Prognostic grade for resecting hepatocellular carcinoma: multicentre retrospective study
Tadatoshi TakayamaShintaro YamazakiYutaka MatsuyamaYutaka MidorikawaShuichiro ShiinaNamiki IzumiKiyoshi HasegawaNorihiro KokudoMichiie SakamotoShoji KuboMasatoshi KudoTakamichi MurakamiO Nakashima
4
Citation
28
Reference
10
Related Paper
Citation Trend
Abstract:
Abstract Background Surgical treatment for hepatocellular carcinoma (HCC) is advancing, but a robust prediction model for survival after resection is not available. The aim of this study was to propose a prognostic grading system for resection of HCC. Methods This was a retrospective, multicentre study of patients who underwent first resection of HCC with curative intent between 2000 and 2007. Patients were divided randomly by a cross-validation method into training and validation sets. Prognostic factors were identified using a Cox proportional hazards model. The predictive model was built by decision-tree analysis to define the resection grades, and subsequently validated. Results A total of 16 931 patients from 795 hospitals were included. In the training set (8465 patients), four surgical grades were classified based on prognosis: grade A1 (1236 patients, 14.6 per cent; single tumour 3 cm or smaller and anatomical R0 resection); grade A2 (3614, 42.7 per cent; single tumour larger than 3 cm, or non-anatomical R0 resection); grade B (2277, 26.9 per cent; multiple tumours, or vascular invasion, and R0 resection); and grade C (1338, 15.8 per cent; multiple tumours with vascular invasion and R0 resection, or R1 resection). Five-year survival rates were 73.9 per cent (hazard ratio (HR) 1.00), 64.7 per cent (HR 1.51, 95 per cent c.i. 1.29 to 1.78), 50.6 per cent (HR 2.53, 2.15 to 2.98), and 34.8 per cent (HR 4.60, 3.90 to 5.42) for grades A1, A2, B, and C respectively. In the validation set (8466 patients), the grades had equivalent reproducibility for both overall and recurrence-free survival (all P < 0.001). Conclusion This grade is used to predict prognosis of patients undergoing resection of HCC.Keywords:
Grading (engineering)
Milan criteria
Vascular invasion
We thank Dr. Sugawara Y and Dr. Kim R for their insightful comments on our recent study (1). Organ allocation and selection of eligible candidates have always been a dilemma in liver transplantation for hepatocellular carcinoma (HCC). Milan criteria successfully defined a subset of patients with acceptable outcomes. However, several groups have presented excellent outcomes when extending Milan criteria. And strict adherence to Milan criteria denies access to a possible curative liver transplant in around 1/3 of potential recipients (2). To approach an optimized patient selection criteria, our group proposed Hangzhou criteria, which use a strategy combining tumor biological behavior and morphology (3). About Hangzhou criteria, both the two commentaries provide interesting but incisive insights, which are noteworthy.
Milan criteria
Waiting list
Liver Cancer
Cite
Citations (1)
Milan criteria
Cite
Citations (0)
Abstract The incidence of hepato cellular carcinoma (HCC) and the shortage of grafts restrict liver transplantation (LT) in HCC patients with a low risk of recurrence. The risk of recurrence is mainly related to the presence of vascular invasion which increases in parallel with tumour size and number of nodules. A favourable post‐transplant outcome has been observed in patients who meet the empirically defined Milan criteria, namely, a single nodule < 5 cm or two or three nodules each < 3 cm in the absence of macroscopic vascular invasion, based on pre‐transplant imaging. These criteria were felt to be too restrictive, leading several centers to propose expanded criteria for LT. However, increasing both the size and number of nodules resulted in an increased risk of recurrence. It has not been demonstrated that loco‐regional treatment in HCC patients listed for LT (bridging therapies) improve post‐transplant survival. More precise predictors of negative prognostic factors including elevated α‐feto protein level, poor differentiation and molecular techniques should be considered in order to optimize the use of grafts and achieve zero recurrence.
