肝细胞癌相关三级淋巴样结构免疫细胞组成

目的 探讨肝细胞癌(hepatocellular carcinoma,HCC)相关三级淋巴样结构(tertiary lymphoid structure,TLS)的免疫细胞组成.方法 以2016年4月至2019年10月北京大学第一医院收治的112例原发性HCC患者为研究对象,收集其手术切除及HCC穿刺活检样本...     

小肝细胞癌术后早期复发的危险因素分析

目的 探讨小肝细胞癌（sHCC）患者术后早期复发的危险因素。方法 收集2004至2006年上海东方肝胆外科医院手术切除肿瘤的sHCC患者75例。选取20项临床和病理学参数,以2年为早期复发的时限,应用COX风险比例模型进行单因素和多因素分析,筛选影响早期复发的独立危险因素。结果 本组75例sHCC患者经手术切除肿瘤后,1～5 a累积肿瘤复发率分别为10.7%、46.7%、76.0%、86.7%和92.0%;经COX风险比例模型分析,发现术前AFP＞400 μg/L（HR=2.477,95% CI=1.100～5.576,P=0.029）和肿瘤分布超过半肝（HR=5.801,95% CI=1.831～18.379,P=0.003）是sHCC患者术后早期复发的独立危险因素。结论 对于术前AFP＞400 μg/L和肿瘤分布超过半肝的sHCC患者,应加强术后随访,及早发现复发肿瘤并给予积极的治疗,以改善患者预后。     

Factors for early tumor recurrence of single small hepatocellular carcinoma after percutaneous radiofrequency ablation therapy

AIM: To evaluate the factors affecting the early tumor recurrence within one year in cirrhotic patients having a single small hepatocellular carcinoma (HCC) after complete tumor necrosis by radiofrequency ablation (RFA) therapy. METHODS: Thirty patients with a single small HCC received RFA therapy by a RFA 2000 generator with LeVeen needle. Tri-phase computerized tomogram was followed every 2 to 3 mo after RFA. The clinical effects and tumor recurrence were recorded. RESULTS: The initial complete tumor necrosis rate was 86.7%. Twenty-two patients were followed for more than one year. The local and overall recurrence rates were 13.6% and 36.4%, 33.3% and 56.2%, 46.6% and 56.2% at 12, 24 and 30 mo, respectively. No major complication or procedure-related mortality was found. The risk factors for early local tumor recurrence within one year were larger tumor size, poor pathologic differentiation of tumor cells and advanced tumor staging. The age of patients with new tumor formation within one year was relatively younger (55.1±8.3 vs 66.7±10.8, P= 0.029). CONCLUSION: Large tumor size, poor pathologic differentiation of tumor cells and advanced tumor staging are the risk factors for early local tumor recurrence within one year, and young age is the positive predictor for new tumor formation within one year.     

Tumor vaccine against recurrence of hepatocellular carcinoma

AIM: To investigate the effects of autologous tumor vaccine on recurrence of hepatocellular carcinoma (HCC). METHODS: Sixty patients with HCC who had undergone curative resection, were randomly divided into HCC vaccine group and control group. Three vaccinations at 2-wk intervals were performed after curative hepatic resection. Delayed-type- hypersensitivity (DTH) test was performed before and after vaccination. Primary endpoints were the time of recurrence. RESULTS: Four patients in control group and 6 patients in HCC vaccine group were withdrawn from the study. The vaccine containing human autologous HCC fragments showed no essential adverse effect in a phase II clinical trial and 17 of 24 patients developed a DTH response against the fragments. Three of 17 DTH-positive response patients and 5 of 7 DTH- negative response patients had recurrences after curative resection. After the operation, 1-, 2- and 3-year recurrence rates of HCC vaccine group were 16.7%, 29.2% and 33.3%, respectively. But, 1-, 2- and 3-year recurrence rates of the control group were 30.8%, 53.8% and 61.5%, respectively. The time before the first recurrence in the vaccinated patients was significantly longer than that in the control patients (P<0.05). CONCLUSION: Autologous tumor vaccine is of promise in decreasing recurrence of human HCC.     

