located in the hepatic falciform ligament, we evaluated clinical expression, radiological characteristics, histopathology, immunohistochemistry, and biological behavior; we also reviewed the relevant literature. CASE PRESENTATION: Clear cell myomelanocytic tumor is a benign soft-tissue neoplasm that often occurs in women, and is expressed as a painless mass. The falciform ligament is its most frequent site of occurrence. The imaging characteristics of this lesion were uneven enhancement in the arterial phase, continuing to strengthen in the venous phase, and equal density in the balance phase. Histological and immunohistochemical analysis revealed the main transparent epithelioid cells and smooth muscle spindle cells to be HMB-45(+), smooth muscle actin(+), and melan-A (+). CONCLUSION: Hepatic vascular epithelioid cell tumors are very rare mesenchymal neoplasms. Few studies have investigated this tumor in the hepatic falciform ligament; consequently, its diagnosis and the selection of an appropriate treatment and follow-up protocol are challenging. Treatment outcome remains unpredictable. Therefore, clear cell myomelanocytic tumor should be viewed as a tumor with uncertain malignant potential requiring long-term follow-up.


Assuntos
Neoplasias de Células Epitelioides Perivasculares/patologia , Adulto , Biomarcadores Tumorais/metabolismo , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Neoplasias de Células Epitelioides Perivasculares/metabolismo
6.
Psychiatry Clin Neurosci ; 68(5): 344-52, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24373005

RESUMO

AIMS: Increasing evidence suggests that the catechol-O-methyltransferase (COMT) gene might be associated with cognition in patients with mental disorders and healthy people. The metabolic pathways of COMT and methylenetetrahydrofolate reductase (MTHFR) are closely interconnected. In this study, we aimed to examine whether the COMT-MTHFR genotype interacted with cognitive function in late-onset depression (LOD) patients and COMT Val/Val homozygous individuals who also carried the MTHFR T allele and had poor neuropsychological test performance. METHODS: Ninety-seven unrelated LOD patients who met DSM-IV criteria for major depressive disorder were recruited for the study and 103 normal controls were recruited from the local community. All of these patients and 44 normal controls completed a series of neuropsychological tests. Patients and normal controls were genotyped for COMT (rs4680) and MTHFR (rs1801133) variants using polymerase chain reaction-restriction fragment length polymorphism. RESULTS: There were no significant differences in the frequencies of the single alleles and genotypes of two polymorphisms between LOD patients and normal controls. No main effects of COMT or MTHFR genotype on any neuropsychological test performance were observed. There was a significant interactive effect of COMT Val158Met and MTHFR C677T polymorphisms on the Symbol Digit Modalities Test independent of diagnosis (P < 0.05). After controlling for covariates, the subjects with COMT Met/ Met and MTHFR C/C genotype had better Symbol Digit Modalities Test performance. CONCLUSIONS: The results suggest no major effect of COMT or MTHFR on cognitive function alone. However, an interaction of COMT Val158Met and MTHFR C677T polymorphisms may be associated with cognitive function. Further studies in a large sample are needed to replicate the genetic role in the LOD patients.


Assuntos
Catecol O-Metiltransferase/genética , Cognição , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/psicologia , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Idade de Início , Idoso , Alelos , Estudos de Casos e Controles , Transtorno Depressivo Maior/epidemiologia , Epistasia Genética/genética , Feminino , Genótipo , Humanos , Masculino , Testes Neuropsicológicos , Polimorfismo de Nucleotídeo Único/genética
7.
World J Clin Cases ; 12(20): 4272-4288, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39015929

