RESUMEN
BACKGROUND: Surgical therapy is the most optimal treatment for hepatocellular carcinoma (HCC) combined with bile duct tumor thrombus (BDTT) patients. However, whether to perform bile duct resection (BDR) is still controversial. The purpose of this multicenter research is to compare the effect of BDR on the prognosis of extrahepatic BDTT patients. METHODS: We collected the data of 111 HCC patients combined with extrahepatic BDTT who underwent radical hepatectomy from June 1, 2004 to December 31, 2021. Those patients had either received hepatectomy with extrahepatic bile duct resection (BDR group) or hepatectomy without bile duct resection (NBDR group). Inverse probability of treatment weighting (IPTW) was used to reduce the potential bias between two groups and balance the influence of confounding factors in baseline data. Then compare the prognosis between the two groups of patients. Cox regression model was used for univariate and multivariate analysis to further determine the independent risk factors that influence the prognosis of HCC-BDTT patients. RESULTS: There were 38 patients in the BDR group and 73 patients in the NBDR group. Before and after IPTW, there were no statistical significance in OS, RFS and intraoperative median blood loss between the two groups (all P > 0.05). Before IPTW, the median postoperative hospital stay in the NBDR group was shorter (P = 0.046) and the grade of postoperative complications was lower than BDR group (P = 0.014). After IPTW, there was no difference in postoperative hospital stay between the two groups (P > 0.05). The complication grade in the NBDR group was still lower than that in the BDR group (P = 0.046). The univariate analysis showed that TNM stage and portal vein tumor thrombus (PVTT) were significantly correlated with OS (both P < 0.05). Preoperative AFP level, TNM stage and prognostic nutritional index (PNI) were significantly correlated with postoperative RFS (all P < 0.05). Multivariate analysis showed that tumor TNM stage was an independent risk factor for the OS rate (P = 0.014). TNM stage, PNI and AFP were independent predictors of RFS after radical hepatectomy (all P < 0.05). CONCLUSIONS: For HCC-BDTT patients, hepatocellular carcinoma resection combined with choledochotomy to remove the tumor thrombus may benefit more.
Asunto(s)
Conductos Biliares Extrahepáticos , Carcinoma Hepatocelular , Hepatectomía , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/complicaciones , Masculino , Femenino , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/complicaciones , Persona de Mediana Edad , Pronóstico , Conductos Biliares Extrahepáticos/cirugía , Conductos Biliares Extrahepáticos/patología , Trombosis/cirugía , Trombosis/etiología , Trombosis/patología , Estudios Retrospectivos , Neoplasias de los Conductos Biliares/cirugía , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/complicaciones , Neoplasias de los Conductos Biliares/mortalidad , Anciano , AdultoRESUMEN
BACKGROUND: Hypertension is a risk factor for cholangiocarcinoma (CCA). The effect of anti-hypertensive drugs on the prognosis of CCA is not clear. METHODS: This is a retrospective study of 102 patients (56.9% males, median age 66 years) diagnosed with CCA and hypertension concurrently and received radical surgery (R0), with a median follow-up of 36.7 months. Kaplan-Meier analysis, Cox regressions, and propensity score (PS) matching were applied for statistical analysis. RESULTS: Results of multivariable cox analysis showed that renin-angiotensin system inhibitors (RASis) usage was a protective factor for progression-free survival (PFS) (hazard ratio [HR] = 0.55, 95% confidence interval [95% CI]: 0.32-0.96) and overall survival (OS) (HR = 0.40, 95% CI: 0.20-0.79), respectively. Calcium channel blockers, diuretics, and ß-blockers didn't show significant associations. The association of RASis usage and PFS and OS was derived by PS matching, with a cohort of 28 RASis users and 56 RASis non-users. The median PFS and OS of RASis users (PFS, 17.6 months (9.2-34.4); OS, 24.8 months (16.5-42.3)) were longer than RASis non-users (PFS, 10.5 months (4.1-24.1); OS, 14.6 months (10.6-28.4)). The 1 year, 2 years, and 3 years' survival rates of RASis users (89.1%, 77.0%, and 65.5%) were higher than RASis non-users (70.9%, 54.0%, and 40.0%). CONCLUSIONS: RASis usage improves the survival of patients with CCA and hypertension concurrently.
Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Hipertensión , Masculino , Humanos , Anciano , Femenino , Antihipertensivos , Estudios de Cohortes , Estudios Retrospectivos , Puntaje de Propensión , Sistema Renina-Angiotensina , Inhibidores Enzimáticos , Conductos Biliares IntrahepáticosRESUMEN
The Long-read RNA-Seq Genome Annotation Assessment Project (LRGASP) Consortium was formed to evaluate the effectiveness of long-read approaches for transcriptome analysis. The consortium generated over 427 million long-read sequences from cDNA and direct RNA datasets, encompassing human, mouse, and manatee species, using different protocols and sequencing platforms. These data were utilized by developers to address challenges in transcript isoform detection and quantification, as well as de novo transcript isoform identification. The study revealed that libraries with longer, more accurate sequences produce more accurate transcripts than those with increased read depth, whereas greater read depth improved quantification accuracy. In well-annotated genomes, tools based on reference sequences demonstrated the best performance. When aiming to detect rare and novel transcripts or when using reference-free approaches, incorporating additional orthogonal data and replicate samples are advised. This collaborative study offers a benchmark for current practices and provides direction for future method development in transcriptome analysis.
RESUMEN
Background: The application of robotic-assisted radical resection in perihilar cholangiocarcinoma (pCCA) remains poorly defined. This study aimed to evaluate the safety and efficacy of robotic-assisted radical resection for pCCA in our institute. Methods: Between July 2017 and July 2022, pCCA patients undergoing robotic-assisted and open radical resection at First Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) were included. The short-term outcomes were compared by using propensity-scored matching (PSM) analysis. Results: Eighty-six pCCA patients were enrolled. After PSM at a ratio of 1:2, 10 and 20 patients were assigned to the robotic-assisted and open groups, respectively. There were no significant disparities in the clinicopathological features between the two groups. The robotic-assisted group had significantly longer operation time (median: 548 vs 353 min, P = 0.004) and larger total number of lymph nodes examined (median: 11 vs 5, P = 0.010) than the open group. The robotic-assisted group tended to have a lower intraoperative blood loss (median: 125 vs 350 mL, P = 0.067), blood transfusion rates (30.0% vs 70.0%, P = 0.056), and post-operative overall morbidities (30.0% vs 70.0%, P = 0.056) than the open group, even though the differences were not statistically significant. There were no significant differences in the negative resection margin, post-operative major morbidities, or post-operative length-of-stay between the robotic-assisted and open groups (all P > 0.05). Conclusions: Robotic-assisted radical resection of pCCA may get a larger total number of lymph nodes examined than open surgery. Provided robotic-assisted surgery may be a feasible and safe technique for selected pCCA patients.
RESUMEN
Background and objective: The value of debulking surgery for unresectable well-differentiated metastatic pancreatic neuroendocrine tumor (m-PNET) remains poorly defined. This study aimed to evaluate the outcomes of m-PNET following debulking surgery in our institute. Methods: Patients with well-differentiated m-PNET in our hospital between February 2014 and March 2022 were collected. Clinicopathological and long-term outcomes of patients treated with radical resection, debulking surgery, and conservative therapy were compared retrospectively. Results: Fifty-three patients with well-differentiated m-PNET were reviewed, including 47 patients with unresectable m-PNET (debulking surgery, 25; conservative therapy, 22) and 6 patients with resectable m-PNET (radical resection). Patients undergoing debulking surgery had a post-operative Clavien-Dindo ≥ III complication rate of 16.0% without mortality. The 5-year overall survival (OS) rate of patients treated with debulking surgery was significantly higher than that of those treated with conservative therapy alone (87.5% vs 37.8%, log-rank P = 0.022). Besides, the 5-year OS rate of patients treated with debulking surgery was comparable to that of patients with resectable m-PNET undergoing radical resection (87.5% vs 100%, log-rank P = 0.724). Conclusions: Patients with unresectable well-differentiated m-PNET who underwent resection had better long-term outcomes than those who received conservative therapy alone. The 5-year OS of patients undergoing debulking surgery and radical resection were comparable. Debulking surgery could be considered for patients with unresectable well-differentiated m-PNET if no contraindication exists.
