Anatomical basis and histopathological changes resulting from selective internal radiotherapy for liver metastases

Abstract

BackgroundKnowledge that liver tumours preferentially take their blood supply from the arterial blood supply rather than the portal venous system can be used for local delivery of treatment or for embolisation to cut off the blood supply to tumours.AimsTo present histological evaluation of malignant and non-malignant hepatic tissue of one such therapy, selective internal radiation therapy (SIRT) with yttrium-90 microspheres, to decipher its principal mechanism of action.MethodsThe H&E stained sections of hepatic resection specimens from three patients with liver metastases from colorectal (CRC) cancer, who underwent hepatic surgery 4–9 months following SIRT, were examined and the pathological changes documented.ResultsResin microspheres were identified in the vascular tumour bed and vessels within the portal tracts of the background liver parenchyma. Microspheres were usually associated with giant cell reaction or histiocytes. In the tumour bed, tumour necrosis, mucinous alteration, collections of foamy histiocytes, ectatic vessels, calcification and fibrosis were observed. There was minimal cellular inflammatory response observed, suggestive of direct radiation injury as a non-immune mediated process.ConclusionsWe describe in detail the spectrum of histopathological changes in malignant tissue and liver parenchyma in patients with metastatic CRC treated with SIRT. Our findings are consistent with the hypothesis that the principal mechanism of action of SIRT appears to be via arterially directed delivery of highly radioactive microspheres in and around the vascular tumour bed rather than by micro-arterial embolisation.

KRAS Status as an Independent Prognostic Factor for Survival after Yttrium-90 Radioembolization Therapy for Unresectable Colorectal Cancer Liver Metastases

“…Histopathologic analyses of specimens treated by 90 Y radioembolization suggests that tumor necrosis in response to 90 Y radioembolization relies most critically on delivering a lethal dose of radiation-induced cell and DNA damage, with the embolic effect of the microspheres contributing little to their efficacy (25). Immunohistochemical analyses of metastatic CRC specimens treated by 90 Y radioembolization showing a correlation between treatment-induced changes in expression of Bcl-2 and other antiapoptotic factors and response rates provide additional evidence of the significance of apoptosis in the mechanism of 90 Y radioembolization (26).…”

Prevention and treatment of complications of selective internal radiation therapy: Expert guidance and systematic review

“…Gastroesophageal varices have been anecdotally identified years after SIRT . Histological findings observed in these patients indicate nodular regenerative hyperplasia (unpublished data) with or without bridging fibrosis. Encephalopathy and variceal bleeding have not been reported in patients who do not have cirrhosis.…”

“…REILD resembles other forms of sinusoidal obstruction syndrome. Indeed, in the most severe cases liver biopsy shows veno‐occlusive disease, the histological hallmark of sinusoidal obstruction syndrome . Importantly, sinusoidal obstruction syndrome may also occur in CRC patients who receive oxaliplatin‐based or irinotecan‐based chemotherapy regimes, which is the clinical setting for many SIRT‐treated patients.…”

Arterial and portal venous liver perfusion using selective spin labelling MRI

“…Furthermore, selective SL-MRI provides direct imaging of the arterial and portal venous blood supply, instead of discrimination on different contrast bolus arrival times. The arterial and portal venous perfusion fraction of focal lesions could potentially be obtained, although further research is needed before SL-MRI could be used to identify an increased arterial blood supply in malignancies [30]. Meanwhile, metastatic renal cell carcinoma has already been successfully imaged using the ASL-MRI technique [6], as well as liver metastases in a mice model [31,32].…”