RESUMO

BACKGROUND: Education, cognition, and intelligence are associated with cholelithiasis occurrence, yet which one has a prominent effect on cholelithiasis and which cardiometabolic risk factors mediate the causal relationship remain unelucidated. AIM: To explore the causal associations between education, cognition, and intelligence and cholelithiasis, and the cardiometabolic risk factors that mediate the associations. METHODS: Applying genome-wide association study summary statistics of primarily European individuals, we utilized two-sample multivariable Mendelian randomization to estimate the independent effects of education, intelligence, and cognition on cholelithiasis and cholecystitis (FinnGen study, 37041 and 11632 patients, respectively; n = 486484 participants) and performed two-step Mendelian randomization to evaluate 21 potential mediators and their mediating effects on the relationships between each exposure and cholelithiasis. RESULTS: Inverse variance weighted Mendelian randomization results from the FinnGen consortium showed that genetically higher education, cognition, or intelligence were not independently associated with cholelithiasis and cholecystitis; when adjusted for cholelithiasis, higher education still presented an inverse effect on cholecystitis [odds ratio: 0.292 (95%CI: 0.171-0.501)], which could not be induced by cognition or intelligence. Five out of 21 cardiometabolic risk factors were perceived as mediators of the association between education and cholelithiasis, including body mass index (20.84%), body fat percentage (40.3%), waist circumference (44.4%), waist-to-hip ratio (32.9%), and time spent watching television (41.6%), while time spent watching television was also a mediator from cognition (20.4%) and intelligence to cholelithiasis (28.4%). All results were robust to sensitivity analyses. CONCLUSION: Education, cognition, and intelligence all play crucial roles in the development of cholelithiasis, and several cardiometabolic mediators have been identified for prevention of cholelithiasis due to defects in each exposure.

8.
BMC Cancer ; 13: 306, 2013 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-23800357

RESUMO

BACKGROUND: We studied the relationships among Cx43, CD105, and VEGF in specimens of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) with different serum AFP levels with respect to recurrence and metastasis. METHODS: Expressions of Cx43, CD105, and VEGF in 234 HCC tissue specimens were examined using tissue microarray and immunohistochemistry. Cx43 mRNA expression was examined in 38 frozen HCC specimens using RT-PCR. Correlations between these expressions and tumor recurrence, metastasis, and prognosis were analyzed using Kaplan-Meier and Cox regression analyses. RESULTS: Cx43 expression correlated with early tumor recurrence (P = 0.001), disease-free survival (P = 0.026), and overall survival (P = 0.000) in patients with serum AFP < 400 ng/ml, but not in those with serum AFP ≥ 400 µg/L. Cx43 expression is an independent predictor of later recurrence and longer overall survival and is inversely correlated with expression of CD105 and VEGF (P = 0.018 and 0.023, respectively), histological differentiation (P = 0.002), vessel tumor embolism (P = 0.029), and focal number (P = 0.017). Immunohistochemistry showed that Cx43 expression in patients with low AFP was lower in patients with distant metastases than in those with no metastasis or those with liver metastasis. Patients with early recurrence expressed less Cx43 mRNA than did those with no recurrence (χ2 = 9.827, P = 0.002). CONCLUSIONS: Cx43 expression can delay early HCC recurrence, metastasis, and poor prognosis after radical hepatectomy in patients with HBV-related HCC and low AFP.


Assuntos
Carcinoma Hepatocelular/metabolismo , Conexina 43/biossíntese , Neoplasias Hepáticas/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/análise , Antígenos CD/biossíntese , Biomarcadores Tumorais/análise , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , Conexina 43/análise , Intervalo Livre de Doença , Endoglina , Feminino , Hepatectomia , Hepatite B Crônica/complicações , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/virologia , Prognóstico , Modelos de Riscos Proporcionais , RNA Mensageiro/análise , Receptores de Superfície Celular/análise , Receptores de Superfície Celular/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise Serial de Tecidos , Fator A de Crescimento do Endotélio Vascular/análise , Fator A de Crescimento do Endotélio Vascular/biossíntese , Adulto Jovem , alfa-Fetoproteínas/análise , alfa-Fetoproteínas/metabolismo
9.
Zhonghua Zhong Liu Za Zhi ; 34(10): 753-8, 2012 Oct.
Artigo em Zh | MEDLINE | ID: mdl-23291069

