Prognosis of patients with intrahepatic recurrence after hepatic resection for hepatocellular carcinoma: A retrospective study

Aims

Hepatic resection is the most effective therapy for hepatocellular carcinoma (HCC); however, intrahepatic recurrence is common. Predictors of survival after intrahepatic recurrence have not been fully investigated. To clarify the prognosis and choice of treatment of intrahepatic recurrence after hepatic resection, we conducted a comparative retrospective analysis of 147 patients with HCC who underwent hepatic resection.

Methods

We retrospectively examined the relations between clinicopathologic factors, including the number of recurrent intrahepatic tumors and long-term prognosis after recurrence in 147 HCC patients who underwent resection. We also examined long-term survival after recurrence based on treatment types and recurrence pattern.

Results

Patients with multiple tumors (n = 83) showed less tumor differentiation, more frequent portal invasion, a higher alpha-fetoprotein level, and larger tumors than did patients with solitary tumor (n = 64). In the solitary tumor group, local ablation therapy and repeat hepatic resection were performed in 25 and 10, respectively. In the multiple tumor group, 59 were treated by transarterial chemoembolization. Multivariate analysis showed intraoperative blood transfusion and multiple tumors to be independent risk factors for poor cancer-related survival after recurrence. By subset analysis based on treatment types and recurrence pattern, survival after recurrence was significantly better in patients treated by local ablation therapy than those treated by other therapies in both solitary and multiple tumor groups.

Conclusions

For patients with solitary recurrence, a good prognosis is predicted. Local ablation therapy is a best candidate for treatment of solitary and multiple intrahepatic recurrences after hepatic resection.     

肝细胞癌切除术后肝内复发患者的预后影响因素分析

目的 探讨肝细胞癌(HCC)切除术后肝内复发的预后影响因素以及复发后治疗方式的选择.方法 收集184例HCC切除术后肝内复发患者的临床病理资料,回顾性分析21项临床病理学因素以及复发后治疗方式对HCC患者肝内复发后生存期的影响.结果 单因素分析结果 表明,术前血清甲胎蛋白(AFP)水平较高(>100 ng/ml)、有微血管浸润、首次诊断复发时肿瘤的Child-Pugh分级为B或C级、有多个肝内复发肿瘤以及早期肝内复发(≤12个月)的患者预后不良.Cox多因素分析结果 表明,首次诊断复发时肿瘤的Child-Pugh分级、复发肿瘤的数目和复发时间是影响HCC患者复发后生存期的独立危险因素.69例单个复发肿瘤患者中,经再次肝切除手术和局部消融治疗患者的复发后中位生存期分别为34和23个月,而经肝动脉插管化疗栓塞治疗和未进行治疗患者的复发后中位生存期分别为15和9个月,4种治疗方式患者的生存期差异有统计学意义(P<0.05).结论 首次诊断复发时肿瘤的Child-Pugh分级为A级、单个复发肿瘤、复发时间较晚(>12个月)、经过再次肝癌切除手术或局部消融治疗的HCC肝内复发患者的预后较好.     

Radiation therapy for intrahepatic recurrence after hepatectomy for hepatocellular carcinoma

Background. The intrahepatic recurrence rate after curative hepatectomy for hepatocellular carcinoma (HCC) is high, and management of recurrence is thus important for long-term survival. The use of radiation therapy has been relatively uncommon in the treatment of recurrent HCC.Methods. Eight patients underwent radiation therapy for recurrent HCC 12–98 months after hepatectomy. Five of them were treated with protons (250MeV; 68.8–84.5Gy), and three were treated with X-rays (6MV; 60 or 70Gy). One patient received radiation therapy twice for another lesion with a 79-month interval. The target tumors were 1.2–4.5cm. All patients also underwent transcatheter arterial embolization or other regional therapy.Results. Although transient ascites was found in three patients after radiation therapy, no patient died as a result of the irradiation. Seven patients died 9 months to 4 years (median 1 year 6 months) after radiation therapy. Re-recurrence was observed in the irradiated liver in two patients (local control 78%). Four patients died of lung metastasis after radiation therapy. The median survival time was 3 years 3 months (range 1 year 1 month to 8 years 6 months) after recurrence.Conclusion. Multimodality therapy is necessary for the management of recurrence. Radiation therapy could be beneficial when other therapies present some difficulty regarding application or are performed incompletely. It must be emphasized that radiation therapy should be considered in addition to other regional therapies for the treatment of recurrent or re-recurrent HCC, and that radiation therapy can be repeated in selected patients.     

