Abstract

Simple SummaryHepatocellular carcinoma (HCC) is the third most commonly diagnosed cancer in the world, and surgical resection is the commonly used curative management of early-stage disease. However, the recurrence rate is high after resection, and liver fibrosis has been thought to increase the risk of recurrence. Conventional histological staging of fibrosis is highly subjective to observer variations. To overcome this limitation, we used a fully quantitative fibrosis assessment tool, qFibrosis (utilizing second harmonic generation and two-photon excitation fluorescence microscopy), with multi-dimensional artificial intelligence analysis to establish a fully-quantitative, accurate fibrotic score called a “combined index”, which can predict early recurrence of HCC after curative intent resection. Therefore, we can pay more attention on the patients with high risk of early recurrence.Background: Liver fibrosis is thought to be associated with early recurrence of hepatocellular carcinoma (HCC) after resection. To recognize HCC patients with higher risk of early recurrence, we used a second harmonic generation and two-photon excitation fluorescence (SHG/TPEF) microscopy to create a fully quantitative fibrosis score which is able to predict early recurrence. Methods: The study included 81 HCC patients receiving curative intent hepatectomy. Detailed fibrotic features of resected hepatic tissues were obtained by SHG/TPEF microscopy, and we used multi-dimensional artificial intelligence analysis to create a recurrence prediction model “combined index” according to the morphological collagen features of each patient’s non-tumor hepatic tissues. Results: Our results showed that the “combined index” can better predict early recurrence (area under the curve = 0.917, sensitivity = 81.8%, specificity = 90.5%), compared to alpha fetoprotein level (area under the curve = 0.595, sensitivity = 68.2%, specificity = 47.6%). Using a Cox proportional hazards analysis, a higher “combined index” is also a poor prognostic factor of disease-free survival and overall survival. Conclusions: By integrating multi-dimensional artificial intelligence and SHG/TPEF microscopy, we may locate patients with a higher risk of recurrence, follow these patients more carefully, and conduct further management if needed.

Highlights

  • Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer deaths around the world [1]

  • Adult patients who were diagnosed and staged by liver tumor biopsy, abdomen triphasic computed tomography (CT), and alpha fetoprotein (AFP) as resectable hepatocellular carcinoma (HCC) with known hepatitis B virus (HBV) or hepatitis C virus (HCV) infection and planning to have curative intent surgical resection were enrolled in this study

  • Group, local treatment such as transarterial embolization (TAE), radiofrequency ablation (RFA) or partial hepatectomy were performed previously in 5 patients; TAE and RFA were done in 2 patients in the nonalcoholic steatohepatitis (NASH) group

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Summary

Introduction

Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer deaths around the world [1]. It is the fifth most commonly diagnosed cancer and is the second most common cause of cancer deaths in Taiwan [2]. In early-stage HCC, potentially curative treatments are available. They include surgical resection, percutaneous ablation, and liver transplantation. Liver fibrosis has been thought to increase the risk of intrahepatic recurrence after hepatectomy in the case of HCC [7]. Liver fibrosis is thought to be associated with early recurrence of hepatocellular carcinoma (HCC) after resection. To recognize HCC patients with higher risk of early recurrence, we used a second harmonic generation and two-photon excitation fluorescence (SHG/TPEF)

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