RESUMO

OBJECTIVE: To investigate the expression of CK19 in HBV-related hepatocellular carcinoma (HCC) tissues in patients with low serum AFP concentration and the relationship between them and the recurrence and prognosis of HCC after R0 radical hepatectomy. METHODS: The expressions of CK19 and Ki67 in HCC tissues of 235 cases were examined using tissue microarray and two-step methods of PV-6000 immunohistochemistry. The expression of CK19 mRNA in 20 frozen HCC specimens was examined by RT-PCR. The correlation between gene expressions and tumor recurrence and prognosis was analyzed. RESULTS: Among the 235 HBV-related HCC patients after R0 radical hepatectomy, the median disease-free survival (DFS) was 31.2 months in the patients with serum AFP < 400 µg/L and 13.8 months in the patients with serum AFP ≥ 400 µg/L (P = 0.041), the overall survival (OS) was 84.0 and 58.6 months in the two subgroups (P = 0.125), and the tumor recurrence within one year was in 43 cases (27%) and 37 cases (49.3%), respectively, (P = 0.001). The DFS was 11.6 months in the CK19-positive cases and 27.0 months in the CK19-negative cases (P > 0.05). The OS was significantly lower in the CK19-positive cases than that in the CK19-negative cases (P = 0.023). Both DFS and OS in the CK19-positive cases with AFP < 400 µg/L were significantly lower than those in the CK19-negative cases with AFP < 400 µg/L (both P < 0.05). The CK19 expression was significantly correlated with histological differentiation (P = 0.023), number of tumor foci (P = 0.044), vascular tumor embolism (P = 0.005), regional lymph node metastasis (P = 0.023), and 1-year recurrence (P = 0.006). Among the patients with AFP < 400 µg/L, the 1-year recurrence was 53% in the CK19-positive cases and 23% in the CK19-negative cases (P < 0.001), the median DFS was 11.3 months in CK19-positive cases and 34.0 months in CK19-negative cases (P = 0.010), and the median OS was 19.5 months in the CK19-positive cases, significantly lower than 84.0 months in the CK19-negative cases (P = 0.001). Cox regression analysis showed that CK19-positive expression was an independent factor affecting early HCC recurrence and prognosis. CONCLUSION: In HBV-related HCC patients after radical hepatectomy with AFP < 400 µg/L, positive expression of CK19 indicates a higher proliferation and invasiveness of HCC, and is an important factor of early recurrence and poor prognosis.


Assuntos
Carcinoma Hepatocelular , Vírus da Hepatite B , Queratina-19/metabolismo , Neoplasias Hepáticas , alfa-Fetoproteínas/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/virologia , Intervalo Livre de Doença , Feminino , Hepatectomia/métodos , Humanos , Queratina-19/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/virologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , RNA Mensageiro/metabolismo , Taxa de Sobrevida , Adulto Jovem
10.
Zhonghua Wai Ke Za Zhi ; 49(9): 784-8, 2011 Sep 01.
Artigo em Zh | MEDLINE | ID: mdl-22177430