Local recurrence of hepatocellular carcinoma after radiofrequency ablation

A 51-year-old Chinese male with a 20-year history of hepatitis B was diagnosed with hepatocellular carcinoma in the right anterior portion of the liver, sized 3.5 cm × 3.2 cm, and was treated with radiofrequency ablation (RFA) on December 18, 2001. The patient did not receive antiviral therapy for hepatitis B virus after RFA. The treated lesion reduced gradually and reached its minimum size of 1.7 cm × 1.5 cm seven years later on November 18, 2008. However computed tomography findings revealed that a recurr...     

Development of pre and post-operative models to predict early recurrence of hepatocellular carcinoma after surgical resection

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The prognostic factor for outcome following second resection for intrahepatic recurrence of hepatocellular carcinoma with a hepatitis B virus infection background

Purpose Second resection has been proved to be a safe and effective treatment for patients with intrahepatic recurrent HCC after primary resection; however, preoperative prognostic factors for outcome following second resection in patients with a hepatitis B virus (HBV) infection background remains to be clarified.Methods Fifty-seven patients with intrahepatic recurrent an HCC and HBV infection background received second resection from 1997 to 2003 in our institute. All of them were negative for anti-hepatitis C virus (HCV) and positive regarding HBV profile. Patient and tumor factors were analyzed.Results At the time of preparing this paper, 31 had re-recurrence and 21patients had died. No postoperative mortality was noted. The 1-, 3-, and 5-year overall survival after second resection were 69.9%, 61.2%, and 30.6%, respectively. Univariate and multivariate analysis showed that vascular invasion and time to recurrence were the independent prognostic factors for overall survival following second resection. The 3- and 4-year overall survival after second resection were 57.7% and 46.6% in patients with the presence of any of two risk factors (n=46), and 100% and 100% in those with absence of both risk factors (n=11, P=0.008).Conclusions Vascular invasion and time to recurrence were the prognostic factors for overall survival following second resection of intrahepatic recurrent HCC.This study was jointly supported by a grant from the Shanghai Medical Center Project, the Promising Young Doctor of Shanghai grant from the Bureau of Public Health of Shanghai, and the Project 211 grant from Ministry of Education of China.     

GST polymorphisms are associated with hepatocellular carcinoma risk in Chinese population

AIM： To investigate the association between GSTM1 and GSTT1 polymorphisms and the risk of hepatocellular carcinoma （HCC） in Chinese population. METHODS： Literature databases including PubMed, ISI web of science and other databases were searched.Pooled odds ratio （OR） and 95% CI were calculated using random- or fixed-effects model. Subgroup analysis and sensitivity analysis were also performed. RESULTS： Nineteen studies of GSTM1 （2660 cases and 4017 controls） and 16 studies of GSTT1 （2410 cases and 3669 controls） were included. The GSTM1/GSTT1 null genotypes were associated with increased risk of HCC in Chinese population （for GSTM1, OR = 1.487, 95% CI： 1.159 to 1.908, P = 0.002; for GSTT1, OR = 1.510, 95% CI： 1.236 to 1.845, P = 0.000）. No publication bias was detected. In subgroup analysis, glutathione S-transferases polymorphisms were significantly associated with HCC risk among the subjects living in high-incidence areas, but not among the subjects living in low-incidence areas. CONCLUSION： The present meta-analysis suggests that GSTM1/GSTT1 null genotypes are associated with increased risk of HCC in Chinese population.     

