Postoperative outcomes of minimally invasive versus conventional nipple-sparing mastectomy with prosthesis breast reconstruction in breast cancer: a meta-analysis.

Breast cancer is the most common malignant tumor worldwide, and mastectomy remains the primary strategy for treating early stage breast cancer. However, the complication rates, surgical variables, and oncologic safety of minimally invasive nipple-sparing mastectomy (MINSM) have not been fully addressed. We systematically searched PubMed, Web of Science, Embase, and the Cochrane Library for randomized-controlled trials (RCTs) and non-RCTs that compared MINSM with conventional nipple-sparing mastectomy (CNSM), both followed by Prosthesis Breast Reconstruction (PBR). The main outcomes observed included overall complications, (Grade III) complications, skin and nipple necrosis, wound dehiscence, infection, seroma, hematoma, implant loss, and oncologic safety (positive margins and recurrence). Secondary outcomes included operation time, blood loss, hospital stay, cost-effectiveness, and patient satisfaction. Binary and continuous variables were compared using odds ratios (OR) and mean differences (MD) with 95% confidence intervals (CI). A total of 10 studies involving 2,166 patients were included. There were no statistically significant differences between MINSM and CNSM in terms of skin necrosis, wound dehiscence, infection, seroma, hematoma, implant loss, or oncologic safety. However, MINSM significantly reduced overall complications (OR = 0. 74, 95% CI [0. 58, 0. 94], p = 0. 01) and (Grade III) complications (OR = 0. 47, 95% CI [0. 31, 0. 71], p = 0. 0003). Nipple necrosis events were also significantly reduced in the MINSM group (OR = 0. 49, 95% CI [0. 30, 0. 80], p = 0. 005). Patient satisfaction improved notably in the MINSM group. Additionally, compared with the CNSM group, the MINSM group had longer operating times (MD = 46. 88, 95% CI [19. 55, 74. 21], p = 0. 0008) and hospital stays (MD = 1. 39, 95% CI [0. 65, 2. 12], p < 0. 001), while intraoperative blood loss was significantly reduced (MD = -29. 05, 95% CI [-36. 20, -21. 90], p < 0. 001). Compared with CNSM, MINSM offers advantages in reducing complications and intraoperative blood loss, as well as improving aesthetic outcomes and patient satisfaction. Therefore, MINSM may become a viable option for breast surgery. Nevertheless, a long-term evaluation of the oncologic safety of this approach is necessary to ensure its efficacy and safety for patients.

Molecular subtype and risk of local recurrence after nipple­sparing mastectomy for breast cancer.

The present study aimed to investigate whether local recurrence (LR) after nipple-sparing mastectomy (NSM) and reconstruction was associated with i) Ki67 values and molecular subtypes of the initial lesions, and ii) the size of the initial tumor and the size of the implant. A total of 156 patients with breast cancer with a mean age of 51.58 years (age range, 26-75 years) who underwent NSM with primary implant breast reconstruction were analyzed. After surgery, the mean follow-up time was 59.26 months (range, 17-85 months). Molecular subtypes, Ki67 values, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status were recorded for each patient. Additionally, information regarding the size of the implant and the initial tumor size were collected. The information was used to assess LR. For univariate analyses of risk factors, χ2 test, Fisher's exact test, Mann-Whitney U test and Student's t-test for independent samples were used. For multivariate analyses, a Cox proportional-hazards model was used. NSM was the primary treatment for breast cancer in 34/156 patients (21.8%), while 122/156 (78.2%) of patients received neoadjuvant chemotherapy followed by surgery. Luminal B was the most frequent molecular subtype, detected in 82/156 patients (52.6%), whereas the luminal A subtype was detected in 37 patients (23.7%) and the HER2-enriched subtype was detected in 17/156 patients (10.9%). Ki67 expression was low in 13/156 patients (8.3%), while medium expression was detected in 78/156 patients (50.0%) and high expression was present in 58/156 patients (37.2%). LR was noted in 17/156 patients (10.9%). As determined by univariate analysis, lower ER (P=0.010) and PR (P=0.008) expression were indicated to be significant risk factors for LR. In conclusion, in the present patient cohort, low ER and PR expression were risk factors for LR of breast cancer, whereas Ki67 status and molecular subtype were not statistically significant risk factors for LR. Additionally, the size of the initial tumor and the size of the implant were not risk factors for LR. These findings are consistent with the current literature, and should be utilized when discussing treatment options and potential clinical outcomes with patients prior to surgical management.

