Impact of Histological Grade of Hepatocellular Carcinoma on the Outcome of Liver Transplantation

Tamura, Sumihito; Kato, Tomoaki; Berho, Mariana; Misiakos, Evangelos P.; O’Brien, Christopher; Reddy, K. Rajender; Nery, Jose; Burke, George W.; Schiff, Eugene R.; Miller, Joshua; Tzakis, Andreas G.

doi:10.1001/archsurg.136.1.25

Cited by 240 publications

(179 citation statements)

References 36 publications

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“…Furthermore, the Pittsburgh group observed that in 30% of the cases, the same combination of tumor characteristics in their prognostic model did not correlate well with clinical outcome as predicted. 19 Several published studies have found poorly differentiated histologic grade, 17,20,21 or microvascular invasion, 11,22 or both 23 to be independent predictors of impaired survival after OLT. The present study suggests a strong correlation of these histologic features with more advanced tumor stage exceeding the limits of the Milan and UCSF criteria, albeit to a lesser degree for the latter (Table 4).…”

Section: Discussionmentioning

confidence: 99%

Liver transplantation for hepatocellular carcinoma: Comparison of the proposed UCSF criteria with the Milan criteria and the Pittsburgh modified TNM criteria

Yao¹

2002

Liver Transplantation

383

268

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We previously proposed modified staging criteria for predicting acceptable outcome after orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC). These were solitary tumor <6.5 cm, or three or fewer nodules with the largest lesion <4.5 cm and total tumor diameter <8 cm, without gross vascular invasion (University of California, San Francisco [UCSF] criteria). In this study, we further evaluated the performance of the Milan criteria (solitary tumor <5 cm, or three or fewer lesions none >3 cm), the UCSF criteria, and the Pittsburgh modified tumor-node-metastasis (TNM) criteria. Pathologic HCC staging according to each set of criteria was performed in 70 patients. The difference in survival when comparing 24 patients with HCC exceeding Milan criteria versus 46 patients meeting Milan criteria did not reach statistical significance (HR, 2.0; P ‫؍‬ .12). Using our definition for acceptable 2-year survival to be >70%, the 14 patients (20%) meeting UCSF criteria but exceeding Milan criteria had a 2-year survival of 86% (95% CI, 54% to 96%). Survival for Pittsburgh stage I, II, and IIIA patients as a group was significantly better than for stages IIIB and IVA patients combined (HR, 4.2; P ‫؍‬ .007), and similar to survival for patients meeting UCSF criteria. Advanced tumor exceeding UCSF criteria served reasonably well as a surrogate marker for poorly differentiated grade and microvascular invasion. In conclusion, our analyses suggest that UCSF criteria better predict acceptable posttransplant outcome than Milan criteria. UCSF criteria confer a different advantage over Pittsburgh criteria, which require information on microvascular invasion that is difficult to ascertain preoperatively without the attendant risk of biopsy. (Liver Transpl 2002;8:765-774.)

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Section: Discussionmentioning

confidence: 99%

Liver transplantation for hepatocellular carcinoma: Comparison of the proposed UCSF criteria with the Milan criteria and the Pittsburgh modified TNM criteria

Yao¹

2002

Liver Transplantation

383

268

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“…Hence, the serum biomarkers alpha-fetoprotein (AFP) and protein induced by vitamin K absence-II (PIVKA-II) are used as prognostic markers 7,8 and also as surrogate markers for microvascular invasion and tumor differentiation. 9,10 AFP is associated with grade differentiation, 11 whereas PIVKA-II is related to vascular invasion. 12,13 However, these tumor markers have limited sensitivity and are less predictive than microvascular invasion, 14,15 which is the most potent determinant of recurrence and survival in HCC patients undergoing a hepatectomy.…”

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confidence: 99%

Identification of novel serum biomarkers of hepatocellular carcinoma using glycomic analysis

