Technical Refinements and Outcomes Assessment in Prepectoral Pocket Conversion After Postmastectomy Radiotherapy.

BACKGROUND: Several studies show how submuscular breast reconstruction is linked to animation deformity, shoulder dysfunction, and increased postoperative chest pain, when compared to prepectoral breast reconstruction. In solving all these life-impairing side effects, prepectoral implant pocket conversion has shown encouraging results. OBJECTIVES: The aim of this study was to propose a refinement of the prepectoral implant pocket conversion applied to previously irradiated patients. METHODS: We conducted a retrospective study on 42 patients who underwent previous nipple- or skin-sparing mastectomy and immediate submuscular reconstruction, followed by radiotherapy. We performed fat grafting sessions as regenerative pretreatment. Six months after the last fat graft, we performed the conversion, with prepectoral placement of micropolyurethane foam-coated implants. We investigated the preconversion and postconversion differences in upper limb range of motion, Upper Extremity Functional Index, and patient satisfaction with the breast and physical well-being of the chest. RESULTS: We reported a resolution of animation deformity in 100% of cases. The range of motion and the Upper Extremity Functional Index scores were statistically improved after prepectoral implant pocket conversion. BREAST-Q scores for satisfaction with the breast and physical well-being of the chest were also improved. CONCLUSIONS: The refined prepectoral implant pocket conversion is a reliable technique for solving animation deformity and improving quality of life in patients previously treated with submuscular reconstruction and radiotherapy.

Implant-Based Breast Reconstruction After Nipple-Sparing and Skin-Sparing Mastectomy in Breast-Augmented Patients: Prepectoral or Submuscular Direct-to-Implant Reconstruction?

BACKGROUND: Patients with breast augmentation facing a breast cancer diagnosis pose unique challenges for both breast and plastic surgeons in terms of treatment and reconstruction. Traditional submuscular direct-to-implant (DTI) breast reconstruction is often considered the standard approach, regardless of the previous implant pocket. However, recent trends in prepectoral reconstruction provide an innovative solution for patients with previous subglandular and submuscular implants. OBJECTIVES: In this study we aimed to share our experiences with DTI breast reconstruction in patients with a history of breast augmentation, with a specific focus on the viability of prepectoral reconstruction. METHODS: A retrospective review was conducted on 38 patients with previous breast augmentation who underwent either skin-sparing mastectomy or nipple-sparing mastectomy for breast cancer followed by DTI reconstruction between January 2015 and July 2023. Our analysis considered various factors, including previous implant positioning, capsular and implant status, and mastectomy flap thickness (MFT), offering insights into the rationale behind choosing the new implant positioning. RESULTS: Patients with a history of subglandular breast augmentation and an MFT greater than 1 cm were candidates for prepectoral reconstruction. When the MFT was less than 1 cm but flap vascularity was sufficient, a prepectoral reconstruction was performed; otherwise, retropectoral reconstruction was preferred. Patients with submuscular breast augmentation were evaluated similarly, with submuscular reconstruction chosen when the MFT was less than 1 cm and prepectoral reconstruction preferred when the MFT exceeded 1 cm. CONCLUSIONS: Immediate prepectoral DTI reconstruction represents a feasible option for specific patients with a history of breast augmentation. Decisions regarding the reconstructive approach are influenced by variables such as mastectomy flap thickness, implant status, and capsular conditions.

When to Consider Prepectoral Implant Conversion After Subpectoral Implant Breast Reconstruction and How to Plan It.

Many deformities occur after subpectoral implant-based breast reconstruction. Today, immediate prepectoral reconstruction with implants shows a significant increase in popularity because it has many advantages over subpectoral positioning: absence of muscle deficit and breast animation deformity, reduced implant dislocation, and less postoperative pain and easy recovery. Implant pocket conversion from the submuscular to prepectoral plane has become our preferred strategy for solving most problems related to the submuscular implant position. The authors performed a retrospective review (from June 2018 to December 2022) of patients who underwent prepectoral implant conversion for correction of animation deformity, dysfunctional chronic pain, or to ameliorate poor cosmetic results. Acellular dermal matrix (ADM) was utilized in the first 7 cases; in the remaining 56 patients polyurethane-covered implants were placed. Resolution of animation deformity and chronic pain were evaluated, as were cosmetic results and any postoperative complications. Sixty-three patients (87 breasts) underwent prepectoral implant conversion with complete resolution of animation deformity and chronic pain as well as improved cosmetic results. Preventive lipofilling was done in 18 patients. Complication rate included 3 periprosthetic seromas in ADM group. All resolved after ultrasound-guided aspiration. Rippling was noted in 3 patients, and edge visibility was documented in 1 patient. There were no incidences of grade 3 or 4 capsular contracture. The prepectoral implant conversion improves functional and aesthetic results, reaching excellent outcomes. Preparation for this surgery with fat grafting is considered a complementary procedure that increases the indications for prepectoral implant conversion.

