Evaluation of the current guidelines for resection of hepatocellular carcinoma using the Appraisal of Guidelines for Research and Evaluation II instrument.

BACKGROUND & AIMS: Numerous guidelines for the management of hepatocellular carcinoma (HCC) have been developed. The Appraisal of Guidelines for Research & Evaluation (AGREE II) is the only validated instrument to assess the methodological quality of guidelines. We aim to appraise the methodological quality of existing guidelines for the resection of HCC using the AGREE II instrument. METHODS: Cochrane, Medline, Google Scholar and Embase were searched using both PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria and free text. The assessment of the included clinical practice guidelines and consensuses were performed using the AGREE II instrument, version 2013. Guidelines with a score ⩾80% for the overall appraisal item were considered as applicable without modifications. RESULTS: Literature searches identified 22 clinical practice guidelines. Five out of 22 guidelines passed the 70% mark on overall assessment, 11 out of 22 had shortcomings on indications, contraindications, side effects, key recommendations, technical aspects, transparency and health economics. Ten of 22 scored below the 50% mark showing that the guideline had low methodological and overall quality. Only 3/22 clinical practice guidelines were considered applicable without modifications. CONCLUSIONS: The methodological quality of guidelines for the surgical management of HCC is generally poor. Future guideline development should be informed by the use of the AGREE II instrument. Guidelines based upon high quality evidence could improve stratification of patients and individualized treatment strategies. Lay summary: The methodology of clinical practice guidelines for resection for hepatocellular carcinoma (HCC) evaluated with the Appraisal of Guidelines for Research & Evaluation (AGREE II) instrument is generally poor. However, there are some clinical practice guidelines that are based upon higher quality evidence and can form the framework within which patients with HCC can be selected for surgical resection. Future guideline development should be informed by the use of the AGREE II instrument.

Development and Validation of a New Prognostic System for Patients with Hepatocellular Carcinoma.

BACKGROUND: Prognostic assessment in patients with hepatocellular carcinoma (HCC) remains controversial. Using the Italian Liver Cancer (ITA.LI.CA) database as a training set, we sought to develop and validate a new prognostic system for patients with HCC. METHODS AND FINDINGS: Prospective collected databases from Italy (training cohort, n = 3,628; internal validation cohort, n = 1,555) and Taiwan (external validation cohort, n = 2,651) were used to develop the ITA.LI.CA prognostic system. We first defined ITA.LI.CA stages (0, A, B1, B2, B3, C) using only tumor characteristics (largest tumor diameter, number of nodules, intra- and extrahepatic macroscopic vascular invasion, extrahepatic metastases). A parametric multivariable survival model was then used to calculate the relative prognostic value of ITA.LI.CA tumor stage, Eastern Cooperative Oncology Group (ECOG) performance status, Child-Pugh score (CPS), and alpha-fetoprotein (AFP) in predicting individual survival. Based on the model results, an ITA.LI.CA integrated prognostic score (from 0 to 13 points) was constructed, and its prognostic power compared with that of other integrated systems (BCLC, HKLC, MESIAH, CLIP, JIS). Median follow-up was 58 mo for Italian patients (interquartile range, 26-106 mo) and 39 mo for Taiwanese patients (interquartile range, 12-61 mo). The ITA.LI.CA integrated prognostic score showed optimal discrimination and calibration abilities in Italian patients. Observed median survival in the training and internal validation sets was 57 and 61 mo, respectively, in quartile 1 (ITA.LI.CA score ≤ 1), 43 and 38 mo in quartile 2 (ITA.LI.CA score 2-3), 23 and 23 mo in quartile 3 (ITA.LI.CA score 4-5), and 9 and 8 mo in quartile 4 (ITA.LI.CA score > 5). Observed and predicted median survival in the training and internal validation sets largely coincided. Although observed and predicted survival estimations were significantly lower (log-rank test, p < 0.001) in Italian than in Taiwanese patients, the ITA.LI.CA score maintained very high discrimination and calibration features also in the external validation cohort. The concordance index (C index) of the ITA.LI.CA score in the internal and external validation cohorts was 0.71 and 0.78, respectively. The ITA.LI.CA score's prognostic ability was significantly better (p < 0.001) than that of BCLC stage (respective C indexes of 0.64 and 0.73), CLIP score (0.68 and 0.75), JIS stage (0.67 and 0.70), MESIAH score (0.69 and 0.77), and HKLC stage (0.68 and 0.75). The main limitations of this study are its retrospective nature and the intrinsically significant differences between the Taiwanese and Italian groups. CONCLUSIONS: The ITA.LI.CA prognostic system includes both a tumor staging-stratifying patients with HCC into six main stages (0, A, B1, B2, B3, and C)-and a prognostic score-integrating ITA.LI.CA tumor staging, CPS, ECOG performance status, and AFP. The ITA.LI.CA prognostic system shows a strong ability to predict individual survival in European and Asian populations.

Survival Benefit of Liver Transplantation Versus Resection for Hepatocellular Carcinoma: Impact of MELD Score.

BACKGROUND: We sought to measure the impact of model for end stage liver disease (MELD) score, tumor staging, and microvascular invasion (MVI) on the relative survival benefit of liver transplantation (LT) versus liver resection (LR) for hepatocellular carcinoma (HCC). METHODS: The study population comprised 1,106 HCC patients with cirrhosis undergoing LR from one Eastern (n = 424) and two Western (n = 682) surgical units. Exclusion criteria were very large (>10 cm) tumors, macrovascular invasion, and metastases. We identified three tumor stages: stage I (within Milan, n = 806), stage II (beyond Milan within Up-to-7, n = 123), and stage III (beyond Milan and Up-to-7, n = 177). Patient survival after LR was compared to that predicted after LT by the Metroticket calculator in relationship with staging, MVI, and MELD score using Monte Carlo simulation. RESULTS: Two hundred eighty-three patients (26 %) with a MELD score of ≥10 had an acceptable 5-year survival after LR of 47 %, while that of patients with a low MELD score was 67 % (p < 0.0001). Mean 5-year LT benefit was -4.50 months (95 % confidence interval [CI] -4.73 to -4.27) for patients with a MELD score of <10, and 0.81 months (95 % CI 0.58 to 1.04) for those with a MELD score of ≥10. MELD score and MVI were the strongest predictors of transplant survival benefit. LT reached a survival benefit, versus LR only in HCC patients with a MELD score of ≥10 and without MVI (3.08 months, 95 % CI 2.78 to 3.39), whatever the tumor stage. CONCLUSIONS: LT proved to be harmful in patients with resectable HCC with a low MELD score (<10) or with aggressive tumors (with MVI). As a result of a shortage of donors, only selected resectable tumors with a MELD score of ≥10 should be considered for transplantation.