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.

BCLA CLEAR Presbyopia: Management with contact lenses and spectacles.

This paper seeks to outline the history, market situation, clinical management and product performance related to the correction of presbyopia with both contact lenses and spectacles. The history of the development of various optical forms of presbyopic correction are reviewed, and an overview is presented of the current market status of contact lenses and spectacles. Clinical considerations in the fitting and aftercare of presbyopic contact lens and spectacle lens wearers are presented, with general recommendations for best practice. Current options for contact lens correction of presbyopia include soft simultaneous, rigid translating and rigid simultaneous designs, in addition to monovision. Spectacle options include single vision lenses, bifocal lenses and a range of progressive addition lenses. The comparative performance of both contact lens and spectacle lens options is presented. With a significant proportion of the global population now being presbyopic, this overview is particularly timely and is designed to act as a guide for researchers, industry and eyecare practitioners alike.

A Decade of Nipple-Sparing Mastectomy: Lessons Learned in 3035 Immediate Implant-Based Breast Reconstructions.

BACKGROUND: Nipple-sparing mastectomy is commonly performed for breast cancer treatment or prevention. The authors present one of the largest breast reconstruction series in the literature. METHODS: A single-institution retrospective review was conducted from 2007 to 2019. RESULTS: The authors' query identified 3035 implant-based breast reconstructions after nipple-sparing mastectomy, including 2043 direct-to-implant and 992 tissue expander-to-implant reconstructions. The overall major complication rate was 9.15%, and the nipple necrosis rate was 1.20%. Therapeutic mastectomy was associated with higher overall complications and explantations compared with prophylactic mastectomy ( P < 0.01). In comparisons of unilateral and bilateral procedures, bilateral mastectomy had an increased risk for complications (OR, 1.46; 95% CI, 0.997 to 2.145; P = 0.05). Tissue-expander reconstructions had higher rates of nipple necrosis (1.9% versus 0.88%; P = 0.015), infection (4.2% versus 2.8%; P = 0.04), and explantation (5.1% versus 3.5%; P = 0.04) compared with direct-to-implant reconstruction. When assessing plane of reconstruction, the authors found similar rates of complications between subpectoral dual-plane and prepectoral reconstruction. There was no difference in complications between reconstruction with acellular dermal matrix or mesh compared with total or partial muscle coverage without acellular dermal matrix/mesh (OR, 0.749; 95% CI, 0.404 to 1.391; P = 0.361). Multivariable regression analysis revealed preoperative radiotherapy (OR, 2.465; 95% CI, 1.579 to 3.848; P < 0.001), smoking (OR, 2.53; 95% CI, 1.581 to 4.054; P < 0.001), and a periareolar incision (OR, 3.657; 95% CI, 2.276 to 5.875; P < 0.001) to be the strongest predictors of complications and nipple necrosis ( P < 0.05). CONCLUSIONS: Nipple-sparing mastectomy and immediate breast reconstruction has a low rate of complications. In this series, radiation therapy, smoking, and incision choice predicted overall complications and nipple necrosis, whereas direct-to-implant reconstruction and acellular dermal matrix or mesh did not increase risk. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Oncologic Safety of Nipple-Sparing Mastectomy for Breast Cancer in BRCA Gene Mutation Carriers: Outcomes at 70 Months Median Follow-Up.

BACKGROUND: Retention of the nipple-areola complex with nipple-sparing mastectomy (NSM) techniques provides a more natural cosmetic result than procedures that sacrifice the nipple. While the oncologic safety of NSM is established by several studies, there is little long-term data on outcomes in BRCA mutation carriers with breast cancer. PATIENTS AND METHODS: BRCA1/2 mutation carriers who underwent NSM and immediate reconstruction from 2008 to 2019 were reviewed and patients with breast cancer on biopsy or final pathology were included. Patient demographics and tumor characteristics, as well as treatment, recurrence, and survival data were collected. RESULTS: A total of 114 therapeutic NSM were performed in 105 BRCA mutation carriers (56 BRCA1, 47 BRCA2, and two women with both mutations). Median age was 45 years. Cancers were 18% stage 0, 52% stage I, 27% stage II, and 3% stage III. Mean invasive tumor size was 1.6 cm and 33 (35%) invasive tumors were triple negative. There were five (4.4%) positive nipple margins on final pathology; all underwent nipple excision. Most patients (80, 76%) received systemic therapy: 65 (62%) received chemotherapy and 48 (46%) received endocrine therapy. At 70 months median follow-up (range 15-150 months), no patient had developed a recurrence in the retained nipple-areola complex or at the site of a nipple excised for a positive margin. The rate of locoregional recurrence outside the nipple was 2.6%, and the rate of distant recurrence was 3.8%. Overall survival was 96%. CONCLUSIONS: NSM is a safe option for BRCA1 and BRCA2 mutation carriers who undergo mastectomy for breast cancer.

Comparison of Wireless Localization Alternatives with Wire Localization for Nonpalpable Breast Lesions.

