Laparoscopic microwave thermal ablation for late recurrence of local hepatocellular carcinoma after liver transplant: case report Liver transplant is the preferred treatment for hepatocellular carcinoma in patients with cirrhosis, as both neoplastic and cirrhotic liver tissue can be removed. Treatment of recurring neoplasms is a difficult issue, especially in long-term survivors of liver transplant. No consensus has been reached on the treatment of recurrent hepatocellular carcinoma. Although patients with extrahepatic metastases are generally not candidates for local therapy, successful multimodal salvage therapy including resection or ablation can be achieved in liver transplant recipients with local recurrence of hepatocellular carcinoma. Microwave ablation is safe and effective for treating unresectable hepatocellular carcinoma, achieving excellent results in local disease down-staging or as a “bridge” to liver transplant, with no significant differences in local recurrence and complications compared with the more commonly used radiofrequency ablation. A patient with local recurrence of hepatocellular carcinoma 36 months after liver transplant for multifocal hepatocellular carcinoma and cirrhosis due to hepatitis C was successfully treated with laparoscopic microwave ablation without any postoperative complications. The patient is disease free 24 months after microwave ablation. (Progress in Transplantation. 2014;24:142-145) ©2014 NATCO, The Organization for Transplant Professionals doi: http://dx.doi.org/10.7182/pit2014632

Enrico Gringeri, MD, PhD, Riccardo Boetto, MD, Domenico Bassi, MD, Francesco Enrico D’Amico, MD, Marina Polacco, MD, Maurizio Romano, MD, Daniele Neri, MD, Paolo Feltracco, MD, Giacomo Zanus, MD, PhD, Umberto Cillo, MD, PhD, FEBS Azienda Università di Padova, Italy Corresponding author: Boetto Riccardo, MD, General Surgery and Organ Transplantation, Hepatobiliary Surgery and Liver Transplant Unit, Azienda Università di Padova, Via Giustiniani, 2-35128 Padova, Italy (e-mail: [email protected]) To purchase electronic or print reprints, contact: American Association of Critical-Care Nurses 101 Columbia, Aliso Viejo, CA 92656 Phone (800) 899-1712 (ext 532) or (949) 448-7370 (ext 532) Fax (949) 362-2049 E-mail [email protected]

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epatocellular carcinoma is the third leading cause of cancer death worldwide, accounting for more than 500 000 deaths annually. 1 Since 1996, when Mazzaferro et al2 introduced the widely adopted macromorphologic “Milan criteria,” liver transplant for hepatocellular carcinoma has been associated with a 5- and 10-year survival rates of 73% and 70%, respectively.3 Yoo et al4 also reported that survival rates after liver transplant improved dramatically after the strict adoption of this preoperative selection, with a 5-year survival rate of 25% for “pre-Milan criteria” versus 61% for “post-Milan criteria” (P < .001).

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The reported incidence of recurrent hepatocellular carcinoma after liver transplant has ranged from 6% to 56%,5-8 reflecting differences in selection of patients for the initial liver transplant. Primary tumor size, number of lesions, and presence of vascular invasion have been reported in several studies5,8-11 to be the most significant clinical risk factors for both recurrence and survival after liver transplant for hepatocellular carcinoma. Locoregional treatments play a key role in the management of hepatocellular carcinoma. In the past 25 years, several methods for chemical or thermal destruction of tumors have been developed and clinically

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Laparoscopic microwave thermal ablation tested. More recently, new options that use novel, nonchemical nonthermal ablative techniques have been clinically investigated. The technique used for chemical ablation of hepatocellular carcinoma has been percutaneous injection of ethanol. Ethanol induces coagulation necrosis of the lesion as a result of cellular dehydration, protein denaturation, and chemical occlusion of small tumor vessels. An alternative method for chemical ablation is injection of acetic acid. However, acetic acid injection has been used by very few investigators worldwide. The thermal ablative therapies involved in clinical practice can be classified as either hyperthermic treatments—including radiofrequency ablation, microwave ablation, and laser ablation—or cryoablation. The thermal damage caused by heating is dependent on both the tissue temperature achieved and the duration of heating. Heating of tissue at 50°C to 55°C for 4 to 6 minutes produces irreversible cellular damage. At temperatures between 60°C and 100°C, near-immediate coagulation of tissue is induced, with irreversible damage of mitochondrial and cytosolic enzymes in the cells. At more than 100°C, tissue vaporizes and carbonizes. On the other hand, the freezing of tissue with temperatures between 20°C and 60°C followed by rapid thawing results in cell membrane disruption and induces cell death.12 The more common energy sources include radiofrequency, which is currently considered the “gold standard.” Radiofrequency ablation has yielded important clinical results, and its survival rates compare favorably with those for partial resection in small colorectal metastases and particularly in early hepatocellular carcinoma; moreover, in these patients, radiofrequency ablation is less expensive, is less invasive, and has lower complication rates than partial resection.13 Recently, there has been continued interest in the clinical application of microwave ablation with the goal of achieving larger areas of necrosis than those achieved with radiofrequency ablation.14,15 Microwave ablation is the term used for all electromagnetic methods of inducing tumor destruction by using devices with frequencies of 900 kHz or higher. The passage of microwaves into cells results in the rotation of individual molecules. This rapid molecular rotation generates and uniformly distributes heat, which is instantaneous and continuous until the radiation is stopped. Microwave irradiation creates an ablation area around the needle in a column or round shape, depending on the type of needle used and the generating power.12 In the past, the limitations of microwave ablation were related to the small area of ablation, the long duration of treatment, and the burning of superficial tissue. Novel different technologies for microwave ablation have been conceived, with everyone trying to Progress in Transplantation, Vol 24, No. 2, June 2014

