Potential predictive factors for microvascular invasion in hepatocellular carcinoma classified within the Milan criteria

Hepatocellular carcinoma represents the most frequent primary liver tumor; curative options are only surgical resection and liver transplantation. From 1996, Milan Criteria are applied in consideration of patients with cirrhosis and hepatocellular for liver transplantation; nonetheless, more recently, Milan Criteria have been criticized because they appear over conservative. Apart from number and size of lesions and biomarker levels, which already have been associated with poorer prognosis, overall survival and recurrence rates after transplantation are affected also by the presence of vascular invasion. Microvascular invasion suggests a poor prognosis but it is often hard to detect before transplant. Diagnostic imaging and tumor markers may play an important role and become the main tools to define microvascular invasion. In particular, a possible role could be found for computed tomography, magnetic resonance imaging, and positron emission tomography. In this paper, we analyze the possible role of positron emission tomography as a preoperative imaging biomarker capable of predicting microvascular invasion in patients with hepatocellular carcinoma and thus selecting optimal candidates for liver transplantation.

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Predictive Factors of Downstaging of Hepatocellular Carcinoma Beyond the Milan Criteria Treated with Intra-arterial Therapies

CardioVascular and Interventional Radiology ◽

10.1007/s00270-012-0458-1 ◽

2012 ◽

Vol 36 (2) ◽

pp. 433-439 ◽

Cited By ~ 20

Author(s):

Valentina Bova ◽

Roberto Miraglia ◽

Luigi Maruzzelli ◽

Giovanni Battista Vizzini ◽

Angelo Luca

Keyword(s):

Hepatocellular Carcinoma ◽

Predictive Factors ◽

Milan Criteria

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Microvascular Invasion Is a Better Predictor of Tumor Recurrence and Overall Survival Following Surgical Resection for Hepatocellular Carcinoma Compared to the Milan Criteria

Annals of Surgery ◽

10.1097/sla.0b013e31821ad884 ◽

2011 ◽

Vol 254 (1) ◽

pp. 108-113 ◽

Cited By ~ 178

Author(s):

Kheng-Choon Lim ◽

Pierce Kah-Hoe Chow ◽

John C. Allen ◽

Ghim-Song Chia ◽

Miaoshan Lim ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Surgical Resection ◽

Tumor Recurrence ◽

Microvascular Invasion ◽

Milan Criteria

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Predictive Factors of Microvascular Invasion in Patients with Hepatocellular Carcinoma Larger Than 5 cm

World Journal of Surgery ◽

10.1007/s00268-008-9585-x ◽

2008 ◽

Vol 32 (10) ◽

pp. 2218-2222 ◽

Cited By ~ 31

Author(s):

Yasuhiko Nagano ◽

Hiroshi Shimada ◽

Kazuhisa Takeda ◽

Michio Ueda ◽

Kenichi Matsuo ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Predictive Factors ◽

Microvascular Invasion

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Predictive Factors of Tumor Recurrence and Survival in Patients with Hepatocellular Carcinoma treated with Transarterial Chemoembolization

Journal of Gastrointestinal and Liver Diseases ◽

10.15403/jgld.2014.1121.274.fcr ◽

2018 ◽

Vol 27 (4) ◽

pp. 409-417

Author(s):

Razvan Cerban ◽

Carmen Ester ◽

Speranta Iacob ◽

Mugur Grasu ◽

Liliana Pâslaru ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Predictive Factors ◽

