Radiofrequency ablation of unresectable hepatic malignancies

Introduction
Since radiation and chemotherapy have little impact on survival and offer no prospect for cure, surgical resection offers the best potentially curative option in patients with liver tumors. However, over 70% of a lot of patients with liver tumors are not resectable due to stage combined with health problems, or poor liver function reserve (1, 2). Patients with disease confined to the liver may not be candidates for resection because of multifocal disease, vascular invasion or inadequate functional hepatic reserve related to coexistent cirrhosis.
Hepatic radiofrequency ablation (RFA) is a novel treatment by which tumors are destroyed in situ by thermal coagulation and protein deaturation. High frequency alternating current flows from uninsulated electrode tips into surrounding tissue. This differs from direct heating from a probe. Although there are several potential mechanisms for cellular injury due to radiofrequency energy, the predominant mechanism is most likely thermal injury due to RF - induced heating of tissue. It is presumed that tissue heating drives extracellular and intracellular water out of the tissue, resulting in coagulative necrosis.
Thermal ablation produces direct cytodestruction in treated tissues. In this study, our preliminary clinical reports in patients with unresectable liver tumors treated with RFA have demonstrated radiologic evidence of tumor necrosis.

Patients and Methods
This study involved a total of 28 liver tumors in 19 patients (including 17 patients with hepatomas and 2 patients with metastases). The mean age was 68.9 years old. The size of tumor was more than 3 cm in 17 patients. The approaches to the tumors were laparoscopic in 1 patients and open surgical in 18 patients. Hepatic vascular occulusion was combined with RFA in 5 cases. The reasons for unresectable were defines as total bilirubin, ICGR 15, cardiopulmonary function and multiplicity (table 1).

Results
There was no serious morbidity such as bleeding and infection. The tumor necrosis was shown in 15 patients (78.9%). The survival rates at the time up to 12 months were 84.2% for patients.
Case reports
Case no 2: A 58 year old woman was admitted because of second recurrence of HCC. The patient has been received percutaneous ethanol injection (PEI) and two times of transarterial embolization (TAE). The clinical evaluation in this patient with child B cirrhosis and double recurrent nodules measuring 3.0 cm in S6 and S8 was shown. Preoperative examination showed the number of platelet count was 2,0x104 /ml and total bililubin level was 2.5 mg/dl, which was considered to be difficult in liver resection. Laparoscopic RFA was performed (figure 2). There were no episode of post-operative bleeding and intrahepatic abscess.
Case no 9: A 83 year old woman with hepatitis C presented with 4 cm in diameter of HCC which was located close to inferior vena cava by US and CT scan. Laboratory data showed that ICG 15’ was 23% and platelate count was 5.4x104 /ml. Curative liver resection was considered to be difficult. The patient rejected the TAE, then was treated by RFA. Overlapping ablation for this tumor was performed during RFA. Postoperative CT scan showed the complete necrosis was obtained (figure 3). No complication was found in postoperative course.
Case no 11: A 79 year old man with hepatitis C with multiple HCC. CT scan showed that two tumors with 2.5 cm and 3 cm in diameter were in left lateral segment and 9 cm tumor was located in segment 4 and 8. TAE was performed because of his age and poor pulmonary function.
CT scan after TAE was shown incomplete necrosis of tumor, particularly, for segment 4 and 8. Tumor markers did not drop into the normal level. Partial liver resection combined use with RFA was underwent be cause of difficulty in extended left lobectomy. This patients was treated with partial left lateral segmentectomy, partial resection of tumor in segment 4 and 8 plus RFA of remnant tumor in left lobe (figure 4). Patient discharged without any complications and serum tumor marker was normalized.
Case no 18: 73 years old female admitted because of metastatic liver tumor due to breast cancer with mastectomy in 15 years ago. Pathohistrogical findings showed invasive ductal carcinoma and clinical stage was T2NIMO. CT scan showed that liver tumor was located in segment 4 and 5 with 8 cm in diameter involved in hepatic hilum particularly with P3 and P4. Culative liver resection was considered to be difficult. Overlapping ablation with laparotomy and catheterization for chemoaterial infusion through gastroduodenal artery was performed. Postoperative CT scan showed the necrosis was remarkably (figure 5A and 5B) and tumor marker of NCC-ST 439 was decreased downed to normal level within 4 months. Chemoarterial infusion therapy was given up because of catheter trouble. Patient was alived for 3 years at present time.

Discussion
RFA, the most recent ablative modality, destroys tumor by generating heat within the lesion RF electrocautery devices have been used for more than 70 years to achieve direct tissue ablation, usually for hemostasis. Advances in electrocautery technology led to the development of monopolar and bipolar tissue ablation devices designed to destroy larger areas of tissue, particularly malignant tumors (3-6). Ionic vibration occurs as a result of alternating current, and this results in frictional heating of the tissue
surrounding the electrode. Protein denaturation is followed by thermal coagulation and tissue desiccation (7). The tissue temperature in the tumor to be ablated can be controlled between 70º and 120º by increasing the RF power and current delivered. The geometry of the RF current pathway around the ablation electrode creates a relatively uniform zone of radiant / conductive heat. The needle electrode shaft is placed into the tumor with the array retracted. Using real time ultrasound guidance, the array is then developed from the needle tip into the tumor. The multiple array electrode is one technologic innovation that permits ablation of much larger zones of tissue than simple needle electrodes. These multiple array hooks creates a series of electrodes with a diameter up to 4 cm across which the RF current can be passed (8). Liver tumors respond poorly to chemotherapy and radiation, and 30% of patients are candidates for curative resection (1-3). Therefore, there is a need for a simple and precise technique, with low morbidity, that will destroy the tumors. An advantage that focal ablative treatments have over surgical resection is that they spare more normal liver tissue. The ideal ablation method should achieve a controlled lethal cellular effect which can be monitored with imaging.
The majority of patients in this study underwent RFA by open surgical procedure because of large tumor or multiple tumors. Based on our experience with RFA of liver tumors, an apparent advantage of RFA over PEI or TAE is to obtain the more complete necrosis and lower treatment - related complication rate. Curley et al. (19) reported the treatment - related complications were two perihepatic abscess and one hemorrhage out of 123 patients (2.4%). They also reported lower local recurrence rate was only 8%. As well, it has been recognized that RFA has the advantage of nonablation near major blood vessels (10, 11). This “heat sink“ effect of blood vessels has been observed in vivo as a negative influence on RF lesion shape.
Thus, potential advantage of the heat sink effect are it may self - protect blood vessels and bile ducts from thermal injury.
Resection, when possible, remains the standard for management of hepatic tumors. However, a surgeon should have experience with the multimodality approach to hepatic tumors, which provide the most appropriate treatment to the wide spectrum of patients with hepatic malignant tumors. Our initial experience with RFA as a
treatment for malignant liver tumors encouraged us because it is safe, well tolerated, associated with well circumscribed areas of necrosis and few complications.

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