Pathological Appearance of Focal Liver Reactions after Radiotherapy for Hepatocellular Carcinoma

We studied five pathological specimens from five patients at 1.5, 3.0, 4.0, 13.5, and 14.0 months after radiotherapy for HCC. Four needle biopsies were obtained to investigate liver parenchyma of focal liver reaction (FLR) around treated HCC, when patients had newly developed HCC or local recurrence appeared in the liver. Liver resection was performed in one case where insufficient radiotherapy effect for HCC was suspected. In all patients, FLR was recognized as a hypervascular area around the HCC on enhanced CT and enhanced Gd-EOB-DTPA (EOB-MRI). Liver specimens were analyzed to assess the pathological characteristics of FLR. FLR was recognized as prolonged liver enhancement in enhanced CT and EOB-MRI. From pathological understanding, sinusoidal dilatation with degeneration and desquamation was caused by direct endothelial cell injury following radiotherapy. Hepatocytes and endothelium fell off, and so the portal tract came close, and hepatic arteries increase simultaneously, resulting in FLR around HCC after radiotherapy. In conclusion, the prolapse of hepatocytes and sinusoidal endothelium induced neovascularization of hepatic arteries due to the repair mechanisms; in addition, these prolapse may shorten the distance between each portal region and the hepatic arteries flowing through the portal region become more prominent in FLR.

[1]  O. Matsui,et al.  Pathology and images of radiation-induced hepatitis: a review article , 2018, Japanese Journal of Radiology.

[2]  R. Ma,et al.  Stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma: imaging evaluation post treatment. , 2018, The British journal of radiology.

[3]  M. Kudo,et al.  Validation and Potential of Albumin-Bilirubin Grade and Prognostication in a Nationwide Survey of 46,681 Hepatocellular Carcinoma Patients in Japan: The Need for a More Detailed Evaluation of Hepatic Function , 2017, Liver Cancer.

[4]  Jieun Kim,et al.  Radiation-induced liver disease: current understanding and future perspectives , 2017, Experimental &Molecular Medicine.

[5]  E. Kunieda,et al.  Phase 2 study of stereotactic body radiotherapy and optional transarterial chemoembolization for solitary hepatocellular carcinoma not amenable to resection and radiofrequency ablation , 2016, Cancer.

[6]  Manabu Watanabe,et al.  Evaluation of contrast-enhanced ultrasonography for hepatocellular carcinoma prior to and following stereotactic body radiation therapy using the CyberKnife® system: A preliminary report , 2015, Oncology letters.

[7]  K. Awai,et al.  Clinical utility of gadoxetate disodium-enhanced hepatic MRI for stereotactic body radiotherapy of hepatocellular carcinoma , 2015, Japanese Journal of Radiology.

[8]  B. Sangro,et al.  Assessment of liver function in patients with hepatocellular carcinoma: a new evidence-based approach-the ALBI grade. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[9]  E. Kunieda,et al.  Threshold doses for focal liver reaction after stereotactic ablative body radiation therapy for small hepatocellular carcinoma depend on liver function: evaluation on magnetic resonance imaging with Gd-EOB-DTPA. , 2014, International journal of radiation oncology, biology, physics.

[10]  E. Kunieda,et al.  Stereotactic ablative body radiotherapy for previously untreated solitary hepatocellular carcinoma , 2014, Journal of gastroenterology and hepatology.

[11]  Sang‐wook Lee,et al.  Radiation-induced liver disease after stereotactic body radiotherapy for small hepatocellular carcinoma: clinical and dose-volumetric parameters , 2013, Radiation oncology.

[12]  J. Bruix,et al.  Management of hepatocellular carcinoma: An update , 2011, Hepatology.

[13]  E. Kunieda,et al.  CT evaluations of focal liver reactions following stereotactic body radiotherapy for small hepatocellular carcinoma with cirrhosis: relationship between imaging appearance and baseline liver function. , 2010, The British journal of radiology.

[14]  G. van Kaick,et al.  Assessment of focal liver reaction by multiphasic CT after stereotactic single-dose radiotherapy of liver tumors. , 2003, International journal of radiation oncology, biology, physics.

[15]  G. McDonald,et al.  Toxic injury to hepatic sinusoids: sinusoidal obstruction syndrome (veno-occlusive disease). , 2002, Seminars in liver disease.