RESUMEN
Background: The feasibility of spleen-preserving distal pancreatectomy (SPDP) to treat well-differentiated non-functioning pancreatic neuroendocrine tumors (NF-pNETs) located at the body and/or tail of the pancreas remains controversial. Distal pancreatectomy with splenectomy (DPS) has been widely applied in the treatment of NF-pNETs; however, it may increase the post-operative morbidities. This study aimed to evaluate whether SPDP is inferior to DPS in post-operative outcomes and survivals when being used to treat patients with NF-pNETs in our institute. Methods: Clinicopathological features of patients with NF-pNETs who underwent curative SPDP or DPS at the First Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) between January 2010 and January 2022 were collected. Short-term outcomes and 5-year survivals were compared between patients undergoing SPDP and those undergoing DPS. Results: Sixty-three patients (SPDP, 27; DPS, 36) with well-differentiated NF-pNETs were enrolled. All patients had grade 1/2 tumors. After identifying patients with T1-T2 NF-pNETs (SPDP, 27; DPS, 15), there was no disparity between the SPDP and DPS groups except for tumor size (median, 1.4 vs 2.6 cm, P = 0.001). There were no differences in operation time (median, 250 vs 295 min, P = 0.478), intraoperative blood loss (median, 50 vs 100 mL, P = 0.145), post-operative major complications (3.7% vs 13.3%, P = 0.287), clinically relevant post-operative pancreatic fistula (22.2% vs 6.7%, P = 0.390), or post-operative hospital stays (median, 9 vs 9 days, P = 0.750) between the SPDP and DPS groups. Kaplan-Meier curve showed no significant differences in the 5-year overall survival rate (100% vs 100%, log-rank P > 0.999) or recurrence-free survival (100% vs 100%, log-rank P > 0.999) between patients with T1-T2 NF-pNETs undergoing SPDP and those undergoing DPS. Conclusions: In patients with T1-T2 well-differentiated NF-pNETs, SPDP could achieve comparable post-operative outcomes and prognosis compared with DPS.
RESUMEN
BACKGROUND: Routine lymphadenectomy in pancreatic neuroendocrine tumors (pNETs) is debated. There lacks accurate model to predict lymph node metastasis (LNM) preoperatively in pNETs. Therefore, this study aimed at developing a nomogram in predicting LNM in pNETs preoperatively. METHODS: Patients undergoing surgery from Surveillance, Epidemiology, and End Results (SEER) database (design cohort, n = 2742) and First Affiliated Hospital of Sun Yat-sen University (validation cohort, n = 136) were enrolled. Nomogram was developed based on risk factors determined by logistic regression analyses. The performance of nomogram was evaluated by area under receiver operating characteristics curve (AUC), calibration curve, and decision curve analysis. RESULTS: In design cohort, 915 of 2742 patients had LNM. Tumor in the pancreatic head, T stage, and tumor size were significantly associated with LNM (all p < 0.05). Prediction of nomogram was accurate with AUC of 0.776 in design cohort and 0.622 in validation cohort. The nomogram showed good agreement between prediction and observation in the design and validation cohort. Based on nomogram-predicted risk, patients with higher risk of LNM had worse overall survival over patients with lower risk of LNM (log-rank p < 0.001). CONCLUSIONS: The novel nomogram could accurately predict LNM in pNET preoperatively. For patients with high risk of LNM, lymphadenectomy was recommended.
Asunto(s)
Tumores Neuroendocrinos , Neoplasias Pancreáticas , Humanos , Metástasis Linfática , Tumores Neuroendocrinos/cirugía , Nomogramas , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/patología , Escisión del Ganglio LinfáticoRESUMEN
AIM: There lacks a predictive model for overall survival (OS) of node-negative perihilar cholangiocarcinoma (PHC). This study aimed at developing and validating a prognostic nomogram to predict OS of node-negative PHC after resection. METHODS: We established a nomogram via multivariate regression analysis by using the design cohort (n = 410, obtained from Surveillance, Epidemiology, and End Results database), and its external verification was done in the validation cohort (n = 100, the First Affiliated Hospital of Sun Yat-sen University). Predictive accuracy of the nomogram was assessed by concordance-index (C-index), calibration curves, and decision curve analysis (DCA). Performance of the nomogram was compared with the American Joint Committee on Cancer (AJCC) staging system. RESULTS: Multivariate regression analysis revealed that age, tumor grade, and the count of examined lymph nodes were independent prognostic factors for OS of node-negative PHC. The nomogram had a C-index of 0.603 and 0.626 in design cohort and validation cohort, respectively, which was better than that of AJCC staging system (both p < 0.05). The calibration curves showed good consistency between actual and nomogram-predicted OS probabilities. DCA showed that nomogram had better clinical usefulness. Furthermore, the nomogram-predicted scores could stratify the patients into three risk groups, and patients in higher risk group had worse prognosis than those in lower risk group (all p < 0.05). CONCLUSION: The proposed nomogram had a better prognostic accuracy than the AJCC staging system in predicting postoperative OS of node-negative PHC. It was helpful to guide the adjuvant therapeutic strategies for node-negative PHC.
