Shetty Kirti, Timmins Kate, Brensinger Colleen, Furth Emma E, Rattan Sushil, Sun Weijing, Rosen Mark, Soulen Michael, Shaked Abraham, Reddy K Rajender, Olthoff Kim M
Division of Gastroenterology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Liver Transpl. 2004 Jul;10(7):911-8. doi: 10.1002/lt.20140.
Appropriate patient selection is crucial in ensuring acceptable outcomes from orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC). The United Network for Organ Sharing (UNOS) has elected to prioritize HCC patients for OLT based on criteria of tumor burden. However, it is unclear whether these criteria correlate with outcome, or with the pathobiological features associated with tumor recurrence. Therefore, we analyzed 109 consecutive patients undergoing OLT for HCC at our center, to determine the utility of present selection criteria in predicting outcome. Pathologic tumor staging of the explanted liver was based on the American Tumor Study Group modified tumor node metastases (pTNM) classification system. Multifocality was defined as >4 tumor nodules on explant. Survival analysis was performed using Kaplan-Meier and Cox proportional hazards regression methods. At a median follow-up of 18.9 months, the overall mortality was 19% with 15 patients (14%) dying of recurrent HCC. Kaplan-Meier 1, 3 and 5-year survival rates were 89.5%, 68%, and 65%, respectively. Recurrence-free rates of 1, 3, and 5 years were 89%, 75%, and 65%, respectively. On univariate analysis, the factors found to be significantly associated with recurrence of HCC were explant features of macrovascular invasion, tumor size (per centimeter increase), pTNM stage (per 1-stage increase), and pre-transplant serum alphafetoprotein (AFP) >300 ng/mL. In defining a threshold level, we found that explant tumor diameter > or =3 cm, and those tumors classified as at least pT3 on pathological examination, were significantly associated with recurrence (P =.01 and.03, respectively). Tumor size on explant was found to be strongly correlated with multifocality (P =.017) and vascular invasion (P =.02). Patients exceeding pathological UNOS criteria were 3.1 times more likely to have recurrence of HCC (P =.03). In conclusion, we found that tumor size appears to be a surrogate marker for negative pathobiological predictors of outcome, i.e., vascular invasion and multifocality. Present UNOS selection criteria for HCC based on tumor burden appear to provide adequate discriminatory power in predicting outcome of OLT.
合适的患者选择对于确保肝细胞癌(HCC)原位肝移植(OLT)取得可接受的结果至关重要。器官共享联合网络(UNOS)已决定根据肿瘤负荷标准将HCC患者列为OLT的优先对象。然而,尚不清楚这些标准是否与预后相关,或与肿瘤复发相关的病理生物学特征相关。因此,我们分析了在我们中心连续接受OLT治疗HCC的109例患者,以确定当前选择标准在预测预后方面的效用。移植肝的病理肿瘤分期基于美国肿瘤研究组改良的肿瘤结节转移(pTNM)分类系统。多灶性定义为移植肝上有>4个肿瘤结节。使用Kaplan-Meier和Cox比例风险回归方法进行生存分析。在中位随访18.9个月时,总死亡率为19%,15例患者(14%)死于复发性HCC。Kaplan-Meier法计算的1年、3年和5年生存率分别为89.5%、68%和65%。1年、3年和5年的无复发生存率分别为89%、75%和65%。单因素分析发现,与HCC复发显著相关的因素有大血管侵犯的移植肝特征、肿瘤大小(每增加1厘米)、pTNM分期(每增加1期)以及移植前血清甲胎蛋白(AFP)>300 ng/mL。在确定阈值水平时,我们发现移植肝肿瘤直径≥3 cm以及病理检查分类为至少pT3的肿瘤与复发显著相关(分别为P = 0.01和0.03)。发现移植肝上的肿瘤大小与多灶性(P = 0.017)和血管侵犯(P = 0.02)密切相关。超过病理UNOS标准的患者HCC复发的可能性高3.1倍(P = 0.03)。总之,我们发现肿瘤大小似乎是预后负面病理生物学预测指标(即血管侵犯和多灶性)的替代标志物。目前基于肿瘤负荷的UNOS对HCC的选择标准在预测OLT预后方面似乎具有足够的鉴别力。