Serum biomarkers and risk of hepatocellular carcinoma recurrence after liver transplantation

Liver transplantation(LT) is the only potentially curative treatment for selected patients with cirrhosis and hepatocellular carcinoma(HCC) who are not candidates for resection. When the Milan criteria are strictly applied, 75% to85%of 3-to 4-year actuarial survival rates are achieved, but up to 20% of the patients experience HCC recurrence after transplantation. The Milan criteria are based on the preoperative tumor macromorphology, tumor size and number on computed tomography or magnetic resonance imaging that neither correlate well with posttransplant histological study of the liver explant nor accurately predict HCC recurrence after LT, since they do not include objective measures of tumor biology. Preoperative biological markers, including alpha-fetoprotein, desgamma-carboxiprothrombin or neutrophil-to-lymphocyte ratio and platelet-tolymphocyte ratio, can predict the risk for HCC recurrence after transplantation.These biomarkers have been proposed as surrogate markers of tumor differentiation and vascular invasion, with varied risk magnitudes depending on the defined cutoffs. Different studies have shown that the combination of one or several biomarkers integrated into prognostic models predict the risk of HCC recurrence after LT more accurately than Milan criteria alone. In this review, we focus on the potential utility of these serum biological markers to improve the performance of Milan criteria to identify patients at high risk of tumoral Published online: January 27, 2019 recurrence after LT.Liver transplantation(LT) is the only potentially curative treatment for selected patients with cirrhosis and hepatocellular carcinoma(HCC) who are not candidates for resection. When the Milan criteria are strictly applied, 75% to85%of 3-to 4-year actuarial survival rates are achieved, but up to 20% of the patients experience HCC recurrence after transplantation. The Milan criteria are based on the preoperative tumor macromorphology, tumor size and number on computed tomography or magnetic resonance imaging that neither correlate well with posttransplant histological study of the liver explant nor accurately predict HCC recurrence after LT, since they do not include objective measures of tumor biology. Preoperative biological markers, including alpha-fetoprotein, desgamma-carboxiprothrombin or neutrophil-to-lymphocyte ratio and platelet-tolymphocyte ratio, can predict the risk for HCC recurrence after transplantation.These biomarkers have been proposed as surrogate markers of tumor differentiation and vascular invasion, with varied risk magnitudes depending on the defined cutoffs. Different studies have shown that the combination of one or several biomarkers integrated into prognostic models predict the risk of HCC recurrence after LT more accurately than Milan criteria alone. In this review, we focus on the potential utility of these serum biological markers to improve the performance of Milan criteria to identify patients at high risk of tumoral recurrence after LT.     

Predictive value of gross classification of hepatocellular carcinoma on recurrence and survival after hepatectomy

BACKGROUND/AIM: A new gross classification of hepatocellular carcinoma in which Eggel's nodular type is subclassified into type 1 (single nodular type), type 2 (single nodular type with extranodular growth), and type 3 (contiguous multinodular type) has been widely used in Japan. The aim of the study was to determine whether this classification is correlated with patient outcome. METHODS: Sixty-five resected hepatocellular carcinoma nodules (< or = 5 cm) were classified using this new classification. RESULTS: The 65 tumors were classified into 30 type 1 (46%), 20 type 2 (31%), and 15 type 3 (23%) hepatocellular carcinomas. The rate of microscopic vascular invasion significantly increased from type 1 to type 2, and to type 3 tumors (p=0.03). Kaplan-Meier estimates showed that type 1 was significantly associated with lower recurrence rate (type 1 vs. type 2, p=0.01; type 1 vs. type 3, p=0.004; log-rank test), and higher disease-specific survival (type 1 vs. type 2, p=0.02; type 1 vs. type 3, p=0.002). Cox's proportional-hazards model demonstrated that type 1 was an independent factor for low risk of recurrence (p=0.002) and low risk of disease-specific death (p=0.02). CONCLUSION: The gross classification of hepatocellular carcinoma is of clinical value in predicting patient outcome.     

