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PubMed2005

Simultaneous reconstruction of breast and well-projected nipple after expansion of mammary skin.

The problem of postoperative reduction of projecting reconstructed nipples remains to be resolved. To this end we did a clinical study of reconstructing the nipple at the same time as the breast. A tissue-expander was placed under the skin of the breast at the first operation, and then the breast and nipple were reconstructed at the second. A nipple was reconstructed using a dermal-fat flap harvested from the myocutaneous flaps used for reconstruction of the breast. A small hole was made in the corresponding site of the skin of the breast, and the reconstructed nipple was projected through the hole. This method was used in 8 cases. This method is useful in reconstructing a breast without a pad of skin and a projected nipple simultaneously. Its disadvantages are the relatively weak blood supply of the flaps, and difficulty in calculating the position of the nipple. The procedure may be beneficial for selected cases.

Adult↗
PubMed2001

Androgen-mediated development in male rat offspring exposed to flutamide in utero: permanence and correlation of early postnatal changes in anogenital distance and nipple retention with malformations in androgen-dependent tissues.

Male offspring exposed in utero to antiandrogens often display alterations in androgen-dependent developmental markers (e.g., anogenital distance [AGD], nipple retention) together with clearly adverse responses such as genital malformations and reproductive tract lesions. The objectives of this study were to determine whether in utero exposure to flutamide results in permanent changes in male AGD and nipple retention, characterize the dose-response relationship between flutamide-mediated alterations in these landmarks and clearly adverse antiandrogenic effects, and establish the predictive value and relationship between AGD and nipple retention, and other adverse manifestations. Male offspring were exposed in utero to 0, 6.25, 12.5, 25, or 50 mg/kg/day (po) of flutamide from gestation days 12 to 21. Offspring were uniquely identified at birth, and various androgen-mediated end points (AGD, areola/nipple retention, cryptorchidism, reproductive tract weights, and malformation incidence) were examined throughout life. In utero flutamide exposure significantly decreased the AGD on postnatal day (PND) 1 and increased areola/nipple retention in male rats on PND 13. Flutamide-induced alterations in AGD and areolae/nipples in early postnatal life correlated with a reduction in AGD and retained nipples observed in the adult. Prenatal flutamide exposure resulted in dose-responsive increases in cryptorchidism. Hypospadias were observed in all flutamide-exposed offspring. In utero flutamide exposure induced partial or complete prostate agenesis and decreased the weights of the seminal vesicles, levator ani bulbocavernosus (LABC) muscle, testes, and epididymides in a dose-dependent manner. Epididymal malformations were observed mainly in the 50 mg/kg/day flutamide dose group. In general, flutamide-induced alterations in dihydrotestosterone (DHT)- and testosterone (T)-dependent development each had similar respective dose-response curves. DHT-mediated development was more sensitive to in utero flutamide exposure than T-dependent processes. However, the dose-response curves for flutamide-induced changes in cryptorchidism and seminal vesicle weight were intermediate between the dose-response curves for DHT- and T-mediated development, indicating that proper development of these tissues may require both androgens. The LABC also displayed a dose-dependent decrease in weight that was similar to dose-response observed with seminal vesicle weight and was the most sensitive T-dependent end point measured. Flutamide-induced decreases in AGD predicted subsequent malformations as evidenced by logistic regression and receiver operator characteristic analysis of malformations versus AGD. However, the AGD that would predict a 10% incidence of seminal vesicle malformations is equivalent to a female AGD. An almost fully feminized phenotype of 10-12 nipples was observed in animals that had malformations in T-dependent tissues, whereas 6 or more nipples were observed in animals with malformation in DHT-dependent tissues. These data suggest that flutamide-mediated changes in AGD and nipple retention are not sensitive predictors of altered T-mediated development.

Anal Canal↗
PubMed1985

Role of nipple stimulation in the suppression of estrous cyclicity during extended lactation in the rat.