Nonneoplastic and neoplastic sclerosing lesions of the breast.

Sclerosing lesions of the breast encompass a spectrum of benign and malignant entities and often pose a diagnostic challenge. Awareness of key morphologic features and pitfalls in the assessment of morphology and immunophenotype is essential to avoid over- or underdiagnosis and ensure optimal clinical management. This review summarizes nonneoplastic sclerosing lesions such as radial scar/complex sclerosing lesion, sclerosing adenosis, sclerosing intraductal papilloma, sclerosing variants of ductal adenoma and nipple adenoma, and fibroadenoma with extensive sclerosis, including their clinical presentation, characteristic morphology, differential diagnostic considerations, appropriate immunohistochemical work-up, when needed, and the clinical significance. In addition, atypical or neoplastic entities (such as atypical ductal hyperplasia, ductal carcinoma in situ, low-grade adenosquamous carcinoma, and fibromatosis-like metaplastic carcinoma) that can involve these sclerosing lesions are also briefly discussed.

Hyperbaric Oxygen Therapy for Complications in Nipple-Sparing Mastectomy with Breast Reconstruction: A Systematic Review.

Background: Research advancing effective treatments for breast cancer is crucial for eradicating the disease, reducing recurrence, and improving survival rates. Nipple-sparing mastectomy (NSM), a common method for treating breast cancer, often leads to complications requiring re-operation. Despite advancements, the use of hyperbaric oxygen therapy (HBOT) for treating these complications remains underexplored. Therefore, we analyze the efficacy of HBOT in the post-operative care of patients undergoing NSM. Methods: A systematic search was conducted using PubMed, Scopus, and the Cochrane Library. Studies were assessed for eligibility using the PICO (Population, Intervention, Comparison, Outcome) framework and classified based on American Society of Plastic Surgeons (ASPS) levels of evidence. Seven studies, totaling a pool of 63 female patients, met the inclusion criteria. Among these studies, four were categorized as Level III (57.1%), one as Level IV (14.3%), and two as Level V (28.6%). These studies focused on HBOT's role in wound healing, the successful salvage of breast reconstruction, and the optimal timing for HBOT. Results: This review revealed that HBOT indeed has potential for improving tissue oxygenation, vascularization, and, consequently, wound healing. It is noted that HBOT is efficacious for mitigating post-NMS complications, including infections, re-operation, flap loss, seroma, and hematoma. Conclusions: Overall, HBOT could be beneficial in standard post-surgical care protocols for patients undergoing NSM due to its role in mitigating common adverse effects that occur after mastectomy. Despite promising outcomes, the recent literature lacks rigorous clinical trials and well-defined control groups, underscoring the need for further research to establish standardized HBOT protocols.

Pituitary Hyperplasia Due to Longstanding Primary Hypothyroidism: A Case Report and Comprehensive Review of the Literature.

Hypothyroidism is a frequently diagnosed endocrine disorder. Common signs and symptoms include fatigue, cold intolerance, hoarseness, dry skin, constipation, a slow relaxation phase of deep tendon reflexes, and bradycardia. However, some patients may exhibit atypical signs and symptoms, which can result in diagnostic confusion. Pituitary hyperplasia resulting from longstanding primary hypothyroidism was first described by Niepce in 1851. It is usually asymptomatic, but sometimes, in addition to symptoms of overt hypothyroidism, patients may complain of headaches, hypopituitarism, visual field impairment, and hyperprolactinemia. Furthermore, on imaging, pituitary hyperplasia can be mistaken for a pituitary adenoma. Distinguishing between the two is crucial, as their management differs; the former often responds to thyroid hormone replacement therapy, while the latter might need treatment with surgery and/or radiotherapy. Here we describe a patient who developed pituitary hyperplasia in the setting of longstanding uncompensated primary hypothyroidism due to a lack of compliance with levothyroxine replacement therapy. We also review the clinical, laboratory, and radiologic findings of the case reports available in the literature up to now in order to improve the knowledge and the care of the disease.