Asunto(s)
Neoplasias de los Conductos Biliares , Tumor de Klatskin , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/cirugía , Humanos , Tumor de Klatskin/cirugía , Estadificación de Neoplasias , Nomogramas , PronósticoRESUMEN
BACKGROUND: The study aimed at establishing a nodal staging score (NSS) to quantify the likelihood that pathologic node-negative gallbladder cancer (GBC) patients are indeed free of lymph node (LN) metastasis. METHODS: Clinicopathological data of 1374 GBC patients with T1b-T2 stages were collected from the Surveillance, Epidemiology and End Result database (design cohort [DC], n = 1289) and the First Affiliated Hospital of Sun Yat-sen University (validation cohort [VC], n = 85). NSS was derived from the count of examined LNs (ELNs) and T stage by using a beta-binomial model, and represented the probability that a node-negative patient is correctly staged. The prognostic value of NSS in node-negative GBC was evaluated by survival analysis. RESULTS: The probability of missing a nodal disease in node-negative GBC patients with T1b-T2 stages (pT1bN0 and pT2N0) decreased as the number of ELNs increased. NSS increased as the number of ELNs increased. For pT1bN0 and pT2N0 patients, examination of 5 and 27 lymph nodes could ensure an NSS of 90.0%, respectively. Multivariate analysis revealed that NSS was an independent predictor for overall survival in pT1bN0 and pT2N0 GBC patients (DC, HR:0.53, 95%CI: 0.42-0.66, p < 0.001; VC, HR: 0.33, 95%CI: 0.14-0.76, p = 0.009). CONCLUSION: NSS could evaluate the adequacy of nodal staging and predict the prognosis in pT1bN0 and pT2N0 GBC patients, and hence was helpful to guide their treatment strategies.
Asunto(s)
Neoplasias de la Vesícula Biliar , Neoplasias de la Vesícula Biliar/cirugía , Humanos , Escisión del Ganglio Linfático , Ganglios Linfáticos , Metástasis Linfática , Modelos Estadísticos , Estadificación de Neoplasias , PronósticoRESUMEN
BACKGROUND: There lacks an ideal model for accurately predicting clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreatoduodenectomy (PD). This study aimed at developing a nomogram with high accuracy in predicting CR-POPF after PD. METHODS: A total of 1182 patients undergoing PD in the First Affiliated Hospital of Sun Yat-sen University (FAHSYSU, n = 762) and Fudan University Shanghai Cancer Center (FUSCC, n = 420) between January 2010 and May 2018 were enrolled. The patients from FAHSYSU were assigned as testing cohort, and those from FUSCC were used as external validation cohort. Univariate and multivariate logistic regression analyses were performed to determine the predictive factors for CR-POPF. Nomogram was developed on the basis of significant predictors. The performance of nomogram was evaluated by area under receiver operating characteristic (ROC) curve (AUC), calibration curve, and decision curve analysis. RESULTS: In testing cohort, 87 out of 762 patients developed CR-POPF. Three predictors were significantly associated with CR-POPF, including body mass index ≥24.0 kg/m2, pancreatic duct diameter <3 mm, and drainage fluid amylase on postoperative day 1 ≥2484 units/L (all p ≤ 0.001). Prediction of nomogram was accurate with AUC of 0.934 (95% confidence interval [CI]: 0.914-0.950) in testing cohort and 0.744 (95% CI: 0.699-0.785) in external validation cohort. The predictive accuracy of nomogram was better than that of previously proposed fistula risk scores both in testing and external validation cohort (all p < 0.05). CONCLUSIONS: The novel nomogram based on three easily available parameters could accurately predict CR-POPF after PD. It would have high clinical value due to its accuracy and convenience.
Asunto(s)
Fístula Pancreática , Pancreaticoduodenectomía , China , Humanos , Nomogramas , Páncreas/cirugía , Fístula Pancreática/diagnóstico , Fístula Pancreática/etiología , Pancreaticoduodenectomía/efectos adversos , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Factores de RiesgoRESUMEN
BACKGROUND: Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) is a rare subtype of primary liver cancers. Its prognostic factors remain unclear. The study aimed to evaluate its long-term outcome and prognostic factors by retrospectively reviewing the series of cHCC-CC after curative resection from our institute. METHODS: A total of 55 pathologically confirmed cHCC-CC patients undergoing curative resections between January 2003 and January 2018 at the First Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) were included. The clinicopathological and follow-up data were retrieved. Overall survival (OS) and recurrence-free survivals (RFS) were analysed by Kaplan-Meier curve. The independent prognostic factors were determined by using univariate and multivariate Cox analyses. RESULTS: There were 41 males and 14 females, with a median age of 51.0 (interquartile range, 44.0-60.0) years. The 1-, 3-, and 5-year OS and RFS rates in cHCC-CC were 80.0%, 25.5%, and 16.4%, respectively, and 52.7%, 21.8%, and 10.9%, respectively. The median OS and RFS were 24.9 and 14.5 months, respectively. Univariate and multivariate analyses revealed that elevated alpha-fetal protein (AFP) and/or CA19-9, vascular invasion, local extra-hepatic invasion, and lymph-node metastasis (LNM) were independent unfavorable prognostic factors for OS and RFS (all P < 0.005). Furthermore, elevated AFP and/or CA19-9 were independent unfavorable prognostic factors in various subgroups of cHCC-CC, including patients aged <60 years, positive hepatitis B surface antigen, cirrhosis, single tumor, tumor size ≥5 cm, no vascular invasion, no LNM, and no local extra-hepatic invasion (all P < 0.05). CONCLUSIONS: Elevated AFP and/or CA19-9, vascular invasion, local extra-hepatic invasion, and LNM were independent unfavorable prognostic factors for long-term survival of cHCC-CC undergoing curative resections. Patients with normal levels of AFP and CA19-9 had better prognosis.
