Iatrogenic injury to the healthy ureter during ureteroscope-guided ablation of malignant or nonmalignant disease can result in ureteral stricture. Transforming growth factor (TGF)-β₁-mediated scar formation is considered to underlie ureteral stricture, but the cellular sources of this cytokine and the sequelae preceding iatrogenic stricture formation are unknown. Using a swine model of ureteral injury with irreversible electroporation (IRE), we evaluated the cellular sources of TGF-β₁ and scar formation at the site of injury and examined in vitro whether the effects of TGF-β₁ could be attenuated by pirfenidone. We observed that proliferation and α-smooth muscle actin expression by fibroblasts were restricted to injured tissue and coincided with proliferation of macrophages. Collagen deposition and scarring of the ureter were associated with increased TGF-β₁ expression in both fibroblasts and macrophages. Using in vitro experiments, we demonstrated that macrophages stimulated by cells that were killed with IRE, but not LPS, secreted TGF-β₁, consistent with a wound healing phenotype. Furthermore, using 3T3 fibroblasts, we demonstrated that stimulation with paracrine TGF-β₁ is necessary and sufficient to promote differentiation of fibroblasts and increase collagen secretion. In vitro, we also showed that treatment with pirfenidone, which modulates TGF-β₁ activity, limits proliferation and TGF-β₁ secretion in macrophages and scar formation-related activity by fibroblasts. In conclusion, we identified wound healing-related macrophages to be an important source of TGF-β₁ in the injured ureter, which may be a paracrine source of TGF-β₁ driving scar formation by fibroblasts, resulting in stricture formation.

The purpose of this study is to assess the impact of duration of energy delivery on adverse events (AEs) and heat sink effects during high power microwave ablation (MWA) of normal swine lung. High power (100 W) MWA was performed with short (2 min, 18 ablations) or long (10 min, nine ablations) duration of energy delivery in unilateral lung of swine (n = 10). CT imaging was done prior to sacrifice at 2 or 28 d post-treatment, with additional imaging at 7 and 14 d for the latter cohort. Ablation zones were assessed with CT imaging and histopathology analysis. Differences in AEs and ablation characteristics between groups were compared with Fisher's exact test and Student's t-test, respectively. There were no significant differences in formation of air-filled needle tract, cavitation, and pneumonia (p > 0.5) between the treatment groups. Intra-procedural pneumothorax requiring chest tube placement occurred in three animals. Substantial (>20%, p = 0.01) intra-procedural ablation zone distortion was observed in both groups. The presence of large airways or blood vessels did not result in heat sink effect within the ablation zones and was not indicative of reduced ablation size. Increased energy delivery yielded larger (8.9 ± 3.1 cm3 vs. 3.4 ± 1.7 cm3, p < 0.001) spherical ablations (sphericity: 0.70 ± 0.10 vs. 0.56 ± 0.13, p = 0.01). High power MWA of normal lung with longer duration of energy delivery can create larger spherical ablations, without significant differences in post-procedure AEs when compared with shorter energy delivery time.