Annals of Oncology 15:460-466, 2004
© 2004 European Society for Medical Oncology
Original Paper |
Severe hepatic sinusoidal obstruction associated with oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer
Received 15 July 2003; revised 29 September 2003; accepted 16 December 2003Background:
In advanced metastatic colorectal adenocarcinoma, the addition of a neo-adjuvant systemic treatment to surgery might translate into a survival advantage, although this is yet to be confirmed by ongoing randomized trials. The objective of this study was to assess the effects of preoperative systemic chemotherapy on the morphology of non-tumoral liver.
Patients and methods:
A large series of surgically resected liver metastases (n = 153) was selected. Light microscopy, electron microscopy, and immunohistochemistry using antibodies against endothelial cells (CD31) and hepatic stellate cells (
-SM actin, CRBP-1) were performed to identify sinusoidal wall integrity.
Results:
We found that 44 (51%) of the 87 post-chemotherapic liver resection specimens had sinusoidal dilatation and hemorrhage, related to rupture of the sinusoidal barrier. In contrast, the 66 livers treated by surgery alone remained normal. In 21 out of the 44 post-chemotherapy patients (48%), perisinusoidal and veno-occlusive fibrosis also developed. Sinusoidal injury persisted several months after end of chemotherapy, and fibrosis may progress. Development of lesions was strongly correlated to the use of oxaliplatin; 34 out of 43 patients (78%) treated with this drug showed striking sinusoidal alterations.
Conclusions:
Systemic neo-adjuvant chemotherapy in metastatic colorectal cancer frequently causes morphological lesions involving hepatic microvasculature. Sinusoidal obstruction, complicated by perisinusoidal fibrosis and veno-occlusive lesion of the non-tumoral liver revealed by this study, should be included in the list of the adverse side-effects of colorectal systemic chemotherapy, in particular related to the use of oxaliplatin.
Divisions of 1 Clinical Pathology, 3 Oncosurgery and 6 Digestive Surgery, University Hospital, Geneva, Switzerland; Services 2 d’Anatomie Pathologique, 4 Gastroenterology and 5 Surgery, Hôpital Cochin, Paris, France
Key words: drug liver injury, 5-fluorouracil, neo-adjuvant chemotherapy, sinusoidal obstruction syndrome, veno-occlusive disease
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