RESUMEN
BACKGROUND: The accuracy of the current staging system for predicting the overall survival (OS) of patients with ampullary carcinoma (AC) is still unsatisfactory, especially in node-negative (N0) patients. We aimed at establishing a nomogram to accurately predict OS in N0 AC. METHODS: This study enrolled 697 N0 AC patients from the Surveillance, Epidemiology, and End Results database (design cohort [DC], n = 697) and the First Affiliated Hospital of Sun Yat-sen University (validation cohort [VC], n = 112), who underwent surgical resection. The nomogram was established by using prognostic factors determined by univariate and multivariate regression analyses. RESULTS: The nomogram for OS was developed by using four independent prognostic factors, including age, grade, T stage, and a number of examined lymph nodes. The C-index of a nomogram for OS in DC and VC was 0.665 and 0.731, respectively. Calibration curves showed good consistency of the nomogram. The nomogram had a better accuracy in predicting OS compared with conventional staging system (P < .05). On the basis of nomogram-predicted scores, the patients were stratified into groups with different risk. The OS of low-risk patients was significantly longer than high-risk ones (P ≤ .010). CONCLUSIONS: The nomogram could be used to predict the OS of N0 AC. It could help guide further treatment in clinical practice.
Asunto(s)
Ampolla Hepatopancreática/patología , Neoplasias del Conducto Colédoco/mortalidad , Neoplasias del Conducto Colédoco/cirugía , Nomogramas , Anciano , China/epidemiología , Neoplasias del Conducto Colédoco/patología , Femenino , Humanos , Estimación de Kaplan-Meier , Ganglios Linfáticos/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Reproducibilidad de los Resultados , Análisis de Supervivencia , Estados Unidos/epidemiologíaRESUMEN
Heat shock proteins are a highly conserved group of cellular proteins and are up-expressed in hepatocellular carcinoma (HCC). As a member of the heat shock protein-90 family, glycoprotein 96 (gp96) modulates immunity and tumorigenicity, is increased during the development of HCC from normal liver tissue, and is considered a pro-oncogenic chaperone. However, the prognostic value of gp96 has not been well clarified. The purpose of this study was to investigate the relationship between gp96 and survival of postoperative HCC patients. The expressions of gp96 protein and messenger RNA were measured by immunohistochemistry and real-time quantitative polymerase chain reaction, respectively. The relations between gp96 expression level and clinicopathological factors were analyzed. Kaplan-Meier survival and Cox regression analyses were used to identify factors associated with prognosis. All normal liver tissue exhibited low gp96 expression, whereas high gp96 expression was present in 54% of HCC tissues. The expression of gp96 protein was inversely correlated with TNM stage (Pâ¯=â¯.037) and tumor recurrence (Pâ¯=â¯.004). Low gp96 expression was an independent risk factor for poor postoperative disease-free survival (hazard ratio,â¯0.385; 95% confidence interval, 0.226-0.655; Pâ¯<â¯.001), and overall survival (hazard ratio, 0.345; 95% confidence interval, 0.187-0.637; Pâ¯=â¯.001). Stratification analysis indicated that high gp96 had better predictive value for tumor recurrence in HCC patients with normal serum α-fetoprotein levels or with TNM stage I and tumor differentiation I-II HCC. In conclusion, gp96 is a potential and reliable prognostic biomarker for tumor recurrence and overall survival in HCC patients after curative resection.
