Severe Hepatic Sinusoidal Obstruction W/ Oxaliplatin

Severe hepatic sinusoidal obstruction associated with oxaliplatin (L-OHP)-based chemotherapy (CT) in patients with metastatic colorectal cancer (MCRC).

B. Terris, V. Audard, P. Sartoretti, A. Roth, C. Brezault, B. Dousset, J. Alexandre, S. Chaussade, G. Mentha, L. Rubbia;

Cochin Hospital, Paris, France; Geneva Hospital, Geneve, Switzerland

Abstract: Background: In MCRC, surgery combined with neo-adjuvant CT has an overall benefit, compared with surgery alone. The objective of this retrospective study was to assess the effects of preoperative systemic CT on the morphology of non-tumoral liver.

Methods: A large panel of surgically resected liver metastasis (n=153) between 1995 and 2002 was selected: 66 patients were treated by surgery alone and 87 received systemic CT before surgery (31% treated by L-OHP, 18% by L-OHP and CPT, 20% by CPT and 31% by 5FU alone). Light microscopy, electron microscopy and immunohistochemistry were performed to identify sinusoidal wall integrity.

Results: In contrast with the 66 livers treated by surgery alone which did not exhibit vascular abnormalities, 44 (51%) of the 87 post-chemotherapic liver resection specimens had sinusoidal dilatation and hemorrhage, related to rupture of the sinusoidal barrier.

In 21 out of 44 patients (48%), perisinusoidal and veno-occlusive fibrosis were observed. Sinusoidal injury persisted several months after end of chemotherapy and fibrosis may progress.

Development of such lesions was strongly correlated to the use of L-OHP: 34 of the 43 (79%) patients treated with L-OHP based chemotherapy developed sinusoidal alterations, as opposed to 10 of the 44 (23 %) who received CPT or 5FU alone (p<0.001).

Conclusions: Systemic neo-adjuvant CT in MCRC 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 CT, in particular related to the use of L-OHP.

The clinical consequences of such abnormalities have to be evaluated, in regards to the potential impaired liver regeneration after extended liver resection in these patients.

Abstract No: 3541

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