Effect of steatohepatitis associated with irinotecan or oxaliplatin pretreatment on resectability of hepatic colorectal metastases.
ABSTRACT The objective was to evaluate the effect of preoperative administration of newer chemotherapeutic agents (irinotecan and oxaliplatin) on development of steatohepatitis, which could limit surgical options.
Thirty-seven patients were referred for resection of hepatic colorectal metastases. Thirteen patients received no neoadjuvant therapy (NO CHEMO group); 10 received neoadjuvant 5-fluorouracil only (5-FU group), and 14 received neoadjuvant irinotecan (n = 12), or oxaliplatin, or both (n = 4), in conjunction with 5-FU (IRI-OXALI group). Specimens were graded for the presence of nonalcoholic steatohepatitis (NASH) according to established criteria. Specimens were also evaluated by a nine-criteria liver injury score (LIS).
Mean biopsy scores were: NO CHEMO: NASH, 1.2, LIS, 5.2; 5-FU only: NASH, 1.1, LIS 5.7; and IRI-OXALI: NASH, 1.9, LIS, 9.4. Biopsy scores were significantly worse for IRI-OXALI compared with NO CHEMO or 5-FU only for NASH score, p = 0.003, and close to significantly worse for LIS score, p = 0.057. A multivariate analysis showed that both being in the IRI-OXALI group and body mass index were independent risk factors for developing this type of steatohepatitis.
Severe steatohepatitis can be associated with preoperative administration of irinotecan or oxaliplatin, especially in the obese. It can affect the ability to perform large liver resections. Consideration should be given to performing resections before commencing these agents and to obtaining preoperative biopsy in those who have received these agents.
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ABSTRACT: Background:The FOLFOXIRI regimen produces a high rate of radiological and histopathological responses. Bevacizumab added to chemotherapy showed an improvement in pathological response and necrosis of colorectal liver metastases (CLMs). FOLFOXIRI plus bevacizumab produced promising early clinical results and is under investigation in several randomised trials, although no data are currently available on its effects on response of CLMs and on liver toxicities.Methods:Starting from 499 patients enrolled in first-line phase II/III trials, we selected on the basis of tissue sample availability 18 patients treated with FOLFOXIRI/XELOXIRI and 24 patients treated with FOLFOXIRI plus bevacizumab who underwent secondary resection of CLMs. The 28 untreated patients who underwent primary resection of CLMs were included as control group. Responses of CLMs and chemotherapy-induced toxicities were assessed.Results:Among the patients, 63% of those treated with FOLFOXIRI plus bevacizumab, as compared with 28% of those treated with only FOLFOXIRI/XELOXIRI, showed a histopathological response (P=0.033). In the two groups, 52% and 12.5%, respectively, showed necrosis 50% (P=0.017). The incidence of liver toxicities was not significantly increased in patients treated with FOLFOXIRI plus bevacizumab.Conclusion:The addition of bevacizumab to FOLFOXIRI produces high rates of pathologic responses and necrosis of CLM without increasing liver toxicity.British Journal of Cancer advance online publication, 23 May 2013; doi:10.1038/bjc.2013.245 www.bjcancer.com.British Journal of Cancer 05/2013; 108(12). DOI:10.1038/bjc.2013.245 · 4.82 Impact Factor
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ABSTRACT: Background and Aims. Chemotherapy of colorectal liver metastases can induce hepatotoxicity in noncancerous liver. We describe these lesions and assess risk factors and impacts on postresection morbidity and mortality in naive patients to chemotherapy before the era of bevacizumab. Methods. Noncancerous liver tissue lesions were analysed according to tumour, chemotherapy, surgery, and patient characteristics. Results. Fifty patients aged 62 ± 9.3 years were included between 2003 and 2007. Thirty-three (66%) received chemotherapy, with Folfox (58%), Folfiri (21%), LV5FU2 (12%), or Xelox (9%) regimens. Hepatotoxicity consisted of 18 (36%) cases of severe sinusoidal dilatation (SD), 13 (26%) portal fibrosis, 7 (14%) perisinusoidal fibrosis (PSF), 6 (12%) nodular regenerative hyperplasia (NRH), 2 (4%) steatosis >30%, zero steatohepatitis, and 16 (32%) surgical hepatitis. PSF was more frequent after chemotherapy (21% versus 0%, P = 0.04), especially LV5FU2 (P = 0.02). SD was associated with oxaliplatin (54.5% versus 23.5%, P = 0.05) and low body mass index (P = 0.003). NRH was associated with oxaliplatin (P = 0.03) and extensive resection (P = 0.04). No impact on mortality and morbidity was observed, apart postoperative elevation of bilirubin levels in case of PSF (P = 0.03), longer hospitalization in case of surgical hepatitis (P = 0.03), and greater blood loss in case of portal fibrosis (P = 0.03). Conclusions. Chemotherapy of colorectal liver metastases induces sinusoidal dilatation related to oxaliplatin and perisinusoidal fibrosis related to 5FU, without any impact on postoperative mortality.03/2013; 2013:314868. DOI:10.1155/2013/314868
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ABSTRACT: We have previously reported that neoadjuvant therapy with modified FOLFIRI enabled nearly a third of patients with metastatic colorectal cancer (mCRC) to undergo surgical resection of liver metastases. Here, we present data from the long-term follow-up of these patients. Forty patients received modified FOLFIRI: irinotecan 180 mg m(-2), day 1; folinic acid, 200 mg m(-2); and 5-fluorouracil: as a 400 mg m(-2) bolus, days 1 and 2, and a 48-h continuous infusion 1200 mg m(-2), from day 1. Treatment was repeated every 2 weeks, with response assessed every six cycles. Resected patients received six further cycles of chemotherapy postoperatively. Nineteen (47.5%) of 40 patients achieved an objective response; 13 (33%) underwent resection. After a median follow-up of 56 months, median survival for all patients was 31.5 months: for non-resected patients, median survival was 24 months and was not reached for resected patients. Median time to progression was 14.3 and 5.2 months for all and non-resected patients, respectively. Median disease-free (DF) survival in resected patients was 52.5 months. At 2 years, all patients were alive (8 DF), and at last follow-up, eight were alive (6 DF). Surgical resection of liver metastases after neoadjuvant treatment with modified FOLFIRI in CRC patients achieved favourable survival times.British Journal of Cancer 11/2007; 97(8):1035-9. DOI:10.1038/sj.bjc.6603988 · 4.82 Impact Factor