From the SIR Residents and Fellows Section

Teaching Topic: Determining efficacy of RF ablation for primary or metastatic lung cancer based on tumor characteristics and environment.

Qiuxia Yang, MD, Han Qi, MD, Rong Zhang, MD, Chao Wan, MD, Ze Song, MD, Liang Zhang, MD, and Weijun Fan, MD. Risk Factors for Local Progression after Percutaneous Radiofrequency Ablation of Lung Tumors: Evaluation Based on a Review of 147 Tumors. 2017. 28 (4): 481-9.

Click here for abstract

Tumor-related factors that influence local tumor progression (LTP) include, size, site, orientation, organ, histology, and biology. The decision to treat primary or metastatic lung cancer with surgery or minimally invasive RF ablation is generally based on size. Larger tumors > 3 cm are considered to be more amenable to surgery. For smaller tumors or those close to 3 cm, the authors retrospectively reviewed factors influencing the complete ablative rate (CAR) and LTP. 147 tumors with an average maximum diameter of 1.8 cm +/- 1.2 receiving a single ablation and followed > 6 months were evaluated in 93 patients. 26% of patients had primary lung cancer and 74% had metastatic disease.

Clinical Pearls

What is the mechanism of action of radiofrequency ablation?

The Bovie knife is the first well-known medical device to incorporate RF ablation, which functions as cautery (pulsed current) and cutting (continuous current). Radiofrequency refers to the 3 Hz – 300 GHz range of the electromagnetic spectrum, which can cause thermal ablation of tissue. As with the Bovie knife, RF ablation devices operate in a closed electrical circuit, with the cathode (RF electrode or probe) transmitting energy through the patient’s tissue toward an anode (dispersing pads). Coagulative necrosis is achieved as dipole molecules (mostly water) next to the electrode remain aligned to the direction of the current and are forced to vibrate as rapidly as the applied current. Frictional energy released by adjacent molecules is deposited in surrounding tissue, resulting in local temperature increase. As the energy is dispersed by the pads, tissue damage is limited to the area surrounding the electrode tip. Application of too high of a generator power too quickly can cause tissue to desiccate or “char,” which acts as insulation and limits further extension of ablation.

What is meant by the “heat sink” effect?

Induced coagulation necrosis = (energy deposited x local tissue interactions) – heat loss. “Heat sink” is a cooling effect, which limits the effect of all thermal ablation methods. Flowing blood in vessels 3 mm or larger adjacent to a target lesion limit temperature variation in that area. This is potential cause for residual, unablated tissue and local tumor progression. Other studies have also postulated that tumors with proximal vascular or bronchial extension might lead to larger microscopic extension beyond the edge of the tumor. In this study, contact between tumor and blood vessels was determined as an independent risk factor for incomplete ablation in this study, and the CAR was significantly reduced.

What is considered effective tumor ablation?

A slow method of energy deposition, as to avoid desiccation with quick temperature rises, is used to heat tissue to 50-100 degrees Celsius for 4-6 minutes. Data extrapolation from surgery has established a general guideline to achieve an ablation margin 0.5 – 1.0 cm of ablated normal tissue, which is thought to account for microscopic tumor extension beyond the visualized confines of the lesion. The authors determined a complete ablative margin in this study to correspond to ground-glass opacities completely encircling the ablated lesion. In practice, it is difficult to distinguish inner necrosis areas from outer peripheral hemorrhage and inflammatory reaction on CT images and as a result, the shortest distance of overall ablative margin was measured and recorded in this study. Tumors can be monitored for local progression by determining contrast enhancement at the ablation margins on follow-up CT studies, as was done in this retrospective review. In the first three months following ablation, an enhancement zone that is peripheral, concentric, symmetric, and uniform and has smooth inner margins can be considered to correspond to reactive hyperemia, inflammation, or granulation at the marginal parenchyma. For tumors that are PET-avid prior to ablation, follow up PET studies may also be used. 

Questions to Consider

Which factors related to the efficacy of complete tumor ablation in this study?

The authors retrospectively investigated variables of tumor related factors before ablation including, tumor type, tumor size, morphology (smooth margins, lobulated and/or spiculated), and contact with blood vessels. For tumors < 3 cm, the CAR was 68.55%. For tumors > 3 cm, the CAR was 17.39%. CAR of tumors with a smooth margin was significantly greater than CAR of tumors with lobulated and/or spiculated edges. CAR of tumors with no surrounding blood vessels was 75%, which was remarkably higher than CAR of tumors with blood vessel contact. In tumors with complete ablative margin, the CAR was 74.77%, whereas it was 16.67% for tumors with incomplete ablative margin. Further, in tumors with complete ablative margins, completely ablated tumors had significantly larger ablative margin than incompletely ablated tumors (5.04 mm +/- 2.29 vs 3.71 mm +/- 2.51). Multivariate analysis showed that incomplete ablative margin and an ablative margin of 1–4 mm were independent risk factors for incomplete RF ablation of lung tumor.

Which factors related to local tumor progression (LTP)?