RESUMO

OBJECTIVE: To analyze the high risk factors for tumor recurrence in short term after hepatectomy for the patients with primary hepatocellular carcinoma (HCC). METHODS: Five hundreds and two patients with primary HCC underwent hepatectomy were included from January 1997 to December 2008. Among these patients, males were 419 cases and females were 83 cases. The age was 14 to 82 years (average age 54 years). The results of evaluation on 2 months after resection and tumor recurrence and survival were analyzed. RESULTS: According to the operative and pathologic findings and the evaluation on 2 months after hepatectomy, the patients with vascular invasion, palliation resection, cutting edge pathologic residual tumor, lymph notes metastasis, serum AFP level continuing higher after resection or(and) positive TACE (tumor dyeing on TACE within 1 month and a deposit of lipiodol on CT scan) were high risk factors (high-risk group, 106 cases, 21.1%), the recurrence-free survival was 22%, 9% and 3% (1, 2 and 5 year) and overall survival was 52%, 25% and 8%. On the non-high risk group patients, the recurrence-free survival was 84%, 67%, 42% and 31% (1, 2, and 5 year) and overall survival was 97%, 85%, 56% and 35%. The bigger tumor, poor differentiation, tumor invading to liver capsule, satellite focus and TNM III-IV stage in high-risk groups were more significantly than that in non-high-risk groups. CONCLUSION: The vascular invasion, palliation resection, cutting edge pathologic residual tumor, lymph notes metastasis, serum AFP level continuing higher or (and) positive TACE within 2 months after resection are high risk factors for HCC patients in short term after hepatectomy, which mean tumor remnant.


Assuntos
Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Recidiva Local de Neoplasia/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Intervalo Livre de Doença , Feminino , Hepatectomia , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
11.
Hepatobiliary Surg Nutr ; 10(2): 172-179, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33898558

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common causes of cancer worldwide. Although many studies have focused on oncogene characteristics, the genomic landscape of Chinese HCC patients has not been fully clarified. METHODS: A total of 165 HCC patients, including 146 males and 19 females, were enrolled. The median age was 55 years (range, 27-78 years). Corresponding clinical and pathological information was collected for further analysis. A total of 168 tumor tissues from these patients were selected for next-generation sequencing (NGS)-based 450 panel gene sequencing. Genomic alterations including single nucleotide variations (SNV), short and long insertions and deletions (InDels), copy number variations, and gene rearrangements were analyzed. Tumor mutational burden (TMB) was measured by an algorithm developed in-house. The top quartile of HCC was classified as TMB high. RESULTS: A total of 1,004 genomic alterations were detected from 258 genes in 168 HCC tissues. TMB values were identified in 160 HCC specimens, with a median TMB of 5.4 Muts/Mb (range, 0-28.4 Muts/Mb) and a 75% TMB of 7.7 Muts/Mb. The most commonly mutated genes were TP53, TERT, CTNNB1, AXIN1, RB1, TSC2, CCND1, ARID1A, and FGF19. SNV was the most common mutation type and C:G>T:A and guanine transformation were the most common SNVs. Compared to wild-type patients, the proportion of Edmondson grade III-IV and microvascular invasion was significantly higher in TP53 mutated patients (P<0.05). The proportion of tumors invading the hepatic capsule was significantly higher in TERT mutated patients (P<0.05). The proportion of Edmondson grade I-II, alpha fetoprotein (AFP) <25 µmg/L, and those without a history of hepatitis B was significantly higher in CTNNB1 mutated patients (P<0.05). CTNNB1 mutations were associated with TMB high in HCC patients (P<0.05). Based on correlation analysis, the mutation of TP53 was independently correlated with microvascular invasion (P=0.002, OR =3.096) and Edmondson grade III-IV (P=0.008, OR =2.613). The mutation of TERT was independently correlated with tumor invasion of the liver capsule (P=0.001, OR =3.030), and the mutation of CTNNB1 was independently correlated with AFP (<25 µmg/L) (P=0.009, OR =3.414). CONCLUSIONS: The most frequently mutated genes of HCC patients in China were TP53, TERT, and CTNNB1, which mainly lead to the occurrence and development of HCC by regulating the P53 pathway, Wnt pathway, and telomere repair pathway. There were more patients with microvascular invasion and Edmondson III-IV grade in TP53 mutated patients and more patients with hepatic capsule invasion in TERT mutated patients, while in CTNNB1 mutated patients, there were more patients with Edmondson I-II grade, AFP <25 µmg/L, and a non-hepatitis B background. Also, the TMB values were significantly higher in CTNNB1 mutated patients than in wild type patients.