Factors influencing intraoperative conversion from double- to single-incision mastectomy with free nipple grafts in 352 transgender and non-binary patients.

BACKGROUND: Double-incision mastectomy (DIM) with free nipple grafts (FNG) is a common technique employed in gender-affirming mastectomy (GAM), but is associated with a high scar burden. Intraoperatively, the surgeon may opt for a single-incision mastectomy (SIM) along the inframammary folds (IMF) to optimize aesthetic outcomes. This study sought to identify factors predictive of intraoperative conversion. METHODS: From February 2018 to November 2022, TGNB patients who underwent GAM at a single institution were retrospectively reviewed. Data regarding patient characteristics, perioperative details, postoperative complications, and aesthetic satisfaction were collected. RESULTS: A total of 352 patients were identified. Median age and body mass index (BMI) were 25.0 years (IQR: 9.0) and 28.5 kg/m2 (IQR: 8.5), respectively. Most patients received IMF incisions (n = 331, 94.0%); of whom, 66 (19.9%) underwent intraoperative conversion from DIM to SIM with FNG. Larger breast cup-size (p < 0.001) and a greater degree of ptosis (p = 0.002) preoperatively were significantly associated with intraoperative conversion to SIM. There was no significant association between intraoperative conversion and the ratio of intermammary distance to the width of the chest wall (p = 0.086). Overall complication rates were significantly higher among patients with diabetes mellitus (p = 0.015) and a greater degree of ptosis (p = 0.018). 77.8% (n = 274) of patients were satisfied with their aesthetic outcome. NPWT usage was associated with higher rates of aesthetic satisfaction (83.6% vs. 77.8%; p = 0.005). CONCLUSION: Patients with larger breast cup size and greater degree of ptosis should be counseled preoperatively that they may be at a higher risk of conversion to a singular incision.

Noninvasive Real-Time Assessment of Nipple-Areola Complex Perfusion Using Laser Speckle Contrast Imaging in Direct-to-Implant Breast Reconstruction.

BACKGROUND: Nipple-areola complex (NAC) necrosis is a major complication for breast reconstruction after nipple-sparing mastectomy. Although intraoperative indocyanine green angiography helps to assess the viability of tissue, the imaging could be conservative which may lead to aggressive resection. The plastic surgeons are eager to know the perfusion changes of NAC throughout the perioperative period. METHODS: In this prospective cohort study, the authors enrolled patients who underwent NSM and immediate direct-to-implant breast reconstruction. All patients underwent laser speckle contrast imaging before surgery, immediately after mastectomy, after implant placement, and 24 h and 72 h after surgery. RESULTS: A total of 94 breasts were analyzed, including 64 breasts healed with viable NAC and 30 breasts with NAC necrosis. In viable NACs, the average blood supply decreased to 56% after NSM and 42% after reconstruction, then recovered to 68% and 80% at 24-h and 72-h post-operation. In necrotic NACs, the average blood supply decreased to 33% after NSM and 24% after reconstruction, and partial perfusion recovery was also recorded at 24-h (31%) and 72-h (37%) post-operation. The cutoff value for predicting NAC viability is 40% after NSM and 25% after implant placement. CONCLUSIONS: The study quantified the NAC perfusion changes during the perioperative period. NAC perfusion decreased significantly after NSM and would be the lowest after the end of breast reconstruction. Viable NACs displayed more perfusion during the operation and showed significant nipple revascularization after breast reconstruction. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. 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 .

Early detection of breast cancer through the diagnosis of Nipple Aspirate Fluid (NAF).