BACKGROUND: Radiofrequency identification tag localization (TL) and magnetic seed localization (MSL) are alternatives to wire localization (WL) for excision of nonpalpable breast lesions. We sought to compare localization methods with respect to operative time, specimen volume, and re-excision rate. STUDY DESIGN: A retrospective cohort analysis was performed on TL, MSL, and WL lumpectomies and excisional biopsies at a single institution. Association between localization method and operative time, specimen volume, and re-excision rate was assessed by multiple logistic regression using odds ratios (ORs) and 95% CIs. RESULTS: A total of 506 procedures were included: 147 TL (29.0%), 140 MSL (27.7%), and 219 WL (43.3%). On logistic regression analysis, MSL was associated with longer operative times than WL for excisional biopsies only (OR 4.24, 95% CI 1.92 to 9.34, p < 0.001). Mean excisional biopsy time was 39.1 minutes for MSL and 33.0 minutes for WL. Specimen volume did not vary significantly across surgery types between localization methods. In an analysis of all lumpectomies with an indication of carcinoma, marker choice was not associated with rate of re-excision (TL vs WL OR 0.64, 95% CI 0.26 to 1.60, p = 0.342; MSL vs WL OR 1.22, 95% CI 0.60 to 2.49, p = 0.587; TL vs MSL OR 0.65, 95% CI 0.26 to 1.64, p = 0.359). CONCLUSION: TL, MSL, and WL are comparable in performance for excision of nonpalpable breast lesions. Although increased operative time associated with MSL vs WL excisional biopsies is statistically significant, clinical significance warrants additional study. With similar outcomes, physicians may choose the marker most appropriate for the patient and setting.

One-Year Experience of Same-Day Mastectomy and Breast Reconstruction Protocol.

BACKGROUND: The prevalence of same-day mastectomy with reconstruction has continued to increase across the United States in recent years. Prior studies have shown that same-day mastectomy with reconstruction leads to increased patient satisfaction and allows hospitals to use resources better. This study sought to evaluate the implementation of same-day mastectomy with a reconstruction recovery protocol for patients undergoing mastectomy at our institution. METHODS: Under an institutional review board-approved protocol, a retrospective cohort analysis compared patients who underwent mastectomy April 2016 through April 2017 with those who had mastectomy March 2020 through March 2021. Length of stay, postoperative intravenous (IV) opioid administration, safety end points, and cost were the main variables examined. RESULTS: The study compared 457 patients in 2016-2017 with 428 patients in 2020-2021. The median hospital length of stay decreased from 24.6 h in 2016-2017 to 5.5 h in 2020-2021 (p < 0.001). The percentage of patients requiring postoperative IV opioids decreased from 69.1 % in 2016-2017 to 50 % in 2020-2021 (p < 0.001). The rates of unplanned readmissions within 30 days after mastectomy did not differ between the two groups, with a rate of 3.7 % in 2016-2017 and a rate of 5.1 % in 2020-2021 (p = 0.30). Reducing the rate of overnight admissions after mastectomy by 65.8 % resulted in a cost reduction of 65.8 %. CONCLUSIONS: Implementation of same-day mastectomy with a reconstruction protocol across a large academic center and two satellite sites was a safe alternative to conventional mastectomy recovery plans.

Magnetic Seeds: An Alternative to Wire Localization for Nonpalpable Breast Lesions.

INTRODUCTION: Magnetic seeds have emerged as an alternative to wires for localization of nonpalpable breast lesions. The purpose of this study was to evaluate the utility of magnetic seeds compared to wires for preoperative localization. MATERIALS AND METHODS: A retrospective cohort analysis of magnetic seed localization (MSL) and wire localization (WL) excisional biopsies and lumpectomies performed at a single institution was conducted. Indication, age, BMI, number of markers, procedure type, operative time, and postoperative opioid administration were reviewed. Impact of localization method on operative time, specimen volume, postoperative opioid administration, and re-excision rate were assessed. RESULTS: A total of 608 MSL procedures in 601 patients were compared to 628 WL procedures in 620 patients. MSL excisional biopsies were significantly longer (37.0 minutes) than WL excisional biopsies (31.9 minutes, P< .001), but in lumpectomies without axillary surgery, MSL procedures (42.3 minutes) were significantly shorter than WL procedures (46.9 minutes, P = .017). Significantly less tissue was excised during MSL lumpectomies (68.5 cm3) and excisional biopsies (32.3 cm3) than WL lumpectomies (78.1 cm3, P = .039) and excisional biopsies (38.7 cm3, P = .018). Postoperative opioid administration was similar for MSL and WL procedures (P = .076). Re-excision rates for MSL lumpectomies were significantly higher for ductal carcinoma in situ (35.3% MSL vs. 18.5% WL, P = .013), but were similar for invasive carcinoma (14.4% MSL vs. 17.7% WL, P = .290). Logistic regression analysis showed no association between localization method and re-excision (OR 1.007, 95% CI 0.681-1.488; P = .973). CONCLUSION: MSL is a feasible alternative to WL for excision of nonpalpable breast lesions with regard to surgical outcomes.

How Protective are Nipple-Sparing Prophylactic Mastectomies in BRCA1 and BRCA2 Mutation Carriers?