Milan criteria
Economic shortage
Nodule (geology)
Vascular invasion
Liver Cancer
Cite
Citations (14)
Expansion of the hepatocellular carcinoma Milan criteria in liver transplantation: Future directions
Milan criteria are currently the benchmark related to liver transplantation (LT) for hepatocellular carcinoma.However, several groups have proposed different expanded criteria with acceptable results.In this article, we review the current status of LT beyond the Milan criteria in three different scenarios-expanded criteria with cadaveric LT, downstaging to Milan criteria before LT, and expansion in the context of adult living donor LT.The review focuses on three main questions: what would the impact of the expansion beyond Milan criteria be on the patients on the waiting list; whether the dichotomous criteria (yes/ no) currently used are appropriate for LT or continuous survival estimations, such as the one of "Metroticket" and whether it should enter into the clinical practice; and, whether the use of living donor LT in the context of expansion beyond Milan criteria is justified.
Milan criteria
Cite
Citations (55)
To compare microvascular invasion (McVI) with parameters defined by the Milan criteria in predicting tumor recurrence and overall survival (OS) in patients with surgical resection (SR) for hepatocellular carcinoma (HCC).Although the Milan criteria is discriminatory for selecting patients with good outcomes in liver transplantation and SR for HCC, it neither adequately predict tumor recurrence nor explain differences in survival for patients with good liver function. McVI is a strong indicator of intrahepatic metastasis in HCC, but its relative significance for predicting clinical outcomes compared to the Milan criteria is unclear.Patients undergoing SR with curative intent from January 2000 to March 2009 at the Singapore General Hospital were followed up for long-term outcomes till January 1, 2010. They were stratified first by the Milan criteria and then by the presence of McVI and compared relative to OS.Altogether, 454 of the 515 patients received curative SR. There were stratified into 4 groups (Milan+, McVI-), (Milan+, McVI+), (Milan-, McVI-), and (Milan-, McVI+). All pair-wise comparisons between groups relative to OS were significant except (Milan+, McVI-) (OS, 90%, 73%, and 60% at 1, 3, and 5 years) with (Milan-, McVI-) (OS, 86%, 71%, and 61% at 1, 3, 5 years) and (Milan+, McVI+) with (Milan-, McVI+). Multivariate Cox regression analysis showed that McVI was predictive of OS, after which Milan status did not add additional discriminative information.McVI is a better predictor of tumor recurrence and OS than the Milan criteria after SR for HCC. Assessment of McVI should aid in patient selection for adjuvant treatments to improve outcomes after SR.
Milan criteria
Cite
Citations (456)
Milan criteria
Liver disease
Liver Cancer
Cite
Citations (9)
Bloom, Roy; Naraghi, Robert; Cibrik, Diane; Angelis, Michael; Mulgoankar, Shamkant; Kaplan, Bruce; Gaston, Robert; Gordon, Robert Author Information
Milan criteria
Vascular invasion
Cite
Citations (0)
Milan criteria
Vascular invasion
Cite
Citations (15)
To evaluate the risk factors for recurrence in patients with hepatocellular carcinoma (HCC) after liver transplantation (LT).One hundred and fifteen small HCC patients, who met Milan criteria (single<5 cm or showing up to three nodules, each of them<3 cm without major vascular invasion or distant metastasis) and underwent LT in our hospital from January 2007 to November 2013, were enrolled in the study. The risk factors for recurrence were analyzed by Cox regression and the influence of the Milan criteria and microvascular invasion (MVI) on the disease-free survival (DFS) and recurrence of patients were assessed with survival analysis and ROC method.Ninety-eight out of 115 small HCC patients were included for analysis, the 1-,3-, 5-year overall survival of patients was 91.8%, 80.6%, 79.6% and DFS was 87.8%, 74.5%, 73.5%, respectively. Survival analysis identified that MVI, macro-vascular invasion, exceeding the Milan criteria and pre-transplant down-staging treatment were related to tumor recurrence (P<0.05). Multivariate Cox regression analysis showed that MVI and exceeding the Milan criteria were two independent prognostic indicators for early recurrence of small HCC after LT. The 1-,3-,5-year DFS for 69 patients without MVI and 29 patients with MVI were 92.8%, 85.5%, 85.5% and 75.9%, 55.2%, 48.3%, respectively (P<0.01). The 1-,3-,5-year DFS for 84 patients meeting the Milan criteria and 14 exceeding the Milan criteria were 91.7%, 83.3%, 79.8% and 64.3%, 42.9%, 42.9%, respectively (P<0.01).For early HCC patients undergoing LT, the presence of MVI would predict tumor recurrence and can be an indicator for the adjuvant treatment or other salvage treatments.
Milan criteria
Vascular invasion
Cite
Citations (2)
Milan criteria
Vascular invasion
Cite
Citations (0)