Mamoplastia de reducción y medialización del complejo areola-pezón en paciente acondroplásica con gigantomastia. Caso clínico / Reduction mammoplasty and nipple medialization in achondroplasic patient with gigantomastia. Case report

La acondroplasia es una enfermedad genética rara que representa la forma más común de enanismo de extremidades cortas. Existen pocos casos reportados de gigantomastia y subsecuente cirugía mamaria en esta población. Presentamos el caso de una paciente con acondroplasia, gigantomastia y medialización de pezón que requirió mamoplastia reductora y reposición de complejo areola pezón (CAP). Se utilizó la técnica de T invertida con pedículo inferior. La planeación quirúrgica y el correcto marcaje en pacientes acondroplásicos son pasos importantes para una cirugía exitosa teniendo en cuenta que las referencias anatómicas habituales no son guías confiables para un posicionamiento ideal de la mama en el tórax o del CAP en la mama. (AU)

Achondroplasia is a rare genetic disease representing the most common form of short-limb dwarfism, and there are a few case reports of gigantomastia and subsequent breast surgery in this patient population. We present the case of a patient with achondroplasia, gigantomastia and nipple medialization who required a reduction mammaplasty and reposition of the nipple areola complex (NAC). An inverted T technique with an inferior pedicle was used. Surgical planning and correct marking in achondroplasic patients are important steps for a successful surgery considering that common anatomical landmarks are not a reliable guide for ideally positioning the breast on the thoracic wall or the NAC on the breast. (AU)

Deep Water Polymastiidae (Porifera, Polymastiida) from the South West Pacific.

This study reports on some deep water sponges in the family Polymastiidae collected during the 2017 Abyss Cruise off the East Coast of Australia and the 2003 NORFANZ Expedition to the Lord Howe and Norfolk Ridges in the Tasman Sea, Southwest Pacific Ocean. Species of Radiella, Spinularia, Ridleia, Tentorium and Polymastia were collected from abyssal and bathyal depths. From these collections, seven new species were discovered: Radiella nidula sp. nov., Radiella pumix sp. nov., Radiella sclera sp. nov., Spinularia flagellata sp. nov., Tentorium labium sp. nov., Ridleia echidna sp. nov. and Polymastia norfanzii sp. nov. In addition, two species previously known are redescribed based on the new collections: viz. Polymastia zitteli and Polymastia invaginata.

A New Technique in Correction of Nipple Inversion Using Dermal C Flaps.

BACKGROUND: Nipple inversion, which is defined as a nipple located on a plane deeper than the areola, presents both functional and cosmetic problems. Surgical repair of severe cases involves suture or flap techniques. In the present study, an alternative repair technique using two cross dermal areolar flaps to correct challenging inverted nipples is presented. Releasing the inverted nipple is performed by severing the underlying tight fibrous tissue bands and canaliculi. METHODS: This is a retrospective case series. Fifteen patients who had been operated between January 2010 and January 2016 were included in the study. Seven of these had bilateral inverted nipples. Patient age at operation ranged from 26 to 47 years (mean age, 32.5 years). All nipples were congenital, with no previous operations. The follow-up period ranged between 8 and 16 months (mean of 13 months). RESULTS: There were no complications associated with surgery, including infection, hematoma, permanent sensory disturbance, or nipple necrosis. Unilateral recurrence occurred in one patient on the 26th postoperative day. This patient was reoperated on successfully using the same method. Adequate projection was achieved in all patients. All patients were satisfied with their results. CONCLUSIONS: The authors conclude that their procedure is a reliable, simple, safe, and effective method for correction of inverted nipples. The alignment of the scar with the junction of the nipple and the areola leads to a more aesthetic appearance with no apparent scarring. This technique can be applied to any type of inverted nipple as a primary surgical procedure. 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 .

Differential Diagnosis of a Unique Vulvar Mass in an Adolescent.