The development of breast cancer has been mainly reported in women who have reached the post-menopausal stage; therefore, it is the primary factor responsible for death amongst postmenopausal women. However, if treated on time it has shown a survival rate of 20 years in about two-thirds of women. Cases of breast cancer have also been reported in younger women and the leading cause in them is their lifestyle pattern or they may be carriers of high penetrance mutated genes. Premenopausal women who have breast cancer have been diagnosed with aggressive build-up of tumors and are therefore at more risk of loss of life. Mammography is an effective way to test for breast cancer in women after menopause but is not so effective for premenopausal women or younger females. Imaging techniques like contrast-enhanced MRI can up to some extent indicate the presence of a tumor but it cannot adequately differentiate between benign and malignant tumors. Although the 'omics' strategies continuing for the last 20 years have been helpful at the molecular level in enabling the characteristics and proper understanding of such tumors over long-term longitudinal monitoring. Classification, diagnosis, and prediction of the outcomes have been made through tissue and serum biomarkers but these also fail to diagnose the disease at an early stage. Considerably there is no adequate detection technique present globally that can help early detection and provide adequate specificity, safety, sensitivity, and convenience for the younger and premenopausal women, thereby it becomes necessary to take early measures and build efficient tools and techniques for the same. Through biopsies of nipple aspirate fluid (NAF) biomarker profiling can be performed. It is a naturally secreted fluid from the cells of epithelium found in the breast. Nowadays, home-based liquid biopsy collection kits are also available through which a routine check on breast health can be performed with the help of NAF. Herein, we will review the biomarker screening liquid biopsy, and the new emerging technologies for the examination of cancer at an early stage, especially in premenopausal women.

Invasive cribriform carcinoma of the breast presenting as an erythematous papule on the nipple: A case report.

Invasive cribriform carcinoma (ICC) is a rare form of invasive breast carcinoma with good prognosis. To date, case reports considering skin manifestations of ICC are scarce. We herein report a case of pure ICC presenting as an erythematous papule on the nipple with mammary Paget's disease in the epidermis. We aim to bring awareness to skin manifestation of ICC.

Mammographically and sonographically occult male DCIS seen only on breast MRI.

Male breast cancer is a rare entity consisting of less than 1% of all breast cancer diagnoses, in which pure ductal carcinoma in situ (DCIS) without an invasive component accounts for approximately 10% of these diagnoses. Early diagnosis and appropriate management are essential to ensure favorable outcomes. We present a rare case of mammographically and sonographically occult pure DCIS in a male patient presenting with unilateral bloody nipple discharge, highlighting imaging features and the potential utility of breast MRI that aided diagnosis and management.

Evaluation of Nipple-Areola Circulation in Central Pedicle Mastopexy Patients with Subpectoral Implant Placement: A Quasi-Experimental Study.

OBJECTIVE: Mastopexy is a procedure which is used in breast lift and reconstruction surgery and requires a small amount of parenchymal resection. In this procedure, the preservation of nipple-areola circulation is vital. The purpose of this study is to evaluate nipple-areola circulation in patients undergoing central pedicle mastopexy with subpectoral implant placement. MATERIAL AND METHOD: In this observational quasi-experimental study, data were collected retrospectively from electronic medical records. The perioperative nipple-areola circulation of patients undergoing central pedicle mastopexy with subpectoral implant placement was evaluated by integrated laser Doppler flowmetry. Descriptive statistics, one-way analysis of variance, and Tukey's range tests were used to analyze the data. RESULTS: The preoperative, skin dissection, pectoral elevation, implant placement, 24th hour, and 2nd week nipple-areola circulation statuses of each patient who underwent central pedicle mastopexy with subpectoral implant placement were examined using an integrated laser Doppler flowmeter, and the results were compared. At each stage, all measurements were in the range of 1.8-3.6 ml/min/100g. There was no statistically significant difference between the measurement results. CONCLUSION: Central pedicle mastopexy with subpectoral implant placement seems highly advantageous in terms of better functionality and aesthetics in the reconstruction of heavy and sagging breasts. 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/0026.

Nonpharmacological Interventions for Treating Breastfeeding Nipple Pain: Systematic Review and Meta-Analysis.