12.
World J Clin Cases ; 8(22): 5639-5644, 2020 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-33344555

RESUMO

BACKGROUND: Plexiform fibromyxoma (PF) is a rare mesenchymal tumor of the stomach. The clinical features of PF frequently include upper abdominal pain, abdominal discomfort, hematemesis, melena, pyloric obstruction and an upper abdominal mass. We herein report a case of PF resected by laparoscopic radical distal gastrectomy plus Roux-en-Y gastrojejunostomy. CASE SUMMARY: The patient was admitted to hospital, due to a 1-wk history of an abdominal space-occupying lesion identified during a health examination. He underwent complete resection by laparoscopic radical distal gastrectomy plus Roux-en-Y gastrojejunostomy. During the operation, the tumor was located in the anterior wall of the gastric antrum (approximately 7 cm × 6 cm × 5.5 cm) and did not show evidence of invasion of the serosa. Histology showed that the tumor cells were oval fibroblast-like and spindle-shaped cells, with numerous thin-walled blood vessels and abundant myxoid stroma. Cellular atypia and mitosis were both rare. Immunohistochemistry showed that the tumor cells were immunoreactive for smooth muscle actin, S-100 and CD-10, but were negative for CD-117, CD-34, DOG-1, and ALK. In this case, S-100 was positive and no significant disease was observed during the follow-up period. CONCLUSION: The fact that PF is a rare tumor with only a few cases in this region can lead to misdiagnosis of this entity and pose a real diagnostic challenge for general surgeons and pathologists when encountering such patients and differentiating PF from other primary tumors of gastric mesenchymal origin. Our report may help increase awareness of this rare, but important new disease entity.

13.
Biomed Res Int ; 2019: 6959637, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31662990

RESUMO

AIM: Little is known about the association between cancer antigen 125 (MUC16/CA125) concentrations and tumor diameter of patients with hepatocellular carcinoma (HCC) and low AFP levels. To fill this gap in our knowledge, we conducted a retrospective study of 427 patients with HCC with AFP ≤200 ng/mL who underwent R0 resection at our center. METHODS: The associations between CA125 concentrations and patients' clinicopathological characteristics were analyzed. Survival vs CA125 levels was also evaluated between patient groups with CA125 ≤30 U/mL or CA125 >30 U/mL. Independent risk factors of disease-free survival (DFS) and overall survival (OS) were analyzed with Cox hazard regression model. RESULTS: Elevated preoperative serum CA125 was significantly associated with maximal tumor diameter (MTD) >5 cm and female sex (P < 0.001 and P=0.044, respectively). The DFS and OS of patients with CA125 ≤30 U/mL (n = 392) were significantly higher compared with those with CA125 >30 U/mL (n = 35) (P=0.003 and P=0.001 respectively). Multivariate analysis revealed that MTD >5 cm was an independent risk factor of DFS (HR = 1.891, 95% CI: 1.379-2.592, P < 0.001) and OS (2.709, 1.848-3.972, P < 0.001). CONCLUSIONS: In conclusion, elevated preoperative serum CA125 predicted larger tumor diameter and poor prognosis after patients with HCC with AFP ≤200 ng/mL underwent R0 resection, which may be explained by the elevation of the preoperative serum CA125 level significantly associated with MTD>5 cm.


Assuntos
Antígeno Ca-125/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/patologia , Proteínas de Membrana/sangue , alfa-Fetoproteínas/metabolismo , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/metabolismo , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Hepáticas/metabolismo , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Período Pré-Operatório , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco
14.
Eur J Surg Oncol ; 45(9): 1684-1690, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31027944