An Innovative Scoring System to Select the Optimal Surgery in Breast Cancer after Neoadjuvant Chemotherapy.

INTRODUCTION: The selection of surgery post-neoadjuvant chemotherapy (NACT) is difficult and based on surgeons' expertise. The aim of this study was to create a post-NEoadjuvant Score System (pNESSy) to choose surgery, optimizing oncological and aesthetical outcomes. METHODS: Patients (stage I-III) underwent surgery post-NACT (breast-conserving surgery (BCS), oncoplastic surgery (OPS), and conservative mastectomy (CMR) were included. Data selected were BRCA mutation, ptosis, breast volume, radiological response, MRI, and mammography pre- and post-NACT prediction of excised breast area. pNESSy was created using the association between these data and surgery. Area under the curve (AUC) was assessed. Patients were divided into groups according to correspondence (G1) or discrepancy (G2) between score and surgery; oncological and aesthetic outcomes were analyzed. RESULTS: A total of 255 patients were included (118 BCS, 49 OPS, 88 CMR). pNESSy between 6.896-8.724 was predictive for BCS, 8.725-9.375 for OPS, and 9.376-14.245 for CMR; AUC was, respectively, 0.835, 0.766, and 0.825. G1 presented a lower incidence of involved margins (5-14.7%; p = 0.010), a better locoregional disease-free survival (98.8-88.9%; p < 0.001) and a better overall survival (96.1-86.5%; p = 0.017), and a better satisfaction with breasts (39.8-27.5%; p = 0.017) and physical wellbeing (93.5-73.6%; p = 0.001). CONCLUSION: A score system based on clinical and radiological features was created to select the optimal surgery post-NACT and improve oncological and aesthetic outcomes.

The Effect of Adjuvant Radiotherapy on One- and Two-Stage Prosthetic Breast Reconstruction and on Autologous Reconstruction: A Multicenter Italian Study among 18 Senonetwork Breast Centres.

Purpose: In modern breast cancer treatment, a growing role has been observed for breast reconstruction together with an increase in clinical indications for postmastectomy radiotherapy (PMRT). Choosing the optimum type of reconstructive technique is a clinical challenge. We therefore conducted a national multicenter study to analyze the impact of PMRT on breast reconstruction. Methods: We conducted a retrospective case-control multicenter study on women undergoing breast reconstruction. Data were collected from 18 Italian Breast Centres and stored in a cumulative database which included the following: autologous reconstruction, direct-to-implant (DTI), and tissue expander/immediate (TE/I). For all patients, we described complications and surgical endpoints to complications such as reconstruction failure, explant, change in type of reconstruction, and reintervention. Results: From 2001 to April 2020, 3116 patients were evaluated. The risk for any complication was significantly increased in patients receiving PMRT (aOR, 1.73; 95% CI, 1.33-2.24; p < 0.001). PMRT was associated with a significant increase in the risk of capsular contracture in the DTI and TE/I groups (aOR, 2.24; 95% CI, 1.57-3.20; p < 0.001). Comparing type of procedures, the risk of failure (aOR, 1.82; 95% CI, 1.06-3.12, p=0.030), explant (aOR, 3.34; 95% CI, 3.85-7.83, p < 0.001), and severe complications (aOR, 2.54; 95% CI, 1.88-3.43, p < 0.001) were significantly higher in the group undergoing DTI reconstruction as compared to TE/I reconstruction. Conclusion: Our study confirms that autologous reconstruction is the procedure least impacted by PMRT, while DTI appears to be the most impacted by PMRT, when compared with TE/I which shows a lower rate of explant and reconstruction failure. The trial is registered with NCT04783818, and the date of registration is 1 March, 2021, retrospectively registered.

Predicting Mastectomy Skin Flap Necrosis: A Systematic Review of Preoperative and Intraoperative Assessment Techniques.

