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

BACKGROUND: Capsular contracture is traditionally evaluated using the Baker classification. However, this classification has notable limitations in reproducibility and objectivity. OBJECTIVES: 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 using multivariable logistic regression to identify those most associated with capsular contracture. Significant parameters (p < 0.05) were selected for the scoring systems and assigned weighted scores (1-10). Validation was performed using area under the curve (AUC) and mean absolute error (MAE). RESULTS: A total of 720 biopsies from 542 patients were included. Four parameters were selected for the augmentation scoring system including 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 was 81% and 0.8% which is considered strong. Three parameters were selected for the reconstruction scoring system including fiber organization, collagen layer cellularity, and inflammatory infiltration, providing a combined maximum score of 19. The AUC and MAE of the reconstruction scoring system was 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 the capsular contracture diagnosis in the clinical setting, for research, and for implant manufacturers and insurance providers in need of a confirmed capsular contracture diagnosis.

Breast reconstruction after mastectomy.

Patients requesting breast reconstruction after mastectomy is an increasing group at plastic- and breast surgery departments in Denmark. This review summarises the present surgical techniques for reconstruction with/without postoperative chemotherapy and/or radiation therapy. These surgical techniques are continuously updated. The most determining factor when selecting a reconstructive technique, is postoperative radiation therapy. Each patient is unique, and an individual assessment is made when planning surgery. The concept of a "babysitter implant" is currently being investigated in Denmark and might be an option for selected patients.

Pharmacokinetics of Locally Applied Antibiotic Prophylaxis for Implant-Based Breast Reconstruction.

Importance: Antibiotic irrigation of breast implants is widely used internationally, but no clinical study has investigated the pharmacokinetics of antibiotic prophylaxis in the breast implant pocket. Objectives: To evaluate how long locally applied gentamicin, cefazolin, and vancomycin concentrations in the implant pocket remain above the minimum inhibitory concentration (MIC) for the most common bacterial infections and to measure systemic uptake. Design, Setting, and Participants: This prospective cohort study was performed at the Department of Plastic Surgery and Burns Treatment, Rigshospitalet, Copenhagen, Denmark, between October 25, 2021, and September 22, 2022, among 40 patients undergoing implant-based breast reconstruction who were part of the ongoing BREAST-AB trial (Prophylactic Treatment of Breast Implants With a Solution of Gentamicin, Vancomycin and Cefazolin Antibiotics for Women Undergoing Breast Reconstructive Surgery: a Randomized Controlled Trial). Patients were randomized to receive locally applied gentamicin, cefazolin, and vancomycin or placebo. Samples were obtained from the surgical breast drain and blood up to 10 days postoperatively. Exposures: The breast implant and the implant pocket were irrigated with 160 µg/mL of gentamicin, 2000 µg/mL of cefazolin, and 2000 µg/mL of vancomycin in a 200-mL saline solution. Main Outcomes and Measures: The primary outcome was the duration of antibiotic concentrations above the MIC breakpoint for Staphylococcus aureus according to the Clinical and Laboratory Standards Institute: gentamicin, 4 µg/mL; cefazolin, 2 µg/mL; and vancomycin, 2 µg/mL. Secondary outcomes included the time above the MIC for Pseudomonas aeruginosa and other relevant bacteria, as well as systemic uptake. Results: The study included 40 patients (median age, 44.6 years [IQR, 38.3-51.4 years]; median body mass index, 23.9 [IQR, 21.7-25.9]) with a median number of 3 drain samples (range, 1-10 drain samples) and 2 blood samples (range, 0-6 blood samples). Vancomycin and cefazolin remained above the MIC for S aureus significantly longer than gentamicin (gentamicin, 0.9 days [95% CI, 0.5-1.2 days] for blood samples vs 6.9 days [95% CI, 2.9 to 10.9 days] for vancomycin [P = .02] vs 3.7 days [95% CI, 2.2-5.2 days] for cefazolin [P = .002]). The gentamicin level remained above the MIC for P aeruginosa for 1.3 days (95% CI, 1.0-1.5 days). Only cefazolin was detectable in blood samples, albeit in very low concentrations (median concentration, 0.04 µg/mL [range, 0.007-0.1 µg/mL]). Conclusions and Relevance: This study suggests that patients treated with triple-antibiotic implant irrigation during breast reconstruction receive adequate prophylaxis for S aureus and other common implant-associated, gram-positive bacteria. However, the protection against P aeruginosa may be inadequate.