BACKGROUND: Vulvar masses in adolescents have a broad differential diagnosis, yet few reports exist detailing masses of mammary origin. CASE: A nulliparous, healthy 16-year-old adolescent presented with a longstanding, ulcerated, 17-cm vulvar mass of unknown origin and pronounced inguinal lymphadenopathy. The patient underwent a left radical partial vulvectomy, with pathology revealing terminal duct lobular units consistent with polymastia. CONCLUSION: Differential diagnosis of a vulvar mass in an adolescent should include polymastia.

Scalp-Ear-Nipple syndrome: first report of a Potassium channel tetramerization domain-containing 1 in-frame insertion and review of the literature.

OBJECTIVES: Pathogenic missense variants in the potassium channel tetramerization domain-containing 1 (KCTD1) gene are associated with autosomal dominant Scalp-Ear-Nipple syndrome (SENS), a type of ectodermal dysplasia characterized by aplasia cutis congenita of the scalp, hairless posterior scalp nodules, absent or rudimentary nipples, breast aplasia and external ear anomalies. We report a child with clinical features of an ectodermal dysplasia, including sparse hair, dysmorphic facial features, absent nipples, 2-3 toe syndactyly, mild atopic dermatitis and small cupped ears with overfolded helices. We also review the published cases of SENS with molecularly confirmed KCTD1 variants. METHODS AND RESULTS: Using whole-exome sequencing, we identified a novel, de novo in-frame insertion in the broad-complex, tramtrack and bric-a-brac (BTB) domain of the KCTD1 gene. By comparing to the previously reported patients, we found that our patient's clinical features and molecular variant are consistent with a diagnosis of SENS. CONCLUSIONS: This is only the 13th KCTD1 variant described and the first report of an in-frame insertion causing clinical features, expanding the mutational spectrum of KCTD1 and SENS.

Classical toxicity endpoints in female rats are insensitive to the human endocrine disruptors diethylstilbestrol and ketoconazole.

Developmental exposure to endocrine disrupting chemicals can have negative consequences for reproductive health in both men and women. Our knowledge about how chemicals can cause adverse health outcomes in females is, however, poorer than our knowledge in males. This is possibly due to lack of sensitive endpoints to evaluate endocrine disruption potential in toxicity studies. To address this shortcoming we carried out rat studies with two well-known human endocrine disruptors, diethylstilbestrol (DES) and ketoconazole (KTZ), and evaluated the sensitivity of a series of endocrine related endpoints. Sprague-Dawley rats were exposed orally from gestational day 7 until postnatal day 22. In a range-finding study, disruption of pregnancy-related endpoints was seen from 0.014 mg/kg bw/day for DES and 14 mg/kg bw/day for KTZ, so doses were adjusted to 0.003; 0.006; and 0.0012 mg/kg bw/day DES and 3; 6; or 12 mg/kg bw/day KTZ in the main study. We observed endocrine disrupting effects on sensitive endpoints in male offspring: both DES and KTZ shortened anogenital distance and increased nipple retention. In female offspring, 0.0012 mg/kg bw/day DES caused slightly longer anogenital distance. We did not see effects on puberty onset when comparing average day of vaginal opening; however, we saw a subtle delay after exposure to both chemicals using a time-curve analysis. No effects on estrous cycle were registered. Our study shows a need for more sensitive test methods to protect the reproductive health of girls and women from harmful chemicals.

KCTD1 mutants in scalp­ear­nipple syndrome and AP­2α P59A in Char syndrome reciprocally abrogate their interactions, but can regulate Wnt/ß­catenin signaling.