Mastectomy skin-flap necrosis (MSFN) is one of the most feared complications of immediate implant-based breast reconstruction (IIBR). Traditionally, mastectomy skin-flap viability was based only on surgeons' clinical experience. Even though numerous studies have already addressed the patients' risk factors for MSFN, few works have focused on assessing quality of breast envelope. This review investigates mastectomy's flap viability-assessment methods, both preoperative (PMFA) and intraoperative (IMFA), to predict MSFN and its sequalae. Between June and November 2022, we conducted a systematic review of Pubmed/MEDLINE and Cochrane electronic databases. Only English studies regarding PMFA and IMFA applied to IIBR were selected. The use of digital mammography, ultrasound, magnetic resonance imaging, and a combination of several methods before surgery was shown to be advantageous by several authors. Indocyanine performed better than other IMFA, however both thermal imaging and spectroscopy demonstrated novel and promising results. Anyway, the best prediction comes when preoperative and intraoperative values are combined. Particularly in prepectoral reconstruction, when mastectomy flaps are essential to determine a successful breast reconstruction, surgeons' clinical judgment is insufficient in assessing the risk of MSFN. Preoperative and intraoperative assessment techniques play an emerging key role in MSFN prediction. However, although there are several approaches to back up the surgeon's processing choice, there is still a dearth of pertinent literature on the subject, and more research is required.

Improving Decision-making in Prepectoral Direct-to-implant Reconstruction After Nipple Sparing Mastectomy: The Key Role of Flap Thickness Ratio.

We report our experience in direct-to-implant breast reconstruction with prepectoral polyurethane implants, with a focus on intraoperative mastectomy flap thickness compared to preoperative data (flap thickness ratio) as a reliable predictive variable of ischemic complications and reconstructive outcomes (satisfaction with breast). BACKGROUND: The optimization of nipple sparing mastectomy and implant-based reconstruction techniques led to an increase in the popularity of prepectoral reconstruction. The aim of this study is to explore the ratio between the intraoperative and preoperative breast tissue coverage assessment as reliable tool in order to predict the risk of ischemic complications in prepectoral reconstruction. METHODS: We analyzed 124 preoperative digital mammograms of 100 patients who underwent prepectoral implant-based reconstruction. We applied a Rancati modified score for breast tissue coverage classification, adding 4 measurements on the craniocaudal view. The intraoperative mastectomy flap thickness was measured using an intraoperative ultrasound assessment. We investigated the differences between the groups with and without ischemic complications related to the preoperative, intraoperative, and flap thickness ratio data. RESULTS: The flap thickness ratio was lower in ischemic complication group compared to no ischemic complication group (0.4 vs. 0.8) with statistically significant differences for all ischemic complication subgroups: major mastectomy flap necrosis (P = .000), minor mastectomy flap necrosis (P = .005), partial nipple areola complex necrosis (P = .007), and implant exposure (P = .001).

Preventing Soft Tissue Complications in Secondary Aesthetic Breast Surgery Using Indocyanin Green Angiography.

BACKGROUND: Secondary cosmetic breast surgery after primary augmentation with implant can be associated with an increased risk of adverse events. Partial/complete nipple-areola complex necrosis is particularly feared. In this preliminary study, the authors propose the utilization of indocyanine green (ICG) angiography to assess the blood supply of breast tissue after implant removal. OBJECTIVES: The main objective was to prevent skin and gland necrosis in revision breast surgery. METHODS: The authors performed a retrospective comparative analysis of 33 patients who underwent secondary breast surgery between 2018 and 2021 by a single surgeon (M.S.). Breast tissue perfusion was assessed in 16 patients by intraoperative ICG angiography at the end of implant removal and possible capsulectomy. Non-stained/non-fluorescent areas were judged to be low perfusion areas and were excised with short scar mastopexy. RESULTS: In the ICG angiography group, 7 patients (44%) showed an area of poor perfusion along the inferior pole; all of these patients underwent subglandular breast augmentation. Resection of the poor perfusion areas allowed an uneventful postoperative course. In the non--- ICG angiography group (17 patients), 5 patients experienced vertical-scar dehiscence/necrosis. We found a statistically significant association between the non-ICG angiography group and vertical scar dehiscence/necrosis, and also between vertical scar dehiscence/necrosis and subglandular implant placement (P = 0.04). CONCLUSIONS: Safer secondary surgery can be offered to patients undergoing secondary aesthetic breast procedures, especially when the first augmentation surgery is unknown-for example, implant plane, type of pedicle employed, if the implant is large and subglandular, and if capsulectomy is performed.

The Ultrasound Evolution of Lateral Thoracic Perforator Flaps Design and Harvest for Partial and Total Breast Reconstruction.

