The Up-to-seven (UTS) criteria (sum of tumor size and number not exceeding 7) for indicating liver transplantation (LT) in hepatocellular carcinoma (HCC) were originally based on explant pathology features and absence of microvascular invasion (MVI). 18F-fludeoxyglucose (18F-FDG) positron emission tomography (PET) was shown to indicate the risk of MVI and tumor recurrence. The aim of this study was to analyze the prognostic significance of the clinical UTS criteria when being combined with PET-status of the tumor. Data of 116 liver transplant patients were subject to retrospective analysis. Five-year recurrence-free survival (RFS) rates in patients meeting (n = 85) and exceeding (n = 21) the radiographic UTS criteria were 81% and 55.1%, respectively (p = 0.014). In the UTS In subset, RFS was significantly better in PET-negative (94.9%) than in PET-positive patients (48.3%; p < 0.001). In the UTS Out subset, 5-year RFS rates were 87.1% and 19% in patients with non- 18F-FDG-avid and 18F-FDG-avid tumors (p < 0.001), respectively. Positive PET-status was identified as the only independent clinical predictor of tumor recurrence in beyond UTS patients (Hazard ratio [HR] 19.25; p < 0.001). Combining radiographic UTS criteria with FDG-PET may safely expand the HCC selection criteria for LT.
Background and Objectives: Albumin-bilirubin (ALBI) score was shown to correlate with liver function and tumor recurrence after hepatectomy for hepatocellular carcinoma (HCC). The aim of this study was to assess the prognostic value of ALBI grade in liver transplantation (LT) patients with HCC.Methods: Pre-LT available independent predictors of recurrence-free survival (RFS) and microvascular tumor invasion (MVI) were determined in 123 patients with HCC.Results: Posttransplant HCC recurrence rates were 10.5%, 15.9%, and 68.2% in ALBI grade 1, 2, and 3, respectively (P < .001). Along with serum α-fetoprotein (AFP) and Creactive protein (CRP) levels, ALBI grades 1 or 2 was identified as an independent predictor of RFS (hazard ratio, 3.52; 95% confidence interval [CI], 1.577-7.842; P = .002). Furthermore, ALBI grade 3 proved to be the strongest indicator of MVI (odds ratio, 11.59; 95% CI, 3.412-39.381; P < .001). A novel oncological risk scorebased on AFP, CRP, and ALBI grade provided the best discriminative capacity (cstatistic 0.806) in selecting liver recipients with low oncological risk profile.Conclusion: Preoperative ALBI grade seems to be valuable for refinement of oncological risk stratification at LT for HCC. K E Y W O R D Salbumin-bilirubin grade, hepatocellular carcinoma, liver transplantation, microvascular invasion, tumor recurrence
Liver transplantation (LT) has become standard of care in patients with non-resectable early stage hepatocellular carcinoma (HCC) in liver cirrhosis. Currently, patient selection for LT is strictly based on tumor size and number, provided by the Milan criteria. This may, however, exclude patients with advanced tumor load but favourable biology from a possibly curative treatment option. It became clear in recent years that biological tumor viability rather than tumor macromorphology determines posttransplant outcome. In particular, microvascular invasion and poor grading reflect tumor aggressiveness and promote the risk of tumor relapse. Pretransplant biopsy is not applicable due to tumor heterogeneity and risk of tumor cell seeding. 18F-fludeoxyglucose (18F-FDG) positron emission tomography (PET), an established nuclear imaging device in oncology, was demonstrated to non-invasively correlate with unfavorable histopathologic features. Currently, there is an increasing amount of evidence that 18F-FDG-PET is very useful for identifying eligible liver transplant patients with HCC beyond standard criteria but less aggressive tumor properties. In order to safely expand the HCC selection criteria and the pool of eligible liver recipients, tumor evaluation with 18F-FDG-PET should be implemented in pretransplant decision process.
The rising incidence of esophageal adenocarcinoma (EAC) is mirrored by the increasing prevalence of Barrett’s Esophagus (BE), a precursor lesion resulting in a large number of individuals “at risk” for this lethal malignancy. Among BE patients only ~0.3% annually will develop EAC. Since large numbers of patients are followed in endoscopic surveillance, there is a need for risk prediction among a growing population of BE patients. We identified 4 potential biomarkers from an inflammation (IL-1β)-dependent mouse model of Barrett’s esophagus and tested them in 189 BE patients with and without HGD/early cancer (T1). The primary goal was to distinguish BE patients with no evidence of dysplasia from those with dysplasia. Increasing stem cell marker LGR5 and niche cell marker DCLK1 and decreasing differentiation marker (secretory mucus cells, TFF2+ cells) correlated with elevated tumor score in the mouse. Having outlined the origin of those markers in the BE mouse model we showed the applicability for human BE: We compared 96 patients with non-dysplastic BE tissue to 97 patients with BE and HGD or early cancer. Low levels of TFF2 (AUC 87.2%) provided the best discrimination between non-dysplastic BE and BE with cancer, followed by high levels of DCLK1 (AUC 83.4%), low GC ratio (AUC 79.4%) and high LGR5 (AUC 71.4%). The GC ratio, rather than the presence of GCs per se, was found to be an important discriminator. These findings may be useful in developing future risk prediction models for BE patients and ultimately to improve EAC surveillance.
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