Asunto(s)
Carcinoma Hepatocelular/metabolismo , Proteínas HSP90 de Choque Térmico/metabolismo , Hepatectomía , Neoplasias Hepáticas/metabolismo , Hígado/metabolismo , Anciano , Biomarcadores de Tumor , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/cirugía , Femenino , Humanos , Inmunohistoquímica , Hígado/patología , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Tasa de SupervivenciaRESUMEN
BACKGROUND: Embryonic Liver Fodrin (ELF) is an adaptor protein of transforming growth factor (TGF-ß) signaling cascade. Disruption of ELF results in mislocalization of Smad3 and Smad4, leading to compromised TGF-ß signaling. c-Myc is an important oncogenic transcription factor, and the disruption of TGF-ß signaling promotes c-Myc-induced hepatocellular carcinoma (HCC) carcinogenesis. However, the prognostic significance of c-Myc in HCC is less understood METHODS: The expression of c-Myc protein and mRNA were measured by immunohistochemistry (IHC) and qRT- PCR, respectively. IHC was performed to detect TGF-ß1 and ELF expression in HCC tissues. Their relationship with clinicopathological factors and overall survival (OS) and disease free survival (DFS) were examined. RESULTS: The expression of c-Myc protein and mRNA in HCC tissues were significantly higher in HCC area than those in normal liver tissues. However, the expression were low compared with those adjacent to HCC area. c-Myc protein was independently predictive of DFS and OS, and it was negatively correlated with tumor size (P = 0.031), tumor number (P = 0.038), and recurrence (P = 0.001). Low c-Myc expression was associated with short-term recurrence and poor prognosis. The predictive value of c-Myc combined with TGF-ß1 or/and ELF was higher than that of any other single marker. Low c-Myc, high TGF-ß1 or/and low ELF expression was associated with the worst DFS and OS. CONCLUSIONS: Low expression of c-Myc protein predicts poor outcomes in patients with HCC with hepatectomy. The combination of the expression of c-Myc, TGF-ß1, and ELF can be used to accurately predict outcomes of patients with HCC.
Asunto(s)
Biomarcadores de Tumor , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidad , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidad , Proteínas Proto-Oncogénicas c-myc/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/cirugía , Femenino , Expresión Génica , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/cirugía , Masculino , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Unión Proteica , Proteínas Proto-Oncogénicas c-myc/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Recurrencia , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
Eye absent homolog 4 (EYA4) was initially found as key gene in controlling eye development in Drosophila. We recently found that EYA4 was an independent prognostic factor in hepatocellular carcinoma. Its biological functions in malignancies remained unknown. The present study aimed at investigating its biological functions, molecular mechanisms and prognostic values in pancreatic ductal adenocarcinoma (PDAC). Overexpression of EYA4 in PDAC cells inhibited proliferation and invasion in vitro and tumor growth in vivo. Depletion of EYA4 in PDAC cells enhanced proliferation and invasion in vitro and tumor growth in vivo. Mechanistically, armed with the serine/threonine-specific protein phosphatase activity, EYA4 dephosphorylated ß-catenin at Ser675, blocked ß-catenin nuclear translocation and inhibited ID2 transactivation. Consistently, EYA4 expression inversely correlated with the levels of p-Ser675-ß-catenin and ID2 in tissues. EYA4 expression in PDAC tissues was significantly reduced as compared with adjacent non-tumoral tissues. EYA4 expression was an independent prognostic factor in PDAC, with a lower EYA4 level in association with shorter long-term survival and disease-free time. We showed that EYA4 functioned as tumor suppressor gene in PDAC via repressing ß-catenin/ID2 activation, and was an independent prognostic factor in PDAC.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Proteína 2 Inhibidora de la Diferenciación/metabolismo , Neoplasias Pancreáticas/metabolismo , Transactivadores/metabolismo , Proteínas Supresoras de Tumor/metabolismo , beta Catenina/metabolismo , Transporte Activo de Núcleo Celular , Adulto , Anciano , Anciano de 80 o más Años , Animales , Biomarcadores de Tumor/genética , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/terapia , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Supervivencia sin Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Proteína 2 Inhibidora de la Diferenciación/genética , Estimación de Kaplan-Meier , Masculino , Ratones Desnudos , Persona de Mediana Edad , Invasividad Neoplásica , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/terapia , Fosforilación , Interferencia de ARN , Transducción de Señal , Factores de Tiempo , Transactivadores/genética , Transfección , Carga Tumoral , Proteínas Supresoras de Tumor/genéticaRESUMEN
BACKGROUND: The molecular prognostic markers and carcinogenesis of intrahepatic cholangiocarcinoma (ICC) have not been well documented. The purpose of this study was to investigate the prognostic value of the eyes absent homolog 4 (EYA4) gene in ICC and its biological effects on ICC growth in vitro and in vivo. METHODS: One hundred twelve patients with ICC who underwent hepatectomy were enrolled in the study. EYA4 mRNA and EYA4 protein levels in ICC and adjacent non-tumoral tissues were evaluated using real-time quantitative polymerase chain reaction and immunohistochemical staining, respectively. EYA4 protein levels in ICC cells were determined using western blot analysis. The associations between EYA4 expression and clinicopathologic features of ICC were analyzed. To identify independent prognostic factors, univariate and multivariate analyses were performed. The biological effects of EYA4 on ICC cells were evaluated by establishing stable EYA4-overexpressing transfectants in vitro, and EYA4's effects on tumor growth were evaluated by intra-tumoral injection of EYA4-expressing plasmids in a NOD/SCID murine model of xenograft tumors. RESULTS: ICC tissues had significantly lower EYA4 mRNA and protein levels compared with adjacent non-tumoral tissues (both P < 0.001). Univariate and multivariate analyses showed that EYA4 protein level, tumor number, adjacent organ invasion, lymph node metastasis, and tumor differentiation were independent prognostic factors for disease-free survival and overall survival (all P < 0.05). In vitro, EYA4 overexpression inhibited tumor cell growth, foci formation, and cell invasiveness. In vivo, intra-tumoral injection of EYA4-expressing plasmids significantly inhibited ICC growth in the murine xenograft model compared with the control group (P < 0.05). CONCLUSION: EYA4 gene functioned as a molecular prognostic marker in ICC, and its overexpression inhibited tumor growth in vitro and in vivo.