Factors affecting local control and survival after treatment of carcinoma of the rectum by endocavitary radiation: a retrospective study of 97 cases

PURPOSE: Endocavitary radiation therapy constitutes an alternative to surgical therapy for some early rectal carcinomas. We studied the prognostic factors for locoregional or metastatic relapse after endocavitary radiation, and their impact for therapeutic strategy. METHODS AND MATERIALS: Our study reports the outcome of 97 patients with adenocarcinomas of the rectum treated from 1978 to 1998 by endocavitary irradiation (100 Gy), exclusive or combined with an interstitial brachytherapy boost of 20 Gy. The indications consisted mostly of polypoid, mobile tumors, less than 4 cm in diameter, and well differentiated. But the indications were extended to elderly patients, who presented with a high surgical risk or who refused mutilating surgery. RESULTS: The mean follow-up was 82 months. One patient presented with an isolated distant metastatic relapse, and 27 patients presented with locoregional recurrence, surgically salvaged in 16 cases. Disease-free survival was 71% at 5 years and 68% at 10 years. Multifactorial analysis suggests that clinical stage T1A, well-differentiated tumors, and early and complete response are favorable prognostic factors for disease-free survival. Response to therapy is the most powerful prognostic factor for relapse. CONCLUSION: This retrospective study confirms the efficacy of endocavitary radiotherapy combined with brachytherapy as a safe conservative treatment in well-selected patients.     

A novel ferroptosis-related gene signature for clinically predicting recurrence after hepatectomy of hepatocellular carcinoma patients

High recurrence rate in HCC is the primary cause of the poor prognosis after hepatectomy. Therefore, in this study, we aimed to construct a gene signature for predicting the recurrence rate in HCC. The mRNA expression profiles and clinical information of HCC patients from GEO and TCGA databases were used, and ferroptosis-related gene list was obtained from the FerrDb database. We identified 39 ferroptosis-related genes (FDEGs) that were differentially expressed between HCC samples and normal tissues from the {"type":"entrez-geo","attrs":{"text":"GSE14520","term_id":"14520"}}GSE14520 dataset. The univariate and multivariate Cox regression analyses were employed to construct a prognostic signature. Seven FDEGs (MAPK9, SLC1A4, PCK2, ACSL3, STMN1, CDO1, and CXCL2) were included to construct a risk model, which was validated in the TCGA dataset. Patients in high-risk groups exhibited a significantly poor prognosis compared with patients in low-risk groups in both the training set ({"type":"entrez-geo","attrs":{"text":"GSE14520","term_id":"14520"}}GSE14520 cohort) and the validation set (TCGA cohort). Multivariate cox regression analyses demonstrated that the 7-gene signature was an independent risk factor for RFS in HCC patients. KEGG analysis showed that FDEGs were mainly enriched in Ferroptosis, Hepatocellular carcinoma pathway, and MAPK signaling pathway. GSEA analysis suggested that the high-risk group was correlated with multiple oncogenic signatures and invasive-related pathways. These results indicated that this risk model can accurately predict recurrence after hepatectomy and offer novel research directions for personalized treatment in HCC patients.     

Long-term prognosis in hepatocellular carcinoma patients after hepatectomy

Background: The hepatocellular carcinoma is very common in China. Our aim in this report was to investigate clinical and pathological factors based on the current decade data that could influence prognosis of HCC patients after hepatectomy. Methods: Between 2002 and 2009, all patients undergoing hepatectomy for HCC were followed up and reviewed retrospectively. Prognostic factors were studied by univariate and multivariate analysis, with Kaplan-Meier and Cox multivariate survival analyses. Results: Complete clinicopathologic and follow-up data were available for 114 patients. The estimated cumulative survival rates at 1, 3, and 5 yr were 84.6%, 60.2% and 51.8%, respectively. On univariate analysis, key prognostic factors were AFP level, GGT level, tumor size, number of tumors, portal vein invasion, liver cirrhosis status and TNM stage. In the multivariate analysis, tumor size, GGT level, liver cirrhosis status and portal vein invasion were significantly associated with patients’ prognosis. Conclusion: Through follow-up of a relatively large cohort of Chinese patients, tumor size, GGT level, liver cirrhosis status, portal vein invasion were revealed as important factors for long-term survival after hepatectomy. Early diagnosis for tumor and the improvement of liver function before surgery are important ways to improve the prognosis.     

Predictive factors for intrahepatic recurrence of hepatocellular carcinoma after partial hepatectomy.

To establish useful predictors of the intrahepatic recurrence of hepatocellular carcinoma (HCC) after partial hepatectomy, retrospective analyses of clinical and pathologic factors were done in 112 of 206 patients treated by partial hepatectomy. The absence or presence of intrahepatic recurrence was confirmed by a follow-up study. Cancer-free survival rates after 1, 2, 3, and 5 years were 54.8%, 36.7%, 32.5%, and 25.6%, respectively. The significant factors affecting recurrence were tumor size, number of tumors, cancer cell infiltration of the fibrous capsule of the tumor, portal involvement, and stage of the tumor, but the grade of anaplasia according to Edmondson-Steiner's classification and the severity of associated liver cirrhosis did not show a correlation with the incidence of recurrence. According to Akaike's Information Criteria (AIC), tumor number is useful for predicting early prognosis, and capsular infiltration is a good indicator of long-term survival. However, portal involvement gives much prognostic information throughout the entire postoperative period.     