肝脏超声造影诊断肝癌术后肝内肿瘤复发的价值探讨

目的探讨超声造影在肝癌术后肝内肿瘤复发中的诊断价值。方法48例肝癌切除术后患者经常规超声检查发现肝内直径≤2.0 cm的单发病灶患者进行超声造影检查和血清AFP检测。结果在术后平均（32.86±7.54）个月,常规超声检查发现48例肝癌术后患者肝内出现直径≤2.0 cm单发病灶,48个单发病灶呈圆形或者类圆形占位性病变,其中44个呈低回声,4个呈高回声;超声造影检查判断肿瘤复发病灶35个,良性结节13个;在32例血清AFP>200 μg/L患者,肝内肿瘤发生率为87.50%,明显高于16例血清AFP≤200 μg/L患者的43.75%,具有统计学差异（x²=10.338,P=0.001）;在48个单发病灶中,超声造影诊断正确44个（91.67%）,包括复发病灶33个和良性结节11个;超声造影对肝癌术后患者肝内直径≤2.0 cm单发病灶诊断的准确度为91.67%（44/48）,灵敏度为94.29%（33/35）,特异度为84.62%（11/13）。结论超声造影可以对肝癌术后患者肝内复发病灶进行早期诊断,对于提高患者的治疗疗效和生存期具有重要的临床意义。     

Thrombocytopenia for prediction of hepatocellular carcinoma recurrence: Systematic review and meta-analysis

AIM: To investigate the association between thrombocytopenia and relapse after treatment for hepatocellular carcinoma (HCC).METHODS: We searched the PubMed, EMBASE, and Web of Science databases to obtain eligible studies. The hazard ratios (HRs) values and 95% confidence intervals (CIs) were pooled by random effects model. Subsequently, we estimated the heterogeneity, performed a sensitivity analysis, determined the publication bias, and performed subgroup and meta-regression analyses. Study quality was assessed by using the Oxford Center for Evidence Based Medicine tool.RESULTS: We identified 18 eligible studies by retrieval (published during 2000-2014). Out of the 4163 patients with HCC who were recruited, 2746 (66.0%) experienced recurrence. In general, our meta-analysis suggested that low platelet count (PLT) before therapy significantly increased the probability of postoperative recurrence (HR = 1.53, 95%CI: 1.29-1.81). PLT was also valuable in the prediction of intrahepatic distant recurrence (HR = 1.49, 95%CI: 1.25-1.77). Subgroup and meta-regression analyses identified various therapeutic modalities as the source of a high degree of heterogeneity. The pooled HR values showed no obvious change when a single study was removed, but otherwise, an opposite-effects model was used. In addition, no significant publication bias was detected.CONCLUSION: Thrombocytopenia before treatment might be an inexpensive and useful predictor of postoperative recurrence in patients with HCC.     

Clinical analysis of patients with hepatocellular carcinoma recurrence after living-donor liver transplantation

AIM: To evaluated patterns and outcomes of hepatocellular carcinoma(HCC) recurrence after living donor liver transplantation(LDLT).METHODS: From 2001 to 2014, 293 patients underwent LDLT for HCC at our transplant center. We retrospectively reviewed 54(18.4%) patients with HCC recurrence after LDLT. We evaluated patterns and outcomes of HCC recurrence after LDLT, with particular attention to the Milan criteria at transplantation, treatments for HCC-recurrent patients, and factors related to survival after HCC recurrence. Furthermore, we evaluated the efficacy of combination treatment of sorafenib and an mT OR inhibitor.RESULTS: The 1-, 2-, and 3-year overall survival rates after HCC recurrence were 41.1%, 20.5%, and 15.4%, respectively. The median time interval between LDLT and HCC recurrence was 6.5 mo. Although recurrence rates according to the Milan criteria at LDLT were significantly different, HCC recurrence patterns and survival rates after HCC recurrence were not significantly different between the two groups. Time to recurrence 12 mo(P = 0.048), multiple recurrences at HCC recurrence(P = 0.038), and palliative treatment for recurrent tumors(P = 0.003) were significant independent prognostic factors for poor survival after HCC recurrence in a multivariate analysis. The combination treatment of sorafenib and sirolimus showedsurvival benefits in the palliative treatment group(P = 0.005).CONCLUSION: Curative treatment for recurrent HCC after LDLT is the most important factor in survival rates after HCC recurrence and combination treatments of sorafenib and an m TOR inhibitor could have survival benefits in patients with HCC recurrence after LT in the palliative treatment group.     

