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Colorectal liver metastases: making the unresectable resectable using irreversible electroporation for microscopic positive margins – a case report
© Schoellhammer et al.; licensee BioMed Central. 2015
Received: 23 October 2014
Accepted: 26 March 2015
Published: 12 April 2015
Irreversible electroporation (IRE) is a non-thermal injury tissue ablation technique that uses electrical pulses to cause cell death. IRE damages the endothelial cells of blood vessels; however these cells re-grow, and thus IRE does not result in permanent damage to blood vessels. We report the novel use of IRE for ablation of microscopically positive margins after resection of colorectal liver metastases (CRLM) impinging on hepatic veins.
A 68-year-old female was found to have colon cancer and synchronous bilateral unresectable liver metastases. Chemotherapy with FOLFOX and cetuximab was initiated, with subsequent conversion to resectability of the CRLM. The patient underwent colectomy followed by right liver posterior sectionectomy with wedge resection of segment 5. Resection of tumor impinging on the left and middle hepatic veins would have required left hepatectomy, with insufficient remnant liver volume. The CRLM were meticulously dissected off the hepatic veins leaving a microscopically positive margin, and IRE was then used for margin ablation, leaving intact hepatic veins and venous blood flow. The patient is alive and without recurrent disease now 30 months after resection. Herein we review the IRE technology and its use in ablation of liver metastases.
Use of IRE margin ablation for microscopically-positive CRLM resection may lead to long-term patient survival; further prospective randomized trials are needed to confirm this finding.
Resection of colorectal liver metastases (CRLM) has been well described, with reports of five-year survival up to 58% after complete resection of disease . The overarching goals of liver resection for CRLM are to obtain tumor-free margins and a functioning liver remnant with intact portal venous and arterial inflow, venous outflow, and biliary-enteric drainage [2,3]. An operation should be undertaken with the intent of a margin-negative resection, as patients with a positive resection margin have significantly increased risk for local recurrence as well as significantly decreased overall survival compared with margin-negative patients . The extent of liver resection, and the success of a margin-negative resection, may be limited by concomitant intrinsic liver disease, chemotherapy-induced liver damage, and the anatomic location of the metastases. Tumors adjacent to major hepatic blood vessels may pose a challenge to resection if, in taking the tumor and associated blood vessel, an inadequate amount of liver is left behind to support hepatic function post-operatively.
In the past, tumor adjacent to major hepatic blood vessels (e.g., hepatic vein, portal vein) has been a relative contraindication to surgery if tumor-free margins are unable to be achieved while maintaining a sufficient liver remnant; however, with the use of irreversible electroporation (IRE), a relatively new ablation technique, in combination with hepatic resection, tumors may be safely treated while preserving the hepatic vasculature. Irreversible electroporation is a non-thermal injury tissue ablation technique that uses electrical pulses of short duration to permanently create defects in cell membranes leading to irreversible permeabilization and ultimately cell death . Vessels adjacent to the zone of ablation do not cause a heat sink effect, as may be seen in radiofrequency or microwave ablation. Furthermore, IRE has a very low incidence of collateral damage to adjacent structures, making it possible to ablate tumors adjacent to major hepatic vessels . In this report we describe a novel technique of hepatic resection followed by margin ablation using IRE as a treatment for CRLM near major vascular structures, resulting in long-term and durable patient survival.
The patient was referred to medical oncology and began chemotherapy with fluorouracil, oxaliplatin, and leucovorin (FOLFOX) with cetuximab. The patient underwent seven cycles of chemotherapy over three months and was subsequently referred to our institution for evaluation.
The patient was taken to the operating room and underwent a right colectomy with ileocolic anastomosis without incident and attention was then turned to the liver. Intra-operative hepatic ultrasound revealed three multi-lobulated lesions within segments 6 and 7, a small segment 5 lesion, as well as a segment 2 and 4A lesion between the middle and left hepatic veins. The metastases were resectable, and the liver, while appearing to have some damage as a result of chemotherapy, was felt to have adequate volume for a functioning liver remnant.