RESUMO

BACKGROUND: Management of recurrent hepatocellular cancer (HCC) after liver resection is challenging, with unsatisfactory long-term patient outcomes. Liver re-resection, in theory, is a good treatment option. We therefore studied prognosis and risk factors of patients who undergo re-hepatectomy. METHODS: We retrospectively analyzed 103 patients who underwent re-hepatectomy. RESULTS: The re-resection postoperative complication rate was 31.1% (32/103). Patients with gross vascular invasion (GVI), cirrhosis, or hepatitis B (HBV) infections not treated with antiviral therapy had higher morbidity than patients without these diseases (per chi-square tests). In bivariate regression analysis, cirrhosis (odds ratio [OR]: 10.308, P = 0.031) and HBV not treated with antiviral therapy (OR: 3.982, P = 0.011) were associated with immediate postoperative morbidity. Median overall survival (OS) after re-resection was 65.0 months (range: 2.1-119.3 months); cumulative OS rates were 1-year: 92.1%, 2-year: 78.2%, and 5-year: 54.4%. Independent risk factors for worse survival were serum AFP level > 20 ng/mL at first resection, portal hypertension (PH) and GVI at recurrence. In the non-PH group, microvascular invasion (micro-VI), GVI and pTNM III-IV disease were associated with poor prognosis; patients with pTNM I-II disease had significantly less micro-VI and GVI than did patients with advanced disease. CONCLUSION: Repeat hepatectomy has favorable long-term outcomes. Cirrhosis and HBV not treated with antiviral therapy were associated with immediate postoperative morbidity. Serum AFP > 20 ng/mL at first resection, PH, and GVI at recurrence are independent prognostic factors. For patients without PH, TNM staging can predict prognosis.


Assuntos
Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia/cirurgia , Adulto , Idoso , Biomarcadores Tumorais/análise , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Feminino , Hepatectomia , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Estadiamento de Neoplasias , Complicações Pós-Operatórias , Prognóstico , Reoperação , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
15.
Medicine (Baltimore) ; 97(37): e12408, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30213016

RESUMO

RATIONALE: Primary hepatic neuroendocrine tumors (PHNETs) are extremely rare and are difficult to diagnose preoperatively.We report a case of PHNET diagnosed preoperatively and successfully resected using associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). PATIENT CONCERNS: A 72-year-old woman was admitted to our hospital for a hepatic mass, which was incidentally identified during a routine health checkup. The patient has no other obvious symptoms of discomfort. DIAGNOSES: Physical examination revealed a palpable mass in the right upper quadrant of her abdomen. Dynamic contrast-enhanced abdominal computed tomography (CT) showed a low-density mass measuring 13 × 7 × 6 cm in both, the right and left hepatic lobes. F-fluorodesoxyglucose positron emission tomography (F-FDG PET) and fused PET/CT showed increased uptake by the mass, which was indicative of a hepatic tumor. INTERVENTIONS: We use a novel ALPPS surgical procedure to safely and radically remove primary neuroendocrine tumors. OUTCOMES: No postoperative bleeding and bile leakage were reported, and the patient recovered uneventfully.The patient was followed-up for a year without recurrence. LESSONS: PHNETs are rare tumors, and confirming the diagnosis using the best possible preoperative examination is important. An optimal treatment plan is selected based on the patient's condition to ensure a favorable prognosis. Tumors too large to undergo surgical removal can be resected using the ALPPS procedure, as described in this case report.


Assuntos
Hepatectomia/métodos , Ligadura/métodos , Neoplasias Hepáticas/cirurgia , Tumores Neuroendócrinos/cirurgia , Veia Porta/cirurgia , Idoso , Feminino , Humanos , Fígado/irrigação sanguínea , Fígado/cirurgia , Resultado do Tratamento
16.
Am J Med Sci ; 354(3): 262-267, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28918833