Preventive effect of regional radiotherapy with phosphorus-32 glass microspheres in hepatocellular carcinoma recurrence after hepatectomy

AIM： To evaluate the preventive effects of phosph- orus-32 glass microspheres （P32-GMS） in the recurrence of massive hepatocellular carcinomas （HCCs） after tumor resection. METHODS： Twenty-nine patients with massive HCCs received local P^32-GMS implantation after liver tumors were removed, while the other 38 patients with massive HCCs were not treated with P^32-GMS after hepatectomies. The radioactivity of the blood, urine and liver were examined. The complications, HCC recurrence and overall survival rates in the patients were analyzed. RESULTS： P^32-GMS implanted in the liver did not cause systemic absorption of p^32. There were no significant differences of postoperative complications between the patients with and without P^32-GMS treatment. The shortterm （six months and 1 year） and long-term （2, 3 and over 3 years） recurrence rates in patients who received P^32-GMS radiotherapy were significantly decreased, and the overall survival rates in this group were significantly improved. CONCLUSION： P^32-GMS implantation in the liver can significantly decrease the postoperative recurrence and improve the overall survival in HCCs patients after hepatectomy. This therapy may provide an innovative method in prevention of HCC recurrence after operation.     

Metastatic recurrence to a solitary lymph node four years after hepatic lobectomy for primary hepatocellular carcinoma

This report describes a patient that developed recurrent metastatic hepatocellular carcinoma (HCC) to a suprapancreatic lymph node four years after being treated for primary HCC via complete left hepatectomy. Metastatic HCC was proven by pathologic confirmation. The report addresses the role of surgical resection as a treatment modality for recurrent HCC to solitary lymph nodes. The role of biological chemotherapy as adjuvant treatment is also addressed.     

Therapeutic strategies for post-transplant recurrence of hepatocellular carcinoma

Despite stringent selection criteria, hepatocellular carcinoma recurrence after liver transplantation (LT) still occurs in up to 20% of cases, mostly within the first 2–3 years. No adjuvant treatments to prevent such an occurrence have been developed so far. However, a balanced use of immunosuppression with minimal dose of calcineurin inhibitors and possible addition of mammalian target of rapamycin inhibitors is strongly advisable. Moreover, several pre- and post-transplant predictors of recurrence have been identified and may help determine the frequency and duration of post-transplant follow-up. When recurrence occurs, the outcomes are poor with a median survival of 12 mo according to most retrospective studies. The factor that most impacts survival after recurrence is timing (within 1–2 years from LT according to different authors). Several therapeutic options may be chosen in case of recurrence, according to timing and disease presentation. Surgical treatment seems to provide a survival benefit, especially in case of late recurrence, while the benefit of locoregional treatments has been suggested only in small retrospective studies. When systemic treatment is indicated, sorafenib has been proved safe and effective, while only few data are available for lenvatinib and regorafenib in second line. The use of immune checkpoint inhibitors is controversial in this setting, given the safety warnings for the risk of acute rejection.     

肝细胞癌冷冻消融术后早期复发的危险因素

目的:探讨肝细胞癌(hepatocellular carcinoma,HCC)患者冷冻消融术后影响早期复发的相关危险因素.方法:回顾分析90例直径≤5.0 cm的HCC行冷冻消融治疗后复发的患者的临床资料,分析影响冷冻消融术后早期复发的危险因素.结果:本组患者随访8-47(平均随访时间21.9±10.1)mo,共有57...     

Predictors of early and late hepatocellular carcinoma recurrence

Hepatocellular carcinoma(HCC) is the most frequent liver neoplasm, and its incidence rates are constantly increasing. Despite the availability of potentially curative treatments(liver transplantation, surgical resection, thermal ablation), long-term outcomes are affected by a high recurrence rate(up to 70% of cases 5 years after treatment). HCC recurrence within 2 years of treatment is defined as “early” and is generally caused by the occult intrahepatic spread of the primary neoplasm and relate...