obtain better results in terms of feasibility, local effectiveness, and safety. Microwave ablation has a much broader zone of active heating than other techniques and does not rely on the conduction of electricity into the tissue, thus, the transmission of this energy is not limited by tissue charring. Therefore, intratumor temperatures can be greater, leading to a larger zone of ablation in a shorter treatment time. A few single-center studies 16-18 on the complication rates of microwave ablation have already been published and show promising results. We recently reported complete histological necrosis in the explanted liver in 6 cases of hepatocellular carcinoma up to 5 cm in diameter treated with microwave ablation before liver transplant with the goal of “bridge” to transplant or down-staging of the tumor.19 To our knowledge, no cases of local recurrence of hepatocellular carcinoma after liver transplant treated with laparoscopic microwave ablation technology have been reported in any publications. Case Report A 47-year-old man underwent split liver transplant (June 2007) for cirrhosis related to infection with hepatitis C virus and multifocal hepatocellular carcinoma. The patient received a bridge to liver transplant therapy for hepatocellular carcinoma (percutaneous radiofrequency ablation and chemoembolization). Histopathologic examination of the explanted liver revealed 5 nodules of hepatocellular carcinoma with a median diameter of 16 mm, a maximum diameter of 25 mm, G2/G3 Edmondson Steiner grade with microvascular invasion, a mitotic index of 30 per 10 high-power fields, and an α-fetoprotein level of 145.2 µg/L before liver transplant. No adjuvant therapy was given and close radiological monitoring was performed. A follow-up abdominal computed tomography scan 36 months after liver transplant revealed a hypervascular 15-mm nodule in segment 7 (see Figure, A) that aspiration biopsy cytology showed was hepatocellular carcinoma. The αfetoprotein level was normal and no other biohumoral or clinical signs were suggestive of local recurrence of hepatocellular carcinoma or hepatic decompensation. Despite the long interval since the liver transplant surgery, we decided on laparoscopic peritoneal exploration with microwave ablation because of the posterior location of the lesion and the possibility of safer treatment with visually guided hemostasis. A 12-mm trocar was placed on the patient’s right side beside the rectum because of a ventral hernia and a 10-mm trocar was placed on the right flank, through which a simple adhesiolysis of the right upper quadrant was performed with an ultrasonic scalpel. Intraoperative ultrasonography mapping showed a posterior 20-mm hypoechoic lesion with regular margins.

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Figure A, Preoperative computed tomography (CT) scan shows a 15-mm recurrence of hepatocellular carcinoma in segment 7. B, Follow-up CT scan at 1 month shows a 40-mm hypodense area in segment 7 compatible with complete necrosis. Ablated tissue along the “needle track” also is visible. C, CT scan at 24 months confirms complete ablation with the area of necrosis reduced to 30 mm.

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A 14-gauge needle was inserted transperitoneally into the lesion under ultrasound laparoscopic guidance, and microwave ablation (3 minutes at 40 watts; AMICA, HS Hospital Service SpA) was performed without intraoperative or postoperative bleeding or any other complications; no abdominal drainage tubes were placed. The patient was discharged on postoperative day 2; the immunosuppressive regimen was low-dose cyclosporine (blood cyclosporine level at 2 hours after administration

Laparoscopic microwave thermal ablation for late recurrence of local hepatocellular carcinoma after liver transplant: case report.

Liver transplant is the preferred treatment for hepatocellular carcinoma in patients with cirrhosis, as both neoplastic and cirrhotic liver tissue can...
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