RESUMO

BACKGROUND: The Barcelona Clinic Liver Cancer (BCLC) staging system is widely used to classify hepatocellular carcinoma (HCC). This study was performed to investigate the prognostic factors for patients with BCLC stage A HCC after R0 hepatectomy. METHODS: A total of 592 patients with BCLC stage A HCC following R0 hepatectomy from 1997-2012 were enrolled in this study. Kaplan-Meier analysis and Cox regression were used to analyze the risk factors associated with recurrence. Receiver operating characteristic curves were used to establish a new scoring system to evaluate the independent risk factors for recurrence. Furthermore, subgroup analyses were performed to evaluate surgical margins on tumor recurrence between the anatomic and nonanatomic resection group. RESULTS: Independent risk factors for BCLC stage A HCC recurrence were preoperative alanine transaminase >40U/L, liver cirrhosis, surgical margin <5mm, nonanatomic resection and maximum tumor diameter >5cm. Based on these 5 risk factors, we established a new scoring system, named "HCC recurrence scoring system." Patients with a high score (≥3 points, 1 point for each factor) composed the high recurrence risk group. Moreover, the subgroup analyses demonstrated that different surgical margins had no significant effect on tumor recurrence in the anatomic resection group (P = 0.408), while it had a significant effect in the nonanatomic resection group (P = 0.000). CONCLUSIONS: For patients with BCLC stage A with scores ≥3 points, close postoperative follow-up and positive measures to prevent recurrence are particularly important. Anatomic resection is preferred for patients with BCLC stage A. Adequate surgical margins are necessary for patients with poor liver function.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/epidemiologia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Cirrose Hepática/complicações , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/epidemiologia , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/etiologia , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
17.
Genet Test Mol Biomarkers ; 21(5): 286-291, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28277785

RESUMO

AIM: Interleukin-17 (IL-17) can accelerate the release of many pro-inflammatory cytokines. The purpose of our study was to investigate the potential association between polymorphisms in the IL-17 gene and susceptibility to hepatitis B virus (HBV) infection in the Han Chinese population. METHODS: We recruited 596 HBV-infected patients and 612 ethnically matched controls, who were then genotyped for the IL-17A and IL-17F polymorphisms, rs2275913 and rs763780, respectively, by using TaqMan probe-based real-time polymerase chain reaction. The frequencies of the alleles and genotypes in patients and controls were compared by the χ2 test. RESULTS: Statistically significant differences in genotypic and allelic frequencies were revealed at both polymorphic sites between HBV-positive patients and controls (rs2275913: genotype χ2 = 37.74, p < 0.001 and allele χ2 = 22.17, p < 0.001, odds ratio [OR] = 0.654, 95% confidence interval [CI] = 0.548-0.781. rs763780: genotype χ2 = 19.80, p < 0.001 and allele χ2 = 18.78, p < 0.001, OR = 0.507, 95% CI = 0.371-0.692). CONCLUSIONS: These results indicate that the IL-17A rs2275913 and IL-17F rs763780 polymorphisms are associated with HBV infection in the Han Chinese population. We conclude that possession of the GG genotype and the G allele at rs2275913, and the TT genotype and the T allele at rs763780 might increase the risk of HBV infection. Larger-scale, multiracial studies are necessary to evaluate the role of IL-17 polymorphisms in relation to an enhanced risk of HBV infection.


Assuntos
Vírus da Hepatite B/genética , Interleucina-17/genética , Adulto , Alelos , Povo Asiático/genética , Estudos de Casos e Controles , China , Etnicidade/genética , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença/genética , Genótipo , Hepatite B/genética , Humanos , Interleucina-17/sangue , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único/genética , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Risco
18.
Oncotarget ; 8(25): 40583-40593, 2017 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-28489564

