TY - JOUR
T1 - Sinusoidal obstruction syndrome and nodular regenerative hyperplasia are frequent oxaliplatin-associated liver lesions and partially prevented by bevacizumab in patients with hepatic colorectal metastasis
AU - Rubbia-Brandt, Laura
AU - Lauwers, Gregory Y.
AU - Wang, Huamin
AU - Majno, Pietro E.
AU - Tanabe, Kenneth
AU - X Zhu, Andrew
AU - Brezault, Catherine
AU - Soubrane, Olivier
AU - Abdalla, Eddie K.
AU - Vauthey, Jean Nicolas
AU - Mentha, Gilles
AU - Terris, Benoit
PY - 2010/3
Y1 - 2010/3
N2 - Aims: Because of its efficacy, oxaliplatin (OX) is increasingly used as a chemotherapeutic agent in the treatment of colorectal liver metastases (CRLM). Oxaliplatin-associated liver toxicity has been reported and can affect clinical practice, but studies on its prevalence and a full pathological description are lacking. The aims of this study were to fill this gap by providing, from a pathologist's perspective, a detailed assessment of the spectrum of hepatic lesions associated with OX, to suggest a scoring system to quantify them, and to investigate the protective effect of bevacizumab against OX-associated damage. Methods and results: The spectrum of oxaliplatin-associated liver lesions was investigated in a multi-institutional series of surgically resected CRLM (n = 385). Among 274 patients treated by OX, 54% had moderate/severe sinusoidal obstruction syndrome (SOS). Peliosis, centrilobular perisinusoidal/venular fibrosis and nodular regenerative hyperplasia (NRH) developed in 10.6%, 47% and 24.5%, respectively. The 111 patients treated by surgery alone had no lesions. Hepatic lesions were less severe in patients treated with OX/bevacizumab (n = 70) compared with the group treated by OX alone (n = 204), with an incidence of moderate/severe SOS (31.4% versus 62.2%), peliosis (4.3% versus 14.6%), NRH (11.4% versus 28.9%, respectively) and centrilobular/venular fibrosis (31.4% versus 52%, respectively) (P < 0.001). Conclusions: Pathologists should be aware of the distinctive lesions associated with OX and of their high prevalence. OX-related lesions are less frequent in patients treated with bevacizumab, suggesting that this drug has a preventive effect. Uniform criteria for diagnosis and grading of OX-associated lesions should help to include histological data in the optimal multidisciplinary management of CRLM.
AB - Aims: Because of its efficacy, oxaliplatin (OX) is increasingly used as a chemotherapeutic agent in the treatment of colorectal liver metastases (CRLM). Oxaliplatin-associated liver toxicity has been reported and can affect clinical practice, but studies on its prevalence and a full pathological description are lacking. The aims of this study were to fill this gap by providing, from a pathologist's perspective, a detailed assessment of the spectrum of hepatic lesions associated with OX, to suggest a scoring system to quantify them, and to investigate the protective effect of bevacizumab against OX-associated damage. Methods and results: The spectrum of oxaliplatin-associated liver lesions was investigated in a multi-institutional series of surgically resected CRLM (n = 385). Among 274 patients treated by OX, 54% had moderate/severe sinusoidal obstruction syndrome (SOS). Peliosis, centrilobular perisinusoidal/venular fibrosis and nodular regenerative hyperplasia (NRH) developed in 10.6%, 47% and 24.5%, respectively. The 111 patients treated by surgery alone had no lesions. Hepatic lesions were less severe in patients treated with OX/bevacizumab (n = 70) compared with the group treated by OX alone (n = 204), with an incidence of moderate/severe SOS (31.4% versus 62.2%), peliosis (4.3% versus 14.6%), NRH (11.4% versus 28.9%, respectively) and centrilobular/venular fibrosis (31.4% versus 52%, respectively) (P < 0.001). Conclusions: Pathologists should be aware of the distinctive lesions associated with OX and of their high prevalence. OX-related lesions are less frequent in patients treated with bevacizumab, suggesting that this drug has a preventive effect. Uniform criteria for diagnosis and grading of OX-associated lesions should help to include histological data in the optimal multidisciplinary management of CRLM.
KW - Avastin
KW - Bevacizumab
KW - Colorectal cancer
KW - Drug liver injury
KW - Neoadjuvant chemotherapy
KW - Nodular regenerative hyperplasia
KW - Oxaliplatin
KW - Sinusoidal obstruction syndrome
KW - Veno-occlusive disease
UR - http://www.scopus.com/inward/record.url?scp=77949612000&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77949612000&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2559.2010.03511.x
DO - 10.1111/j.1365-2559.2010.03511.x
M3 - Article
C2 - 20459550
AN - SCOPUS:77949612000
SN - 0309-0167
VL - 56
SP - 430
EP - 439
JO - Histopathology
JF - Histopathology
IS - 4
ER -