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Original Report |
1 Department of Diagnostic Radiology, Mayo Clinic College of Medicine, 200
1st St. SW, Rochester, MN 55905.
2 Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine,
Rochester, MN.
3 Department of Surgery, Mayo Clinic College of Medicine, Rochester, MN.
Received April 13, 2004;
accepted after revision July 1, 2004.
Address correspondence to T. D. Atwell.
Abstract
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CONCLUSION. Our limited experience indicates that percutaneous radiofrequency ablation is both safe and effective in the treatment of the small hepatocellular adenoma in carefully selected patients.
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Radiofrequency ablation is currently used to effectively treat both primary and secondary malignancies of the liver [4–7]. We recently treated three hepatocellular adenomas using percutaneous radiofrequency ablation. Although each adenoma was resectable by standard subsegmental surgical approaches, percutaneous radiofrequency ablation was used as a less invasive alternative, with the realization that resection remained feasible in the event of ablation failure.
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Patient 1
A 32-year-old woman (Figs.
1A,
1B, and
1C) was admitted to the liver
transplantation service at our hospital after an acetaminophen overdose. The
patient had been taking oral contraceptives for an unknown period of time.
Sonography and subsequent CT revealed a 3.1-cm solid mass in the lateral
sector of the left lobe of the liver. MRI revealed foci of intratumoral
hemorrhage, and the mass was consistent with hepatocellular adenoma. A liver
biopsy was performed that confirmed this diagnosis.
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After surgical consultation, we elected to proceed with radiofrequency ablation of the adenoma. This was chosen because of the favorable size and location of the tumor (which we believed could be thoroughly destroyed with current electrodes) and because it was the patient's preference to avoid an operation.
Patient 2
A 48-year-old woman (Figs.
2A,
2B,
2C, and
2D) with a history of oral
contraceptive use was found to have an incidental 2.4-cm liver mass during
evaluation for an inflammatory muscle disorder. MRI revealed fat in the mass,
and subsequent sonographically guided biopsy confirmed hepatocellular adenoma.
After consultation with a liver surgeon, percutaneous radiofrequency ablation
of this adenoma was deemed appropriate because of its small size and
peripheral location.
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Patient 3
A 31-year-old otherwise healthy woman presented to her outside hospital
with acute onset of epigastric pain. As part of her emergency evaluation,
serum liver tests found abnormal results. Results of hepatitis serology
studies were negative. Subsequent CT of her abdomen revealed a complex 5-cm
hepatic mass. MRI revealed increased T1 and T2 signal in this mass, consistent
with hemorrhage.
Given the patient's young age, lack of underlying liver disease, and 12-year history of oral contraceptive use, the consensus diagnosis was hepatocellular adenoma with intratumoral hemorrhage. She discontinued the oral contraceptive, and repeated sonography at our institution 4 months later showed persistence of the mass, which had decreased to 1.3 cm in diameter. After consultation with both a liver surgeon and an interventional radiologist, it was thought that this neoplasm would be best treated with percutaneous radiofrequency ablation.
Ablation Technique
All three patients were referred for ablation after thorough discussion of
treatment options with their primary hepatologist and a liver surgeon. The
patients elected radiofrequency ablation to avoid invasive surgery. Informed
consent for the percutaneous ablation was obtained from all three patients.
All of our percutaneous radiofrequency ablation patients receive general
anesthetic during the procedure.
We use real-time sonographic guidance with an Acuson Sequoia system (Siemens) and either a 4- or 6-MHz curved probe. In all three cases, a Starburst XL electrode (RITA Medical Systems) was used, coupled to a 1500x generator (RITA Medical Systems). The electrode was deployed to 4 cm (patient 1), 4 cm (patient 2), and 3 cm (patient 3), completely encompassing the tumor and a small margin of normal liver parenchyma. A single ablation was performed in patients 2 and 3 (15 and 10 min, respectively), and two overlapping ablations were performed in patient 1 (each 8 min).
In all patients undergoing percutaneous radiofrequency ablation, dual-phase (25- and 70-sec delay) CT with IV contrast material is performed the same day immediately after the ablation. This allows us to detect any residual neoplasm and provides a valuable baseline for future imaging. In addition, follow-up dual-phase CT is performed at 3, 6, and 12 months after ablation to detect any recurrent or residual neoplasm.
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Follow-up CT with IV contrast material was available in the three patients at 17, 3, and 11 months, respectively, after ablation (mean, 10.3 months) (at time of this writing). CT showed a reduction in tumor size with no abnormal enhancement or other evidence of recurrent or residual tumor. All patients have discontinued oral contraceptives.
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These adenomas typically occur in young women with a history of prolonged use of oral contraceptives [2, 8, 9]. Historically, use of oral contraceptives for longer than 5 years has been associated with increased risk for the development of hepatocellular adenoma [10]. A study conducted jointly by the U.S. Centers for Disease Control and Prevention and the Armed Forces Institute of Pathology showed a correlation between duration of oral contraceptive use and risk of developing hepatocellular adenoma [1]. This study reported a 500-fold increased risk of developing hepatocellular adenoma in women using oral contraceptives for more than 85 months. Indeed, 41–100% of patients with hepatocellular adenoma have a history of oral contraceptive use [2, 3, 8, 9, 11].