BACKGROUND: The lateral thoracic area is a known source for perforator flaps for partial breast reconstruction. In this paper, we report our experience in designing and harvesting lateral thoracic perforator flaps for partial and total breast reconstruction with the introduction of the "propuller" concept. PATIENTS AND METHODS: Between September 2013 and August 2021, 95 flaps were performed for immediate, partial and total breast reconstruction. On a total of 95 flaps, 30 (19 thoracodorsal artery perforator(TDAP) flaps, 10 lateral intercostal artery perforator(LICAP) flaps and 1 lateral thoracic artery perforator(LTAP) flap) were harvested in the traditional fashion (control group) and 65 (57 LICAP, 2 LTAP and 6 TDAP flaps) according to the propeller concept (study group). All cases were preoperatively planned with Color-Coded Duplex Ultrasound. RESULTS: No flap losses were experienced in both groups. The mean operative time was 156 minutes (range 118-234) for the control group and 75 minutes (range 53-125) for the study group (p < 0.0001). A significantly higher number of LICAP flaps were chosen in the study group compared to control group. None of the patients had donor site complications. Patients' and Surgeons' satisfaction was high to very high. CONCLUSION: The ultrasound preoperative planning led to the development of an easier and safer method of local perforator flap harvesting, that we named as propuller design. Its novelty lies in that perforator intraoperative selection and fully skeletonization are not needed and a more efficient flap movement (propeller plus advancement) which transfers more tissue into the new breast can be achieved safely, faster and easier.

Rest/Stress Intradermal Lymphoscintigraphy for the Functional Imaging of the Lymphatic System.

PURPOSE: Lymphoscintigraphy is the criterion-standard method for diagnosing lymphedema, and there is no universally standardized imaging modality. In our center, we use a new approach: rest/stress intradermal lymphoscintigraphy. METHODS: We tested 231 consecutive patients with suspected lymphedema. All patients were studied after a complex physical therapy program to reduce edema. Two doses of 99m Tc-nanocolloid were injected intradermally. Two static planar scans were taken at rest following tracer injection. Next, patients performed an isotonic muscular exercise for 2 minutes followed by postexercise scans. Subsequently, a prolonged exercise was performed for 30 to 40 minutes, after which delayed scans were taken. Abnormal patterns were distinguished into minor or major findings, according to severity. RESULTS: We identified superficial lymphatic vessels and regional lymph nodes in approximately 80% of limbs. Deep vessels were visualized in 26% of limbs. Minor findings were reported in 22.7% of limbs examined, whereas major findings were reported in 53.2% of limbs. CONCLUSION: We observed major findings including lymph stagnation, extravasation, or dermal backflow in a significantly higher percentage of limbs with secondary lymphedema than in primary. We also observed the deep lymphatic pathways in a significantly higher percentage of limbs with primary lymphedema. Intradermal radiotracer injection, combined with isotonic muscular exercise, may offer a better and faster imaging of lymphatic pathways, evaluating the effects of muscular exercise on lymphatic drainage. Based on the in-depth information of the lymphatic pathways provided by rest/stress intradermal lymphoscintigraphy, microsurgeons can obtain important functional information to perform supermicrosurgical lymphatic-venous anastomosis or vascularized lymph node transfer.

Prepectoral vs. Submuscular Immediate Breast Reconstruction in Patients Undergoing Mastectomy after Neoadjuvant Chemotherapy: Our Early Experience.

BACKGROUND: Conservative mastectomy with immediate prosthetic breast reconstruction (IPBR) is an oncologically accepted technique that offers improved esthetic results and patient quality of life. Traditionally, implants have been placed in a submuscular (SM) plane beneath the pectoralis major muscle (PMM). Recently, prepectoral (PP) placement of the prosthesis has been increasingly used in order to avoid morbidities related to manipulation of the PMM. The aim of this study was to compare outcomes of SM vs. PP IPBR after conservative mastectomy in patients with histologically proven breast cancer treated with neoadjuvant chemotherapy (NAC). METHODS: In this retrospective observational study, we analyzed two cohorts of patients that underwent mastectomy with IPBR after NAC in our institution from January 2018 to December 2021. Conservative mastectomy was performed in 146 of the 400 patients that underwent NAC during the study period. Patients were divided into two groups based on the positioning of implants: 56 SM versus 90 PP. RESULTS: The two cohorts were similar for age (mean age 42 and 44 years in the SM and PP group respectively) and follow-up (33 and 20 months, respectively). Mean operative time was 56 min shorter in the PP group (300 and 244 min in the SM and PP group). No significant differences were observed in overall major complication rates. Implant loss was observed in 1.78% of patients (1/56) in the SM group and 1.11% of patients (1/90) in PP group. No differences were observed between the two groups in local or regional recurrence. CONCLUSIONS: Our preliminary experience, which represents one of the largest series of patients undergoing PP-IPBR after NAC at a single institution documented in the literature, seems to confirm that PP-IPBR after NAC is a safe, reliable and effective alternative to traditional SM-IPBR with excellent esthetic and oncological outcomes; it is easy to perform, reduces operative time and minimizes complications related to manipulation of PPM. However, this promising results need to be confirmed in prospective trials with longer follow-up.

