Introduction and Objectives: The objective of this study was to explore the potential relationship between tumor abnormal protein (TAP) and the prognosis of hepatocellular carcinoma (HCC) after a radical hepatectomy. Patients or Materials and Methods: This retrospective study included 168 HCC patients (tumor recurrence in 78 patients) who underwent a curative resection from January 2018 to June 2020. The whole population was categorized into a TAP high (≥224.6 μm2) or a TAP low group (<224.6 μm2). Results: There was no correlation between maximum tumor size and TAP. In the whole population or subgroups stratified by maximum tumor size, the recurrence-free survival (RFS) rate of the TAP low group was significantly higher than TAP high group (P < 0.05 for all). The multivariate analysis revealed that TAP (hazard ratio [HR], 3.47; 95% confidence interval [CI], 2.18–5.51; P < 0.001), large tumor size (HR, 2.18; 95% CI, 1.36–3.49; P < 0.001), poor tumor differentiation (HR, 0.53; 95% CI, 0.33–0.84; P = 0.007), and presence of microvascular invasion (MVI) (HR, 2.03; 95% CI, 1.28–3.22; P = 0.003) were independently associated with RFS. The prognostic implication of the nomogram incorporating TAP, maximum tumor diameter, tumor differentiation, and MVI was stronger than the model without TAP. Conclusion: The present study suggests that higher preoperative TAP is correlated with undesirable prognosis in HCC patients who underwent a radical hepatectomy. Our study provides a robust nomogram for RFS of postoperative HCC patients.
Objective:The study aimed to study the efficacy and safety of combined dual therapy using anti-programmed death (PD)-1 and tyrosine kinase inhibitor (TKI) with combined triple therapy using anti-PD-1, TKI and locoregional intervention triple therapy in patients with postoperative refractory recurrent liver cancer.Methods:Patients with postoperative refractory recurrent liver cancer who had undergone either anti-PD-1 and TKI dual therapy or anti-PD-1, TKI and locoregional intervention triple therapy between July 2016 and March 2019 at the First Medical Center, Chinese PLA General Hospital were retrospectively studied. Tumor responses were assessed by the modified response evaluation criteria in solid tumors and overall survival and progression free survival were compared. Adverse events were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events.Results:Of 63 patients who were included in this study, there were 25 patients in the dual therapy group (16 males and 9 females, aged 54.3±8.8 years) and 38 patients in the triple therapy group (31 males and 7 females, aged 55.5±8.4 years). The 1-year survival rate of the triple therapy group was significantly higher than the dual therapy group (94.5%vs 54.9%) ( P<0.01). The disease control rate was 64.0% (16/25) in the dual therapy group and 84.2% (32/38) in the triple therapy group, and the difference was not significant ( P>0.05). The incidence of treatment-related adverse events in the triple therapy group and the dual therapy group were 78.9% (30/38) and 80% (20/25), respectively. There was no treatment-related death in the 2 groups. Conclusions:Anti-PD-1 and TKI dual therapy and anti-PD-1, TKI and locoregional intervention triple therapy were effective and tolerable treatments for postoperative refractory recurrent liver cancer. The latter treatment had a significantly better clinical benefit on survival outcomes.
Background: TAP (tumor abnormal protein) has been used as an important indicator in the early diagnosis of cancers, and some literatures showed that TAP can act as a prognostic factor in different kinds of cancer. The objective of this study was to explore the potential relationship between TAP and the prognosis of HCC after radical hepatectomy, and attempted to construct a robustly predictive nomogram on the strength of TAP and other prognostic variables of HCC patients.Methods: This retrospective study included 168 HCC patients (tumor recurrence occurred in 78 patients) who had undergone curative resection during January 2018 to June 2020 at the Department of Hepatopancreatobiliary Surgery of Liaoning Cancer Hospital & Institute. Serum TAP was detected by Abnormal Sugar Chain Structure of Glycoproteins, and according to the area of condensation particle, the whole population was categorized into the TAP high group (TAP≥225μm 2 ) and TAP low group (TAP<225μm 2 ).Results: There was no correlation between maximum tumor size and TAP. In the whole population or subgroups stratified by maximum tumor size, the recurrence-free survival (RFS) rate of the TAP low group was distinctly higher than TAP high group (P<0.05 for all). The multivariate analysis revealed that TAP (hazard ratio [HR], 3.47; 95% CI, 2.18-5.51; P<0.001), large tumor size (HR, 2.18; 95% CI, 1.36-3.49; P<0.001), poor tumor differentiation (HR, 0.53; 95% CI, 0.33-0.84; P=0.007) and presence of microvascular invasion (MVI) (HR, 2.03; 95% CI, 1.28-3.22; P=0.003) were independently associated with RFS. The prognostic implication of nomogram incorporating TAP, maximun tumor diameter, tumor differentiation and MVI was stronger than the model that integrated maximun tumor diameter, degree of tumor differentiation and MVI only.Conclusion: The present study suggested that higher preoperative TAP was correlated with undesirable prognosis in HCC patients who had undergone radical hepatectomy,and on the strength of prognostic variables identified by multivariate analysis, we constructed a robust nomogram for RFS of postoperative HCC patients.