The segment 5 lesion was wedged out in a standard fashion using electrocautery and hemostatic clips. This was a margin-negative resection despite its close proximity to the portal venous system. A right posterior sectionectomy was performed removing segments 6 and 7, along with a cholecystectomy. The right hepatic vein as well as the right posterior portal pedicles, and a few tertiary branches of the right anterior portal vein, were seen entering the tumor and were taken. Intraoperative pathologic assessment of this specimen reported negative margins (3-4 mm).
Given the microscopic positive margins at the middle and left hepatic veins, we decided to ablate the vein margins using IRE (NanoKnife System, AngioDynamics, Latham, NY). The resection bed of segments 2 and 4A was ablated using electroporation needle pairs placed 1.5 cm apart and 1.5 cm deep into the hepatic parenchyma that remained just adjacent to the hepatic veins. The needle pairs were placed parallel to the veins and the covered with a free flap of omental fat that had been harvested to add extra tissue through which the electrical current would travel such that the positive surfaces of the veins would be treated. Treatments were performed with settings of 3000 V using 100 microsecond pulses for a total of 90 pulses between each needle pair. A total of seven overlapping ablations were performed across the entire raw surface area. The omental fat pad was discarded, and following the completion of IRE, adequate flow was again confirmed through the left and middle hepatic veins without evidence of thrombosis. The patient tolerated the procedure well and her post-operative course was uneventful. The patient was discharged home on post-operative day 9 in good condition with normal liver function.
Resection of CRLM has been widely described, and survival has been reported to range anywhere from 25-70% following surgical resection [2,7,8]. Previously-held traditional resection principles, such as obtaining 1 cm margins  have changed, and eligibility for curative resection now depends on the ability to obtain negative margins on all lesions with an adequate liver remnant [3,10].
Irreversible electroporation is a non-thermal ablation technique whereby electrical pulses delivered to tissue between two or more probes cause the creation of permanent cell membrane nanopores, with subsequent breakdown of cell membranes and death by apoptosis . Notably, after IRE the extracellular matrix is left intact, which allows for the preservation of blood vessels and bile ducts ; this quality makes IRE an attractive adjunctive treatment in the management of tumors abutting major vascular and biliary structures by limiting collateral damage done to these critical structures during ablation. In addition, thermal ablation modalities that depend on heating the tissue to be ablated to 60°C for cell death may fail to reach the target temperature in areas adjacent to large vessels due to a heat sink effect with risk for incomplete ablation and recurrence ; this is not the case with the use of IRE near large vessels.
Selected reports of irreversible electroporation (IRE) in the treatment of hepatic metastases
The role of IRE in the spectrum of treatment for tumors metastatic to the liver currently is in evolution and will continue to be refined with time. Currently it appears that the role of IRE will be for local ablation of unresectable masses adjacent to major vascular or biliary structures or for margin ablation to facilitate extended resections, and at the present time IRE will not replace the need for systemic neoadjuvant or adjuvant chemotherapy. It is also currently unclear if disease requiring the use of both liver resection and ablation with IRE indicates more aggressive disease biology, although it is certain that patients with positive surgical margins after resection of CRLM will have worse biology of disease with decreased outcomes and survival .
Herein we describe the use of IRE to treat resection margins when the likelihood of positive margins is significant, and the use of IRE in this fashion allows completion of major liver resections in one stage as opposed to the use of a two-stage operation with portal vein embolization. In our case the multiple areas of metastatic disease and disease abutting major vascular structures were impediments to performing a traditional metastasectomy with negative margins. Our resection left microscopic disease behind at the margin abutting the vasculature; however the addition of IRE allowed for ablation of this tissue and destruction of the remaining microscopic disease, thus allowing for complete eradication of the patient’s metastatic disease with preserved hepatic venous flow, an adequately functioning liver remnant, and long-term survival benefit.
Large prospective trials studying the use of IRE for ablation of unresectable hepatic disease are ongoing; however long-term outcomes data on the use of IRE are currently lacking. We present a novel technique that combines liver resection with ablation of surgical margins using IRE with the intent to eradicate all disease in an area where use of standard microwave or radiofrequency ablation would have resulted in damage to the hepatic veins and a potentially disastrous patient outcome. We believe this technique is especially useful in those patients with poor hepatic reserve, tumors abutting major vasculature or bile ducts, and in those patients with large tumor burdens, and may offer patients the possibility of long-term disease-free survival.
Written informed consent was obtained from the patient for publication of this Case Report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.
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