Is radiofrequency ablation an acceptable alternative to resection for gallbladder cancer?

June 11, 2007
Surgical Rounds®, June 2007, Volume 0, Issue 0

Michele McElroy, General Surgery Resident, Department of Surgery, University of California San Diego, General Surgery Resident, Department of General Oncologic Surgery, Section of Hepatobiliary Cancer, City of Hope National Medical Center, Duarte, CA; Yale D. Podnos, Clinical Surgical Fellow, Department of General Oncologic Surgery, Section of Hepatobiliary Cancer, City of Hope National Medical Center, Duarte, CA; Lawrence D. Wagman,

Michele McElroy, MD

General Surgery Resident

Department of Surgery

University of California San Diego

General Surgery Resident

Department of General

Oncologic Surgery

Section of Hepatobiliary Cancer

City of Hope National

Medical Center

Duarte, CA

Yale D. Podnos, MD, MPH

Clinical Surgical Fellow

Department of General

Oncologic Surgery

Section of Hepatobiliary Cancer

City of Hope National

Medical Center

Duarte, CA

Lawrence D. Wagman, MD

Chair, Division of Surgery

Department of General

Oncologic Surgery

Section of Hepatobiliary Cancer

City of Hope National

Medical Center

Duarte, CA

Optimal treatment for adenocarcinoma of the gallbladder is controversial because of the poor prognosis for patients with this disease and the major liver resection and lymphadenectomy that may be necessary for local control. While these operations are relatively safe, they are often contraindicated in patients with poor hepatic reserve or multiple comorbidities. Many patients who develop gallbladder cancer are elderly and poor candidates for aggressive surgical resection. Unfortunately the outcomes for patients treated nonoperatively are extremely poor. Radiofrequency ablation (RFA) is a recently developed and well-described therapy for hepatoma and metastatic colorectal cancer that results in predictable tissue destruction.

We present the case of an infirm, elderly woman with stage II adenocarcinoma of the gallbladder who was treated successfully with RFA of the gallbladder bed. This modality offers an alternative therapy for patients in whom liver resection would carry a substantial mortality risk.

Case report

A 74-year-old woman with poorly controlled diabetes, hypertension, and cardiac arrhythmias presented to our institution for treatment of gallbladder cancer. She was initially worked up at an outside institution because of right upper quadrant pain. Ultrasonography revealed gallstones and slight thickening of the gallbladder wall, although the gallbladder, periportal areas, and liver appeared normal. The patient underwent an uneventful laparoscopic cholecystectomy, and no suspicious masses were observed. Pathologic evaluation of the gallbladder revealed gallstones and a 1.2-cm focus of moderately differentiated invasive adenocarcinoma with full-thickness involvement of the gallbladder wall but without invasion into the liver; it was staged a T2 NX MX tumor (Figure 1). Computed tomography (CT) scanning of the chest, abdomen, and pelvis was performed approximately 2 weeks later to stage the patient's cancer, and this revealed a 1.9-cm nodule in the right chest. A CT-guided biopsy of the right chest mass found old granulomatous disease with no evidence of malignancy.

Following normal diagnostic laparoscopy the patient underwent exploratory laparotomy and intraoperative ultrasonography of the liver. No lesions were found during ultrasonography and palpation of the abdominal contents. RFA was performed in the gallbladder bed and the periportal, paraduodenal, and pericaval lymph nodes were resected en bloc. RFA was used twice to ablate the gallbladder bed according to radiofrequency interstitial tissue ablation (RITA) protocol, first with a 4-cm radius of thermal ablation followed by a 3-cm radius (Figure 2).

The patient's postoperative course was uneventful, and she was discharged to home on postoperative day 6. The pathology report from her node dissection found three lymph nodes, none of which showed evidence of malignancy. Final pathologic and clinical staging of the tumor was T2 N0 M0 (stage II). The patient has undergone follow-up in our outpatient clinic on a monthly basis and is doing well with no evidence of local or distant recurrent disease 18 months postoperatively.

