AIM\nTo evaluate the prognostic value of pretreatment FDG positron emission tomography computed tomography (PET-CT) in patients with hepatocarcinoma treated by liver transplantation (LT).\n\n\nMETHODS\nThe authors retrospectively analyzed the data of 27 patients (mean age 58 ± 9 years) who underwent FDG PET-CT before LT for hepatocarcinoma. Mean follow-up was 26 ± 18 mo. The FDG PET/CT was performed according to a standard clinical protocol: 4 MBqFDG/kg body weight, uptake 60 min, low-dose non-enhanced CT. The authors measured the SUVmax and SUVmean of the tumor and the normal liver. The tumor/liver activity ratios (RSUVmax and RSUVmean) were tested as prognostic factors and compared to the following conventional prognostic factors: MILAN, CLIP, OKUDA, TNM stage, alphafoetoprotein level, portal thrombosis, size of the largest nodule, tumor differentiation, microvascular invasion, underlying cirrhosis and liver function.\n\n\nRESULTS\nOverall and recurrence free survivals were 80.7% and 67.4% at 3 years, and 70.6% and 67.4% at 5 years, respectively. According to a multivariate Cox model, only FDG PET/CT RSUVmax predicted recurrence free survival. Even though the MILAN criteria alone were not predictive, it is worth noting that none of the patients outside the MILAN criteria and with RSUVmax < 1.15 relapsed.\n\n\nCONCLUSION\nFDG PET/CT with an RSUVmax cut-off value of 1.15 is a strong prognostic factor for recurrence and death in patients with HCC treated by LT in this retrospective series. Further prospective studies should test whether this metabolic index should be systematically included in the preoperative assessment.

Prognostic value of (18)F-FDG PET/CT in liver transplantation for hepatocarcinoma.

Liver transplantation (LT) is one of the most effective treatments for hepatocellular carcinoma (HCC). Although LT eliminates HCC and greatly reduces recurrence, some patients experience recurrence after LT. Criteria and models for screening patients with a high probability of HCC recurrence after LT, starting with the Milan criteria, have been published. These models have changed over time, but a standard has not been established. We summarized HCC prediction models after LT by focusing on the application of radiologic, serologic, and pathologic factors and recent trends. This review will look at studies that are based on living donor LT and deceased donor LT, as well as studies that downstaging procedures have been performed preoperatively. This ultimately aims to help make decisions for evaluating the HCC state and selecting candidates for LT according to the circumstances of each transplantation center.

/pdf/prediction-models-of-hepatocellular-carcinoma-recurrence-39t5kxm5.pdf

Prediction models of hepatocellular carcinoma recurrence after liver transplantation: A comprehensive review

Hepatocellular carcinoma (HCC) is amongst the cancers with highest mortality rates and is the most common malignancy of the liver. Early detection is vital to provide the best treatment possible and liquid biopsies combined with analysis of circulating tumour DNA methylation show great promise as a non-invasive approach for early cancer diagnosis and monitoring with low false negative rates. To identify reliable diagnostic biomarkers of early HCC, we performed a systematic analysis of multiple hepatocellular studies and datasets comprising > 1500 genome-wide DNA methylation arrays, to define a methylation signature predictive of HCC in both tissue and cell-free DNA liquid biopsy samples. Our machine learning pipeline identified differentially methylated regions in HCC, some associated with transcriptional repression of genes related with cancer progression, that benchmarked positively against independent methylation signatures. Combining our signature of 38 DNA methylation regions, we derived a HCC detection score which confirmed the utility of our approach by identifying in an independent dataset 96% of HCC tissue samples with a precision of 98%, and most importantly successfully separated cfDNA of tumour samples from healthy controls. Notably, our risk score could identify cell-free DNA samples from patients with other tumours, including colorectal cancer. Taken together, we propose a comprehensive HCC DNA methylation fingerprint and an associated risk score for detection of HCC from tissue and liquid biopsies. 

