Evaluating temperature gradients across the posterior left atrium with radiofrequency ablation.

INTRODUCTION: Esophageal injury is a well-known complication associated with catheter ablation. Though novel methods to mitigate esophageal injury have been developed, few studies have evaluated temperature gradients with catheter ablation across the posterior wall of the left atrium, interstitium, and esophagus. METHODS: To investigate temperature gradients across the tissue, we developed a porcine heart-esophageal model to perform ex vivo catheter ablation on the posterior wall of the left atrium (LA), with juxtaposed interstitial tissue and esophagus. Circulating saline (5 L/min) was used to mimic blood flow along the LA and alteration of ionic content to modulate impedance. Thermistors along the region of interest were used to analyze temperature gradients. Varying time and power, radiofrequency (RF) ablation lesions were applied with an externally irrigated ablation catheter. Ablation strategies were divided into standard approaches (SAs, 10-15 g, 25-35 W, 30 s) or high-power short duration (HPSD, 10-15 g, 40-50 W, 10 s). Temperature gradients, time to the maximum measured temperature, and the relationship between measured temperature as a function of distance from the site of ablation was analyzed. RESULTS: In total, five experiments were conducted each utilizing new porcine posterior LA wall-esophageal specimens for RF ablation (n = 60 lesions each for SA and HPSD). For both SA and HPSD, maximum temperature rise from baseline was markedly higher at the anterior wall (AW) of the esophagus compared to the esophageal lumen (SA: 4.29°C vs. 0.41°C, p < .0001 and HPSD: 3.13°C vs. 0.28°C, p < .0001). Across ablation strategies, the average temperature rise at the AW of the esophagus was significantly higher with SA relative to HPSD ablation (4.29°C vs. 3.13°C, p = .01). From the start of ablation, the average time to reach a maximum temperature as measured at the AW of the esophagus with SA was 36.49 ± 12.12 s, compared to 16.57 ± 4.54 s with HPSD ablation, p < .0001. Fit to a linear scale, a 0.37°C drop in temperature was seen for every 1 cm increase in distance from the site of ablation and thermistor location at the AW of the esophagus. CONCLUSION: Both SA and HPSD ablation strategies resulted in markedly higher temperatures measured at the AW of the esophagus compared to the esophageal lumen, raising concern about the value of clinical intraluminal temperature monitoring. The temperature rise at the AW was lower with HPSD. A significant time delay was seen to reach the maximum measured temperature and a modest increase in distance between the site of ablation and thermistor location impacted the accuracy of monitored temperatures.

Clinical and molecular features of subungual melanomas are site-specific and distinct from acral melanomas.

Subungual melanomas (SUM) arise beneath the nails of the hands and feet, and account for 0.7-3.5% of all malignant melanomas. Most studies include SUM in the category of acral melanoma, but understanding the specific features of SUM is critical for improving patient care. In this study, we performed a site-specific comparison of the clinical and molecular features between 54 cases of SUM and 78 cases of nonsubungual acral melanoma. Compared to patients with acral melanoma, patients with SUM were younger at diagnosis, had a higher prevalence of primary melanomas on the hand, and had more frequent reports of previous trauma at the tumor site. SUM was deeper than acral melanoma at diagnosis, which correlated with an increased frequency of metastases. Analysis of common melanoma driver genes revealed KIT and KRAS mutations were predominantly found in SUM, whereas BRAF and NRAS mutations occurred almost exclusively in acral melanoma. We also discovered molecular differences in the cell cycle pathway, where CDK4/CCND1 amplifications were more frequent in SUM and CDKN2A/B loss occurred mostly in acral melanoma, and in the PI3K/mTOR pathway, where RICTOR amplification and TSC1 K587R mutations were exclusively in SUM and PTEN loss and AKT1 mutations were exclusively in acral melanoma. Comparison of hand versus foot tumors revealed more frequent ulceration of SUM foot tumors, which correlated with more distal metastases and poorer overall survival. In summary, we find SUM are both clinically and molecularly distinct from acral melanoma, and our data suggest KIT, CDK4/6, and mTOR inhibitors may be particularly relevant and effective treatments for patients with SUM.