BACKGROUND: Nipple-sparing mastectomy (NSM) is now routinely offered to BRCA mutation carriers for risk reduction. We assessed the rates of ipsilateral cancer events after prophylactic and therapeutic NSM in BRCA1 and BRCA2 mutation carriers. METHODS: BRCA1 and BRCA2 mutation carriers undergoing NSM from October 2007 to June 2019 were identified in a single-institution prospective database, with variants of unknown significance being excluded. Patient, tumor, and outcomes data were collected. Follow-up analysis was by cumulative breast-years (total years of follow-up of each breast) and woman-years (total years of follow-up of each woman). RESULTS: Overall, 307 BRCA1 and BRCA2 mutation carriers (160 BRCA1, mean age 41.4 years [range 21-65]; and 147 BRCA2, mean age 43.8 years [range 23-65]) underwent 607 NSMs, with a median follow-up of 42 months (range 1-143). 388 bilateral prophylactic NSMs had 744 cumulative woman-years of follow-up, with no new cancers seen (< 0.0013 new cancers per woman-years); 251 BRCA1 prophylactic NSMs had 1034 cumulative breast-years of follow-up, with no new ipsilateral cancers seen (< 0.0010 per breast-year); 66 BRCA1 therapeutic NSMs had 328 cumulative breast-years of follow-up, with one ipsilateral cancer recurrence not directly involving the nipple or areola (0.0030 per breast-year); 237 BRCA2 prophylactic NSMs had 926 cumulative breast-years of follow-up, with no new ipsilateral cancers seen (< 0.0011 per breast-year); and 53 BRCA2 therapeutic NSMs had 239 cumulative breast-years of follow-up, with two ipsilateral recurrent cancers, neither of which directly involved the nipple or areola (0.0084 per breast-year). CONCLUSIONS: The risk of new ipsilateral breast cancers is extremely low after NSM in BRCA1 and BRCA2 mutation carriers. NSM is an effective risk-reducing strategy for BRCA gene mutations.

De novo designed coiled coils as scaffolds for lanthanides, including novel imaging agents with a twist.

For much of their history, lanthanides were thought to be biologically inert. However, the last decade has seen the discovery and development of the field of native lanthanide biochemistry. Lanthanides exhibit a variety of interesting photophysical properties from which many useful applications derive. The development of effective functional lanthanide complexes requires control of their coordination sphere; something proteins manage very effectively through their 3D metal-binding sites. α-Helical coiled coil peptides are miniature scaffolds which can be designed de novo and can retain the favourable properties of larger proteins within a much simplified system. Metal binding sites, including those which bind lanthanides can be engineered into the coiled coil sequence. This review will highlight the opportunities presented by the use of coiled coil peptides as scaffolds for lanthanide binding and the potential to control the coordination environment by simple modifications to peptide sequence. Designed lanthanide coiled coils offer opportunities to gain greater insight into native lanthanide biochemistry as well as to develop new functional complexes, including imaging agents.

Unusual Magnetic Field Responsive Circularly Polarized Luminescence Probes with Highly Emissive Chiral Europium(III) Complexes.

Chirality is ubiquitous within biological systems where many of the roles and functions are still undetermined. Given this, there is a clear need to design and develop sensitive chiral optical probes that can function within a biological setting. Here we report the design and synthesis of magnetically responsive Circularly Polarized Luminescence (CPL) complexes displaying exceptional photophysical properties (quantum yield up to 31 % and |glum | up to 0.240) by introducing chiral substituents onto the macrocyclic scaffolds. Magnetic CPL responses are observed in these chiral EuIII complexes, promoting an exciting development to the field of magneto-optics. The |glum | of the 5 D0 → 7 F1 transition increases by 20 % from 0.222 (0 T) to 0.266 (1.4 T) displaying a linear relationship between the Δglum and the magnetic field strength. These EuIII complexes with magnetic CPL responses, provides potential development to be used in CPL imaging applications due to improved sensitivity and resolution.

Recent Advances in the Synthesis of Peptoid Macrocycles.

Over the past two decades, developing medical applications for peptides has, and continues to be a highly active area of research. At present there are over 60 peptide-based drugs on the market and more than 140 in various stages of clinical trials. The interest in peptide-based therapeutics arises from their biocompatibility and their ability to form defined secondary and tertiary structures, resulting in a high selectivity for complex targets. However, there are significant challenges associated with the development of peptide-based therapeutics, namely peptides are readily metabolised in vivo. Peptoids are an emerging class of peptidomimetic and they offer an alternative to peptides. Peptoids are comprised of N-substituted glycines where side-chains are located on the nitrogen atom of the amide backbone rather than the α-carbon as is the case in peptides. This change in structure confers a high degree of resistance to proteolytic degradation but the absence of any backbone hydrogen bonding means that peptoids exhibit a high degree of conformational flexibility. Cyclisation has been explored as one possible route to rigidify peptoid structures, making them more selective, and, therefore more desirable as potential therapeutics. This review outlines the various strategies that have been developed over the last decade to access new types of macrocyclic peptoids.