RESUMO

YY1 is a DNA-binding transcription factor and reported to be involved in cancer progression. Histone deacetylase inhibitor (HDACi) could inhibit proliferation and promote apoptosis of Hepatocellular carcinoma (HCC) cells. However, it is unclear about the roles of YY1 in the sensitivity of HCC cells to HDACi. In this study, firstly, we identified two drug-response profiles to HDACi in HCC cell lines, while our results showed that HDAC1 expression was positively correlated with YY1 in HCC cell lines and primary tumor tissues. Secondly, YY1 decreased the sensitivity of HCC cells to HDACi in vitro and in vivo. Furthermore, we found that YY1 promoted HDAC1 expression by binding to its promoter, while HDAC1 in turn up-regulated the expression of YY1. In conclusion, our results showed that YY1 could reduce the sensitivity of HCC cells to HDACi and might be a potential therapeutic target in HCC.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Histona Desacetilase 1/metabolismo , Inibidores de Histona Desacetilases/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Fator de Transcrição YY1/metabolismo , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Histona Desacetilase 1/genética , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Regiões Promotoras Genéticas/genética , Ligação Proteica , Interferência de RNA , Terapêutica com RNAi/métodos , Fator de Transcrição YY1/genética
19.
Ther Adv Med Oncol ; 9(11): 665-677, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29344104

RESUMO

BACKGROUND: Long noncoding ribonucleic acid (lncRNA) X-inactive-specific transcript (Xist) was reported to affect cell proliferation and metastasis in hepatocellular carcinoma (HCC). However, there are rare reports focusing on the diagnostic evaluation and regulatory mechanism of Xist expression from peripheral blood cells of patients with HCC. METHODS: In this study, a cohort of 206 female participants including healthy volunteers (HVs) and patients with chronic hepatitis B (CHB), cirrhosis and HCC was recruited. Coculture system was used to evaluate the effects of exosomal JPX transcript, XIST activator (Jpx) on Xist expression of blood cells. RESULTS: First, Xist expressions of both peripheral blood mononuclear cells and granulocytes were upregulated in female patients with HCC, and showed significantly increased discriminatory power when differentiating female patients with early-stage HCC from controls or differentiating female patients with HCC from patients with CHB and cirrhosis, compared with alpha fetoprotein (AFP). Then, another lncRNA Jpx that was an activator of Xist was upregulated in exosomes, mononuclear cells and granulocytes of female patients with HCC. Furthermore, our results showed that Jpx could be delivered from HCC cells to blood cells via exosomes and activate Xist expression of blood cells by repressing the transregulatory effects of CCCTC-binding factor (CTCF). CONCLUSIONS: This study revealed an exosome-mediated regulation of Xist expression in blood cells and suggested that Xist expressions of mononuclear cells and granulocytes would be promising biomarkers for diagnosis of female patients with HCC.

20.
Cell Death Dis ; 8(5): e2804, 2017 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-28518144

RESUMO

Hepatocellular carcinoma (HCC) is a malignant tumor and threatens human life worldwide, whereas the etiology and pathogenesis of HCC have not been fully determined. In the past few years, many microRNAs (miRNAs) have been proved to have important roles in tumorigenesis of HCC. In this study, we found that miR-23b was significantly upregulated in tumor tissues of HCC patients. Functional tests showed that miR-23b could promote HCC cell proliferation and metastasis in vitro and in vivo. Then, mechanistic investigations suggested that ST7L was a direct target of miR-23b and involved in the promotion effects of miR-23b on HCC tumorigenesis and metastasis. Furthermore, our study indicated that ST7L could interact with the carboxyl terminal region of AKT and suppress AKT/GSK3ß/ß-catenin pathway in HCC cells. In conclusion, our study revealed important roles of miR-23b and ST7L in progression of HCC.


Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , MicroRNAs/metabolismo , Oncogenes , Proteínas de Ligação a RNA/metabolismo , Transdução de Sinais , Idoso , Animais , Sequência de Bases , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Ativação Enzimática , Feminino , Regulação Neoplásica da Expressão Gênica , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Pessoa de Meia-Idade , Metástase Neoplásica , Ligação Proteica , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas de Ligação a RNA/genética , Ensaio Tumoral de Célula-Tronco , Proteínas Supressoras de Tumor , Regulação para Cima/genética , beta Catenina/metabolismo
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