The King is in the altogether: Radiation therapy after oncoplastic breast surgery.

Breast cancer is the most common malignancy, and the majority of the patients are diagnosed at an early disease stage. Breast conservation is the preferred locoregional approach, and oncoplastic breast conservation surgery is becoming more popular. This narrative review aims to discuss the challenges and uncertainties in target volume definition for postoperative radiation after these procedures, to improve radiation therapy decisions and encourage multidisciplinary.

The impact of neoadjuvant chemotherapy on surgical outcomes following autologous and implant-based immediate breast reconstruction: A systematic review and meta-analysis.

BACKGROUND: The impact of neoadjuvant chemotherapy (NACT) on the complication rate after implant-based and autologous breast reconstruction remains unclear. The aim of this study was to systematically review and perform a meta-analysis of previously published studies on immediate breast reconstruction (IBR) in breast cancer patients treated with NACT compared with controls. METHODS: PubMed and EMBASE were searched to identify studies assessing the impact of NACT on major and minor complications after IBR. The primary effect measures were relative risk (RR), 95% confidence interval (95% CI), and p-value. RESULTS: Eight studies comprising 51,731 patients were included in the meta-analysis. Of these, 5161 patients received NACT and 46,570 patients did not receive NACT. In regard to major complications, NACT did not statistically significant increase the rate of reconstructive failure (RR = 1.35, 95% CI = 0.96-1.91, p = 0.09), the rate of mastectomy skin-flap necrosis (RR = 1.39, 95% CI = 0.61-3.17, p = 0.44), or the rate of reoperation (RR = 1.09, 95% CI = 0.87-1.37, p = 0.45). Regarding minor complications, NACT did not significantly increase the rate of wound complications (RR = 1.05, 95% CI = 0.87-1.28, p = 0.62). In a subgroup analysis of implant-based breast reconstruction following NACT, single-stage direct-to-implant (DTI) had a significantly lower implant failure rate compared with two-staged tissue expander/implant (TE/I) (RR = 0.43, 95% CI = 0.26-0.71, p = 0.0011). CONCLUSION: NACT did not increase the major or minor complication rate after IBR with either autologous tissue or implants. Thus, NACT and IBR should be considered safe procedures. The review of studies describing patients undergoing implant-based breast reconstruction following NACT could indicate that single-stage DTI was a safer procedure than two-staged TE/I. However, the association requires further evaluation.

Indocyanine green angiography in oncoplastic breast surgery, a prospective study.

INTRODUCTION: The use of Indocyanine green angiography (ICG-A) in oncoplastic breast-conserving surgery (OBCS) has not yet been investigated. This prospective trial applied ICG-A in volume displacement and replacement OBCS to localize perforators and determine tissue supplied by the perforator. Furthermore, to investigate and correlate the intraoperative ICG-A to postoperative surgical site infection, skin necrosis, epidermolysis, and timely onset of adjuvant therapy. METHODS: ICG-A was performed at three pre-set timepoints during surgery; after lumpectomy, upon dissection of possible perforators, and after wound closure. All patients were followed with clinical evaluations before surgery, 4 weeks, 4-6 months, and 12 months postoperatively. RESULTS: Eleven patients were included: seven volume displacement and four volume replacement OBCS. ICG-A located the tissue supplied by the perforator and demonstrated sufficient perfusion in all cases. The ICG-A corresponded to the surgeons' clinical assessment. One patient developed a postoperative infection and seroma and was treated conservatively. No patients had postoperative necrosis, loss of reconstruction, or lymphedema of the arm. Edema of the breast occurred in four patients (36.4%). Scar assessments were significantly worse at 4-weeks and 4-6 months. The quality of life improved significantly during follow-up. Adjuvant treatment was administered timely in all cases. CONCLUSION: ICG-A was feasible for OBCS in assessing intraoperative perfusion. Perfusion was sufficient in all patients and corresponded to the surgeon's clinical evaluation. No patients developed postoperative necrosis. Though edema of the breast occurred in 36.4%, a larger sample size is needed to investigate a possible correlation with ICG-A. Further studies, which includes patients requiring extensive tissue replacement challenging the borders of perfusion, are needed.

