Survival Analysis Using Albumin-Bilirubin (ALBI) Grade for Patients Treated with Drug-Eluting Embolic Transarterial Chemoembolization for Hepatocellular Carcinoma

PurposeThe albumin-bilirubin (ALBI) grade has been established as an improved predictor of survival in patients with hepatocellular carcinoma (HCC) treated with conventional transarterial chemoembolization and yttrium-90 radioembolization. The purpose of the study was to investigate the utility of ALBI grade in prognosticating outcomes in patients with HCC treated with drug-eluting embolic (DEE) transarterial chemoembolization (TACE).Materials and MethodsA single-center retrospective review was performed to compare the efficacy of ALBI grade and Child-Pugh (CP) classification in predicting the survival of patients with HCC receiving DEE-TACE. A total of 303 patients with HCC were identified who had received DEE-TACE without concomitant locoregional therapy within 30 days. Survival analysis was performed using Kaplan-Meier methods and censored for curative therapy. Survival curves were stratified based on the ALBI grade, CP class, Barcelona Clinic Liver Cancer (BCLC) stage, Eastern Cooperative Oncology Group performance status, and presence of ascites. The discriminatory ability of survival curves was calculated by C-Index.ResultsKaplan-Meier survival curves stratified by the ALBI grade produced distinct, nonoverlapping curves (P < .001), showing greater discriminatory ability than the CP classification (C-index = 0.568 and 0.545, respectively). The substratification of the BCLC stage by the ALBI grade yielded greater discriminatory ability than the substratification by the CP classification (C-index = 0.573 and 0.565, respectively). For patients with BCLC stage B, the substratification by the ALBI grade yielded distinct curves, whereas the substratification by the CP classification did not (P = .011 and P = .379, respectively).ConclusionsALBI grade showed improved discriminatory ability compared with CP classification in differentiating overall survival among patients with HCC receiving DEE-TACE. Furthermore, ALBI grade was effective in substratifying survival among patients categorized as CP class A and patients with BCLC stage B, whereas CP classification was not effective.     

The impact of the covalently closed circular DNA level on recurrence of hepatocellular carcinoma after initial hepatectomy: an analysis of patients with resolved hepatitis B virus infection

BackgroundWe assessed whether or not covalently closed circular DNA (cccDNA) levels in the background liver influence the recurrence of hepatocellular carcinoma (HCC) in patients with resolved hepatitis B virus (HBV) infection.MethodsAmong 425 patients who underwent initial hepatectomy for HCC between 2010 and 2018, a retrospective review was performed in 44 with resolved HBV infection. The clinicopathologic characteristics were analyzed for correlation with tumor recurrence. The HBV cccDNA levels were tested via a droplet digital polymerase chain reaction assay.ResultsHBV cccDNA was detected in 27 of 44 patients (61%), and the median level was 1.0 copies/1000 ng (range, 0-931.3 copies/1000 ng). Anti-HBc ≥8.9 S/CO was associated with cccDNA detection (odds ratio, 11.08; 95% confidence interval [95% CI], 2.48-49.46; P = 0.002). Twenty-eight patients (64%) developed HCC recurrence after hepatectomy. The overall 3- and 5-year recurrence-free survival rates were 45.7% and 34.3%, respectively.19 HBV cccDNA levels was not significantly associated with HCC recurrence, while the presence of multiple tumors was an independent risk fact or (hazard ratio, 6.53; 95% CI, 2.48-17.19; P < 0.001.ConclusionHBV cccDNA levels did not influence HCC recurrence after hepatectomy. Anti-HBc levels may be used as a surrogate marker for cccDNA.     

Jejunal adenocarcinoma after biliopancreatic diversion. Report of a case

The effects of bariatric surgery on the development of gastrointestinal cancers remain ill defined. We present a case of jejunal adenocarcinoma developing 19 years after biliopancreatic diversion (BPD) procedure according to Scopinaro’s technique. The patient developed a marked distension of the biliopancreatic limb caused by a jejunal mass, evolving towards the so called “duodenal blowout”. Emergency jejunal resection of the biliopancreatic limb, with creation of a new end-to-side jejunal-ileal anastomosis was necessary. The histological examination resulted in a moderately-differentiated ulcerated adenocarcinoma, with reactive lymph nodes and tumor-free resection margins. Tumors of the gastrointestinal system can arise following malabsorptive operations for morbid obesity, and they may be difficult to diagnose, since the symptoms are often attributed to the anatomical-functional changes resulting from this type of surgery. The case reported herein suggests that there is a need for surveillance in patients complaining of digestive symptoms after malabsorptive bariatric surgery.     