Objective: To evaluate the efficacy and safety of nonpharmacological topical interventions for treating breastfeeding nipple pain. Methods: Randomized clinical trials (RCTs) assessing lactating women suffering from breastfeeding painful nipples were included. Primary outcomes were pain, healing process, and adverse events. A comprehensive search was conducted on June 02, 2023, without date or language restrictions. Methodological quality was assessed using the Cochrane risk of bias tool and the certainty of the evidence, the GRADE approach. Results: Nineteen RCTs with unclear to high risk of bias were included. There was uncertain evidence regarding the effects of photobiomodulation versus placebo on pain reduction (mean difference [MD] -0.15; 95% confidence interval [95% CI] -1 0.49 to 1.19; 139 participants, 2 RCTs). There are uncertainties concerning the effects of lanolin versus breast milk on pain (MD -1.80; 95% CI -2.43 to -1.17; 1 RCT; 180 participants), wound healing (MD 0.10; 95% CI -0.26 to -0.46; 1 RCT; 180 participants), and any adverse events (zero events in both groups). Similar effects were observed by the other interventions assessed. Conclusion: The evidence of nonpharmacological topical interventions for painful nipples is imprecise, and future RCTs with higher methodological quality are needed to support recommendations. Considering the accessibility and low cost of these alternative treatments, the findings of this evidence synthesis could support clinical decision-making and guide future research. PROSPERO CRD42020170320.

Masculinization of the Chest in Transmen with Large Breasts.

Background and Objectives Surgery to masculinize the chest is a frequently sought-after procedure by transmen who wish to conform their physical appearance to their gender identity. In our study, the outcomes of surgical masculinization comprising subcutaneous mastectomy through a modified elliptical incision, liposuction, reduced inert nipple-areola grafting, and quilting stitches were analyzed. Materials and Methods Thirty-two transmen with large breasts and hypertrophied nipples and areolae underwent the above-mentioned masculinizing procedure in this prospective cohort study. Our statistically validated institutional aesthetic outcome assessment score (IAOAS) was used to analyze the outcomes at the end of the follow-up period. Results The average period of follow-up was 24.5 months. The average final IAOAS was 23.1. The rate of complications was found to be associated with using breast binders. In all, 22 of 32 patients (68.75%) had an excellent outcome score, while 10 patients (31.25%) had a good outcome score ( p = 0.025). Conclusion Top surgery is crucial for transmasculine patients to achieve their desired gender identity as males. It is imperative that this procedure is performed to their complete satisfaction. Our single-staged comprehensive approach of subcutaneous mastectomy and liposuction with reduced inert nipple and areola grafts, which aids in a swift transition to a male role, is a prerequisite for bottom surgery at our institute.

Pubertal retroareolar cysts presenting as bluish lumps: New cases and literature review.

Retroareolar cysts (RCs) are a benign self-resolving condition primarily affecting pubertal individuals. However, their presentation as asymptomatic bluish areolar lumps remains underreported in the literature, with only six cases previously documented. This lack of awareness may lead to the oversight of RCs during diagnosis. To address this, we conducted a comprehensive literature review using PUBMED, and we further added three more cases. The mean time for clinical resolution was found to be 2.3 years. In light of these findings, we proposed a diagnostic and management algorithm to guide clinicians in their approach to RCs in pediatric patients. The algorithm involves thorough clinical examination, medical history assessment, and echographic investigation with color Doppler analysis. Regular follow-up visits are recommended until resolution of the lesions. Notably, due to the consistently favorable outcome of RCs, aggressive diagnostic interventions can be avoided, providing reassurance to patients and their families. It is crucial for paediatricians to stay updated on this underreported condition to ensure timely recognition and appropriate management. Dermatologists should be the first specialists to be consulted in cases of suspected RCs. Increasing awareness among healthcare professionals will contribute to improved diagnosis and management of this benign condition. In conclusion, RCs are a benign self-resolving condition commonly observed during puberty. Their presentation as asymptomatic bluish areolar lumps may often be overlooked. Through this study, we highlighted the importance of early recognition, proposed a diagnostic and management algorithm, and emphasized the favorable prognosis of RCs, which allows for a conservative approach to their management.

Expression and clinical significance of CA125, CA153 and CEA in nipple discharge of breast cancer patients.