Asunto(s)
Neoplasias de los Conductos Biliares/patología , Conductos Biliares Intrahepáticos/patología , Biomarcadores de Tumor/metabolismo , Proliferación Celular , Colangiocarcinoma/patología , Transactivadores/metabolismo , Adulto , Anciano , Animales , Apoptosis , Neoplasias de los Conductos Biliares/genética , Neoplasias de los Conductos Biliares/metabolismo , Conductos Biliares Intrahepáticos/metabolismo , Biomarcadores de Tumor/genética , Western Blotting , Movimiento Celular , Colangiocarcinoma/genética , Colangiocarcinoma/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Técnicas para Inmunoenzimas , Masculino , Ratones , Ratones Endogámicos NOD , Ratones SCID , Persona de Mediana Edad , Invasividad Neoplásica , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transactivadores/genética , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: The occurrence and development of hepatocellular carcinoma (HCC) depends largely on such non-tumor factors as inflammatory condition, immune state, viral infection and liver fibrosis. Various inflammation-based prognostic scores have been associated with survival in patients with HCC, such as the neutrophil/lymphocyte ratio (NLR), the platelet/lymphocyte ratio (PLR) and the prognostic nutritional index (PNI). The aspartate aminotransferase/platelet count ratio index (APRI) is thought to be a biomarker of liver fibrosis and cirrhosis. This study aims to evaluate the ability of these indices to predict survival in HCC patients after curative hepatectomy, and probe the increased prognostic accuracy of APRI combined with established inflammation-based prognostic scores. METHODS: Data were collected retrospectively from 321 patients who underwent curative resection for HCC. Preoperative NLR, PLR, PNI, APRI and clinico-pathological variables were analyzed. Univariate and multivariate analyses were performed to identify the predictive value of the above factors for disease-free survival (DFS) and overall survival (OS). RESULTS: Univariate analysis showed that NLR, PLR, PNI and APRI were significantly associated with DFS and OS in HCC patients with curative resection. Multivariate analysis showed that NLR and APRI were superior to PLR and PNI, and both were independently correlated with DFS and OS. Preoperative NLR >2 or APRI >1.68 predicted poor prognosis of patients with HCC after hepatectomy. Furthermore, the predictive range of NLR combined with APRI was more sensitive than that of either measure alone. CONCLUSIONS: Preoperative NLR and APRI are independent predictors of DFS and OS in patients with HCC after surgical resection. Higher levels of NLR or APRI predict poorer outcomes in HCC patients. Intriguingly, combining NLR and APRI increases the prognostic accuracy of testing.
Asunto(s)
Aspartato Aminotransferasas/metabolismo , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Linfocitos/inmunología , Neutrófilos/inmunología , Adulto , Anciano , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidad , Femenino , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Evaluación Nutricional , Recuento de Plaquetas , Pronóstico , Análisis de Supervivencia , Adulto JovenRESUMEN
BACKGROUND: Hilar cholangiocarcinoma (HCCA) is a devastating malignancy arising from the bifurcation of the hepatic duct, whether combined vascular resection benefits HCCA patients is controversial. This study was undertaken to assess the effect of combined vascular resection in HCCA patients and to analyze the prognostic factors. METHODS: Clinical data of 154 HCCA patients who had been treated from January 2005 to December 2012 were retrospectively analyzed. The patients were divided into three groups based on vascular resection: those without vascular resection; those with portal vein resection alone and those with hepatic artery resection. The survival and complication rates were compared among the three groups. Multivariate analysis was made to determine prognostic factors. RESULTS: No significant differences were found in survival and complication rates among the three groups (P>0.05). Multivariate analysis showed that 3 factors were related to survival: lymph node metastasis, tumor size (>2.5 cm), and positive resection margin. CONCLUSIONS: Vascular resection improved the survival rate of patients with HCCA involving the hepatic artery or portal vein. Lymph node metastasis, tumor size (>2.5 cm) and positive resection margin were poor prognostic factors in patients with HCCA.
