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THE ASSOCIATION BETWEEN PREOPERATIVE CHEMOTHERAPY AND THE PREVALENCE OF HEPATIC STEATOSIS IN HEPATECTOMY FOR METASTATIC COLORECTAL CANCER Translated title: Associação da quimioterapia pré-operatória e a prevalência de esteatose hepática em hepatectomias por metástase de câncer colorretal

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      Abstract

      Background

      Some studies have suggested that preoperative chemotherapy for hepatic colorectal metastases may cause hepatic injury and increase perioperative morbidity and mortality.

      Aim

      To evaluate the prevalence of hepatic steatosis in patients undergoing preoperative chemotherapy for metastatic colorectal cancer.

      Methods

      Observational retrospective cohort study in which 166 patients underwent 185 hepatectomies for metastatic colorectal cancer with or without associated preoperative chemotherapy from 2004 to 2011. The data were obtained from a review of the medical records and an analysis of the anatomopathological report on the non-tumor portion of the surgical specimen. The study sample was divided into two groups: those who were exposed and those who were unexposed to chemotherapy.

      Results

      From the hepatectomies, 136 cases (73.5%) underwent preoperative chemotherapy, with most (62.5%) using a regimen of 5-fluorouracil + leucovorin. A 40% greater risk of cell damage was detected in 62% of the exposed group. The predominant histological pattern of the cell damage was steatosis, which was detected in 51% of the exposed cases. Exposure to chemotherapy increased the risk of steatosis by 2.2 fold. However, when the risk factors were controlled, only the presence of risk of hepatopathy was associated with steatosis, with a relative risk of 4 (2.7-5.9).

      Conclusion

      Patients exposed to chemotherapy have 2.2 times the risk of developing hepatic steatosis, and its occurrence is associated with the presence of predisposing factors such as diabetes mellitus and hepatopathy.

      Translated abstract

      Racional

      Alguns estudos sugerem que a quimioterapia pré-operatória para metástases hepáticas do câncer colorretal pode causar dano celular e aumentar morbidade e mortalidade.

      Objetivo

      Analisar a prevalência de esteatose hepática em fígados de pacientes expostos à quimioterapia pré-operatória por metástase de câncer colorretal.

      Métodos

      O delineamento do estudo foi observacional de coorte retrospectivo, no qual 166 pacientes foram submetidos a 185 hepactectomias por metástase de câncer colorretal, com e sem quimioterapia pré-operatória, no período de 2004 a 2011. Os dados foram extraídos da revisão dos prontuários e da análise do laudo anatomopatológico da parte não tumoral da peça cirúrgica. A amostra foi dividida em grupo exposto e não-exposto à quimioterapia. Os dados foram analisados por programa estatístico Stata 11.2, e aplicado o teste exato de Fischer para análise bivariada, e a regressão de Poisson, para análise multivariada; valores p< 0,05 foram considerados como significativos.

      Resultados

      Das hepatectomias, 136 casos (73,5%) receberam quimioterapia pré-operatória, e o regime mais utilizado (62,5%) foi 5-fluorouracila+leucovorin. No grupo exposto, a lesão hepatocelular esteve presente em 62% dos casos e correspondeu a risco de 40% em relação ao grupo não-exposto. O padrão histológico da lesão hepatocelular predominante foi a esteatose, em 51% de casos do grupo exposto. A exposição à quimioterapia aumentou em 2,2 vezes a possibilidade de esteatose. Entretanto, quando foram controlados os fatores de risco, somente a hepatopatia prévia esteve associada à presença de esteatose após quimioterapia com risco relativo de 4 (2,7-5,9).

      Conclusões

      Pacientes expostos à quimioterapia têm risco 2,2 maior de desenvolver esteatose, e sua prevalência está associada à presença de fatores predisponentes, como risco de hepatopatia prévia.

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      Most cited references 57

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      The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association.

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        Combination of surgery and chemotherapy and the role of targeted agents in the treatment of patients with colorectal liver metastases: recommendations from an expert panel.

        The past 5 years have seen the clear recognition that the administration of chemotherapy to patients with initially unresectable colorectal liver metastases can increase the number of patients who can undergo potentially curative secondary liver resection. Coupled with this, recent data have emerged that show that perioperative chemotherapy confers a disease-free survival advantage over surgery alone in colorectal cancer (CRC) patients with initially resectable liver disease. The purpose of this paper is to build on the existing knowledge and review the issues surrounding the use of chemotherapy +/- targeted agents combined with surgery in the treatment of CRC patients with liver metastases, with a view to providing clinical recommendations. An international panel of 21 experts in colorectal oncology comprising liver surgeons and medical oncologists reviewed the available evidence. In a major change to clinical practice, the panel's recommendation was that the majority of patients with CRC liver metastases should be treated up front with chemotherapy, irrespective of the initial resectability status of their metastases.
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          Systematic review and meta-analysis of steatosis as a risk factor in major hepatic resection.

          The risk of major hepatic resection in patients with hepatic steatosis remains controversial. A meta-analysis was performed to establish the best estimate of the impact of steatosis on patient outcome following major hepatic surgery. A systematic search was performed following Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. Risk ratios (RRs) for complication and mortality rates were calculated for patients with no, less than 30 per cent and at least 30 per cent steatosis, and a meta-analysis was carried out. Of six observational studies identified, four including a total of 1000 patients were subjected to meta-analysis; two others were tabulated separately. Compared with patients without steatosis, those with less than 30 per cent and at least 30 per cent steatosis had a significantly increased risk of postoperative complications, with a RR of 1.53 (95 per cent confidence interval (c.i.) 1.27 to 1.85) and 2.01 (1.66 to 2.44) respectively. Patients with at least 30 per cent steatosis had an increased risk of postoperative death (RR 2.79, 95 per cent c.i. 1.19 to 6.51). Patients with steatosis had an up to twofold increased risk of postoperative complications, and those with excessive steatosis had an almost threefold increased risk of death. Copyright 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.
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            Author and article information

            Affiliations
            Hepatobiliary Cancer Surgery Unit of Santa Rita Hospital and Post-Graduation Program in Hepatology, Hospital Complex of Irmandade Santa Casa of Porto Alegre (Hospital Santa Rita, Complexo Hospitalar da Irmandade Santa Casa de Porto Alegre), Porto Alegre, RS, Brazil.
            Author notes
            Correspondence: Felix Antônio Insaurriaga dos Santos. E-mail: fejus@ 123456terra.com.br
            Journal
            Arq Bras Cir Dig
            Arq Bras Cir Dig
            Arquivos Brasileiros de Cirurgia Digestiva : ABCD = Brazilian Archives of Digestive Surgery
            Colégio Brasileiro de Cirurgia Digestiva
            0102-6720
            2317-6326
            Apr-Jun 2014
            Apr-Jun 2014
            : 27
            : 2
            : 120-125
            25004290 4678686 10.1590/S0102-67202014000200008

            This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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