Potassium­channel tetramerization-domain-containing 1 (KCTD1) mutations are reported to result in scalp­ear­nipple syndrome. These mutations occur in the conserved broad­complex, tramtrack and bric a brac domain, which is associated with inhibited transcriptional activity. However, the mechanisms of KCTD1 mutants have not previously been elucidated; thus, the present study aimed to investigate whether KCTD1 mutants affect their interaction with transcription factor AP­2α and their regulation of the Wnt pathway. Results from the present study demonstrated that none of the ten KCTD1 mutants had an inhibitory effect on the transcriptional activity of AP­2α. Co­immunoprecipitation assays demonstrated that certain mutants exhibited changeable localization compared with the nuclear localization of wild­type KCTD1, but no KCTD1 mutant interacted with AP­2α. Almost all KCTD1 mutants, except KCTD1 A30E and H33Q, exhibited differential inhibitory effects on regulating TOPFLASH luciferase reporter activity. In addition, the interaction region of KCTD1 to the PY motif (amino acids 59­62) in AP­2α was identified. KCTD1 exhibited no suppressive effects on the transcriptional activity of the AP­2α P59A mutant, resulting in Char syndrome, a genetic disorder characterized by a distinctive facial appearance, heart defect and hand abnormalities, by altered protein cellular localization that abolished protein interactions. However, the P59A, P60A, P61R and 4A AP­2α mutants inhibited TOPFLASH reporter activity. Moreover, AP­2α and KCTD1 inhibited ß­catenin expression levels and SW480 cell viability. The present study thus identified a putative mechanism of disease­related KCTD1 mutants and AP­2α mutants by disrupting their interaction with the wildtype proteins AP­2α and KCTD1 and influencing the regulation of the Wnt/ß­catenin pathway.

Nipple-Areola Complex Reconstruction.

The reconstruction of the nipple-areola complex is the last step in the breast reconstruction process. Several techniques have been described over the years. The aim of this review is to provide clarity on the currently available reconstructive options.

Breast Pathology That Contributes to Dysfunction of Human Lactation: a Spotlight on Nipple Blebs.

Nipple blebs are blister-like fibrinous lesions that form on the surface of the nipple during lactation, and can result in orifice obstruction and mastitis. They likely result from superficial extension of underlying ductal plugging, and can present concurrently with hyperlactation and mammary dysbiosis. Despite their prevalence, few formal reports on nipple blebs exist. In this perspective, we review the experience of a breastfeeding medicine practice that receives referrals for patients with nipple blebs, and provide preliminary insight into etiology, management, and outcomes of these lesions.

Maternal exposure to mixtures of dienestrol, linuron and flutamide. Part I: Feminization effects on male rat offspring.

Exposure to endocrine-disrupting compounds (EDCs) during pregnancy can result in negative health effects in later generations, including sex changes and feminization. The present study assessed the feminization effects on male offspring rats of three EDCs: Dienestrol (DIES), Linuron (LIN), and Flutamide (FLU). Sexually mature female rats were exposed from gestation day (GD) 6 until postnatal day (PND) 21 to: 0.37, 0.75, 1.5, 3.12 or 6.25 µg/kg/day of DIES, 1.5, 3, 6, 12.5, 25 or 50 mg/kg/day of LIN, 3.5, 6.7, 12.5, 25 or 50 mg/kg/day of FLU, and the following mixtures: FLU + DIES (mg/kg/day+µg/kg/day), 3.5 + 0.37, or 3.5 + 3, 25 + 0.37, or 25 + 3; FLU + LIN (mg/kg/day + mg/kg/day), 3.5 + 12.5, or 25 + 12.5; and DIES + LIN (µg/kg/day + mg/kg/day), 0.37 + 12.5, or 3 + 12.5. Anogenital distance (AGD), nipple retention (NR) and cryptorchidism were evaluated. FLU produced a decrease of AGD, an increase of NR, and an increase of cryptorchidism at the highest dose. None of these three endpoints were significantly affected by LIN or DIES treatments alone. Combinations of FLU + LIN and FLU + DIES increased NR, and decreased AGD, while DIES + LIN did not produce any effects in male pups. Results show that FLU is able to induce feminization in male pups, while binary combinations of LIN and DIES did not modify the effects produced by FLU.

Size of supernumerary teats in sheep correlates with complexity of the anatomy and microenvironment.

