Prognostic Significance of the DNA-Index in Liver Transplantation for Hepatocellular Carcinoma in Cirrhosis

Jonas, Sven; Al-Abadi, Houssein; Benckert, Christoph; Thelen, Armin; Hippler-Benscheid, Michael; Sarıbeyoğlu, Kaya; Radtke, Birgit; Pratschke, Johann; Neuhaus, P.

doi:10.1097/sla.0b013e3181b2b195

Cited by 37 publications

(35 citation statements)

References 31 publications

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“…The DNA index, which is the mean nuclear DNA content of the G₀/G 1 compartment of the neoplastic cell population divided by the DNA content of the G₀/G 1 compartment of the similarly processed group of known diploid reference cells, was automatically calculated. For this study, the previously reported cut-off value for a favorable DNA index of ≤1.5 was used to assess tumor biology [25]. …”

Section: Methodsmentioning

confidence: 99%

“…The remaining specimens were used for DNA cytometry, as previously described [25,27,28]. Monolayer smears were prepared using a previously described cell separation technique [35,36] and were stained according to the Feulgen method [37].…”

Section: Methodsmentioning

confidence: 99%

“…Recent studies showed that it is significantly associated with the overall survival of patients undergoing LT for HCC [25,26], liver resection for intrahepatic cholangiocarcinoma [27], and resection of adenocarcinoma of the pancreatic head [28]. Preoperative assessment of the DNA index in liver biopsies using DNA image cytometry may also help identify a subgroup of patients with advanced HCC who may derive a significant survival benefit from LT.…”

Section: Introductionmentioning

confidence: 99%

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Tumor DNA Index and α-Fetoprotein Level Define Outcome following Liver Transplantation for Advanced Hepatocellular Carcinoma

Ανδρέου¹,

Bahra²,

Guel³

et al. 2015

Eur Surg Res

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Background: Patients with hepatocellular carcinoma (HCC) beyond the Milan criteria are expected to have inferior outcome after liver transplantation (LT) and are therefore currently not considered for LT in many countries. The purpose of this study was to identify predictive factors for overall survival following LT for HCC that may support the Milan criteria in the selection of appropriate transplant candidates. Methods: Clinicopathological data on 364 patients with HCC who underwent LT between 1989 and 2010 were retrospectively evaluated. Predictors of overall survival in the entire cohort as well as in subsets of patients within (n = 214) and beyond (n = 150) the Milan criteria were analyzed. Results: Multivariate analysis in the entire cohort identified DNA index >1.5 (p < 0.0001), α-fetoprotein level (AFP) >200 ng/ml (p = 0.005), and HCC beyond the Milan criteria (p = 0.002) to be associated with worse overall survival. In patients within the Milan criteria (median survival: 170 months), DNA index >1.5 (p < 0.0001) was the only predictor of worse overall survival in multivariate analysis. In patients beyond the Milan criteria (median survival: 44 months), DNA index >1.5, AFP >200 ng/ml, microvascular invasion, patient age >60 years, and DNA index >1.5 concomitant with AFP >200 ng/ml were associated with worse overall survival in univariate analysis. Multivariate analysis identified DNA index >1.5 concomitant with AFP >200 ng/ml (p < 0.0001) as the only independent predictor of worse overall survival. Consequently, patients beyond the Milan criteria with a combined favorable DNA index ≤1.5 and AFP ≤200 ng/ml had a median survival (147 months) comparable to that of patients within the Milan criteria. Conclusions: DNA index and AFP level predict overall survival following LT in patients with advanced HCC beyond the Milan criteria. A combined assessment of these markers during the evaluation of transplant candidates can contribute to the selection of patients with HCC who may benefit from LT independently of their tumor burden.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Tumor DNA Index and α-Fetoprotein Level Define Outcome following Liver Transplantation for Advanced Hepatocellular Carcinoma

Ανδρέου¹,

Bahra²,

Guel³

et al. 2015

Eur Surg Res

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“…Other factors, apart from the Milan criteria, that have been found to influence survival are the histopathologic tumor grade, vascular invasion, and DNA cytometry (DNA ploidy, DNA index) [10,11,23,25]. The signifycant association we found between the arterial-venous asymmetry coefficient, i.e., the ratio of contrast enhancement in the arterial phase to that in the venous phase, and the DNA index suggests that a dynamic MRI study of the liver using the hepatocellular contrast agent Gd-EOB-DTPA provides information on malignancy or the biological aggressiveness of HCC.…”

Section: Tialmentioning

confidence: 99%

“…In a univariate analysis, the same study group also identified the cytometric DNA index as a prognostic parameter in liver transplant recipients after HCC in cirrhosis in addition to the Milan criteria, the histopathologic tumor grade, vascular invasion, and the cytometric DNA index. A multivariate analysis identified the DNA index and vascular invasion as prognostic parameters [10].…”

Section: Tialmentioning

confidence: 99%

Assessing the Malignancy of Hepataocellular Carcinoma in Cirrhosis Using the Hepatocellular Contrast Agent Gd-EOB-DTPA and Correlation with the Cytometric DNA Index

Röttgen¹,

Kobi²,

Grieser³

et al. 2013

AMI

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Aim: Investigation whether the signal intensity of hepatocellular carcinoma (HCC) on dynamic magnetic resonance imaging (MRI) with hepatocellular contrast medium (CM) correlates with the histologic malignancy grade and cytometric DNA index. Material and Methods: MRI at 1.5 T with hepatocellular CM Gd-DTPA-EOB of 63 patients (52 men, 11 women; 64.0 ± 8.5 years) with HCC in cirrhosis. SI of the tumor and liver tissue in sequences (T1, T1fs, T2fs, T1fs + CM (arterial, venous, late venous phase) were correlated like the asymmetry coefficient of the SI in the arterial and venous phases respective the native and late venous phases of the tumor with the histologic malignancy grade and DNA index indicating the grade of abnormal DNA steam line respective aneuploid DNA. Results: SI did not significantly correlate with the histologic malignancy grade or DNA index for precontrast or postcontrast images. There is a significant correlation for the asymmetry coefficient of the SI in the arterial and venous phases with the DNA-index (p values of 0.00089 (Pearson) and 0.0082 (Spearman). Conclusion: A highly arterialized hepatocellular carcinoma with rapid washout in the venous phase corresponds to a higher malignant potential. These findings suggest that the MR parameters investigated here may predict the malignant potential and prognosis of HCC before surgery.

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Prognostic significance of DNA cytometry for adjuvant therapy response in pancreatic cancer

et al. 2015

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Prognostic Significance of the DNA-Index in Liver Transplantation for Hepatocellular Carcinoma in Cirrhosis

Abstract: This is the first study to describe the DNA-index as a strong prognostic indicator after liver transplantation for HCC in cirrhosis. At this time, determination of the DNA-index is likely to be the most promising diagnostic tool in the selection of transplant candidates.

Cited by 37 publications

References 31 publications

Tumor DNA Index and α-Fetoprotein Level Define Outcome following Liver Transplantation for Advanced Hepatocellular Carcinoma

Tumor DNA Index and α-Fetoprotein Level Define Outcome following Liver Transplantation for Advanced Hepatocellular Carcinoma

Assessing the Malignancy of Hepataocellular Carcinoma in Cirrhosis Using the Hepatocellular Contrast Agent Gd-EOB-DTPA and Correlation with the Cytometric DNA Index

Prognostic significance of DNA cytometry for adjuvant therapy response in pancreatic cancer

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