老年肝癌根治性切除术后肝癌复发的高危因素分析

目的:探讨老年肝癌根治性切除术后肝癌复发的高危因素。方法:选择我院于2015年1月至2017年1月期间收治的行肝癌根治性切除术的老年肝癌患者300例作为研究对象。所有研究对象均完成术后12个月随访,观察患者复发情况,其中肝癌术后复发时间以影像学检查有明确的肿块存在为确诊依据。运用多因素分析术后复发危险因素。结果:老年肝癌根治性切除术患者300例,术后随访12个月肝癌复发58例,复发率为19.33%。经单因素分析显示,两组性别、合并基础疾病、术前ALT、术前AST和手术时间比较无统计学差异（P>0.05）;两组肿瘤直径、血管侵犯、肿瘤包膜和术中失血比较具有统计学差异（P<0.05）。将上述单因素分析具有统计学意义的纳入多因素分析显示,肿瘤直径、血管侵犯、肿瘤包膜和术中失血为影响老年肝癌根治性切除术后复发危险因素。结论:老年肝癌根治性切除术后肝癌复发影响因素较多,而肿瘤直径、血管侵犯、肿瘤包膜和术中失血为其危险因素。     

Elevation of alpha-fetoprotein level without evidence of recurrence after hepatectomy for hepatocellular carcinoma

Seven Japanese patients showed a gradual rise in serum alpha-fetoprotein (AFP) levels for periods of 4 to 14 weeks after partial hepatectomy for hepatocellular carcinoma. These levels then gradually decreased, but not always to a normal level, and various procedures after surgery failed to detect tumor recurrence. All the cases were complicated with liver cirrhosis. It is suggested that the postoperative elevation in the AFP level may have been caused by hepatic regeneration as a result of the intervention chemotherapy and/or surgery, but it does not exclude the possibility of a tumor recurrence.     

Villin 1 is a predictive factor for the recurrence of high serum alpha-fetoprotein-associated hepatocellular carcinoma after hepatectomy

The prognostic assessment of patients with hepatocellular carcinoma (HCC) after resection is an important clinical issue. The present study investigated those genes associated with high serum alpha-fetoprotein (AFP), and their clinical significance, including prognosis and recurrence after hepatectomy. Based on gene expression analysis of 110 training HCC cases, 20 genes whose mRNA expression levels were significantly upregulated and 50 genes that were downregulated correlated with high serum AFP-associated HCC patients. Gene expression profiles of Villin1 (Vil1) were obtained in high serum AFP-associated HCC tumor tissues. In the present analysis, only VIL1 was significantly correlated with the recurrence of HCC. The results were validated independently using Taqman gene expression assays and immunostaining analysis. Results showed that the upregulation of VIL1 mRNA was also correlated with high serum PIVKAII, vascular invasion (P < 0.05), poor differentiation, an advanced cancer stage (P < 0.01) and recurrence-free survival (P = 0.017). The upregulation of VIL1 mRNA was observed more frequently in the early recurrence patients as compared to the late recurrence patients. Cox regression univariate and multivariate analyses indicated that high serum AFP levels (overall survival, HR 1.675, P = 0.002; FRS, HR 1.359, P = 0.039) and Vil1 protein expression (overall survival, HR 0.253, P = 0.009; FRS, HR 0.401, P = 0.041) were independent, unfavorable prognostic factors for overall and recurrence-free survival of patients. We demonstrated that the VIL1 gene is a potential candidate molecular marker for high serum AFP-associated HCC and a predictive candidate for the postoperative recurrence and poorer prognosis of HCC.     

肝细胞癌患者根治性切除术后的生存影响因素分析

目的 探讨肝细胞癌(hepatocellular carcinoma,HCC)根治性切除术后总生存期(overall survival,OS)的影响因素.方法 回顾性收集于山东第一医科大学第二附属医院及山东大学第二医院行根治性切除术的1744例HCC患者的临床资料,采用Cox回归分析影响OS的因素,利用R语言survm...     