The role of nipple stimulation in the suppression of the estrous cycle during extended lactation was studied in rats subjected to either total, partial, or sham excision of the nipples. Each female cohabited with 4 pups, 4-14 days old, over a period of 70 days postpartum, during which vaginal smears were recorded daily. Initially, regardless of the presence of nipples, all rats exhibited a postpartum diestrus that lasted for 12-20 days. Intact females (bearing 6 pairs of nipples) continued to exhibit successive prolonged diestrous phases over 70 days of lactation. A comparable result was obtained with females bearing only the anterior pair of nipples, which, in a separate experiment, was found to be the most frequently suckled pair. However, females devoid of nipples resumed regular (4-day) estrous cycles between Days 12 and 27 postpartum, in spite of their continuous contact with pups. Thus, when lactation is prolonged beyond the normal time of weaning (Day 21 postpartum), stimulation of the nipples by sucking becomes indispensable for the continued arrest of the estrous cycle. The possible mechanisms underlying this phenomenon are discussed.

Animals↗
PubMed1996

Identification of specific relaxin-binding cells in the cervix, mammary glands, nipples, small intestine, and skin of pregnant pigs.

We previously demonstrated that relaxin promotes growth and softening of the cervix and development of the mammary glands in the pregnant pig. An important aspect of understanding relaxin's mechanism of action in these tissues is to identify the specific cell type(s) that contains relaxin receptors, that is, to identify those cells that initiate relaxin's effects. The objective of the present study was to identify relaxin-binding cells in tissues known to respond to relaxin (cervix and mammary gland) as well as in tissues suspected of being responsive to relaxin (nipple, small intestine, and skin) in the pregnant pig. To accomplish that objective we developed an in vitro modification of an immunohistochemical technique recently developed for identification of relaxin-binding cells. Two groups of pregnant gilts were used: intact control (group C) and ovariectomized progesterone-treated (group OP). Group OP was ovariectomized on Day 40 of gestation (Day 40) and treated with progesterone (50 mg/2 ml corn oil i.m., twice daily) until Day 110 to maintain pregnancy. On Day 110, tissues from both groups were removed, cut into cubes (2-3 cm3), frozen in liquid nitrogen, and cryosectioned (8 microns). Specific cell types that bind relaxin were identified by sequential application of a biotinylated relaxin probe, antibiotin immunoglobulin G conjugated to 1 nm colloidal gold, and silver for signal amplification. The study demonstrates for the first time that relaxin binds with specificity to 1) blood vessels (cervix, mammary glands, nipples, small intestine); 2) smooth muscles in small intestine (circular, longitudinal, muscularis mucosa); and 3) skin from sites other than the mammary nipples (back, ear, thigh, leg). In addition, consistent with previous findings in the rat, prominent labeling was observed in epithelial cells in the cervix, mammary glands, and nipples; in smooth muscle cells in the cervix and mammary nipples; and in the skin of the nipples. There were no apparent differences in relaxin binding between group C and group OP. We conclude that the specific relaxin-binding cells in the cervix, mammary glands, nipples, small intestine, and skin of the pregnant pig probably contain relaxin receptors and, therefore, mediate relaxin's effects in these tissues.

Animals↗
PubMed1999

Benign proliferative nipple duct lesions frequently contain CAM 5.2 and anti-cytokeratin 7 immunoreactive cells in the overlying epidermis.

Benign proliferative nipple duct lesions (PNDLs) pose a diagnostic problem for clinicians and pathologists. Clinically, they may be associated with skin changes typically present in Paget's disease of the nipple. The identification of numerous scattered cells in the epidermis that are immunoreactive for low-molecular-weight cytokeratin may lead to further confusion with Paget's disease. We studied the nipple epidermis in nine cases of PNDL and compared them with 26 histologically normal nipples from mastectomy specimens. CAM 5.2 and anticytokeratin 7 (CK7) immunoreactive cells were identified in the epidermis of seven of nine nipples associated with PNDL. The cytokeratin-positive cells appeared cytologically benign and were dispersed singly (scattered in seven of seven cases and frequent in four of seven cases) or formed small aggregates with occasional tubular structures (three of seven cases) in the basal and middle layers of the epidermis. In two of seven cases, these epidermal immunoreactive cells showed continuity with the underlying PNDL, suggesting the spread or continuation of lesional cells to the epidermis. Dispersed single immunoreactive cells were identified in small numbers (scattered) in the basal layer of the epidermis in 12 of 26 normal nipples and more frequently in 1 of 12 cases. In all cases, the intraepidermal cells were negative for carcinoembryonic antigen (CEA) and Her-2/neu. We conclude that intraepidermal CAM 5.2 and anti-CK7 immunoreactive cells, which are normally present in the nipple epidermis, may proliferate and form aggregates when there is an underlying PNDL. The presence of these cells does not imply Paget's disease when the intraepidermal cells have a bland cytologic appearance, fail to overexpress Her-2/neu, and there is no carcinoma within the PNDL or elsewhere in the breast.

