Parfitt Jeremy R, Marotta Paul, Alghamdi Mohammed, Wall William, Khakhar Anand, Suskin Neville G, Quan Douglas, McAllister Vivian, Ghent Cam, Levstik Mark, McLean Carolyn, Chakrabarti Subrata, Garcia Bertha, Driman David K
Department of Pathology, London Health Sciences Centre and University of Western Ontario, London, Ontario, Canada.
Liver Transpl. 2007 Apr;13(4):543-51. doi: 10.1002/lt.21078.
Milan and University of California at San Francisco (UCSF) criteria are used to select patients with hepatocellular carcinoma (HCC) for liver transplantation (LT). Recurrent HCC is a significant cause of death. There is no widely accepted pathological assessment strategy to predict recurrent HCC after transplantation. This study compares the pathology of patients meeting Milan and UCSF criteria and develops a pathological score and nomogram to assess the risk of recurrent HCC after transplantation. All explanted livers with HCC from our center over the 18-yr period 1985 to 2003 were assessed for multiple pathological features and relevant clinical data were recorded; multivariate analysis was performed to determine features associated with recurrent HCC. Using pathological variables that independently predicted recurrent HCC, a pathological score and nomogram were developed to determine the probability of recurrent HCC. Of 75 cases analyzed, 50 (67%) met Milan criteria, 9 (12%) met only UCSF criteria and 16 (21%) met neither criteria based on explant pathology. There were 20 cases of recurrent HCC and the mean follow-up was 8 yr. Recurrent HCC was more common (67 vs. 12%; P < 0.001) and survival was lower (15 vs. 83% at 5 yr; 15 vs. 55% at 8 yr; P < 0.001) with those who met only UCSF criteria, compared to those who met Milan criteria. Cryptogenic cirrhosis (25 vs. 5%; P = 0.015), preoperative AFP >1,000 ng/mL (20 vs. 0%; P < 0.001) and postoperative OKT3 use (40 vs. 15%; P = 0.017) were more common among patients with recurrent HCC. While microvascular invasion was the strongest pathological predictor of recurrent HCC, tumor size >or=3 cm (P = 0.004; odds ratio [OR] = 7.42), nuclear grade (P = 0.044; OR = 3.25), microsatellitosis (P = 0.020; OR = 4.82), and giant/bizarre cells (P = 0.028; OR = 4.78) also predicted recurrent HCC independently from vascular invasion. The score and nomogram stratified the risk of recurrent HCC into 3 tiers: low (<5%), intermediate (40-65%), and high (>95%). In conclusion, compared to patients meeting Milan criteria, patients who meet only UCSF criteria have a worse survival and an increased rate of recurrent HCC with long-term follow-up, as well as more frequent occurrence of adverse histopathological features, such as microvascular invasion. Application of a pathological score and nomogram could help identify patients at increased risk for tumor recurrence, who may benefit from increased surveillance or adjuvant therapy.
米兰标准和加利福尼亚大学旧金山分校（UCSF）标准被用于选择肝细胞癌（HCC）患者进行肝移植（LT）。复发性HCC是一个重要的死亡原因。目前尚无广泛接受的病理评估策略来预测移植后复发性HCC。本研究比较了符合米兰标准和UCSF标准患者的病理情况，并制定了一个病理评分和列线图来评估移植后复发性HCC的风险。对1985年至2003年这18年间来自我们中心的所有伴有HCC的移植肝脏进行多种病理特征评估，并记录相关临床数据；进行多变量分析以确定与复发性HCC相关的特征。利用独立预测复发性HCC的病理变量，制定了一个病理评分和列线图来确定复发性HCC的概率。在分析的75例病例中，50例（67%）符合米兰标准，9例（12%）仅符合UCSF标准，16例（21%）根据移植肝脏病理既不符合米兰标准也不符合UCSF标准。有20例复发性HCC病例，平均随访时间为8年。与符合米兰标准的患者相比，仅符合UCSF标准的患者复发性HCC更常见（67%对12%；P<0.001），生存率更低（5年时为15%对83%；8年时为15%对55%；P<0.001）。隐源性肝硬化（25%对5%；P = 0.015）、术前甲胎蛋白>1000 ng/mL（20%对0%；P<0.001）和术后使用OKT3（40%对15%；P = 0.017）在复发性HCC患者中更常见。虽然微血管侵犯是复发性HCC最强的病理预测因素，但肿瘤大小≥3 cm（P = 0.004；比值比[OR]=7.42）、核分级（P = 0.0