[Advanced locoregional chest wall recurrence of breast cancer].

Locoregional recurrence of breast cancer continues to be a significant clinical issue involving extensive examination programmes, modified oncologic therapy and advanced surgery. The latter includes tumour resection followed by reconstruction of the thoracic wall. The type of reconstruction depends on tumour location, depth, aetiology and whether the resection involves the stabilising osseous structures as summarised in this review. The treatment strategy is planned at multidisciplinary team conferences with the presence of relevant specialists to ensure evidence-based treatment of consistent quality.

Use of Indocyanine Green Angiography decreases the risk of complications in autologous- and implant-based breast reconstruction: A systematic review and meta-analysis.

INTRODUCTION: Indocyanine Green Angiography (ICG-A) is an imaging technique used to visualize tissue perfusion in real time. The aim of this systematic review and meta-analysis is to evaluate all published papers on breast reconstruction using ICG-A, which provides information on complication rates and to investigate whether the use of this peroperative method decreases the risk of complications. MATERIALS AND METHODS: MEDLINE/PubMed, EMBASE, Cochrane, and UpToDate were searched using relevant terms. The literature was assessed using the PRISMA guidelines. Inclusion criteria were: original articles written in English assessing ICG-angiography in breast reconstruction. The individual studies were evaluated according to Cochrane guidelines. RESULTS: The search yielded 243 papers on ICG-A and breast reconstruction. Twenty-six of these were included for analysis. The risk of overall major complications ([OR] = 0.53, 95% confidence interval (CI) = 0.43-0.66, p = 0.00001) and overall loss of reconstruction ([OR] = 0.58, 95% CI = 0.37-0.92, and p = 0.020) was significantly lower when peroperative ICG-A was used. When using ICG-A to evaluate mastectomy flaps, a statistically lower risk of major complications ([OR] = 0.56 and p = 0.0001) and the loss of reconstruction was found ([OR] = 0.46, p = 0.006). ICG-A used in autologous breast reconstruction significantly reduced the risk of minor ([OR] = 0.62 and p = 0.001) and major complications ([OR] = 0.53 and p = 0.0028). CONCLUSIONS: This is the first systematic review to analyze the use of ICG-A on both mastectomy flaps and autologous reconstruction. The results obtained in the current study indicate that the use of ICG-A in breast reconstructive procedures reduces the complications as well as the loss of reconstruction.

Oncoplastic breast surgery versus conventional breast conserving surgery - a prospective follow-up study of subjective loco-regional late morbidity.