The rationale for recommending treatment of hepatocellular adenoma is based on the small risk of hemorrhage and malignant degeneration [2, 9–13]. More than half of patients with these tumors will be symptomatic [8, 11]. An initial presentation of intratumoral or intraperitoneal hemorrhage is seen in 39–68% of cases [1, 8, 14]. Although some have suggested that the propensity for bleeding and malignant degeneration is proportional to adenoma size (> 5 cm) [2, 15, 16], others have found no such correlation [11]. Of those with intraperitoneal hemorrhage, the consequences can be devastating, with a mortality rate of 9–21% [1, 14].
Several articles in the medical literature report hepatocellular carcinoma developing in women with hepatocellular adenomas who are taking oral contraceptives [8, 12, 14, 17–20]. In most cases, a direct transformation to malignancy has been suggested [8, 9, 12, 14, 19]. On the basis of cytologic studies, it has been postulated that prolonged use of oral contraceptives initiates an irreversible and premalignant dysplastic sequence in the adenoma that causes it to eventually progress to frank malignancy [9]. This theory is also supported by sporadic reports of transient involution of hepatocellular adenoma after withdrawal of oral contraceptives, followed by subsequent malignant transformation [10, 12, 17].
Because of the risk of hemorrhage and malignant change, treatment of hepatocellular adenoma is typically surgical resection or, rarely, liver transplantation [2, 11, 21]. Surgical resection is associated with a morbidity rate of 6–10% and only a single death [8] in several series that included 69 patients [2, 8, 11, 22]. Surgical excision is curative, with no recurrence in two large series [11, 19]. Because hepatocellular adenomas are discrete and benign, only minimal margins of resection are required. Only rarely is major hepatic resection required because of tumor size or location.
In all patients with hepatocellular adenoma, life-long abstinence from oral contraceptives is recommended. In some patients, such abstinence has been attempted as a conservative primary management technique to defer surgical resection. In some of these patients, the adenoma may decrease in size or resolve completely [11]. However, regression has been observed inconsistently, so more definitive treatment of hepatocellular adenoma is appropriate in most situations.
Because of its acknowledged safety and efficacy, percutaneous
radiofrequency ablation is rapidly evolving into a widely accepted method of
treating both primary and secondary neoplasms of the liver
[4,
5,
7,
23,
24]. Using radiofrequency
energy, lethal heat is generated at the probe tip, resulting in cell death in
the adjacent tissues. Such treatment has resulted in complete necrosis of
small (
3 cm) hepatocellular carcinomas in 90% of cases
[5]. Survival after ablation of
small hepatocellular carcinoma may reach 71% at 3 years and 48% at 5 years
[25]. Local control of
colorectal liver metastases is achieved in 70% of treated tumors
[6,
26]. Complications related to
radiofrequency ablation are uncommon, occurring in approximately 10% of
patients, with infection and hemorrhage being most common
[27,
28]. Mortality is
exceptionally rare, with a reported prevalence of 0.5–1.4%
[27,
28].
The current standard of care for treatment of hepatocellular adenoma is surgical excision. Radiofrequency ablation may be a reasonable option in selected cases. Appropriate individuals for radiofrequency ablation may include patients who are not surgical candidates or those who prefer to avoid surgery after discussion and full understanding of available treatment options, as was the case in our three patients. The size of the adenoma must be smaller than 4 cm to allow effective treatment with current ablation electrodes. Unfortunately, this criterion may exclude many patients, because symptomatic tumors are generally much larger than 4 cm. In addition, the adenoma should not be in a critical location, such as adjacent to the porta hepatis or components of the gastrointestinal tract, where thermal injury could lead to biliary or bowel complications.
Limitations of this study include the small number of treated patients and the lack of long-term follow-up. We are willing to accept the limited number of patients given the rarity of hepatocellular adenoma. Because of the benign nature of this tumor, we are assured about the short-term results and anticipate cure in these patients. Nevertheless, imaging follow-up is obtained for 3 years after radiofrequency ablation.
A third limitation is the remote risk that the adenoma actually could represent a low-grade hepatocellular carcinoma and warrant aggressive surgical resection. We are confident that these tumors were adenomas on the basis of multiple factors, including the relatively young age of our patients and their lack of underlying liver disease, the small size and the imaging characteristics of the tumors, and the results of percutaneous biopsy in two of the patients. Nevertheless, we acknowledge that distinguishing hepatocellular adenoma and carcinoma may be challenging in particular patients, such as those with large tumors and concurrent hepatic parenchymal disease, and those patients with no history of oral contraceptive use. We also recognize the difficult histologic distinction between well-differentiated hepatocellular carcinoma and benign liver tumors using core biopsies [29, 30].
Compared with open surgical resection, percutaneous radiofrequency ablation is minimally invasive, requires limited hospitalization, is cheaper, and is associated with a rapid recovery time. Although laparoscopic hepatic resection of adenomas of appropriate size and location will likely reduce the recovery time and invasiveness compared with open resection, percutaneous radiofrequency ablation, if further confirmed to be effective, will remain the least invasive approach.
On the basis of our early experience, we conclude that radiofrequency ablation of hepatocellular adenoma is safe and well tolerated in carefully selected patients.
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