Lymphatic Tissue Transfer: Ultrasound-Guided Description and Preoperative Planning of Vascularised Lymph Nodes, Lymphatic Units, and Lymphatic Vessels Transfers.

BACKGROUND: The modern concept of lymphatic transfer includes vascularised lymph node transfer (VLNT), lymphatic vessels transfer (lymph interpositional flap transfer, LIFT) and lymphatic system transfer (vascularised lymph nodes and afferent lymphatics, LYST). The aim of this paper was to report our experience with different types of lymphatic transfer. PATIENTS AND METHOD: From June 2016 to June 2020, 30 consecutive patients affected by extremity lymphedema and 15 patients affected by post-traumatic lower extremity soft tissue defects, underwent lymphatic transfer (VLNT, LYST or LIFT). All cases were preoperatively evaluated by both high frequency and ultra-high frequency ultrasound. Flap features were recorded, as well as qualitative and quantitative outcomes at 1 year postoperative. RESULTS: The mean postoperative lymphedema index reduction was 7.2 ± 5.7 for upper extremity and 20.7 ± 7.1 for lower extremity. No dismission of compression garments occurred, 12 patients (26%) referred more stable results of physical treatment and 1 case showed a 1-class compression reduction. All the LIFTs aimed as preventive did not develop post-traumatic lymphedema. In all cases of distal placement of VLNT and/or LYST, patients were dissatisfied with the aesthetic appearance of reconstruction, while no donor site scar disappointment was referred. CONCLUSION: When LVA is not feasible, LTT may represent a valid treatment option. This report was aimed at comprehensively describing and assessing how different lymphatic tissue transfer modalities may fulfil the different reconstructive needs of lymphedema patients.

Lymphaticovenular Anastomosis for Advanced-Stage Peripheral Lymphedema: Expanding Indication and Introducing the Hand/Foot Sign.

BACKGROUND: Effective lymphaticovenular anastomosis (LVA) requires identification of functioning lymphatics, which are not always visible with contrast-based imaging in advanced-stage lymphedema patients. Ultrasound (US) allows to identify preoperatively functioning lymphatic vessels even in limbs severely affected by lymphedema. Moreover, in our experience, we observed an interesting clinical sentry in advanced-stage lymphedema patients, the hand/foot sign that is analyzed in this paper. PATIENTS AND METHODS: From January 2016 to January 2019, 76 consecutive advanced-stage secondary lymphedema patients underwent LVA. Preoperative planning included lymphoscintigraphy, indocyanine-green lymphography (ICG-L) and US. Patients' features, the hand/foot sign (preservation of more normal skin on the dorsum of the hand or foot), lymphatic degeneration, quantitative, qualitative, and composite outcomes at 1-year follow-up were evaluated. RESULTS: An average number of 3±0.1 LVA was performed in upper limb lymphedema (ULL) (range 2-5, 47 patients) and of 4±1.08 LVAs in lower limb lymphedema (LLL) cases (range 4-7, 29 patients). The composite outcome was positive in 45 cases (59.7%). The "negative" hand /foot sign was significantly associated with presence of functioning lymphatic channels. The incidence of adverse outcomes was significantly higher in patients with positive hand/foot sign. CONCLUSION: Patients with no functioning lymphatic vessels detectable by lymphoscintigraphy and ICG-L may still have functioning lymphatic channels that can be identified preoperatively by ultra-high-frequency ultrasound and salvaged by LVA. The "hand/foot sign" is a simple clinical sentry that appears to be correlated with higher probability of being able to localize functional lymphatics for potential lymphovenous bypass surgery.

Level II Oncoplastic Surgery as an Alternative Option to Mastectomy with Immediate Breast Reconstruction in the Neoadjuvant Setting: A Multidisciplinary Single Center Experience.