Background and aim: Few studies have focused on the symptoms of loco-regional morbidity in shoulders, arms, and breasts related to oncoplastic breast surgery (OPS). This study aimed to determine if a difference exists in the prevalence or variety of subjective symptoms of shoulder, arm, and breast morbidity in patients undergoing OPS compared with patients receiving conventional breast conserving surgery (C-BCS). Cosmetic result and body image were included as secondary endpoints.Methods: This prospective follow-up study with 18 months of questionnaire-based follow-up included women with breast cancer or ductal carcinoma in situ. They were divided into two groups - C-BCS or OPS - depending on type of surgery performed. Furthermore, patient, disease, and treatment characteristics were recorded.Results: Among 334 completers, 229 (69%) received C-BCS and 105 (31%) received OPS. Participants were comparable regarding age, comorbidity, BMI, re-excision rate (15-16%), and axillary surgery. As for tumor characteristics, a more advanced disease stage was shown in the OPS than in the C-BCS group with larger tumor and lumpectomy size, more multifocality, and the corresponding following systemic adjuvant therapy.The questionnaire revealed that the two groups were comparable with no significant differences in frequency or variety of symptoms of shoulder and arm morbidity. Overall, participants were highly satisfied with the cosmetic results in both groups and no significant inter-group differences were observed.Conclusion: In patients with larger tumors, breast conserving surgery utilizing oncoplastic techniques yields results regarding subjective shoulder, arm, and breast morbidity as well as cosmetic outcome comparable with those of C-BCS performed on smaller tumors.Trial registration: ClinicalTrials.gov, registration number: NCT02159274 (2014).HIGHLIGHTSSubjective symptoms of shoulder, arm, and breast morbidity are comparable when oncoplastic breast surgery is compared to conventional breast conserving surgery.The variety of symptoms of shoulder and arm morbidity following oncoplastic surgery does not differ from symptoms following conventional breast conserving surgery.The cosmetic outcome following oncoplastic breast surgery is comparable to breast conserving surgery without oncoplastic techniques.

Comparison of one-stage direct-to-implant with acellular dermal matrix and two-stage immediate implant-based breast reconstruction-a cohort study.

BACKGROUND: The use of acellular dermal matrix (ADM) in one-stage immediate implant-based breast reconstruction (BR) may offer advantages over the two-stage expander-to-implant technique, but literature shows conflicting results. The aim of the present study was to compare these two techniques for immediate implant-based BR regarding postoperative complications, aesthetic correction procedures and aesthetic outcome. METHODS: The study was designed as an observational cohort study with 44 participants admitted for immediate implant-based BR at Department of Plastic Surgery, Aarhus University Hospital, Denmark. 21 patients underwent BR with a one-stage direct-to-implant technique using ADM and 23 patients underwent BR with a two-stage expander-to-implant technique. Follow-up time was 2 years. RESULTS: The risk of implant loss was equal between groups; one-stage group 16% and two-stage group 17% whereas the risk of implant exchange (but not loss of BR) was 13% in the one-stage group compared to 7% in the two-stage group. The risk of at least one major complication were equal between groups; 28% and 24% but the risk of at least one minor complication was significantly higher in the two-stage group (41%) compared to the one-stage group (3%). Number of aesthetic corrections were equally frequent in the two treatment groups (one-stage group 1.8, two-stage group 1.5). Patient and investigator assessed aesthetic outcome was very high in both groups as well as the degree of symmetry between breasts. No capsular contracture Baker grade 3 or 4 was observed. CONCLUSIONS: The present study design sets limitations for drawing wide conclusions. This study did not reveal any significant differences between the two breast reconstructive techniques besides a higher risk of minor complications in the two-stage group, that did, however, not lead to a higher risk of implant loss. With equally high satisfaction with the aesthetic result and no significant difference in number of aesthetic corrections between the two groups we suggest, that the one-stage approach using ADM may be feasible and allows the patient to achieve an implant-based BR with a minimum of surgeries and outpatient visits. The study was registered in ClinicalTrials.gov (NCT04209010).

Long-term follow-up on shoulder and arm morbidity in patients treated for early breast cancer.

