Fernandez FG, Ritter J, Goodwin JW, Linehan DC, Hawkins WG, Strasberg SMEffect of steatohepatitis associated with irinotecan or oxaliplatin pretreatment on resectability of hepatic colorectal metastases. J Am Coll Surg 200: 845-853

Department of Pathology and Immunology, Washington University in St. Louis, San Luis, Missouri, United States
Journal of the American College of Surgeons (Impact Factor: 5.12). 07/2005; 200(6):845-53. DOI: 10.1016/j.jamcollsurg.2005.01.024
Source: PubMed


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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    • "Steatosis may be a risk factor for liver failure in patients undergoing extended hepatectomy, although not in major hepatectomy in this series, where the risk of this complication is greatest. Previous studies have recommended liver biopsy to investigate the presence of steatosis prior to resection [48, 49]. The current study suggests that the risk of this investigation is not justified due to the lack of effect of steatosis on outcome. "
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    ABSTRACT: Background. This study aimed to assess the relationship between diabetes, obesity, and hepatic steatosis in patients undergoing liver resection and to determine if these factors are independent predictors of major complications. Materials and Methods. Analysis of a prospectively maintained database of patients undergoing liver resection between 2005 and 2012 was undertaken. Background liver was assessed for steatosis and classified as <33% and ≥33%. Major complications were defined as Grade III-V complications using the Dindo-Clavien classification. Results. 504 patients underwent liver resection, of whom 56 had diabetes and 61 had steatosis ≥33%. Median BMI was 26 kg/m(2) (16-54 kg/m(2)). 94 patients developed a major complication (18.7%). BMI ≥ 25 kg/m(2) (P = 0.001) and diabetes (P = 0.018) were associated with steatosis ≥33%. Only insulin dependent diabetes was a risk factor for major complications (P = 0.028). Age, male gender, hypoalbuminaemia, synchronous bowel procedures, extent of resection, and blood transfusion were also independent risk factors. Conclusions. Liver surgery in the presence of steatosis, elevated BMI, and non-insulin dependent diabetes is not associated with major complications. Although diabetes requiring insulin therapy was a significant risk factor, the major risk factors relate to technical aspects of surgery, particularly synchronous bowel procedures.
    HPB Surgery 08/2014; 2014:586159. DOI:10.1155/2014/586159
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    • "However, some cases in which chemotherapy caused liver damage have also been reported. Oxaliplatin, which is frequently used to treat liver metastases of colon cancer, characteristically causes sinusoidal dilatation, whereas irinotecan causes nonalcoholic steatohepatitis (NASH) [2]. Sunitinib and sorafenib, which were developed as molecular-targeted drugs to treat advanced renal cell carcinoma, mainly block vascular endothelial growth factor and platelet-derived growth factor receptor tyrosine kinases, and thereby inhibit tumor growth and angiogenesis. "
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    ABSTRACT: Sunitinib was developed as a molecular-targeted drug to treat advanced renal cell carcinoma. It is not yet known whether liver damage occurs in patients with liver metastases of renal cell carcinoma after sunitinib administration. Here, we report the case of a patient with an inoperable massive liver metastasis of renal cell carcinoma for whom sunitinib administration was dramatically effective with no obvious evidence of liver damage. As a result, the liver metastasis could be resected. We emphasize the dramatic reduction in liver metastasis with sunitinib treatment, and the histopathological effects of sunitinib on the non-tumorous liver parenchyma. A 54-year-old Japanese woman was diagnosed with right renal cell carcinoma and underwent right nephrectomy 12 years earlier. She presented to a local clinic with right abdominal pain. A computed tomography scan showed a massive liver metastasis occupying her right hepatic lobe, and she was referred to our hospital for treatment. The diagnosis was not only liver metastasis, but also left renal metastasis. Oral administration of tyrosine kinase inhibitor sunitinib was started. Adverse events due to sunitinib included liver dysfunction, thrombocytopenia, and decreased hemoglobin, but she completed eight courses with the help of drug holidays and dose adjustments. Post-treatment computed tomography showed a dramatic reduction in size of her liver metastasis, enabling right lobectomy of her liver. Histopathological findings showed no obvious liver damage due to chemotherapy in non-cancerous parenchymal areas. With the availability of sunitinib, some patients with potentially unresectable massive liver metastases of renal cell carcinoma may be able to undergo major hepatectomy curatively and safely with little histopathological damage to non-tumorous liver parenchyma, thus improving their prognosis.
    Journal of Medical Case Reports 10/2013; 7(1):234. DOI:10.1186/1752-1947-7-234
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    • "Oxaliplatin-based regimens can increase the risk of vascular abnormalities in the liver [20,21]. Administration of irinotecan-based chemotherapy has been associated with steatosis and steatohepatitis [22,23]. Second, some liver metastases may disappear on radiologic imaging after neoadjuvant chemotherapy and these lesions may not be treatable. "
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    ABSTRACT: This study evaluated the efficacy of neoadjuvant chemotherapy combining 5-flurouracil/folinic acid with irinotecan (FOLFIRI) in colorectal multiple liver metastases regardless of resectability. Forty-four patients with multiple (at least two) colorectal liver metastases were enrolled at seven tertiary referral hospitals between May 2007 and September 2010. All patients received the FOLFIRI chemotherapeutic regimen. Response to chemotherapy was assessed after three cycles (6 weeks) and once more after six cycles (12 weeks) of treatment. Objective response was noted in 27 patients (61.4%) and 4 patients (9.1%) had progressive disease. Of 44 patients, 10 patients (22.7%) underwent curative surgery (R0 resection) and 34 patients did not receive R0 resection. Grades 3 to 4 hematological toxicity was noted in 12 patients (27.3%) and grades 3 to 4 nonhematologic toxicity was identified in 5 patients (11.4%). FOLFIRI chemotherapy as a neoadjuvant chemotherapy for multiple colorectal liver metastases regardless of resectability demonstrated the possibility of R0 resection, high rate of objective response, and tolerable toxicities in this study.
    Journal of the Korean Surgical Society 10/2013; 85(4):154-160. DOI:10.4174/jkss.2013.85.4.154 · 0.73 Impact Factor
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