AIM:Patients with colorectal cancer and liver metastases can benefit from preoperative chemotherapy and liver disease resection. Adjunction of bevacizumab (BV) to chemotherapy improves survival in these patients, but its impact on surgical complications remains to be fully determined. METHODS:We reviewed all studies addressing mortality and morbidity following hepatectomy in patients preoperatively treated with a combination of BV and chemotherapy. RESULTS:All available data are retrospective. For all patients, the interval between BV and surgery was at least one month. As compared to chemotherapy alone, they demonstrate no significant increase of the incidence of surgical complications, including wound healing delays, hepatocellular insufficiency, infections, and bleeding. CONCLUSION:We still recommend managing an interval of at least 6 weeks from discontinuation of bevacizumab to hepatic resection, and at least 4 weeks from surgery to retreatment with bevacizumab. This recommendation is based on retrospective data and small numbers of patients, all indicating that BV use has no deleterious impact on postoperative morbidity and mortality.
Surgical resection remains the only treatment of colorectal liver metastases that can ensure long-term survival and cure in some patients, but only a minority of patients with liver metastases is directly amenable to surgery. Cancer relapse is observed in the majority of patients after resection of liver metastases despite progress in surgical technique and improved surgical skills. In order to decrease the risk of cancer relapse, it has been proposed to combine surgery and chemotherapy, which could be administered before, after or before and after surgery. It has been demonstrated that perioperative chemotherapy can reduce the risk of cancer relapse and should be considered as the standard of care for most patients with resectable colorectal liver metastases. However perioperative chemotherapy has also potential disadvantages. This review will summarize the current data on the rationale, benefits and potential disadvantages of perioperative chemotherapy in patients with resectable colorectal liver metastases.
Hepatotoxic effect of oxaliplatin and irinotecan on the non-tumourous liver parenchyma has been reported. These two main drugs have been linked to injuries such as vascular changes (sinusoidal obstruction syndrome (SOS) and chemotherapy-associated steatohepatitis (CASH)). Oxaliplatin-based regimens have been associated with an increased risk of vascular lesions and irinotecan-containing regimens have been also associated with increased risks of steatosis and steatohepatitis. SOS increased morbidity after major liver resection, mostly after administration of more than six cycles of neoadjuvant systemic chemotherapy. CASH increased morbidity and mortality rates after hepatectomy. Preliminary results demonstrated that the addition of targeted molecular therapy (bevacizumab or cetuximab) to conventional chemotherapy does not increase the postoperative morbidity and mortality rates after hepatectomy. Furthermore, there was no additional injury to the non-tumorous liver parenchyma.
Le pronostic des patients atteints de métastases hépatiques d’un cancer colorectal (MHCR) a été bouleversé par l’arrivée de nouvelles chimiothérapies comme l’oxaliplatine et l’irinotécan. Toutefois l’enthousiasme lié à l’efficacité évidente de ces drogues est tempéré par les lésions histopathologiques chimio-induites (la stéatohépatite et le syndrome d’obstruction sinusoïdale) aux conséquences cliniques préoccupantes. Le bévacizumab, agent anti-angiogénique inhibant le vascular endothelial growth factor, a une action antitumorale en inhibant l’angiogenèse nécessaire au développement de la tumeur. Toutefois, le bévacizumab inhibe également l’angiogenèse physiologique nécessaire aux mécanismes de cicatrisation et de régénération tissulaire et l’utilisation en phase péri-opératoire doit être évaluée. Les premières données cliniques ont confirmé une meilleure réponse tumorale lorsque le bévacizumab était associé aux agents cytotoxiques, mais ont également démontré un effet protecteur du bévacizumab sur les lésions de SOS dont on sait qu’elles sont associées à une augmentation du VEGF. Aucune conséquence clinique n’a été observée dans le cadre des résections hépatiques encadrées par une administration de bévacizumab. La sécurité des patients repose avant tout sur une évaluation précise des volumes hépatiques et sur une utilisation parcimonieuse des agents cytotoxiques en préopératoire suivi d’un délai suffisant (5 semaines) avant la chirurgie.
Surgical cytoreduction combined with intraperitoneal chemo-hyperthermia (HIPEC) has shown to provide survival benefits in the management of some peritoneal carcinomatosis. The cisplatin (CP) used in HIPEC carries a risk of renal impairment (RI). This risk could be reduced by administration of amifostine (A). The aim of our study was to assess the utility of A in preventing RI during IPCH with CP.Retrospective study including patients who underwent HIPEC between January 2007 and June 2013. The HIPEC involved administration of CP and mitomycin C, between 41 and 43 °C. The peri-anaesthetic management was consistent to use A after 2010. Renal function was assessed from the measured creatinine clearance (CreatCl) and the change between D0 and D4 was compared between patients who received A (group A+) and those who did not (group A−). Severe RI was defined as the development of a CreatCl of <30 ml/min. The statistical analysis used a Student t-test and Fischer's exact test. A p-value of <0.05 was deemed to be statistically significant.Over the studied period, seventy five patients underwent HIPEC and the findings from fifty two patients were analysed: thirty one in group A+ and twenty one in group A−. The change in mean CreatCl from D0 to D4 did not differ between the two groups although between D1 and D4 a significantly higher percentage of severe RI was seen in group A−.This study has shown A to offer benefit in terms of reducing severe RI when CP is used in HIPEC. These results, however, will need to be confirmed in prospective series on larger numbers of patients.