LTP after RF ablation is not rare, and progression at the RF ablation site is associated with poor overall survival in published reports. In this study, the LTP rate was 52% for primary lung cancers and 36.9% for lung metastases. This was higher than rates reported in the previous studies mentioned in the article, which were calculated for a period of several years and included the condition that patients received repeated lung tumor RF ablations. Of the 58 tumors with incomplete ablation, 56 tumors developed local progression at the edge of ablated lesions. 52 tumors locally recurred at the site of incomplete or shortest ablative margin. The site of shortest ablative margin was usually located at the tumor edge of contact with the blood vessels, in front of the ablation electrode, with the maximum radius perpendicular to the ablation electrode, and with protrusion of lobulated and/ or spiculated area of tumors.

Additional Citations:
Hong K, Georgiades C. Radiofrequency Ablation: Mechanism of Action and Devices. J Vasc Interv Radiol. 2010. 21(8): S179-S186

Post Author:
Rajat Chand, MD
Diagnostic Radiology Resident, PGY-2
John H. Stroger Hospital of Cook County

Outcome Results on Ablation versus Surgery for HCC: A Report from the SEER Registry

Summary

The comparative efficacy of percutaneous ablation versus surgical resection for hepatocellular carcinoma (HCC) remains a controversial topic, with conflicting literature reporting equivalent outcomes between modalities or superior outcomes with surgery. This study by Mironov et al used the Surveillance, Epidemiology, and End Results (SEER) database to compare survival outcomes for small solitary HCCs treated with thermal ablation versus surgical resection. Only cases with available Ishak fibrosis score were included in the analysis to account for the effect of cirrhosis. To reduce confounding, patients with metastatic disease, treatment other than ablation or surgery, both surgery and ablation, and liver transplantation were excluded. There were baseline differences in the ablation and surgery patients including a higher prevalence of fibrosis in the ablation group (higher Ishak scores) and smaller tumors in the ablation group (mean 2.6 cm versus 3.0 cm, p<0.001). For tumors ≤2 cm (ablation = 264; resection = 79) and tumors between 2.1 and 4 cm (ablation = 335; resection = 209), there was no significant difference in observed or disease-specific survival between ablation and surgical resection. For tumors between 4.1 and 5 cm (ablation = 46; resection = 66), there was a significantly longer observed and disease-specific survival for surgical resection when stratified by presence of fibrosis (observed survival p=0.009, disease specific survival p=0.046). The 5-year observed survival was 72% (surgery) versus 29% (ablation) and disease-specific survival was 80% (surgery) versus 40% (ablation). Notably, the difference in disease-specific survival was not clinically significant by Cox regression with fibrosis covariate (p=0.145). When all tumors ≤4 cm were pooled, there was again no difference in survival outcomes between ablation and surgical resection. Significant predictive factors for observed and disease-specific survival by Cox model included tumor size and degree of fibrosis.

Commentary

Percutaneous ablation is maturing as an important part of the treatment armamentarium for HCC. The relative efficacy of ablation techniques compared to surgery remains controversial and current guidelines from the Barcelona Clinic Liver Cancer (BCLC) recommend ablation only for patients who are not surgical candidates. These recommendations are derived from a very limited evidence base, with only one prospective study demonstrating superior outcomes after surgery. The SEER registry offers a powerful resource to answer these questions, affording a large patient sample from diverse medical institutions and detailed survival outcome data. The authors of this paper effectively identified potential confounders including patients who had received both treatments or went on to receive a liver transplant. The results of their study demonstrate equivalent survival outcomes in tumors <4 cm, which suggests that it would be reasonable to consider ablation as an alternative to surgery in this patient population. The results in the 4-5 cm tumor group demonstrated superiority of surgery, reflecting limitations of ablation in larger tumor sizes. The SEER population included both patients who had been treated with radiofrequency and microwave ablation (and does not differentiate the two modalities), so it could not be determined in this study whether outcomes in these larger tumors may be superior with microwave. It is important to recognize limitations to the SEER data including lack of BCLC or Child-Pugh scores, performance status, or comorbidities, which may all be important contributors to survival. Nonetheless, this study serves as additional evidence that percutaneous ablation affords equivalent survival outcomes to surgery in HCC ≤4 cm and may help to further define the evolving role of ablation in the treatment of HCC patients.

Click here for abstract

Mironov O, Jaberi A, Kachura JR. Thermal Ablation versus Surgical Resection for the Treatment of Stage T1 Hepatocellular Carcinoma in the Surveillance, Epidemiology, and End Results Database Population. J Vasc Interv Radiol 2017; 28:325-33.

Post Authors:
Jeffrey Forris Beecham Chick, MD, MPH, DABR
Assistant Professor of Vascular and Interventional Radiology
Vice Quality Assurance and Safety Officer
Venous Health Program Faculty
University of Michigan Health System
Michigan Medicine

James X. Chen, MD
Resident in Radiology
Hospital of the University of Pennsylvania

From the SIR residents and fellows section

Topic: Gastric Artery Embolization Trial for the Lessening of Appetite Nonsurgically (GET LEAN): Six Month Preliminary Data 

Syed, M I, Morar K, Shaikh A, Craig P, Khan O, Patel S, Khabiri, H. Gastric Artery Embolization Trial for the Lessening of Appetite Nonsurgically (GET LEAN): Six Month Preliminary Data. J Vasc Interv Radiol. 2016. 27 (10): 1502-8.

