Neurovascular Architecture of Deep Endometriosis and Postoperative Pain Outcomes after Butterfly Peritoneal Excision: A Prospective Pilot Study

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This pilot study examined the neurovascular architecture of deep endometriosis and its correlation with postoperative pain outcomes following butterfly peritoneal excision.

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Abstract

STUDY OBJECTIVE: To evaluate the neurovascular architecture of deep endometriosis using a standardized butterfly excision approach and to explore its association with postoperative pain outcomes. DESIGN: Prospective exploratory pilot study. SETTING: Tertiary referral center specializing in endometriosis surgery. PATIENTS: Fifteen women with advanced posterior deep endometriosis undergoing laparoscopic excision. INTERVENTIONS: Standardized butterfly peritoneal excision with systematic radial sampling from the central lesion to the peripheral peritoneum. MEASUREMENTS AND MAIN RESULTS: Each specimen was divided into 15 segments (7 per side plus central lesion), yielding 240 total samples, including normal peritoneum. Nerve-fiber density showed a significant center-to-periphery decline (β = -0.3169, p <.001), corresponding on average to an estimated 27% reduction per segment, while capillary density demonstrated a parallel but less pronounced decrease (β = -0.100, p <.001), supporting a coordinated neurovascular gradient. No right-left difference was observed. In contrast, tissue pain mediators exhibited heterogeneous spatial distribution rather than a uniform center-dominant pattern. Among evaluated markers, only bradykinin was associated with nerve-fiber density (p <.001). In exploratory multivariable analyses, central nerve growth factor concentration showed an association with 6-month dysmenorrhea improvement (β = 0.012, p = .043), whereas morphometric nerve-fiber density did not. For chronic pelvic pain, baseline pain severity was the only variable associated with postoperative improvement (β = 0.777, p = .030). Clinically, postoperative reductions were observed across multiple pain domains, accompanied by improvements in physical and mental quality-of-life measures. CONCLUSION: Deep endometriosis demonstrated spatial neurovascular gradients with dissociation between structural innervation and inflammatory mediator distribution. Central neurotrophic activity showed an exploratory association with postoperative dysmenorrhea improvement, whereas morphometric nerve-fiber density did not. These findings support the feasibility and potential biological relevance of spatial neurovascular mapping in deep endometriosis and should be considered hypothesis-generating pending validation in larger studies. CLINICAL TRIAL NUMBER: NCT06286371, https://clinicaltrials.gov/study/NCT06286371. DATE OF REGISTRATION: 22.02.2024.

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