/pdf/dna-methylation-fingerprint-of-hepatocellular-carcinoma-from-1vsfjazm.pdf

DNA methylation fingerprint of hepatocellular carcinoma from tissue and liquid biopsies

Autoren M. Bitzer1, S. Voesch1, J. Albert2, P. Bartenstein3, W. Bechstein4, S. Blödt5, T. Brunner6, F. Dombrowski7, M. Evert8, M. Follmann9, C. La Fougère10, P. Freudenberger11, A. Geier12, E. Gkika13, M. Götz14, E. Hammes15, T. Helmberger16, R. T. Hoffmann17, W. P. Hofmann18, P. Huppert19, A. Kautz20, G. Knötgen21, J. Körber22, D. Krug23, F. Lammert24, H. Lang25, T. Langer26, P. Lenz27, A. Mahnken28, A. Meining29, O. Micke30, S. Nadalin31, H. P. Nguyen32, J. Ockenga33, K. Oldhafer34, P. Paprottka35, K. Paradies36, P. Pereira37, T. Persigehl38, M. Plauth39, R. Plentz40, J. Pohl41, J. Riemer42, P. Reimer43, J. Ringwald44, U. Ritterbusch45, E. Roeb46, B. Schellhaas47, P. Schirmacher48, I. Schmid49, A. Schuler50, D. von Schweinitz51, D. Seehofer52, M. Sinn53, A. Stein54, A. Stengel55, N. Steubesand56, C. Stoll57, A. Tannapfel58, A. Taubert59, J. Trojan60, I. van Thiel61, R. Tholen62, A. Vogel63, T. Vogl64, H. Vorwerk65, F. Wacker66, O. Waidmann67, H. Wedemeyer68, H. Wege69, D. Wildner70, C. Wittekind71, M. A. Wörns72, P. Galle72, N. Malek73

/pdf/s3-leitlinie-diagnostik-und-therapie-biliarer-karzinome-20dw2xbw.pdf

S3-Leitlinie Diagnostik und Therapie biliärer Karzinome

Transarterial radioembolization (TARE) with yttrium-90 (90Y) microspheres has been widely adopted for the treatment of HCC. Recent advances in yttrium-90 (90Y) dosimetry have led to durable local responses. Radiation segmentectomy has become a viable alternative to thermal ablation for early-stage HCC (Barcelona Clinic Liver Cancer 0 and A) and has been commonly used as a bridge to transplant. TARE is also commonly used for downstaging to transplant using traditional lobar dosimetry and radiation segmentectomy techniques. Radiation lobectomy has a dual role in local tumor control and induction of contralateral liver lobe hypertrophy as a bridge to resection for patients with an inadequate future liver remnant. TARE continues to provide disease control for patients with limited vascular invasion and may be an alternative to systemic therapy for patients with localized advanced disease. The potential synergy between TARE and immunotherapy has been recognized, and prospective studies evaluating this combination are needed for patients with Barcelona Clinic Liver Cancer B and C HCC. 

Contemporary applications of Y90 for the treatment of hepatocellular carcinoma

Background Recent studies indicate that a group of patients with cirrhosis receiving a liver transplantation for hepatocellular cancer (HCC) beyond the Milan Criteria (MC) can achieve a similar outcome compared to patients within these criteria. This study aims to investigate the value of the Asan critera (AC), up-to-7 criteria (UT7), French alpha-foetoprotein (AFP) model and Metroticket 2.0 (MT2.0) model compared to the MC. Methods 526 patients transplanted for non-metastatic HCC were analyzed. Patient groups within and beyond MC and extended criteria were determined according to radiological assessment and AFP value at listing. Results Overall survival (OS) and recurrence (RR) rates were similar between patients within MC and all extended criteria. Five-year OS within MC was 71.3% compared to 70.9% for AC, 71.4% for UT7, 69.7% for AFP-model and 71.0% for MT2.0 criteria. Five-year RR within MC was 12.3% compared to 13.5% for AC, 13.0% for UT7, 14.3% for AFP-model and 13.2% for MT2.0 criteria. Patients beyond MC but within the extended criteria had tendency towards higher recurrence. Conclusions All validated extended criteria (AC, UT7, AFP-model and MT2.0) could be proposed as alternatives to the MC with similar outcome. Prospective data are awaited to assess recurrence beyond MC.

/pdf/extended-criteria-for-liver-transplantation-in-2ytsdu2d58.pdf

Extended criteria for liver transplantation in hepatocellular carcinoma. A retrospective, multicentric validation study in Belgium.

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Extended criteria for liver transplantation in hepatocellular carcinoma. A retrospective, multicentric validation study in Belgium.