BACHILLERATO Nº Bloque

• Uncontrollable peritoneal disease

• Extensive nodal disease, such as retroperitoneal or mediastinal lymph nodes • Bone or CNS metastases

1.8.3 Techniques of surgical resection !

1.8.3.1 Transection techniques

Technological innovations in liver surgery have mainly focused on minimising blood loss during transection of the hepatic parenchyma, as blood transfusion is associated with increased postoperative morbidity and mortality as well as reduced long-term survival (Kooby et al., 2003). Inflow occlusion (Pringle manoeuvre) and low central venous pressure (CVP) anaesthesia minimises blood loss but may cause liver damage by ischaemia and reperfusion injury. Consequently, there has been an interest in devices that facilitate a more bloodless liver transection, obviating the need for inflow occlusion associated with the traditional clamp- crushing technique.

The most popular of these techniques include the ultrasonic aspirating dissector (CUSA) using ultrasonic energy, the Hydrojet using a pressurised jet of water and the dissecting sealer (TissueLink) using radiofrequency energy. These techniques were compared in a randomised controlled trial (Lesurtel et al., 2005) and in a subsequent Cochrane review (Gurusamy et al., 2009). There was little difference demonstrated between the four techniques, though the clamp-crushing technique was found to be associated with faster tissue transection, and lower transfusion requirements. The Cochrane review also found an association with fewer infective complications. Both studies highlighted the significantly reduced cost associated with the clamp crushing technique, and therefore could not advocate the use of newer techniques in standard practice. A further randomised control trial of

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radiofrequency-assisted versus clamp-crushing transection in 50 patients showed a higher rate of postoperative complications in the radiofrequency group (20%), compared to none in the clamp-crushing group (Lupo et al., 2007).!

1.8.3.2 Ablation for colorectal liver metastases

Ablative therapy takes numerous forms. Cryotherapy, laser hyperthermia and ethanol injection are decreasing in popularity due to high complication rates or lack of efficacy. Radiofrequency ablation (RFA) and microwave ablation (MWA) offer significant advantages over older ablative techniques and are increasingly used. However, there remains a lack of clarity surrounding the precise role of ablation compared to surgery. Recent American Society of Clinical Oncology (ASCO) guidelines highlighted the wide variation in overall survival and local recurrence rates after ablation, and suggested that in the absence of adequate data resection should remain the gold standard treatment for resectable disease (Wong et al., 2010). Despite these concerns, ablation still has a role as an adjunct to resection. Patients with small volume resectable metastases who are not sufficiently fit to undergo liver resection should be considered for ablation as should those with limited liver metastases who have insufficient liver volume to undergo resection (Oshowo et al., 2003; Jansen et al., 2005).!

There is growing interest in the use of ablation alongside systemic chemotherapy for irresectable liver disease. EORTC 40004 compared systemic chemotherapy vs. systemic chemotherapy plus ablation for patients with technically unresectable liver limited disease. 3-year DFS was improved in the combined ablate and chemotherapy arm (27.6% vs. 10%, p=0.03) with a trend towards improved OS (median 45.3 months vs. 40.5, p=0.2) (Ruers et al., 2012). In the French ARF2003 single arm phase II study, 52 patients with unresectable liver limited disease were

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treated with a combined ablate and resect strategy using RFA (Evrard et al., 2012). One year local DFS was 46% (95% CI 32-59) whilst 5 year OS was 43% (21-64), demonstrating that ablation and resection can lead to good long-term survival. The evidence now points towards managing stage IV colorectal cancer as a chronic disease condition, where surgery or ablation is performed in the expectation of potentially treatable disease recurrence rather than a single entity which can only be surgically treated once with curative intent or not. Patients who experience recurrence after liver resection can now often be treated with further interventions including surgery or ablation (Jones et al., 2012). Parenchymal sparing techniques (including ablation) preserve functional liver volume, so maximising the opportunity for further liver directed interventions in the future.

1.8.3.3 Laparoscopic liver surgery

Laparoscopic surgery for hepatic neoplasms aims to provide curative resection while minimising complications. There are no randomized controlled trials comparing laparoscopic and open hepatectomy, and so the evidence is based on retrospective series. A meta-analysis of series published between 1998 and 2005 (Simillis et al., 2007) included eight non-randomised studies, reporting on 409 resections of hepatic neoplasms, of which 165 (40.3%) were laparoscopic and 244 (59.7%) were open. Operative blood loss and duration of hospital stay were reduced significantly after laparoscopic surgery. These findings remained consistent when considering studies matched for the presence of malignancy and segment resection. There was no difference in postoperative adverse events and extent of oncological clearance. This paper concluded that laparoscopic liver resection has the potential to reduce operative blood loss and allow earlier recovery with oncological clearance comparable with open surgery.

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The largest single-centre experience of laparoscopic resection of CRLM included 83 resections within a series of 133 liver resections (Abu Hilal et al., 2012). The authors reported a median operating time of 210 minutes (30-480 minutes), median blood loss of 300ml (10-3000ml) and a median postoperative stay of 4 days (1-15 days). Severe postoperative bleeding occurred in 5 patients (3.7%) requiring intensive care management or reoperation, and overall serious complications occurred in 16 patients (13%). Microscopically negative margins (R0/R1) were achieved in 96% of patients with CRLM. In 2008 a group of 45 experts in hepatobiliary surgery participated in a consensus conference and concluded that the laparoscopic approach to liver resection is a safe and effective technique for appropriately trained surgeons (Buell et al., 2009).

1.9 Chemotherapeutic management of colorectal liver metastases

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In the last 10 years, overall survival (OS) in patients with metastatic CRC has improved substantially (Kopetz et al., 2009) reflecting improved chemotherapeutic manipulation of disease. Before 2000, 5-flourouracil (5-FU) was the only available treatment. With the development of the cytotoxic agents Oxaliplatin and irinotecan, doublet regimens are now considered standard therapy (5-FU/leucovorin/Oxaliplatin as FOLFOX or 5-FU/leucovorin/irinotecan as FOLFIRI).

In the last 5 years, major advances in the management of advanced colorectal cancer have been made by harnessing targeted monoclonal antibodies against extracellular receptors. Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein that utilises tyrosine kinase activity for signal transduction with downstream signaling intrinsically involved in multiple biological processes essential for tumour survival (See section 1.4). Cetuximab is a