Effect of preoperative chemotherapy on liver resection for colorectal liver metastases☆

https://doi.org/10.1016/j.ejso.2007.09.007Get rights and content

Abstract

Aim

To compare the effects of preoperative chemotherapy on liver parenchyma morphology, as well as morbidity and mortality after liver resection for colorectal liver metastases.

Methods

Prospectively collected data on 173 patients undergoing liver resection for CLM between 1/2003 and 9/2005 was analysed in three groups: A: preoperative oxaliplatin (Ox, n = 70); B: other chemotherapeutic agents (OC, n = 60); and C: surgery alone without chemotherapy (SA, n = 43). Blood transfusion, hospital stay, operative procedure, peak postoperative bilirubin levels, complications and histopathology of the resected liver were compared.

Results

Intra-operative blood transfusion requirement (34%) and biliary complications (16%) was higher in patients receiving oxaliplatin-based chemotherapy (p = 0.01 and p = 0.06, respectively). Oxaliplatin-based chemotherapy was also associated with sinusoidal dilatation of mild grade in 52.8% vs. 26.6% and 23.3% patients (p = 0.007 and p = 0.004) in other groups, respectively. Steatosis was similarly distributed across the study group. Postoperative mortality was 2, 1 and 4 patients, respectively (p = ns).

Conclusion

Oxaliplatin-based preoperative chemotherapy is associated with vascular alterations in the liver parenchyma without significantly increasing the risk of steatosis, or postoperative morbidity and mortality.

Introduction

Surgical resection remains the most effective treatment modality for potential long-term survival in CRC patients with liver metastases with 5-year survival rates in carefully selected patients now approaching 60%.1, 2, 3 Traditionally, 5-fluorouracil (5FU)-based chemotherapy with or without leucovarin has been used. These agents seem to have had few hepatotoxic effects and major liver resections have been performed without an obvious increase in risk of mortality and morbidity. Newer chemotherapeutic agents like oxaliplatin, irinotecan and monoclonal antibodies like cetuximab and bevacizumab, as components of standard treatment for metastatic colorectal cancer, have improved response rates and survival considerably.4 The rationale of using preoperative chemotherapy is to improve resectability of the tumour and reduce recurrence rates for patients with colorectal liver metastases.5

However, systemic preoperative chemotherapy with oxaliplatin in metastatic colorectal cancer frequently causes morphological changes involving hepatic microvasculature leading to peliosis and sinusoidal congestion6 with reports of 78% of patients treated with oxaliplatin showing significantly striking sinusoidal changes.7 This can affect the ability to perform extensive liver resections.8 When liver metastases are resectable, the benefit of neoadjuvant chemotherapy on reducing the risks of recurrence after surgery has not yet been demonstrated. However, in case of synchronous metastases and increasingly with metachronous metastases, chemotherapy is often prescribed between the resection of the colorectal primary and the liver surgery.9

This study was aimed with a hypothesis that preoperative chemotherapy with oxaliplatin-based chemotherapy induces morphological changes in the liver, which may increase the morbidity and mortality following liver resection for colorectal liver metastases.

Section snippets

Patients and methods

Data from a prospectively collected database identified 173 patients undergoing liver resection for colorectal liver metastases (CLM) between January 2003 and September 2005. Additional information was obtained by an analysis of patient records. They were further analysed in three different groups depending on the preoperative chemotherapy they received: Group A: those who received preoperative oxaliplatin-based chemotherapy (Ox, n = 70); B: those who were given chemotherapeutic agents other than

Patient characteristics

The median age in the three groups was 64, 67 and 69 years, respectively. A higher number of patients were Duke's stage C in both the chemotherapy groups, whereas those subjected to surgery alone were more evenly distributed between stage B and C (Table 1). More than 50% of patients had synchronous lesions in the oxaliplatin group whereas this was observed in only 25–30% in the other groups (Table 1).

Operative procedure and resource used

Major liver resection was performed in Ox: 75.7%; OC: 80%; and SA: 72% (p = ns). Right

Discussion

Preoperative chemotherapy is increasingly being used to improve resectability and reduce recurrence rates. Oxaliplatin-based chemotherapy has good response rates and forms the mainstay of treatment in such cases.5 It has been previously reported that vascular alterations in the liver parenchyma may be as a direct result of preoperative chemotherapy.10, 11 A detailed histopathological evaluation of liver parenchyma distant from the tumour site was made with an aim to analyse the effect of liver

Conflict of interest

There is no conflict of interest to be declared in this study.

References (16)

There are more references available in the full text version of this article.

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☆

Oral presentation at IHPBA/AUGIS Conference 2006, Edinburgh and published as an abstract only (HPB journal).

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