Background and Aim This study aimed to assess the potential relationship between tumor mutation burden (TMB) and the recurrence risk of hepatocellular cancer (HCC) after curative resection and tried to develop a reliable TMB based nomogram. Methods This retrospective study was conducted in 128 patients (40 patients suffered from a recurrence of HCC) who had received radical hepatectomy by the same surgical team. A nomogram model was constructed using the R and EmpowerStats software. Results TMB was not associated with maximum tumor size and the presence of microvascular invasion (MVI). In the whole population or subgroups, the recurrence-free survival (RFS) rate was significantly lower in the TMB high group. In multivariate analysis, TMB (hazard ratio [HR], 10.12; 95% confidence interval [CI], 5.03-20.31; P < .001), large tumor diameter (HR, 2.91; 95% CI, 1.51-5.63; P = .001), presence of MVI (HR, 1.93; 95% CI, 1.03-3.65; P = .042) were independent predictors of RFS. The predictive power of the nomogram integrating TMB, tumor size and MVI was higher than model only incorporating tumor size and MVI. Conclusion This study demonstrated for the first time that higher TMB was associated with poor prognosis in patients with HCC who had received curative resection, and a TMB based nomogram model had a well predictive performance for RFS in this population.
Purpose. As we all know, curative resection remains the only effective treatment for hepatocellular cancer (HCC). However, systemic inflammatory response syndrome always correlates with surgery, which may impose an impact on the clinical outcome of HCC patients who had undergone curative treatment. The present study is aimed at exploring the correlation between perioperative inflammatory mediators and recurrence risk of HCC. Methods. This study retrospectively included 157 histologically confirmed single HCC patients (88 patients developed HCC again) who had received radical hepatectomy between January 2016 and May 2018 at the Department of Hepatobiliary Surgery, the People’s Liberation Army General Hospital (PLAGH), China. The cut-off values for predicting recurrence were determined by receiver operating characteristic (ROC) curve analysis with estimation of the Youden index. Recurrence-free survival (RFS) was assessed using the Kaplan-Meier method, and the difference was compared between groups by the log-rank test. Univariate/multivariate analysis was performed to identify independent risk factors of postoperative tumor recurrence. Results. The perioperative serum IL1, IL2, and IL10 levels showed no difference between groups, whereas the serum IL6, IL8, and TNF-α levels showed significant differences between groups. High preoperative serum IL6, IL8, and TNF-α levels were significantly associated with shorter RFS. Multivariate analysis revealed that preoperative serum IL6>8.45 pg/ml, preoperative serum IL8>68 pg/ml, preoperative serum TNF−α>14.9 pg/ml, microvascular invasion (MVI), and maximum tumor size>6 cm were independent predictors of RFS. Conclusions. The present study confirmed that high preoperative serum IL6, IL8, and TNF-α levels were distinctly correlated with the postoperative tumor recurrence risk of HCC patients.
