Demonstration of hepatic steatosis by computerized tomography in patients receiving 5-fluorouracil-based therapy for advanced colorectal cancer

Abstract

Summary The frequency and severity of fatty infiltration of the liver in patients receiving 5-fluorouracil (5-FU) and folinic acid has not been documented systematically. Its development can result in difficulty assessing disease progression, and treatment may be altered inappropriately. Twenty-seven patients with colon cancer and liver metastases receiving 5-FU and folinic acid were studied with computerized tomography (CT) before treatment and after six or 12 cycles of chemotherapy. Forty-seven per cent of patients developed hepatic steatosis during treatment. There was no correlation between development of hepatic steatosis and the dose of chemotherapy or the liver function tests. Hepatic steatosis occurs commonly in patients receiving 5-FU and folinic acid and can be severe. Its development can make hepatic metastases difficult to assess and if its benign nature is not appreciated treatment may be inappropriately altered.Keywords: colon cancer; liver steatosis; computerized tomography; chemotherapy; 5-fluorouracilIn the treatment of patients with advanced colorectal cancer, abdominal computerized tomography (CT) is the most widely used technique to determine stage and to monitor the response of liver metastases and other sites of disease to 5-fluorouracil (5-FU)-based chemotherapy. The diagnosis of metastatic disease is either made during laparotomy or by CT-or ultrasound-guided liver biopsy.It has been observed, while scanning such patients, that they may develop a decrease in liver attenuation consistent with steatosis during treatment with 5-FU, which is used extensively alone or in combination with other drugs for adenocarcinoma of the large bowel. Although fatty change of the liver is well recognized after administration of various chemotherapy regimens (Leevy and Tygstrup, 1976), its frequency and severity has not been documented. Also its occurrence after 5-FU alone or with folinic acid has been noted incidentally in one study and found only to occur when administered with interferon in another (Moertel et al, 1993;Sorensen et al, 1995). The accuracy of CT in establishing the presence of fatty change of the liver is well established (Bydder et al, 1980). The decrease in liver attenuation is important because metastases demonstrated on CT are usually of lower attenuation than normal liver parenchyma and as the liver becomes more fatty, and therefore less dense, the metastases can become increasingly difficult to delineate. This may result in the false impression of a therapeutic response. The confusion can be exacerbated particularly in the presence of focal sparring within fatty change that can mimic metastases (Yates and Streight, 1986). Treatment may be stopped if this benign cause for the liver appearances is misinterpreted as progressive disease.Received 11 August 1997 Revised 24 September 1997 Accepted 11 November 1997 Correspondence to: PD Peppercorn The aim of this study is to examine the frequency and severity of fatty change of the liver as seen on CT in patients receiving 5-FU and folinic...

The Oncosurgery Approach to Managing Liver Metastases from Colorectal Cancer: A Multidisciplinary International Consensus

“…The addition of bevacizumab has been associated with a lower incidence of oxaliplatin-induced SOS and NRH lesions [116]. Similarly, irinotecan has been linked to the development of steatohepatitis, a type of nonalcoholic fatty liver disease [117,118], and 5-FU plus leucovorin and/or irinotecan are associated with a higher incidence of hepatic steatosis, particularly in patients with a body mass index Ͼ25 kg/m 2 [119,120]. Many patients with liver metastases from CRC are only referred for surgical resection following numerous prior chemotherapy regimens, but accumulated hepatic toxicity may mean that curative surgery is no longer possible in some of these patients, highlighting the importance of coordinated efforts among medical oncologists, surgeons, and patients to optimize disease management [121].…”

Analysis of Molecular Mechanisms of 5-Fluorouracil Induced Steatosis and Inflammation in Vitro and in Mice

“…An important observation in our study was that 5-FU treatment induced a significant triglyceride accumulation in hepatocytes and HepG2 cells, an incidence known from clinical trials, where up to half of patients receiving 5-FU monotherapy were found to develop hepatic steatosis [14][15][16][17]. One factor contributing to hepatocellular lipid accumulation is endogenous de novo lipogenesis [49,50].…”

“…With the continued rise of obesity in the Western countries, the prevalence of NAFLD has followed a similar trend and is today recognized as the most common liver disease worldwide [18,19]. NAFLD is characterized by hepatic steatosis, which is also the most documented liver pathology observed in association with 5-FU administration [14,16,17,20]. In general, hepatic steatosis is characterized by intravesicular accumulation of fat in the form of triglycerides within hepatocytes [18,19].…”

“…Furthermore, 5-FdUTP incorporation into DNA inhibits DNA synthesis and induces single-and double strand breaks, leading to DNA fragmentation [6][7][8]. Despite its benefits as a chemotherapeutic agent in neoadjuvant and adjuvant treatment, especially for patients suffering from (metastatic) colorectal cancer, several studies indicate that 5-FU can also induce liver injury [9][10][11][12][13][14][15][16][17].…”

Preoperative Imaging in Colorectal Liver Metastases: Current Practices

“…Chemotherapy can also result in steatosis of the liver [39,46]. The ability of noninvasive imaging studies to evaluate steatotic livers continues to evolve [47, 48 • ].…”