Hepatocellular carcinomas in native livers from patients treated with orthotopic liver transplantation: Biologic and therapeutic implications

Kırımlıoğlu, Hale; Dvorchick, Igor; Ruppert, Kristine; Finkelstein, Sydney; Marsh, J. Wallis; Iwatsuki, Shunzaburo; Bonham, Andrew; Carr, Brian I.; Nalesnik, Michael A.; Michalopoulos, George K.; Starzl, Thomas E.; Fung, John J.; Demetris, Anthony J.

doi:10.1053/jhep.2001.26633

Cited by 60 publications

(42 citation statements)

References 39 publications

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“…23 Clearly, HCC recurrence after OLT represents a complex interplay of host-and tumor-related factors, the nature of which has yet to be fully elucidated. 19 In conclusion, our results support a modest expansion of the tumor size limits of the Milan criteria (the UCSF criteria) while still preserving acceptable survival after OLT. The expanded criteria offered the benefits of OLT to about 20% of our patients who would have otherwise been excluded from OLT under the more restrictive Milan criteria.…”

Section: Discussionsupporting

confidence: 69%

“…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%

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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

384

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: Discussionsupporting

confidence: 69%

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

384

268

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“…A recent study suggested that certain histological features may be predictive of a tumor's aggressiveness, such as degree of differentiation and low apoptosis-mitosis ratio. 21 However, more studies are needed to identify factors that would stratify HCC tumors on their predicted growth rates to help triage donor organs more effectively. Until then, policymakers may want to consider adding a MELD adjustment factor for the presence of HCC.…”

Section: Discussionmentioning

confidence: 99%

Predicting the probability of progression-free survival in patients with small hepatocellular carcinoma

Cheng

2002

Liver Transplantation

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Allocation of cadaveric livers to patients based on such objective medical urgency data as the Model for End-Stage Liver Disease (MELD) score may not benefit patients with small hepatocellular carcinomas (HCCs). To ensure that these patients have a fair opportunity of receiving a cadaveric organ, the risk for death caused by HCC and tumor progression beyond 5 cm should be considered. Using a Markov model, two hypothetical cohorts of patients with small hepatomas were assumed to have either (1) Gompertzian tumor growth, in which initial exponential growth decreases as tumor size increases; or (2) rapid exponential growth. The model tracked the number of patients who either died or had tumor progression beyond 5 cm. These results were used to back-calculate an equivalent MELD score for patients with small HCCs. All probabilities in the model were varied simultaneously using a Monte Carlo simulation. The Gompertzian growth model predicted that patients with a 1-and 4-cm tumor have 1-year progression-free survival rates of 70% (HCC-specific MELD score 6) and 66% (HCC-specific MELD score 8), respectively. When assuming rapid exponential growth, patients with a 1-and 4-cm tumor have progression-free survival rates of 69% (HCC-specific MELD score 6) and 12% (HCC-specific MELD score 24), respectively. Our model predicted that the risk for death caused by HCC or tumor progression beyond 5 cm should increase with larger initial tumor size in patients with small hepatomas. To ensure that these patients have a fair opportunity to receive a cadaveric organ, HCC-specific scores predicted by our model could be added to MELD scores of patients with HCC. (Liver Transpl 2002;8:323-328.) T he mandate by the Department of Health and Human Services to allocate livers to the sickest patients based on objective medical urgency data has led to the proposal that prioritization of liver transplant candidates be based on a model developed by the Mayo Clinic, the Model for End-Stage Liver Disease (MELD). 1-3 The MELD formula uses prognostic factors and disease cause to calculate a risk score for mortality on the waiting list. Patients with a higher score have a higher priority for receiving a donor liver. Under the MELD scoring system, patients with early hepatocellular carcinoma (HCC) are unlikely to achieve a high score because many of these patients have well-maintained liver synthetic function. However, without a timely transplant for these patients, HCC may progress in size and lead to death.How could access to timely transplantation be improved for patients with HCC under the MELD system? One approach would be to incorporate into the MELD the likelihood of being removed from the waiting list because of death secondary to HCC or disease progression. In the absence of a published trial, decision analytic modeling is a method that can be used to estimate this likelihood. Previously published decision models have assessed the risk for HCC tumor progression by assuming that tumor growth is constant. 4,5 However, several natural history st...

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“…5 Similarly, HCC development has been speculated to be a multistage process because of its progressively pathologic morphology. 6 However, the stepwise progress in human HCC is ill defined and specific genetic changes associated with HCC progression remain vague. 7 This has been explained by the finding that most HCC tissue specimens used for analysis may be at an advanced stage and most of the changes found in these lesions can be secondary.…”

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confidence: 99%

Cancer-associated molecular signature in the tissue samples of patients with cirrhosis†

et al. 2004

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Several types of aggressive cancers, including hepatocellular carcinoma (HCC), often arise as a multifocal primary tumor. This suggests a high rate of premalignant changes in noncancerous tissue before the formation of a solitary tumor. Examination of the messenger RNA expression profiles of tissue samples derived from patients with cirrhosis of various etiologies by complementary DNA (cDNA) microarray indicated that they can be grossly separated into two main groups. One group included hepatitis B and C virus infections, hemochromatosis, and Wilson's disease. The other group contained mainly alcoholic liver disease, autoimmune hepatitis, and primary biliary cirrhosis. Analysis of these two groups by the cross-validated leave-one-out machine-learning algorithms revealed a molecular signature containing 556 discriminative genes (P < .001). It is noteworthy that 273 genes in this signature (49%) were also significantly altered in HCC (P < .001). Many genes were previously known to be related to HCC.

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Hepatocellular carcinomas in native livers from patients treated with orthotopic liver transplantation: Biologic and therapeutic implications

Cited by 60 publications

References 39 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

Predicting the probability of progression-free survival in patients with small hepatocellular carcinoma

Cancer-associated molecular signature in the tissue samples of patients with cirrhosis†

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