Background: A prospective study on shoulder and arm morbidity was conducted in Denmark in 2003-2005. This study demonstrated that sentinel lymph node biopsy was associated with better outcomes than axillary lymph node dissection 18 months after surgery. We here aimed to describe subjective symptoms and objective findings in these patients 10+ years after they underwent breast cancer surgery and to assess how symptoms and findings developed during this period.Material and methods: Participants in the prospective study completed a questionnaire and underwent an objective, bilateral examination of their shoulder and arm morbidity, which included measurement of arm volume, range of motion, and sensibility.Results: Seventy participants completed follow-up. Thirty-four (49%) had one or more functional impairments, and 64% had one or more subjective loco regional symptoms like pain, swelling of the arm, and decreased shoulder mobility. Objective evaluation showed 34 ml's of increased arm volumes and 3-25% had severe reduced shoulder mobility on the operated side. Compared to the findings at 18 months postoperatively, small but significant differences in occurrence of subjective findings were observed. A significant progression regarding most objective findings was revealed.Conclusion: More than 11 years after breast cancer surgery, the majority of participants complained of one or more subjective symptoms of shoulder and arm morbidity. Objective findings were mild or modest in most cases. During the prolonged follow-up period of 10 years, a worsening in symptoms and objective findings was observed.HIGHLIGHTSShoulder and arm morbidity in relation to breast cancer treatment seems to progress beyond 10 years.The most frequent symptoms were pain, swelling or heaviness of the arm, and decreased shoulder mobility.The objective evaluation showed higher arm volumes and reduced shoulder mobility on the operated side.Objective findings are mild and modest but may affect activities of daily living, and most participants with late symptoms stated that this was a daily problem.

Tumor Ulceration, Reduced Infiltration of CD8-Lymphocytes, High Neutrophil-to-CD8-Lymphocyte Ratio and Absence of MC Virus are Negative Prognostic Markers for Patients with Merkel Cell Carcinoma.

(1) Background: Merkel cell carcinoma (MCC) is caused by the Merkel cell polyomavirus and UV radiation. Understanding of the underlying biology is limited, but identification of prognostic markers may lead to better prognostic stratification for the patients. (2) Methods: Ninety patients diagnosed with MCC (1996-2012) were included. Virus status was estimated by polymerase chain reaction (qPCR) and immunohistochemistry (IHC). Ulceration status, PD-L1, cd66b neutrophils, cd8 lymphocytes and biomarkers of vascularization (cd34 endothelial cells) and migration (e-cadherin) were estimated by IHC and analyzed with digital pathology. (3) Results: Virus was present in 47% of patient samples and correlated with lower E-cadherin expression (p = 0.0005), lower neutrophil-to-CD8 lymphocyte ratio (N:CD8 ratio) (p = 0.02) and increased PD-L1 expression (p = 0.03). Ulceration was associated with absence of virus (p = 0.03), increased neutrophil infiltration (p < 0.0001) and reduced CD8 lymphocyte infiltration (p = 0.04). In multivariate analysis, presence of virus (p = 0.01), ulceration (p = 0.05) and increased CD8 lymphocyte infiltration (p = 0.001) showed independent prognostic impacts on MCC-specific survival. (3) Conclusions: In this study, we found that a high N:CD8 ratio, ulceration, virus-negative status and absence of CD8 lymphocytes are negative prognostic markers. Accurate prognostic stratification of the patients may be important in the clinical setting for determination of adjuvant treatment.

Measured Levels of Human Adipose Tissue-Derived Stem Cells in Adipose Tissue Is Strongly Dependent on Harvesting Method and Stem Cell Isolation Technique.

BACKGROUND: Adipose tissue-derived stem cells are of great interest because of their properties of immune modulation, tissue regeneration, and multipotent differentiation. To advance development of stem cell-based treatments, determination of the physiologic concentration of adipose tissue-derived stem cells in human adipose tissue is relevant for proper guidance of stem cell treatment dosage, oncologic safety, and evaluation of efficacy. METHODS: A prospective comparative case-control study of 20 patients was conducted to determine the yield of adipose tissue-derived stem cells in periumbilical adipose tissue harvested by the widely used method of aspiration and in structurally intact adipose tissue harvested by excision. Stem cells were isolated using conventional enzymatic digestion and by a method combining enzymatic digestion with mechanical distortion. Stem cell yield was quantified by multicolor flow cytometry and colony-forming capacity. RESULTS: When only the conventional enzymatic digestion was used, no significant difference in adipose tissue-derived stem cell yield was observed. However, when enzymatic digestion was combined with mechanical distortion, twice as many stem cells were isolated from excised adipose tissue compared to aspirated adipose tissue. Inclusion of mechanical distortion significantly increased yield 5-fold in excised adipose tissue and 2-fold in aspirated adipose tissue. Combining enzymatic digestion and mechanical distortion, measured levels of excised adipose tissue reached 140 × 10 (95 percent CI, 62 to 220 × 10) adipose tissue-derived stem cells per gram of adipose tissue that corresponded to 26 × 10 (95 percent CI, 18 to 33 × 10) colony-forming units per gram. CONCLUSIONS: The study indicates that harvesting by aspiration halves the concentration of adipose tissue-derived stem cells in adipose tissue samples when compared to structural intact adipose tissue. Furthermore, the study presents stem cell yield higher than previously described in the current literature. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Indocyanine green guided mastectomy and immediate breast reconstruction.