Long-term survival and postoperative complications of pre-liver transplantation transarterial chemoembolisation in hepatocellular carcinoma: A systematic review and meta-analysis

ObjectivesThe aim of this meta-analysis was to conduct a contemporary systematic review of high quality non-randomised controlled trials to determine the effect of pre-liver transplantation (LT) transarterial chemoembolisation (TACE) on long-term survival and complications of hepatocellular carcinoma (HCC) patients.BackgroundTACE is used as a neoadjuvant therapy to mitigate waitlist drop-out for patients with HCC awaiting LT. Previous studies have conflicting conclusions on the effect of TACE on long-term survival and complications of HCC patients undergoing LT.MethodsCINAHL, Cochrane Controlled Register of Trials, Embase, PubMed, and Web of Science were systematically searched. Baseline characteristics included number of patients outside Milan criteria, tumour diameter, MELD score, and time on the waiting list. Primary outcomes included 3- and 5-year overall and disease-free survival. Secondary outcomes included tumour recurrence, 30-day postoperative mortality, and hepatic artery and biliary complications.ResultsTwenty-one high-quality NRCTs representing 8242 patients were included. Tumour diameter was significantly larger in TACE patients (3.49 cm vs 3.15 cm, P = 0.02) and time on the waiting list was significantly longer in TACE patients (4.87 months vs 3.46 months, P = 0.05), while MELD score was significantly higher in non-TACE patients (10.81 vs 12.35, P = 0.005). All primary and secondary outcomes displayed non-significant differences.ConclusionPatients treated with TACE had similar survival and postoperative outcomes to non-TACE patients, however, they had worse prognostic features compared to non-TACE patients. These findings strongly support the current US and European clinical practice guidelines that neoadjuvant TACE can be used for patients with longer expected waiting list times (specifically >6 months). Randomised controlled trials would be needed to increase the quality of evidence.     

三联预康复策略在肝癌腹腔镜肝切除术中的应用价值

目的:探讨三联预康复策略在肝癌腹腔镜肝切除术中的应用价值。方法:选取2015年1月至2018年1月四川大学华西医院胆道外科收治的120例行腹腔镜肝切除术的肝癌患者，按随机数字表法分为观察组及对照组各60例。观察组在门诊收治当日开始三联预康复策略干预，干预时间约2～4周；对照组予以常规肝癌腹腔镜肝切除术术前准备。于干预前、术前1天及术后4周分别记录六分钟步行距离(6MWT)、医院焦虑抑郁量表(HADS)评分、健康调查简表(SF-36)评分及检测血清白蛋白(ALB)、前白蛋白(PA)、转铁蛋白(TRF)水平。结果:术前1天，观察组6MWT、血清ALB、PA、TRF水平高于干预前(P＜0.05)；对照组6MWT、血清ALB、PA、TRF水平与干预前差异无统计学意义(P＞0.05)；术后4周，观察组6MWT、血清ALB、PA、TRF水平与干预前差异无统计学意义(P＞0.05)；对照组6MWT、血清ALB、PA、TRF水平低于干预前(P＜0.05)；术前1天、术后4周观察组HADS评分低于干预前，SF-36评分高于干预前(P＜0.05)；对照组HADS、SF-36评分与干预前差异无统计学意义(P＞0.05)；术前1天、术后4周，观察组6MWT、SF-36评分、血清ALB、PA、TRF水平高于对照组，HADS评分低于对照组(P＜0.05)。结论:三联预康复策略应用于肝癌腹腔镜肝切除术可明显改善患者围术期活动能力、心理状态及营养状况，加速患者术后恢复。     