Discussion

Gallbladder cancer is a relatively uncommon malignancy in the United States, although its worldwide prevalence varies. It is more common in women than in men, and its incidence increases exponentially with age.1,2 Patients with gallbladder cancer have poor outcomes due to the disease's propensity for early dissemination, rapid growth, and often late clinical presentation.3 Additionally, the central location of gallbladder adenocarcinoma generally requires extensive liver resection and biliary reconstruction to control the operable disease. Recent reports concerning patients with gallbladder cancer have determined their overall 1- and 5-year survival rates to be at least as low as 14% and 5%, respectively.4 Patients who are not suitable candidates for surgery or those who are treated nonoperatively generally fare the worst, with a 5-year survival rate lower than 5%.5 Over the past 10 to 15 years, high-volume hepatobiliary centers have shown that major liver resection and biliary reconstruction can be performed safely in patients with gallbladder cancer, producing perioperative mortality rates of 0% to 5% and an improved 5-year rate of survival.5-8 The questions remain, however, as to which patients are appropriate candidates for radical surgical resection and which types of resection offer the best patient outcomes.

The advent of laparoscopic cholecystectomy as the standard of care for non-malignant disease of the gallbladder has resulted in an increasing number of patients whose gallbladder cancer is found incidentally on histopathologic evaluation of the resected gallbladder.1 Deciding whether a more radical resection is appropriate for these patients depends on the depth of the tumor's invasion and the preoperative functional status of the patient.1,9 Given the advanced age of many patients at diagnosis, it is not always possible to offer curative resection since this often involves extensive liver resection and regional lymphadenectomy which often confers prohibitive morbidity in this patient population.

In recent years, destruction of liver tumors using methods such as cryoablation, ethanol injection, and RFA have been examined as alternatives to liver resection for various types of cancer. Increasingly, RFA is being investigated for this purpose, because it has been shown to be relatively safe and effective at causing tumor necrosis.8,10 Mortality rates following RFA of liver lesions have been reported as 0.5%, with rates of complication reported as 7% to 9%.11,12 Most of the current literature has evaluated the use of RFA in patients with hepatocellular carcinoma or metastatic colorectal and neuroendocrine cancer. Ablative modalities are especially useful in those patients whose significant underlying liver disease precludes hepatic resection.8,13-15 There are few randomized controlled clinical trials evaluating the long-term survival of patients whose liver tumors have been treated with RFA. A 2004 study showed limited benefit to providing RFA over chemotherapy alone for metastatic colorectal cancer.16

Navarra and colleagues authored the only report regarding the use of RFA as a treatment modality for gallbladder cancer. The patient was a 66-year-old Jehovah's Witness with a T1b tumor that was found incidentally after laparoscopic cholecystectomy17 After undergoing RFA of the gallbladder bed the patient had follow-up examinations for 9 months and remained disease-free. The patient's refusal of liver resection in the face of full-thickness tumor invasion of the gallbladder wall left few treatment options. Although 9 months is too short a follow-up to comment on the long-term success of this treatment, Navarra and colleagues' report nevertheless demonstrates a plausible alternative to surgery in patients who cannot tolerate or are unwilling to undergo definitive surgical treatment.

Our patient's significant comorbidities convinced us that a liver resection would confer prohibitive risk. The depth of tumor invasion and the lesion's location were instrumental in helping us determine whether our patient was an appropriate candidate for RFA. We also assured ourselves intraoperatively that the structures in the porta hepatis (particularly the proximal bifurcation of the bile ducts) were located far enough away from the gallbladder bed that they would not be damaged by the probe. Biliary strictures and fistulas have been reported following RFA of liver lesions in this central portion of the liver at the confluence of segments IV and V.11,13

Conclusion

Not every patient with gallbladder cancer is a suitable candidate for treatment with RFA. Clearly, younger individuals with greater hepatic reserve should be considered for attempted curative resection, because this procedure significantly improves survival for patients with T2 and T3 cancers. RFA done in the context of oncologic principles of negative margins offers an alternative for those patients who are unable to undergo such an extensive operation. RFA is an important, evolving, adjunctive treatment for many types of cancer. Formal, prospective studies are needed to determine the long-term efficacy of this treatment modality in treating patients with gallbladder cancer.

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