Objective To analyze the impact of Pringle' s maneuver on postoperative serum inflam-matory mediator levels and prognosis in hepatitis B virus-related hepatocellular carcinoma ( HBV related HCC) patients. Methods A retrospective study was conducted on 157 HBV related HCC patients who underwent treatment at the Chinese PLA General Hospital from January 2016 to December 2017. There were 128 males and 29 females. The mean age was (54. 5 ± 12. 1) years. These patients were divided into 106 patients who underwent Pringle' s maneuver ( the Pringle' s maneuver group) . The remaining patients were in the Occlusion-free group. All patients were detected inflammatory mediator levels including the various interleukins ( IL) and were regularly followed up. The recurrence-free survival was evaluated by the Kaplan-Meier method, and compared with the log-rank test. The relationship between the Pringle' s maneuver and risks of postoperative tumor recurrence of these patient were estimated by the univariate and multivariate Cox regression models. Results On postoperation day 1 and day 3, the serum IL-1 and IL-6 levels of the Pring-le's maneuver group were significantly higher than the Occlusion-free group [5. 0(5. 0, 12. 0)ng/L vs. 5. 0 (5. 0, 5. 0)ng/L], [122. 0(74. 5, 173. 8)ng/L vs. 80. 0(40. 0, 120. 0)ng/L]; [5. 0(5. 0,10. 0)ng/Lvs. 5.0(5.0, 5.0)ng/L], [78.3(42.8, 138.5)ng/L vs. 48.1(30.1, 75.0)ng/L]. On day 5, the serum IL-1 and IL-8 levels were also significantly higher than the Occlusion-free group [5. 0(5. 0, 5. 3)ng/L vs. 5. 0(5. 0, 5. 0)ng/L], [100. 6 (44. 2, 186. 5)g/L vs. 68. 0(36. 3, 112. 0)ng/L] (all P<0. 05). There were 42 and 27 patients who did not develop recurrence in the Pringle ' s Maneuver group and the Occlusion-free group, respectively. The recurrence-free survival rates of the Pringle maneuver group and the Occlusion-free group were 40. 0% and 52. 9%, respectively. There were no significant differences between the two groups (P>0. 05). The multivariate Cox regression model suggested that there was no significant correlation between Pringle ' s maneuver and recurrence free survival of these patients with HBV related HCC. Conclusions Pringle's maneuver could significantly elevate the postoperative serum IL-1, IL-6, IL-8 levels, but it was not related with an increased risk of postoperative tumor recurrence.
Background: Matricellular proteins of the extracellular matrix (ECM) include tenascin-C (TNC) and cellular communication network factor 3 (CCN3). This study aimed to investigate the role of TNC and CCN3 as prognostic factors for post hepatectomy liver failure (PHLF) in a rat model of partial hepatectomy and 50 patients following partial hepatectomy. Material/Methods: Sprague-Dawley rats underwent 85% (n=53) or 90% hepatectomy (n=53) in the partial hepatectomy (PHx) model. TNC and CCN3 mRNA expression in residual liver tissue was evaluated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and enzyme-linked immunoassay (ELISA) determined the serum levels of TNC and CCN3. In 50 patients who underwent partial hepatectomy, TNC and CCN3 serum levels were measured on postoperative day 1 and day 3. Results: In the rat partial hepatectomy model, mRNA and serum levels of TNC and CCN3 were significantly increased within the first 24 h, and were higher in the 90% PHx group compared with the 85% PHx group. Fifty patients who underwent partial hepatectomy, included patients with PHLF (n=12) and patients without PHLF (n=38). Multivariate analysis confirmed that serum levels on postoperative day 3 TNChigh+CCN3(high) was a significant predictor of PHLF, which was associated with more than twice the risk of severe morbidity when compared with the low-risk patients (80% vs. 30%) and a significantly longer hospital stay (17 days vs. 8 days). Conclusions: Further studies are needed to evaluate the potential role of the matricellular proteins, TNC and CCN3 as early clinical predictors for PHLF.
患者女性,2018年2月8日于解放军总医院第一医学中心诊断为Ⅳ期肝内胆管细胞癌。2018年3月-10月连续接受15次程序性死亡受体1(PD-1)抗体治疗及右肝主病灶放射治疗,连续治疗7个月后,患者的右肝病灶大小及血供较前明显减少,肝门区及腹膜后转移淋巴结较前明显缩小。2018年10月-2019年4月,患者先后接受阿帕替尼(apatinib)及仑伐替尼(lenvatinib)维持治疗。2019年4月,根据修订的实体瘤疗效评价标准,该患者的疗效评价至少为部分缓解。临床上完成降期,从Ⅳ期降为Ⅱ期。2019年4月16日,该患者接受肝右后叶切除术及肝周、腹膜后原病灶清除术,手术顺利,于术后7日无并发症出院。