The DNA index is a strong predictive marker in intrahepatic cholangiocarcinoma: the results of a five-year prospective study

Kamphues, Carsten; Al-Abadi, Nadine; Dürr, Angelika; Bova, Roberta; Klauschen, Frederick; Bahra, Marcus; Al-Abadi, H.; Neuhaus, P.; Seehofer, Daniel

doi:10.1007/s00595-013-0701-7

Cited by 13 publications

(13 citation statements)

References 20 publications

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“…Surrogate factors for tumor behavior such as the DNA index have already been established by our group as biological markers for the selection of candidates for curative treatment among patients with pancreatic carcinoma [28] and intrahepatic cholangiocarcinoma [27] and also as strong prognostic factors for overall survival in patients undergoing LT for HCC in cirrhosis [25,26]. Pretransplantation percutaneous biopsies from the largest HCC nodule and evaluations of the DNA index can be easily performed, facilitating decision making in the interdisciplinary LT board.…”

Section: Discussionmentioning

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: Discussionmentioning

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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“…Recent studies have described the DNA index as an objective tool to express tumour biology. This tumour marker is defined as the ratio of the DNA content of tumour cells to the DNA content of the diploid reference cells and cut‐off values ≤1.5, ≤1.4 and ≤2 have been reported to be associated with favourable biology and improved survivals after LT for HCC, liver resection for intrahepatic cholangiocarcinoma and resection of adenocarcinoma of the pancreatic head, respectively.…”

Section: Introductionmentioning

confidence: 99%

Patient and tumour biology predict survival beyond the Milan criteria in liver transplantation for hepatocellular carcinoma

Ανδρέου

Gül

Pascher

et al. 2015

HPB

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“…Such conditions lead to 80 % of cases being ineligible for curative surgical treatment [3]. Patients with unresectable HCC cannot generally be cured by systemic chemotherapy or radiotherapy [3], because hepatoma cells respond poorly to conventional approaches [4–6]. Given the limited efficacy of existing treatments for hepatoma cells, the molecular mechanisms underlying the pathogenesis of HCC need to be understood so that novel and efficient targeted therapies may be developed for these patients.…”

Section: Introductionmentioning

confidence: 99%

DNA damage response and sphingolipid signaling in liver diseases

et al. 2015

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Patients with unresectable hepatocellular carcinoma (HCC) cannot generally be cured by systemic chemotherapy or radiotherapy due to their poor response to conventional therapeutic agents. The development of novel and efficient targeted therapies to increase their treatment options depends on the elucidation of the molecular mechanisms that underlie the pathogenesis of HCC. The DNA damage response (DDR) is a network of cell-signaling events that are triggered by DNA damage. Its dysregulation is thought to be one of the key mechanisms underlying the generation of HCC. Sphingosine-1-phosphate (S1P), a lipid mediator, has emerged as an important signaling molecule that has been found to be involved in many cellular functions. In the liver, the alteration of S1P signaling potentially affects the DDR pathways. In this review, we explore the role of the DDR in hepatocarcinogenesis of various etiologies, including hepatitis B and C infection and non-alcoholic steatohepatitis. Furthermore, we discuss the metabolism and functions of S1P that may affect the hepatic DDR. The elucidation of the pathogenic role of S1P may create new avenues of research into therapeutic strategies for patients with HCC.

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The DNA index is a strong predictive marker in intrahepatic cholangiocarcinoma: the results of a five-year prospective study

Cited by 13 publications

References 20 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

Patient and tumour biology predict survival beyond the Milan criteria in liver transplantation for hepatocellular carcinoma

DNA damage response and sphingolipid signaling in liver diseases

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