Adult↗
PubMed1989

Complications of reduction mammaplasty: comparison of nipple-areolar graft and pedicle.

A retrospective study of breast reductions in 268 patients by two plastic surgeons was performed. Particular attention was paid to those patients treated by inferior pedicle techniques; these patients were compared with those treated by free nipple grafts. According to our findings, patients with skin loss were heavier and had longer suprasternal notch-to-nipple distances. Patients who had free nipple grafts were older and heavier and had larger specimen weights and longer suprasternal notch-to-nipple distances. Fifty-four of the original 268 patients were included in a substudy of larger breasts, defined as those with a specimen weight of over 700 g. Nineteen patients underwent free nipple grafts, and 35 underwent inferior pedicle techniques. None of the 19 patients having free nipple grafts developed complications, whereas 6 of the 35 undergoing inferior pedicle techniques sustained significant complications. We conclude that free nipple grafts should be considered over inferior pedicles in heavier patients with breast ptosis.

Adult↗
PubMed1987

The psychological contribution of nipple addition in breast reconstruction.

Two groups of consecutive patients from two different plastic surgical practice populations were evaluated to determine psychosocial differences between those who underwent nipple-areola reconstruction in addition to breast reconstruction (N = 33) versus those who did not undergo nipple-areola reconstruction in addition to breast reconstruction (N = 26). Psychological assessment consisted of a standardized symptom inventory (Brief Symptom Inventory) and a specially designed self-report questionnaire investigating reactions unique to surgeries for breast cancer and breast reconstruction. Both groups were equivalent sociodemographically, with the exception of age, where the nipple-added group was significantly younger (P = 0.035) than the nipple-not-added group. The nipple-added group reported significantly greater satisfaction with breast reconstruction with regard to overall satisfaction (P = 0.004), satisfaction with size (P = 0.02), satisfaction with softness (P = 0.0004), sexual sensitivity (P = 0.006), and satisfaction with nude appearance (P = 0.02). Of the nine scales of clinical symptomatology on the Brief Symptom Inventory, the nipple-added group showed more increased symptoms on seven of the nine. The nipple-added group was significantly higher on two of these scales, namely, paranoid ideation (P = 0.009) and anxiety (P = 0.03).

Adult↗
PubMed1989

The S nipple-areola reconstruction.

Nipple reconstruction is performed as a last stage in breast reconstruction following mastectomy. Various methods of nipple reconstruction have been described, most of them utilizing either free composite grafts or local flaps. The main problem encountered using either method is the gradual absorption and flattening of the nipple. The technique we used in reconstructing 22 nipples, in preference over the various methods accepted in breast reconstruction, achieves a long-standing, protruding nipple constructed from two large local flaps raised from an S-shape design. The technique is simple and permits freedom in choosing the height of the nipple, even in the presence of a mastectomy scar. The size of the nipple thereby constructed is in excess of what was expected. Shrinkage occurs during the first 2 months, and the resulting size is more than adequate. The areola is reconstructed by a full-thickness skin graft harvested from a nonhairy area of the upper inner thigh. The local flaps lack the necessary color, which is achieved by tattooing.

Breast↗
PubMed2003

Nipple or areolar reduction with simultaneous breast augmentation.

Patients requesting nipple or areolar reduction often desire simultaneous breast augmentation. A technique is described for implant placement by means of a nipple base incision with either nipple reduction or intraareolar reduction. Nipple reduction is accomplished by removing a ring of skin from the base of the nipple, while areolar reduction is performed by removing a donut-shaped area of skin whose inner diameter is at the nipple base. The elasticity of the areolar skin allows for access for saline implant placement. The resulting scar is well concealed. Results from 15 patients demonstrate that the technique is safe, practical, and appears to pose no increased risk of sensory changes to the nipple.