Today, breast cancer is treated, and breast reconstruction is performed in specialized centers. Integrated surgical, oncological and reconstructive treatment and care should characterize the comprehensive pathway. In this setting, the women being diagnosed with breast cancer or genetic disposition thereto, should be offered the highest standard of care and treatment. The prerequisite for a successful reconstruction as well as timely onset of adjuvant treatment is uneventful healing. In addition, this may also yield an aesthetically acceptable or even pleasing result. When performing a breast reconstruction or oncoplasty, adequate viability of the tissues left behind and/or added to partially or totally reconstruct the breast, is of utmost importance for a successful outcome. Therefore, tools to assess tissue perfusion are excellent and valuable instruments for the breast reconstructive surgeon. Indocyanine green-angiography (ICG-A) has been shown to be beneficial in delayed and immediate breast reconstruction. The absolute prerequisite for a successful immediate reconstruction is the nipple-sparing or subcutaneous mastectomy using a sufficient incision to spare the perfusion of the native skin. Upon completion of the mastectomy perfusion assessment is performed and the breast reconstructed, using implants or expanders with or without acellular dermal matrix or autologous flaps. The perfusion of the autologous flap may also be assessed using ICG-A. Depending on the assessment score, the mastectomy flaps or the autologous flap are subsequently revised, thereby increasing the probability of saving the patient post-operative revision and take-back to surgery and thus ensuring uneventful healing.

Isolation of Adipose Tissue-Derived Stem Cells: Enzymatic Digestion in Combination with Mechanical Distortion to Increase Adipose Tissue-Derived Stem Cell Yield from Human Aspirated Fat.

Mesenchymal stem cells (MSCs) are of great interest due to their properties of immune modulation, tissue regeneration, and multipotent differentiation. Future developments of clinical applications, however, require a higher yield of MSCs, lower number of passages of cells in culture, and shorter time from harvest to use. Optimization and standardization of techniques for mesenchymal adipose tissue-derived stem cell isolation offers solutions to current bottlenecks as a larger amount of MSCs can be isolated. These improvements result in shorter expansion time, fewer passages, less donor material needed, and higher MSC yield. This paper describes an MSC isolation method combining enzymatic digestion with mechanic disruption. This protocol is a standardized and easy-to-implement method for reaching significantly higher MSC yields compared to conventional enzymatic isolation protocols. Based on the results presented, we hypothesize that the combined enzymatic and mechanical method increases the surface area of the adipose tissue, facilitating digestion by enzymes. This approach reduces the amount of adipose tissue and in vitro expansion time needed to reach sufficient amounts of MSCs for clinical purposes. Importantly, the method does not require increased amounts of collagenase, nor does it impair the viability or differentiability of the MSCs. Using this protocol increases MSC yield by a factor of three. As a consequence, these results indicate that the physiological concentration of MSCs in adipose tissue is higher than previously assumed. © 2018 by John Wiley & Sons, Inc.

[Classification of vascular anomalies].

The classification of vascular anomalies has been revised, as physicians and researchers have recognised an increasing number of vascular anomalies. The International Society for the Study of Vascular Anomalies presents a classification distinguishing between tumours and malformations. Over the years, an inaccurate application of the term haemangioma has been used, which has led to confusion among physicians. By using the classification and combining it with a thorough history and objective examination a classification of the most common vascular anomalies should be possible.