姑息性胃切除联合术后化疗评分在腹膜转移的胃癌患者预后评估中的临床意义

目的:探讨姑息性胃切除联合术后化疗评分在腹膜转移的胃癌患者预后评估中的临床意义。方法:回顾性分析2010年1月至2016年12月7年间收治的287例发生腹膜转移的胃癌患者的临床病理资料。通过χ2检验分析评分与患者临床病理因素间的关系。通过Kaplan-Meier法绘制生存曲线，Log-rank检验比较患者生存率的差异；采用Cox比例风险回归模型对患者进行预后分析。结果:与评分中得分为2分和1分的患者相比，得分为0分的患者肿瘤侵润至T4b 期的患者较少［31%(18/58)比50.8%(63/124)、56.2%(59/105)，P=0.039］。全组患者的中位生存时间仅为8.7月。对患者进行单因素预后分析结果显示，血清白蛋白浓度（≤40 g/L），腹水，腹膜转移范围较大，肿瘤T分期较晚，评分得分较高的患者预后较差（均P＜0.05）。将上述因素纳入Cox多因素分析结果显示:评分［HR（95%CI）:1.384（1.165~1.644），P=0.000］，血清白蛋白浓度［HR（95%CI）:0.759（0.593~0.971），P=0.028］，肿瘤T分期［HR（95%CI）:1.493（1.216~1.832），P=0.000］是患者预后的独立危险因素。结论:评分对于胃癌伴腹膜转移患者的预后生存评估具有重要的临床意义。     

甲状腺乳头状癌伴发桥本甲状腺炎的临床研究

背景与目的：甲状腺乳头状癌（papillary thyroid carcinoma，PTC）和桥本甲状腺炎（Hashimoto’s thyroiditis，HT）的发病率均呈上升趋势，两者之间的关系已成为目前研究的热点。探讨PTC和HT之间的关系。方法：回顾性分析2014—2015年期间在中国科学院大学附属肿瘤医院头颈肿瘤外科行甲状腺癌手术治疗的首诊患者306例，术后病理学检查均明确诊断为PTC，其中术后病理学确诊伴发HT者42例，比较伴发HT与未伴发HT患者的临床病理学特征。结果：PTC患者女性发病年龄高于男性（46.2岁 vs 41.9岁）。相较于与未伴发HT的PTC患者，伴发HT的患者中女性比例更高（93% vs77%），中央区淋巴结数目较多［（5.0±3.4）枚 vs （2.5±2.7）枚］，术前促甲状腺激素（thyroid-stimulating hormone，TSH）水平较高［（3.28±1.91）μU/mL vs （2.12±1.29）μU/mL］，术前抗甲状腺过氧化物酶抗体（thyroid peroxidaseantibody，TPOAb）阳性率较高（55% vs 14%），术前甲状腺球蛋白抗体（thyroglobulin antibodies，TgAb）阳性率较高（69% vs 13%）。发生中央区淋巴结转移的患者中，中央区淋巴结转移数目与中央区淋巴结总数显著相关（Pearson相关系数=0.582）。多因素logistic回归分析发现，男性、低龄、被膜侵犯是PTC患者中央区淋巴结转移的独立危险因素。结论：伴发HT对PTC患者的预后无显著影响。伴发HT的PTC患者TSH水平显著偏高，提示HT可能是PTC发病风险因素之一。中央区淋巴结转移数目与中央区淋巴结总数相关，推测PTC淋巴结转移可能与淋巴结炎症反应相关。     

甲状腺未分化癌发生肺转移的危险因素分析

目的:探讨甲状腺未分化癌(anaplastic thyroid carcinoma,ATC)发生肺转移的危险因素。方法:回顾性分析2010年至2015年SEER数据库中被确诊为ATC的405例患者临床病理资料。通过对年龄、种族、性别、原发灶最大径、原发灶数量、甲状腺外组织侵犯、食管侵犯、气管侵犯、中央区淋巴结转移、颈侧区淋巴结转移10个因素进行单因素分析,进而对单因素分析中有统计学差异的指标行多因素Logistic回归分析,寻找ATC患者发生肺转移的危险因素。结果:405例ATC患者中,发生肺转移107例,未发生肺转移298例。单因素分析显示:原发灶最大径>4 cm、甲状腺外组织侵犯、颈侧区淋巴结转移是预测发生肺转移的显著性因素(均P<0.05)。多因素Logistic回归分析显示:原发灶最大径>4 cm及颈侧区淋巴结转移是ATC患者发生肺转移的独立危险因素(均P<0.05)。结论:原发灶最大径>4 cm、颈侧区淋巴结转移的ATC患者极易发生肺转移,因此,一定要认真参考病理结果,若发现存在以上肺转移危险因素,则积极采取多模式治疗方案,并缩短随访时间,行相关检查(如胸部CT扫描、PET-CT等)。     