Asunto(s)
Neoplasias de los Conductos Biliares/cirugía , Arteria Hepática/cirugía , Tumor de Klatskin/cirugía , Vena Porta/cirugía , Procedimientos Quirúrgicos Vasculares , Adulto , Anciano , Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/patología , Distribución de Chi-Cuadrado , China , Femenino , Arteria Hepática/patología , Humanos , Estimación de Kaplan-Meier , Tumor de Klatskin/mortalidad , Tumor de Klatskin/secundario , Metástasis Linfática , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Análisis Multivariante , Invasividad Neoplásica , Neoplasia Residual , Vena Porta/patología , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Carga Tumoral , Procedimientos Quirúrgicos Vasculares/efectos adversos , Procedimientos Quirúrgicos Vasculares/mortalidadRESUMEN
Hepatectomy is a safe and effective treatment for intrahepatic stones (IHSs). However, the resection plane for right-sided stones distributed within 2 segments is obstacle because of atrophy-hypertrophy complex formation of the liver and difficult dissection of segmental pedicle within the Glissonean plate by conventional approach. Thus, we devised segmental bile duct-targeted liver resection (SBDLR) for IHS, which aimed at completely resection of diseased bile ducts. This study aimed to evaluate the outcomes of SBDLR for right-sided IHSs. From January 2009 to December 2013, 107 patients with IHS treated by SBDLR in our center were reviewed in a prospective database. Patients' intermediate and long-term outcomes after SBDLR were analyzed. A total of 40 (37.4%) patients with localized right-sided stone and 67 (62.7%) patients with bilateral stones underwent SBDLR alone and SBDLR combined with left-sided hepatectomy, respectively. There was no hospital mortality of this cohort of patients. The postoperative morbidity was 35.5%. The mean intraoperative blood loss was 414 âmL (range: 100-2500). Twenty-one (19.6%) patients needed red blood cells transfusion. The intermediate stone clearance rate was 94.4%; the final clearance rate reached 100% after subsequent postoperative cholangioscopic lithotomy. Only 2.8% patients developed stone recurrence in a median follow-up period of 38.3 months. SBDLR is a safe and effective treatment for right-sided IHS distributed within 2 segments. It is especially suitable for a subgroup of patients with bilateral stones whose right-sided stones are within 2 segments and bilateral liver resection is needed.
Asunto(s)
Conductos Biliares Intrahepáticos/cirugía , Cálculos/cirugía , Hepatectomía/métodos , Hepatopatías/cirugía , Adulto , Anciano , China/epidemiología , Femenino , Hepatectomía/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Tumor suppression of Transforming Growth Factor (TGF-ß) signaling pathway requires an adaptor protein, Embryonic Liver Fodrin (ELF). Disruption of ELF expression resulted in miscolocalization of Smad3 and Smad4, then disruption of TGF-ß signaling. However, the prognostic significance of ELF for hepatocellular carcinoma (HCC) hasn't been clarified. This study aimed to investigate whether measuring both TGF-ß1 and ELF provides a more powerful predictor for HCC prognosis than either marker alone. METHODS: TGF-ß1 and ELF protein were detected by immunohistochemistry. The relationship between TGF-ß1/ELF expression and patients' clinicopathologic factors was analyzed. The association between TGF-ß1/ELF expression and disease-free survival and overall survival was analyzed by Kaplan-Meier curves, the log-rank test, and Multivariate Cox regression analyses. RESULTS: The expression of TGF-ß1 in HCC tissues was significantly higher than that in normal liver tissues. Conversely, the expression of ELF in HCC tissues declined markedly. ELF protein was correlated with HBsAg, tumor size, tumor number, TNM and recurrence. Data also indicated a significant negative correlation between ELF and TGF-ß1. Patients with high TGF-ß1 expression or/and low ELF expression appeared to have a poor postoperative disease-free survival and overall survival compared with those with low TGF-ß1 expression or/and high ELF expression. Furthermore, the predictive range of ELF combined with TGF-ß1 was more sensitive than that of either one alone. CONCLUSIONS: TGF-ß1 and ELF protein are potential and reliable biomarkers for predicting prognosis in HCC patients after hepatic resection. Our current study has demonstrated that the prognostic accuracy of testing can be enhanced by their combination.