Background: It is an important clinical means to identify benign and malignant breast diseases caused by nipple discharge through the detection and analysis of components in nipple discharge. This study was aimed to test the expression and clinical significance of carbohydrate antigen 125 (CA125), carbohydrate antigen 153 (CA153) and carcinoembryonic antigen (CEA) in nipple discharge of breast cancer patients. Methods: From January 2017 to December 2018, 86 patients with invasive ductal carcinoma of the breast with nipple discharge (breast cancer group) and 50 patients with ordinary breast duct hyperplasia with nipple discharge (benign control group) were selected, and the levels of CA125, CA153 and CEA in nipple discharge and serum were detected by electrochemiluminescence immunoassay.

Positive Nipple Margins in Nipple-Sparing Mastectomy: Management of Nipples Containing Cancer or Atypia.

BACKGROUND: Nipple-sparing mastectomy (NSM) is an oncologically safe approach for breast cancer treatment and prevention; however, there are little long-term data to guide management for patients whose nipple margins contain tumor or atypia. METHODS: NSM patients with tumor or atypia in their nipple margin were identified from a prospectively maintained, single-institution database of consecutive NSMs. Patient and tumor characteristics, treatment, recurrence, and survival data were assessed. RESULTS: A total of 3158 NSMs were performed from June 2007 to August 2019. Nipple margins contained tumor in 117 (3.7%) NSMs and atypia only in 164 (5.2%) NSMs. Among 117 nipple margins that contained tumor, 34 (29%) margins contained invasive cancer, 80 (68%) contained ductal carcinoma in situ only, and 3 (3%) contained lymphatic vessel invasion only. Management included nipple-only excision in 67 (57%) breasts, nipple-areola complex excision in 35 (30%) breasts, and no excision in 15 (13%) breasts. Only 23 (24%) excised nipples contained residual tumor. At 67 months median follow-up, there were 2 (1.8%) recurrences in areolar or peri-areolar skin, both in patients with nipple-only excision. Among 164 nipple margins containing only atypia, 154 (94%) nipples were retained. At 60 months median follow-up, no patient with atypia alone had a nipple or areola recurrence. CONCLUSIONS: Nipple excision is effective management for nipple margins containing tumor. No intervention is required for nipple margins containing only atypia. Our results support broad eligibility for NSM with careful nipple margin assessment.

Residual cancer burden in two-stage nipple sparing mastectomy after first stage lumpectomy and devascularization of the nipple areolar complex.

PURPOSE: Ischemic complications after nipple-sparing mastectomy (NSM) can be ameliorated by 2-stage procedures wherein devascularization of the nipple-areolar complex (NAC) and lumpectomy with or without nodal staging surgery is performed first (1S), weeks prior to a completion NSM (2S). We report the time interval between procedures in relation to the presence of residual carcinoma at 2S NSM. METHODS: Women with breast cancer who received 2S NSM from 2015 to 2022 were identified. Both patient level and breast level analyses were conducted. Clinical staging at presentation, pathologic staging at 1S and residual disease at 2S pathology are noted. Residual disease was classified as microscopic (1-2 mm), minimal (3-10 mm), and moderate (> 10 mm). RESULTS: 59 patients (108 breasts) underwent 2S NSM. The median time interval between 1 and 2S for all patients was 34 days: 31 days for upfront surgery invasive cancer, 41 days for upfront DCIS surgery and 31 days for those receiving neoadjuvant therapy. Completion NSM was performed within 6 weeks for 72% of the breasts analyzed. Of the 53 breasts with invasive cancer on 1S pathology, 35% (19/53) had no residual invasive disease and 24.5% (13/53) had neither residual invasive nor in situ carcinoma on final 2S. Among the 50 women who had upfront surgery, 16 (32%) had residual invasive cancer found at 2S NSM, 9 of which had less than or equal to 1 cm disease. CONCLUSION: Invasive cancers were completely resected during 1S procedure in 65% of breasts. Residual disease was minimal and there was only one case of upstaging at 2S. Added time of two-stage surgery is offset by a reduction in ischemic mastectomy flap complications.