et al. 2013

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The altered N-glycosylation of glycoproteins has been suggested to play an important role in the behavior of malignant cells. Using glycomics technology, we attempted to determine the specific and detailed N-glycan profile for hepatocellular carcinoma (HCC) and investigate the prognostic capabilities. From 1999 to 2011, 369 patients underwent primary curative hepatectomy in our facility and were followed up for a median of 60.7 months. As normal controls, 26 living Japanese related liver transplantation donors were selected not infected by hepatitis B and C virus. Their mean age was 40.0 and 15 (57.7%) were male. We used a glycoblotting method to purify N-glycans from preoperative blood samples from this cohort (10 lL serum) which were then identified and quantified using mass spectrometry (MS). Correlations between the N-glycan levels and the clinicopathologic characteristics and outcomes for these patients were evaluated. Our analysis of the relative areas of all the sugar peaks identified by MS, totaling 67 N-glycans, revealed that a proportion had higher relative areas in the HCC cases compared with the normal controls. Fourteen of these molecules had an area under the curve of greater than 0.80. Analysis of the correlation between these 14 N-glycans and surgical outcomes by univariate and multivariate analysis identified G2890 (m/z value, 2890.052) as a significant recurrence factor and G3560 (m/z value, 3560.295) as a significant prognostic factor. G2890 and G3560 were found to be strongly correlated with tumor number, size, and vascular invasion. Conclusion: Quantitative glycoblotting based on whole serum N-glycan profiling is an effective approach to screening for new biomarkers. The G2890 and G3560 N-glycans determined by tumor glycomics appear to be promising biomarkers for malignant behavior in HCCs. (HEPATOLOGY 2013;57:2314-2325 H epatocellular carcinoma (HCC) is a common and fatal malignancy with a worldwide occurrence.1 Liver resection has shown the highest level of control among the local treatments for HCC and is associated with a good survival rate.2,3 However, the recurrence rates for HCC are still high even when a curative hepatectomy is performed. 4 Many factors associated with the prognosis and recurrence of HCC have now been reported. Vascular invasion of the portal vein and/or hepatic vein and tumor differentiation are important factors affecting survival and recurrence in HCC cases after a hepatectomy. 5,6 However, microvascular invasion and differentiation can only be detected by pathological examination just after a hepatectomy, and cannot be diagnosed preoperatively, and thus cannot be identified preoperatively either. Hence, the serum biomarkers alpha-fetoprotein (AFP) and protein induced by vitamin K absence-II (PIVKA-II) are used as prognostic markers 7,8 and also as surrogate markers for microvascular invasion and tumor differentiation.9,10 AFP is associated with grade differentiation, 11 whereas PIVKA-II is related to vascularAbbreviations: AFP, alpha-fetoprotein; AFP-L3, lens cul...

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“…Despite size, tumor volume, and absence of extrahepatic disease being the predominant factors in consideration of patients with HCC for LT, molecular, genetic markers, and markers of invasiveness may have a significant role to play in determining the outcomes after transplantation. Functional allelic imbalance [25], high tumor grade (G2 and G3) [26], and mVI [27] have been predictive of early recurrence without adjusting for tumor volume. The correlation between tumor volume and mVI has also not been consistently demonstrated to be linear.…”

Section: History and Evolution Of Liver Transplantation For Hccmentioning

confidence: 99%

Liver Transplantation for HCC: A Review

Kakodkar¹,

Soin²

2011

Indian J Surg

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Hepatocellular carcinoma (HCC) often occurs in patients with chronic liver disease or cirrhosis. Liver transplantation for hepatocellular carcinoma has the potential to eliminate both the tumor as well as the underlying cirrhosis and is the ideal treatment for HCC in cirrhotic liver as well as massive HCC in noncirrhotic liver. Limitations in organ availability, necessitate stringent selection of patients who would likely to derive most benefit. Selection criteria have considered tumor size, number, volume as well as biological features. The Milan criteria set the benchmark for tumors that would benefit from liver transplantation but were found to be excessively restrictive. Modest expansion in criteria has also been shown to be associated with equivalent survival. Microvascular invasion is the single most important adverse prognostic factor for survival. Living donor liver transplantation has expanded donor options and has the advantage of lower waiting period and not impacting the non-HCC waiting list. Acceptable outcomes have been obtained with living donor liver transplantation for larger and more numerous tumors in the absence of microvascular invasion. Downstaging of tumors to prevent progression while waiting for an organ or for reduction in size to allow enrolment for transplantation has met with variable success.

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Impact of Histological Grade of Hepatocellular Carcinoma on the Outcome of Liver Transplantation

Cited by 240 publications

References 36 publications

Liver transplantation for hepatocellular carcinoma: Comparison of the proposed UCSF criteria with the Milan criteria and the Pittsburgh modified TNM criteria

Liver transplantation for hepatocellular carcinoma: Comparison of the proposed UCSF criteria with the Milan criteria and the Pittsburgh modified TNM criteria

Identification of novel serum biomarkers of hepatocellular carcinoma using glycomic analysis

Liver Transplantation for HCC: A Review

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