High cathepsin A protein expression predicts poor prognosis and tumor recurrence of hepatocellular carcinoma patients after curative hepatectomy

Cathepsin A (CTSA) is overexpressed in various types of cancer and is linked to poor clinical outcomes. However, the clinical application of CTSA in HCC has not been explored. In this study, we examined the protein level of CTSA in the archived HCC samples from 161 patients by Immunohistochemistry (IHC). The high protein level of CTSA was significantly correlated to the poor clinicopathological parameters, such as TNM stage, serum AFP level, tumor differentiation, liver cirrhosis, Child-Pugh class, vascular invasion, tumor encapsulation, tumor recurrence, and patient death. In addition, multivariate Cox regression analysis indicated that high CTSA expression was an independent prognostic factor of OS and RFS. We also analyzed the area under the curve (AUC) of the time-dependent receiver operating characteristic (ROC) of CTSA expression for 1-, 3-, and 5-year OS and RFS prediction. Furthermore, we constructed a nomogram that exhibited excellent prediction performance, which was validated by the calibration curve and decision curve analysis. Together, our study demonstrated that CTSA protein level is strongly associated with poor clinical outcome of HCC patients and may be used as a potential diagnostic and prognostic biomarker in HCC.     

A surgical case of solitary lymph node metastatic recurrence of hepatocellular carcinoma after hepatectomy

The patient was a male in the sixties who received interferon therapy against hepatitis C. At first, the patient was pointed to having an increased alpha fetoprotein (AFP) level of 1104 ng/ml. Partial hepatectomy was performed against hepatocellular carcinoma (HCC) (segment 3, 44 mm in diameter) and diagnosed by further exams. The serum AFP level decreased to a normal range after hepatectomy for the time being. A rapid elevation of serum AFP level (11,293 ng/ml) was observed nine months after the surgery. No evidence of recurrence in the intra- and extra hepatic organs such as adrenal gland, lung, bone, and brain except for intra abdominal solitary lymph node metastasis was observed. Then the metastatic lymph node was removed surgically. After the removal of the lymph node, the serum AFP level decreased within a normal limit immediately. This patient currently survives without the disease for 30 months after the initial operation, and for 19 months after a resection of the meatastatic lymph node.     

中晚期肝细胞癌预后影响因素分析

目的研究中晚期肝细胞癌(HCC)患者的预后相关因素,建立具有临床实用性的预后模型.方法根据166例HCC患者临床及随访资料,采用Kaplan-Meier和Cox回归模型方法,分析HCC患者的预后影响因素,并建立预后指数(PI)模型.结果单因素分析显示Child-Pugh分级、肝外转移、腹水、治疗、胆红素、血清钠、碱性磷酸酶、γ-谷氨酰转肽酶、肿瘤形态和大小、临床分期和门静脉癌栓与HCC患者生存率有关.多因素分析表明,肿瘤形态(P=0.001)、肿瘤大小(P=0.002)、甲胎蛋白(P=0.014)、血清钠(P=0.011)和Child-Pugh分级(P=0.001)是独立的预后影响因素.预后指数(PI)定义为回归方程:PI=ey,y=0.585(肿瘤形态-2.0542) 0.747(肿瘤大小-1.879) 0.477(AFP-1.4157)-0.570(血清钠-1.6933) 0.786(Child-Pugh分级-1.7590).PI＜1和≥1患者的中位生存期分别为10.2个月和1.8个月(P＜0.01).结论肿瘤形态、肿瘤大小、甲胎蛋白、血清钠和Child-Pugh分级是中晚期HCC患者独立的预后影响因素,根据独立预后因素建立的预后指数模型可帮助临床预测中晚期HCC患者的预后.     

The prognosis of hepatocellular carcinoma after curative hepatectomy in young patients

Age at diagnosis is a reported prognostic factor in a variety of solid cancers. In hepatocellular carcinomas (HCCs), several previous studies focused on patient age, but demonstrated inconclusive results on prognosis of young patients. Clinical outcome may differ according to the balance between tumor''s own biologic behavior and underlying liver function thus explaining the inconclusive results in previous studies. In this study, we enrolled 282 patients who underwent curative hepatectomy for primary HCCs and had Child Pugh Class A, representing good liver function. Clinicopathologic features were compared between patients aged ≤40 years (young age group) and those aged >40 years (old age group). Thirty-five patients (12.4%) were classified as the young age group and showed larger tumor size (>5cm), higher Edmondson grade, more frequent intrahepatic metastasis and higher alpha-fetoprotein level (>200ng/mL) than old age group. Young age group showed shorter disease specific survival than the old age group. Symptomatic presentation without surveillance was more frequent in the young age group than old age group (45.7% vs. 23.9%). In gene expression profiling analysis, 69 differentially expressed genes between young and old age groups were generated and these genes were mostly associated with cell cycle or cell division. Mitotic rate was significantly higher in HCCs of young patients than those of old patients. In conclusion, HCCs in young patients have distinct clinicopathologic features. Poor prognosis in the young age group could be explained by late detection as well as their own aggressive tumor biology.