Click here for abstract

In the October 2016 edition of JVIR, a report on the 6 month safety and efficacy results of a pilot study of left gastric artery (LGA) embolization for the treatment of morbid obesity was discussed. Four patients, three women, one man, with an average age of 41 y (range 30-54), with a mean weight of 259.3lbs, and mean BMI of 42.4 kg/m2 had their LGA embolized with 300-500-um Bead Block particles for the treatment of morbid obesity.



Weight loss was calculated as a percentage versus baseline, as well as b percentage excess body weight loss as follows, where IBW represents “Ideal Body Weight”, using the Devine formula.



Treatment with a PPI was started one week prior to embolization, and continued one month after the procedure. The procedure was performed via a femoral artery access or a left radial artery access.



No immediate complication other than nausea and mild vomiting was reported. Average body weight loss among the four patients at 6 months was 20.3 lbs. Average body weight loss as a percentage was 8.5%. Average excess body weight loss at 6 months was 17.2%. Patient 4, a diabetic patient taking only oral medications, showed improvement in hemoglobin A1c levels (7.4% to 6.3%) at 3 months, which remained at 6 months. QOL measures showed that the average physical component score improved by 9.5 (on an absolute scale of 0–100), and the average mental component score improved by 9.6 (on an absolute scale of 0–100), at 6 months.



In conclusion, preliminary data supports LGA embolization as a potentially safe procedure that warrants further investigation for weight loss in morbidly obese patients.

Clinical Pearls

What were some patient selection and clinical management steps considered for this procedure?

Patients with morbid obesity, (BMI ≥ 40 kg/m2) whose previous attempts at weight loss through diet, exercise, and behavior modification had failed were recruited for this study. These patients also declined to participate in bariatric surgery, as part of the consent process. A complete history and physical exam was performed prior to the procedure.

All patients had dietary consultations for preoperative evaluation and were followed the procedure by a dietician. Any patient with type II diabetes (n = 1) was evaluated by an endocrinologist before participation in the study. Blood glucose levels were monitored with adjustments of diabetic drugs as needed by the endocrinologist throughout the study. Any female patient of childbearing potential (n = 2) was required to use two forms of contraception during the study (oral and barrier), which was monitored by their primary care provider or gynecologist. An upper endoscopy study was performed at baseline and 3 days after the procedure in all patients.

If any patient had any abnormality on 3-day endoscopy (n = 3), upper endoscopy was repeated at 30 days. Fasting morning, plasma ghrelin, leptin, and CCK measurements, in addition to BMI and other baseline and follow-up tests or procedures, were performed at regular intervals.

What were the confounding factors and limitations of this study?

The presence of superficial symptomatic gastric ulcerations (n = 3) was a confounding variable regarding mechanism of weight loss. One known mechanism of weight loss caused by gastric ulcerations is the postprandial pain that creates a fear of food. This postprandial pain was absent in the patients who had superficial gastric ulcerations after the initial few days. 

One other mechanism of weight loss caused by gastric ulceration is appetite suppression. In the present study, all patients except for patient 2 subjectively reported appetite reduction that persisted beyond 30 days (after documented ulcer healing by endoscopy).

Another potential confounding variable was the medications used (PPI and sucralfate). There is no evidence that the short-term use of a PPI or sucralfate has any effect on weight loss. In fact, according to literature, long-term PPI use may result in weight gain. Notably, no dietary restrictions (to promote healing) were given to patients who had superficial gastric ulcerations.

Another confounding variable is that diet modification and nutritional supervision may have occurred that could have accounted for weight loss.

Limitations of this study included the small sample size and relatively short follow up period. Another limitation of the study was that diet and caloric intake records were not obtained.

Questions to Consider

What physiologic pathway is altered when LGA is embolized?

Left gastric artery (LGA) embolization may fulfill a role as a minimally invasive alternative to the current surgical treatment of gastric bypass or reduction surgery for morbidly obese patients. The LGA supplies the fundus of the stomach, where it is known that the hormone ghrelin (one of the hormones responsible for appetite) is produced. Ghrelin is a 28-amino acid hunger-stimulating peptide and hormone that is produced mainly by P/D1 cells lining the fundus of the stomach and epsilon cells of the pancreas. Ghrelin is the only known circulating orexigenic, or appetite-enhancing, hormone

What are the risks / complications of Bariatric Surgery to manage obesity?

Anastomotic leaks, bowel obstruction, deep vein thrombosis, pulmonary embolism, GI bleed, dumping syndrome, and anesthesia risks. Also reported, the 30 day mortality rate associated with BS is 0.31%, as of 2014, lower than previously reported in 2004. However, it is reported that repeat operation rate is 7%, and the overall complication rate is 17%. It is estimated that only 1% of eligible patients elect to undergo bariatric surgery.

Post author:
Ali Alikhani, MD
Diagnostic Radiology Resident, PGY-4
University of Tennessee Methodist Healthcare