Oncoplastic surgery level II techniques (OPSII) are used in patients with operable breast cancer. There is no evidence regarding their safety and efficacy after neoadjuvant chemotherapy (NAC). The aim of this study was to compare the oncological and aesthetic outcomes of this technique compared with those observed in mastectomy with immediate breast reconstruction (MIBR), in post-NAC patients undergoing surgery between January 2016 and March 2021. Local disease-free survival (L-DFS), regional disease-free survival (R-DFS), distant disease-free survival (D-DFS), and overall survival (OS) were compared; the aesthetic results and quality of life (QoL) were evaluated using BREAST-Q. A total of 297 patients were included, 87 of whom underwent OPSII and 210 of whom underwent MIBR. After a median follow-up of 39.5 months, local recurrence had occurred in 3 patients in the OPSII group (3.4%), and in 13 patients in the MIBR group (6.1%) (p = 0.408). The three-year L-DFS rates were 95.1% for OPSII and 96.2% for MIBR (p = 0.286). The three-year R-DFS rates were 100% and 96.4%, respectively (p = 0.559). The three-year D-DFS rate were 90.7% and 89.7% (p = 0.849). The three-year OS rates were 95.7% and 95% (p = 0.394). BREAST-Q highlighted significant advantages in physical well-being for OPSII. No difference was shown for satisfaction with breasts (p = 0.656) or psychosocial well-being (p = 0.444). OPSII is safe and effective after NAC. It allows oncological and aesthetic outcomes with a high QoL, and is a safe alternative for locally advanced tumors which are partial responders to NAC.

Designing Lateral Thoracic Wall Perforator Flaps for Breast Reconstruction Using Ultrasound.

BACKGROUND: Lateral thoracic flaps represent a precious source for partial and total breast reconstruction, in some cases as first option and in other cases as alternative of free flaps. This article describes the ultrasound (US)-based planning of the lateral thoracic wall perforator adipocutaneous flaps and it reports our experience on 52 consecutive flaps. METHODS: From November 2018 to May 2021, 52 consecutive lateral thoracic wall perforator flaps were performed using the US-based method for reconstruction of partial breast defects and total breast reconstruction. High-frequency US was performed in all cases prior to surgery to select the best perforator and design the flap. RESULTS: Of the 52 cases, 41 were lateral intercostal artery perforator flaps (78.8%), and 11 were thoracodorsal artery perforator (TDAP) flaps. Of the 11 TDAP flaps, 2 cases were based on the direct cutaneous branch. Moreover, in two other cases clinically scheduled for lateral thoracic perforator flaps due to the presence of an appropriate axillary roll, no suitable local/regional perforators were detected with the preoperative US examination and the latissimus dorsi myocutaneous flap was performed. CONCLUSION: Preoperative planning of these flaps using US speeds the surgery and makes it easier and more efficient. Therefore, it is reasonable that the color duplex ultrasound is the operative surgeon's tool for mapping the lateral thoracic wall perforators and to appropriately plan each flap.

The role of fat grafting on contracted breast implant capsules: A retrospective comparative histological and immunohistochemical study.

Capsular contracture, a common complication of breast implant reconstruction following postmastectomy radiotherapy (PMRT), represents a challenge for plastic surgeons. Regenerative surgery with multiple autologous fat grafts (lipobed) before replacing the implant has been proven to be a satisfactory approach in the radio-damaged breast. Currently, in literature, there are no data available on the histological features of irradiated capsules after regenerative surgery. We enrolled 80 patients after immediate subpectoral alloplastic breast reconstruction, with indication for revision surgery due to grade IV capsular contracture developed after PMRT. Forty patients were undergoing multiple fat grafting (lipobed group, mean age 48) and 40 patients were not undergoing multiple fat grafting (non-regenerative surgery (NRS) group, mean age 49). The removed capsules were addressed to histological and immunohistochemical assessment. The capsules of the lipobed group patients compared with NRS group patients showed: a lower mean thickness (602.17 versus 670.43 µm; P = 0.013), a lower collagen fiber alignment (median value of angle deviation: 30.34 versus 18.38; P = 0.001), a lower immunohistochemical positivity for myofibroblasts (α-smooth muscle actin [α-SMA] expression: 12.5% versus 52.5%; P = 0.00), a higher immunohistochemical positivity for estrogen receptor-ß (ER-ß; 80% versus 20%; P = 0.00), and a lower immunohistochemical positivity for estrogen receptor-α (ER-α; 53.3% versus 16.7%; P = 0.00). The histological and immunohistochemical differences found are possibly due to alterations in the extracellular microenvironment determined by grafted fat.