A Histological Assessment Tool for Breast Implant Capsules Validated in 480 Patients with and Without Capsular Contracture.

BACKGROUND: Understanding the impact of breast implants on the histological response in the surrounding fibrous capsule is important; however, consensus is lacking on how to analyze implant capsules histologically. We aimed to develop a standardized histological assessment tool to be used in research potentially improving diagnostic accuracy and treatment strategies for capsular contracture. METHODS: Biopsies of breast implant capsules from 480 patients who had undergone breast augmentation or reconstruction were collected and stained with hematoxylin and eosin. Initially, biopsies from 100 patients were analyzed to select histological parameters demonstrating the highest relevance and reproducibility. Then, biopsies from the remaining 380 patients were used to determine intra- and interobserver agreements of two blinded observers and agreement with a pathologist. Finally, we tested the association between the parameters and capsular contracture. RESULTS: The histological assessment tool included ten parameters assessing the inflammatory, fibrotic, and foreign-body reaction to breast implants, each graded on two-, three-, or four-point scales. Intra- and interobserver agreements were almost perfect (0.83 and 0.80), and agreement with the pathologist was substantial (0.67). Four parameters were significantly correlated with capsular contracture, namely chronic inflammation with lymphocyte infiltration (p < 0.01), thickness of the collagen layer (p < 0.0001), fiber organization (p < 0.01), and calcification (p < 0.001). CONCLUSIONS: This is the first validated histological assessment tool for breast implant capsules. The validated tool not only advances our understanding of capsular contracture but also sets a new standard for histological evaluation in breast implant research and clinical diagnostics. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Development and Validation of a Diagnostic Histopathological Scoring System for Capsular Contracture Based on 720 Breast Implant Capsules.

BACKGROUND: Capsular contracture is traditionally evaluated with the Baker classification, but this has notable limitations regarding reproducibility and objectivity. OBJECTIVES: The aim of this study was to develop and validate procedure-specific histopathological scoring systems to assess capsular contracture severity. METHODS: Biopsies of breast implant capsules were used to develop histopathological scoring systems for patients following breast augmentation and breast reconstruction. Ten histological parameters were evaluated by multivariable logistic regression to identify those most associated with capsular contracture. Significant parameters (P < .05) were selected for the scoring systems and assigned weighted scores (1-10). Validation was assessed from the area under the curve (AUC) and the mean absolute error (MAE). RESULTS: A total of 720 biopsies from 542 patients were included. Four parameters were selected for the augmentation scoring system, namely, collagen layer thickness, fiber organization, inflammatory infiltration, and calcification, providing a combined maximum score of 26. The AUC and MAE for the augmentation scoring system were 81% and 0.8%, which is considered strong. Three parameters were selected for the reconstruction scoring system, namely, fiber organization, collagen layer cellularity, and inflammatory infiltration, providing a combined maximum score of 19. The AUC and MAE of the reconstruction scoring system were 72% and 7.1%, which is considered good. CONCLUSIONS: The new histopathological scoring systems provide an objective, reproducible, and accurate assessment of capsular contracture severity. We propose these novel scoring systems as a valuable tool for confirming capsular contracture diagnosis in the clinical setting, for research, and for implant manufacturers and insurance providers in need of a confirmed capsular contracture diagnosis.

Pharmacokinetics of Repeated Melatonin Drug Administrations Prior to and After Surgery.

BACKGROUND: Recent clinical studies have documented the analgesic, anti-inflammatory, antioxidative and anxiolytic effects of exogenous melatonin. The pharmacokinetic properties of melatonin have primarily been investigated in experimental studies. OBJECTIVE: The aim of this study was to estimate the pharmacokinetics of melatonin in patients undergoing surgery and general anesthesia. METHODS: The study was designed as a prospective, two-phase cohort study. Patients were candidates for subpectoral breast augmentation surgery, and surgical procedures were performed by a single surgeon. The perioperative treatment protocol was standardized between patients. During the study, each patient received two separate oral administrations of melatonin 10 mg. Melatonin was administered 60 min before surgery, and at 9:00 p.m. the evening after surgery. The pharmacokinetic variables absorption half-life (t ½ absorption), time to maximal plasma concentration (T max), maximal plasma concentration (C max), elimination half-life (t ½ elimination), and area under the melatonin plasma concentration-time curve from time zero to infinity (AUC ∞) were estimated for both study phases. RESULTS: Median (interquartile range) values of t ½ absorption and T max were significantly increased during the postoperative phase [10.8 (6.9-15.1) min; 90.0 (48.8-120.0) min] compared with perioperatively [9.5 (6.3-16.5) min; 30.0 (15.0-30.0) min] (p = 0.034; p = 0.002), respectively. C max values were significantly higher during surgery [5497.5 (2077.1-13,233.8) pg/ml] compared with postoperative values [2340.5 (1672.4-8871.4) pg/ml] (p = 0.005). Correspondingly, t ½ elimination was significantly extended during the postoperative phase [103.5 (57.8-237.8) min] compared with the perioperative phase [60.5 (47.8-83.6) min] (p = 0.015). AUC ∞ did not differ between the study phases (p > 0.05). CONCLUSIONS: These preliminary results indicate that postoperative melatonin dose should be augmented compared with preoperative administration if corresponding melatonin plasma levels are intended. Furthermore, postoperative administration times should be advanced compared with preoperative administration.