Breast Implantation↗
PubMed2005

Alteration of nipple and areola sensitivity by reduction mammaplasty: a prospective comparison of five techniques.

The preservation of the sensitivity of the nipple-areola complex after reduction mammaplasty is an important goal. The authors performed this prospective study to accurately assess whether sensitivity changes are influenced by the weight of resection or the surgical technique. Eighty patients who underwent bilateral breast reduction (Lassus, 10 patients; Lejour, 13 patients; McKissock, 18 patients; Wuringer, 20 patients; and Georgiade, 19 patients) were tested for sensitivity changes of the nipple and cardinal points of the areola with Semmes-Weinstein monofilaments before surgery, at 3 weeks, and at 3, 6, and 12 months after surgery. Patient characteristics (age, body mass index, and preoperative sensitivity) were statistically similar in all groups. The mean resection weight was significantly smaller in the Lassus (540 g) and the Lejour groups (390 g) than in the Georgiade group (935 g). The sensitivity of the nipple and the inferior and lateral part of the areola was significantly lower after a superior pedicle technique (Lassus and Lejour) than after any other technique at 3 weeks and at 3, 6, and 12 months postoperatively. Insensate nipples and areolas were found only after breast reductions with the Lassus and the Lejour techniques (47.8 percent). Nipple sensitivity after breast reduction by the other techniques was unchanged (Wuringer, McKissock, and Georgiade) or sometimes even improved (Georgiade) as early as 3 weeks postoperatively. Changes in nipple and areola sensitivity after reduction mammaplasty depend on the surgical technique rather than the weight of resection. Superior glandular pedicle techniques that require tissue resections at the base of the breast are associated with a higher risk of injury to the nerve branches innervating the nipple-areola complex.

Breast↗
PubMed2006

Importance of the new position of the nipple-areola complex in breast augmentation surgery.

BACKGROUND: When the results of breast augmentation surgery are evaluated, the respective points of view of the surgeon and the patient can differ. Because of the nature of plastic surgery, evaluation of the results puts more emphasis on the patient's satisfaction than on medical knowledge. Among the patients who are satisfied with the size of their breasts after breast augmentation surgery, the factor that affects their satisfaction with their breast shape is the position of the nipple-areola complex. This is because the relative position of the nipple-areola complex on the inserted implant makes the most apparent change. Therefore, the relative position of the nipple-areola complex on the implant can be seen as one of the most important standards in evaluating the results. METHODS: Using a standardized protocol and standards based on analysis of the measurements of 100 patients (200 nipples), the author divided breast augmentation patients according to position of the nipple-areola complex. The operations were planned with this factor as the central consideration. The author also provided preoperative education to each group. RESULTS: Between January 1, 2001, and July 31, 2004, 368 patients were divided into four types based on the position of the nipple-areola complex when the patient was in the upright position. CONCLUSIONS: By performing the operations based on the nipple-areola complex, according to individual characteristics, predictable and desirable postoperative results were obtained.

Adult↗
PubMed2005

Avoiding free nipple grafts during reduction mammaplasty in patients with gigantomastia.

Excessive breast hypertrophy or gigantomastia (>2000 g excision of tissue per breast) has traditionally been approached with breast amputation and free nipple grafting during reduction mammaplasty procedures. Disadvantages of free nipple grafts include loss of sensation, poor projection, uneven nipple-areolar complex pigmentation, and loss of lactation. We report our experiences utilizing the inferior pedicle technique of reduction mammaplasty with successful preservation of the nipple-areola complex for patients with gigantomastia. Between 2001 and 2003, 15 patients (ages 19--45) were identified with gigantomastia through review of pathology and operative reports. The inferior pedicle technique was performed in all cases by the attending staff assisted by plastic surgery residents. Patients were followed regularly from 1 week up to 1 year postoperatively. All patients reported relief from the physical sequelae of breast hypertrophy. One patient experienced bilateral partial nipple desquamation; she maintained sensation throughout and healed well with moist dressings. Otherwise, there were no complications and all patients achieved satisfactory esthetic outcomes. Our results suggest that inferior pedicle technique can be successfully performed in patients with gigantomastia. Breast amputation with free nipple grafting need not be considered standard practice for this patient population. Maintaining a wider pedicle base and meticulous intraoperative handling of the pedicle may contribute to the increased viability of the nipple-areolar complex during these cases.