Supernumerary nipples or teats (polythelia) are congenital accessory structures that may develop at any location along the milk line and have been implicated in the pathogenesis of mastitis. We describe the anatomy and histology of 27 spontaneously occurring supernumerary teats from 16 sheep, delineating two groups of teats - simple and anatomically complex - according to the complexity of the anatomy and microenvironment. Anatomically complex supernumerary teats exhibited significantly increased length and barrel diameter compared with simple supernumerary teats. A teat canal and/or teat cistern was present in anatomically complex teats, with smooth muscle fibres forming a variably well-organised encircling teat sphincter. Complex supernumerary teats also exhibited immune cell infiltrates similar to those of normal teats, including lymphoid follicle-like structures at the folds of the teat cistern-teat canal junction, and macrophages that infiltrated the peri-cisternal glandular tissue. One complex supernumerary teat exhibited teat end hyperkeratosis. These anatomical and histological features allow inference that supernumerary teats may be susceptible to bacterial ingress through the teat canal and we hypothesise that this may be more likely in those teats with less well-organised encircling smooth muscle. The teat cistern of anatomically complex teats may also constitute a focus of milk accumulation and thus a possible nidus for bacterial infection, potentially predisposing to mastitis. We suggest that size of the supernumerary teat, and relationship to the main teats, particularly in the case of 'cluster teats', should be considerations if surgical removal is contemplated.

Mammary Dysbiosis and Nipple Blebs Treated With Intravenous Daptomycin and Dalbavancin.

INTRODUCTION: Mammary dysbiosis, also known as subacute mastitis, may be associated with nipple blebs. These overlapping diagnoses represent a challenging clinical scenario during lactation. Little research has been published on etiology, management strategies, and outcomes of these concurrent diagnoses. MAIN ISSUE: We document the treatment and outcome of a patient who presented with left-breast dysbiosis and nipple blebs and whose milk culture grew multi-drug-resistant, methicillin-resistant Staphylococcus aureus. She was treated safely and effectively with intravenous daptomycin and dalbavancin. This has not been described previously in the lactation literature. MANAGEMENT: The 35-year-old lactating gravida 3, para 3 patient presented at 6 months postpartum to a breast surgery clinic with a 1-week history of worsening deep left-breast pain, blebs, and recurrent plugging. She was afebrile and she had no erythema or induration on her breast exam. A culture of her milk grew multi-drug-resistant, methicillin-resistant Staphylococcus aureus, and she was referred to infectious disease for assistance with intravenous antibiotic therapy. She continued to feed expressed milk throughout treatment and demonstrated complete resolution of symptoms 8 weeks later. CONCLUSIONS: We report that in patients with a multi-drug-resistant, methicillin-resistant Staphylococcus aureus-positive human milk culture and a clinical presentation of mammary dysbiosis and nipple blebs, intravenous daptomycin and dalbavancin may be an effective treatment.

Breastfeeding success with the use of the inverted syringe technique for management of inverted nipples in lactating women: a study protocol for a randomized controlled trial.

BACKGROUND: Breastfeeding provides ideal infant nutrition, conferring several health benefits to children and their mothers. Women with inverted nipples, however, face difficulties that force them to prematurely terminate breastfeeding. Whereas available conservative measures for the correction of inverted nipples are of limited success, the use of an inverted syringe may be effective in achieving high rates of infant latching and exclusive breastfeeding. This technique, however, has not been investigated in a clinical trial. METHODS/DESIGN: This open-label randomized controlled trial aims to investigate whether, in women with inverted nipples, the use of an inverted syringe increases the rate of exclusive breastfeeding at one month compared to standard care. One-hundred healthy women with grade 1 or 2 inverted nipples will be recruited as of 37 weeks of gestation. They will be randomly allocated to standard care (control group) or to an intervention group. The intervention consists of using an inverted syringe to evert the nipple before every breastfeed, starting with the first feed after delivery. The primary outcome measure is the rate of exclusive breastfeeding at 1 month. Secondary outcome measures include exclusive breastfeeding rates at 3 and 6 months, nipple eversion rate, successful latching rate, rates of any breastfeeding at 1, 3, and 6 months, breastfeeding-associated complications, maternal satisfaction with breastfeeding, maternal quality of life, and adverse events. Descriptive and regression analysis will be conducted under the intention to treat basis. DISCUSSION: The use of the inverted syringe to evert inverted nipples is a simple, inexpensive, and safe technique that can be performed by mothers with inverted nipples. Findings of this trial, if positive, will provide much needed evidence for a safe, affordable, readily available, and simple intervention to treat inverted nipples, and improve breastfeeding practice among affected women. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03529630. Registered May 8, 2018.