Comparison of survival between adolescent and young adult vs older patients with hepatocellular carcinoma

BACKGROUNDDue to the special clinical features and biologic characteristics of adolescent and young adult (AYA) cancers, AYA cancers are different from cancers in children and elderly individuals. However, there are few reports on AYA hepatocellular carcinoma (HCC).AIMTo investigate the overall survival (OS) of AYA (15-39 years) and elderly (40-74 years) patients with HCC.METHODSThe data of all the HCC cases were extracted from the Surveillance, Epidemiology, and End Results database from 2004 to 2015 and were then divided into two groups based on age: AYA group (15-39 years) and older group (40-74 years). Kaplan-Meier curves and log-rank tests were used to compare the OS of the two groups. Propensity score matching (PSM) was employed to analyze the OS difference between the two groups. The Cox proportional hazards regression model was used to perform multivariate analysis to explore the risk factors for OS of HCC patients.RESULTSCompared to elderly cancer patients, AYA patients with HCC had a worse Surveillance, Epidemiology, and End Results stage, including the distant stage (22.1% vs 15.4%, P < 0.001), and a more advanced American Joint Committee on Cancer (AJCC) stage, including AJCC III and IV (49.2% vs 38.3%, P < 0.001), and were more likely to receive surgery (64.5% vs 47.5%, P < 0.001). Before PSM, the AYA group had a longer survival in months (median: 20.00, interquartile range [IQR]: 5.00-62.50) than the older group (median: 15.00, IQR: 4.00-40.00) (P < 0.001). After PSM, the AYA group still had a longer survival in months (median: 21.00, IQR: 5.00-64.50) than the older group (median: 18.00, IQR: 6.00-53.00) (P < 0.001). The Cox proportional hazards regression model showed that advanced age (hazard ratio [HR] = 1.405, 95%CI: 1.218-1.621, P < 0.001) was a risk factor for OS of HCC patients. In the subgroup analysis, the Cox proportional hazards regression model showed that in AJCC I/II HCC patients, advanced age (HR = 1.749, 95%CI: 1.352-2.263, P < 0.001) was a risk factor for OS, while it was not a risk factor in AJCC III/IV HCC patients (HR = 1.186, 95%CI: 0.997-1.410, P = 0.054) before PSM. After PSM, advanced age (HR = 1.891, 95%CI: 1.356-2.637, P < 0.001) was still a risk factor for OS in AJCC I/II HCC patients, but was not a risk factor for OS in AJCC III/IV HCC patients (HR = 1.192, 95%CI: 0.934-1.521, P = 0.157) after PSM.CONCLUSIONAYA patients with HCC have different clinical characteristics from older adults. In different AJCC stages, the two groups of patients have different OS: In AJCC I/II HCC patients, advanced age is a risk factor for OS, but it is not a risk factor for OS in the AJCC III/IV HCC patient group.     

Noncoding telomeric repeat‐containing RNA inhibits the progression of hepatocellular carcinoma by regulating telomerase‐mediated telomere length

Telomeric repeat‐containing RNA (TERRA) is closely involved in the regulation of telomere length, which plays critical roles in tumorigenesis. However, the biological significance of TERRA in hepatocellular carcinoma (HCC) remains largely unknown. In this study, we found that HCC cells show a frequent downregulation of TERRA and its positive regulator TTAGGG repeat binding factor‐1 (TRF1), whereas the negative regulator TTAGGG repeat binding factor‐1 (TRF2) was upregulated. We found that TERRA, TRF1, and TRF2 contributed to poor prognosis of HCC patients. Importantly, we found that the downregulation of TERRA significantly promoted HCC cell growth and metastasis in vitro and in vivo, whereas the upregulation of TERRA showed an opposite effect. Mechanistically, downregulation of TERRA significantly increased telomerase activity and promoted telomere elongation. Moreover, the inhibitory effects of TERRA overexpression on the growth and metastasis of HCC cells were reversed by treatment with TA‐65 that activates telomerase activity. In contrast, the protumor effect of TERRA downregulation was reversed by treatment with TMPyP4 that inhibits telomerase activity. Our findings reveal that TERRA plays a critical role in HCC cell growth and metastasis, indicating that TERRA is a potential therapeutic target for HCC.