Adult↗
PubMed2006

Twenty-year outcome following central duct resection for bloody nipple discharge.

BACKGROUND: Patients found with pathologic nipple discharge present a diagnostic dilemma to surgeons. No one diagnostic test, including cytology or radiologic imaging, has proved superior to any other in the differentiation of benign versus malignant sources of pathologic nipple discharge. Ductoscopy has been introduced as a way to assist with identification of potential sources of pathologic nipple discharge. Ductoscopy is also useful in the resection of deep or peripheral masses that may be missed with standard blind resection. This report evaluates the risk of missed malignancy following central duct resection (CDR). METHODS: Records of 56 patients who underwent CDR for pathologic nipple discharge greater than 15 years previous were reviewed. Data including type of nipple discharge, future biopsy, and pathology reports were all examined. RESULTS: Of the 56 patients, 36 had bloody, 18 serous, and 2 green initial discharges. Fifty-seven percent were found to have intraductal papilloma as the source of discharge, with fibrocystic disease and ductal ectasia providing the next most common causes. One woman was found to have ductal cancer and one lobular carcinoma in situ at time of CDR. Patients were followed for a mean period of 22 years. Fourteen women required future biopsy. Of these, 10 had benign disease and 4 had cancer, 3 on the ipsilateral side. The 3 women with breast cancer were 9, 13, and 17 years from initial resection. CONCLUSIONS: CDR for pathologic nipple discharge is an effective way to diagnose and treat pathologic nipple discharge without missing underlying cancers.

Adult↗
PubMed2004

Keratin 2e: a marker for murine nipple epidermis.

Mesenchyme-derived signals influence the unique keratinization and appendage formation programs in specialized skin regions. Interactions between primary mammary mesenchyme and epidermal cells result in the formation of the nipple; however, it is unclear whether this represents a site of regionally specialized epidermis. We profiled the ultrastructure and keratin expression of the murine nipple, and the ventral skin of the K14-parathyroid hormone-related protein (PTHrP) transgenic mouse, which models nipple formation. We found the murine nipple and ventral K14-PTHrP epidermis display expanded suprabasal and granular layers, as well as a thickened cornified layer compared to ventral skin of wild-type littermates. We also observed increased levels of filaggrin in extracts from the ventral epidermis of the K14-PTHrP mouse when compared to that of wild-type littermates. Keratin 2e, previously reported to be expressed in various specialized epidermal sites in the mouse, is expressed in the nipple and the ventral skin of the K14-PTHrP mouse. Keratinocytes grown from the ventral epidermis of the K14-PTHrP mouse or wild-type littermates exhibited identical expression of epidermal markers in vitro, suggesting that the modulated differentiation profile observed in the nipple or the ventral K14-PTHrP skin was dependent on interactions with fibroblasts. The lack of appendages, altered stratification pattern and expression of a specialized keratin suggests that the murine nipple is an example of regionally specialized epidermis.

Animals↗
PubMed2000

Nipple shields for preterm infants: effect on milk transfer and duration of breastfeeding.

This study reports breastfeeding outcomes for 34 preterm infants whose mothers used ultrathin silicone nipple shields to increase milk transfer. Mean milk transfer was compared for 2 consecutive breastfeedings without and with the nipple shield. Total duration of breastfeeding was calculated for a maximum of 365 days. Mean milk transfer was significantly greater for feedings with the nipple shield (18.4 ml vs. 3.9 ml), with all 34 infants consuming more milk with the nipple shield in place. Mean duration of nipple shield use was 32.5 days, and mean duration of breastfeeding was 169.4 days; no association between these variables was noted. The nipple shield was used for 24.3% of the total breastfeeding experience, with no significant association between the percentage of time the shield was used and total duration of breastfeeding. These findings are the first to indicate that nipple shield use increases milk intake without decreasing total duration of breastfeeding for preterm infants.