Tumor Size ◽

Elevated Serum ◽

Complete Response ◽

Initial Therapy ◽

Milan Criteria ◽

First Line Therapy ◽

Maximal Diameter ◽

Single Tumor

Background & Aims: To evaluate the predictive factors for recurrence of the disease and overall survival(OS) after achieving complete response (CR) in patients with hepatocellular carcinoma (HCC) treated withtransarterial chemoembolization (TACE).Methods: From January 2013 to December 2017, 168 treatment-naïve patients diagnosed with HCCunderwent TACE as a first-line therapy and the gathered data was retrospectively reviewed. We determined the predictive factors for complete response (CR), for recurrence after CR and for survival using the Cox proportional hazard model.Results: Median follow-up was 27.4 months (range 4-65 months). The mean patient age was 62.2±7.9 years. Eighty-three patients had an α-fetoprotein (AFP) level > 20ng/mL. The median maximal diameter of the tumors was 3.5 cm. Sixty-three patients (37.5%) achieved CR after TACE, and recurrence after CR was detected in 37 patients (58.7%). In multivariate analysis, tumor size (≤4.5 cm) and a single tumor were found to be predictive factors for CR, with hazard ratios (HRs) of 2.352 (p=0.022) and 3.964 (p<0.0001), respectively. After achieving CR the median time to recurrence was 12 months (range 6-24 months). Elevated serum AFP > 25 ng/mL and multiple tumors were demonstrated to have a significant relationship with recurrence after CR, with HRs of 1.650 (p=0.05) and 3.932 (p=0.038), respectively. Increased initial serum AFP > 22 ng/mL, tumorsize > 4.5 cm, outside Milan criteria, not receiving a liver transplant and presence of portal vein thrombosis (PVT) were correlated with poor survival.Conclusions: In patients treated with TACE as an initial therapy, tumor size (≤4.5 cm) and single tumor were predictive factors for CR. Multiple nodules and an elevated serum AFP > 25 ng/mL were predictive factors for recurrence after CR. Outside Milan criteria tumors, elevated AFP levels and the presence of PVT were significantly correlated with decreased survival.

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A Clinical Scoring System for Predicting Microvascular Invasion in Patients with Hepatocellular Carcinoma Within the Milan Criteria

Journal of Gastrointestinal Surgery ◽

10.1007/s11605-019-04134-y ◽

2019 ◽

Vol 23 (4) ◽

pp. 779-787 ◽

Cited By ~ 7

Author(s):

Tomoki Ryu ◽

Yuko Takami ◽

Yoshiyuki Wada ◽

Masaki Tateishi ◽

Takanobu Hara ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Scoring System ◽

Microvascular Invasion ◽

Milan Criteria ◽

Clinical Scoring

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Prediction of Microvascular Invasion and Its M2 Classification in Hepatocellular Carcinoma Based on Nomogram Analyses

Frontiers in Oncology ◽

10.3389/fonc.2021.774800 ◽

2022 ◽

Vol 11 ◽

Author(s):

Shengsen Chen ◽

Chao Wang ◽

Yuwei Gu ◽

Rongwei Ruan ◽

Jiangping Yu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Logistic Regression ◽

Predictive Factors ◽

Calibration Curve ◽

Clinical Utility ◽

Microvascular Invasion ◽

Lasso Regression ◽

Tumor Margin ◽

Tumor Capsule ◽

Tumor Number

Background and AimsAs a key pathological factor, microvascular invasion (MVI), especially its M2 grade, greatly affects the prognosis of liver cancer patients. Accurate preoperative prediction of MVI and its M2 classification can help clinicians to make the best treatment decision. Therefore, we aimed to establish effective nomograms to predict MVI and its M2 grade.MethodsA total of 111 patients who underwent radical resection of hepatocellular carcinoma (HCC) from January 2015 to September 2020 were retrospectively collected. We utilized logistic regression and least absolute shrinkage and selection operator (LASSO) regression to identify the independent predictive factors of MVI and its M2 classification. Integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were calculated to select the potential predictive factors from the results of LASSO and logistic regression. Nomograms for predicting MVI and its M2 grade were then developed by incorporating these factors. Area under the curve (AUC), calibration curve, and decision curve analysis (DCA) were respectively used to evaluate the efficacy, accuracy, and clinical utility of the nomograms.ResultsCombined with the results of LASSO regression, logistic regression, and IDI and NRI analyses, we founded that clinical tumor-node-metastasis (TNM) stage, tumor size, Edmondson–Steiner classification, α-fetoprotein (AFP), tumor capsule, tumor margin, and tumor number were independent risk factors for MVI. Among the MVI-positive patients, only clinical TNM stage, tumor capsule, tumor margin, and tumor number were highly correlated with M2 grade. The nomograms established by incorporating the above variables had a good performance in predicting MVI (AUCMVI = 0.926) and its M2 classification (AUCM2 = 0.803). The calibration curve confirmed that predictions and actual observations were in good agreement. Significant clinical utility of our nomograms was demonstrated by DCA.ConclusionsThe nomograms of this study make it possible to do individualized predictions of MVI and its M2 classification, which may help us select an appropriate treatment plan.

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