Adult↗
PubMed1986

Nipple differentiation in fetal male rats treated with an inhibitor of the enzyme 5 alpha-reductase: definition of a selective role for dihydrotestosterone.

In the rat, androgens are responsible for sexually dimorphic nipple differentiation. Nipples are expressed in the female, while in the male, the nipple anlage regress prenatally. Mammary gland development is present in both sexes. Treatment of pregnant Sprague-Dawley rats from days 12-21 of gestation with the aza-steroid 17 beta-N,N-diisopropylcarbamoyl-4-aza-5 alpha-androstan-3-one, a competitive inhibitor of the enzyme 5 alpha-reductase, resulted in nipple development in male offspring. Additionally, there was feminization of the external genitalia, with urethral displacement to the base of the phallus. The role of androgens in suppression of nipple anlage in the male rat fetus is known. This study, however, suggests for the first time a selective role for 5 alpha-dihydrotestosterone in regression of the nipple anlage in utero. Thus, 5 alpha-dihydrotestosterone may be critical not only for masculinization of the external genitalia, but also for inhibition of nipple development in the male rat fetus.

5-alpha Reductase Inhibitors↗
PubMed1994

Lipid composition of nipple discharges of women with galactorrhea.

The biochemical nature of nipple discharge, including galactorrhea, and the physiology of lactation in patients with nipple discharge have not been studied extensively. Studies of the composition of nipple discharges may provide further insight into the complex processes involved in their secretion. In this study we compared the lipid composition of nipple discharges from patients with galactorrhea with that of human colostrum. The diagnosis of galactorrhea was confirmed by the presence of casein, detected by the anti-casein radial immunodiffusion test. Triglyceride, cholesterol and phospholipid levels in the nipple discharge samples were quite high compared with the colostrum samples. The proportion of 6:0 and 22:1 fatty acids was lower in the discharge samples and the proportion of 18:2 and 20:4 fatty acids was higher. Levels of phospholipid and neutral lipids, determined by quantitative densitometry in situ after separation by thin layer chromatography, also varied between discharge and colostrum, with a higher level of free fatty acids and triglyceride fractions in the nipple discharge. The lipoprotein electrophoretic bands of the nipple discharge samples resembled serum lipoprotein bands while colostrum samples gave no bands on electrophoresis.

Caseins↗
PubMedDate not supplied

Characteristics of clear cells and Toker cells in the epidermis of underlying nipple duct adenoma.

Clinically, it is difficult to differentiate between nipple duct adenomas (NDAs) and Paget's disease of the nipple. These lesions share similar morphological and histological characteristics. Clear cell types present in NDA, epidermal clear cells (ECC) and Toker cells (TC), share immunoreactive similarities to Paget cells which can lead to confusion in classification. The aim of this study was to obtain information on the characteristics and histogenesis of ECC and TC, to distinguish these cells from Paget cells. Ten nipple epidermal with NDA were compared to 25 histologically normal nipples. Samples were analyzed for cytokeratins (CKs) 7, 8 and 18, carcinoembryonic antigen (CEA), c-erbB-2/HER2 expression and human papillomavirus (HPV-) DNA. In 13 out of 25 normal nipples the staining sequence demonstrated that ECC and TC cell types are immunoreactive with CKs 7, 8 and 18 in the basal region of the epidermis. In contrast, aggregated CKs 7, 8 and 18-immunoreactive ECC and TC were identified in the epidermal of 8 of the 10 NDA cases. In 2 cases, TC were continuous with the underlying NDA, suggesting that TC might be of ductal origin and migrate through the galactophorous ostia. In NDAs and 25 histologically normal nipples, ECC and TC were negative for CEA, c-erbB-2/HER2 and HPV-DNA. ECC and TC, normally present in the nipple epidermis, may proliferate and form aggregates in the presence of an underlying NDA. These cells show immunoreactivity for CKs 7, 8 and 18 but are negative for c-erbB-2/HER2, CEA and HPV-DNA and should not lead to the mistaken diagnosis of Paget's disease.

Actins↗