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PubMed1993

Experience with milk and an artificial nipple promotes conditioned opioid activity in the rat fetus.

Milk promotes activity in the kappa opioid system of the rat fetus and reduced responsiveness in a behavioral bioassay of cutaneous sensitivity. In this study, E20 rat fetuses were presented with an artificial nipple (CS) and intraoral infusions of milk (US) to condition opioid activity. Paired presentations of the CS and US resulted in conditioned changes in perioral cutaneous sensitivity, which was not evident in groups exposed to the CS alone, US alone, or explicitly unpaired presentations of US and CS. Selective opioid antagonists administered between conditioning and testing revealed that reexposure to the nipple resulted in activation of the endogenous opioid system. The nipple promoted activity at mu, not kappa, opioid receptors. Conditioned opioid activity to an artificial nipple in the fetus, which lacks experience with milk or other suckling stimuli, implies that conditioned changes in the endogenous opioid system of the newborn rat may develop quickly during the first suckling episodes.

Animals↗

PubMed1990

Bloody nipple discharge during pregnancy: a rationale for conservative treatment.

Five cases of bloody nipple discharge during pregnancy without associated breast masses were seen over the past 3 years by the author. Because of the reported association of breast cancer with bloody nipple discharge, close follow-up of these women at monthly intervals during pregnancy and trimonthly during the postpartum period was carried out. In all instances, the discharge appeared late during the second trimester or during the third trimester of pregnancy. It was unilateral and spontaneous and arose from multiple ducts, and it was associated with an increase in breast size and always with the larger breast of the two. The discharge cytologic study done on all cases was negative for neoplastic cells and the discharges resolved spontaneously within 2 months of onset. Postpartum follow-up ranging from 6 months to 3 years has revealed no evidence of neoplastic changes thus far. Mammograms ordered before these patients were referred were not helpful due to the increase in density of the breast tissue secondary to the pregnancy. Because a few cases of breast cancer during pregnancy have presented solely with a bloody nipple discharge, I recommend extremely close follow-up of these women and no surgical intervention unless a mass is discovered or the nipple discharge cytology is either suspicious or positive at the initial visit or during follow-up.

Adult↗

PubMed1992

The influence of tactile stimulation of nipples on the milk ejection reflex in the rat.

Changes of positive pressure exerted by pups on nipples during sucking were investigated using anesthetized, lactating dams. It was found that, every 50-60 s, individual pups performed bouts of pressure oscillations (3/s) of high amplitude which lasted about 10-12 s and coincided with periods of increased motor activity. During the intervals, when pups were quiet, series of low-amplitude oscillations (3/s) were also observed. Using a strain measuring method to record the activity of sucking pups, synchronization of activity of two or more pups was found to occur periodically every 25-30 s and, most frequently, 10-30 s before the reflex increase of milk pressure. In further experiments, artificial tactile stimulation was applied to the dam's nipples using the joint action of suction and positive pressure. Following a short-term (10-20 s) increase in frequency and amplitude of artificial nipple stimulation, 60%-80% of all reflexive peaks of milk pressure were elicited with a latency of 19 +/- 5 s. This suggests that there are specific conditions under which the stimulation of nipples by pups may trigger the formation of the milk ejection reflex in the rat.

Animals↗

PubMed2004

Evaluation of dynamic studies of MR mammography for the diagnosis of intraductal lesions with nipple discharge.

OBJECTIVES: We assessed the utility of dynamic magnetic resonance imaging (MRI) in differentiating benign from malignant lesions of the breast and then applied MRI to diagnose intraductal breast tumors with nipple discharge. METHODS: Gadolinium (Gd)-enhanced MR mammography was performed on 74 patients with breast tumors and 8 patients with nipple discharge. RESULTS: The steepest slopes of the contrast medium uptake (S slope) s from time-intensity curves were significantly different between malignant and benign lesions. At S slope threshold of 0.95% /second, malignancy was predicted with a sensitivity and specificity of 75% . Six of 8 cases with nipple discharge were successfully identified by MR ductography by injecting Gd-DTPA into discharging ducts. Among them, 2 non-invasive ductal carcinomas were differentiated from benign lesions by the S slope value. CONCLUSIONS: Dynamic MR mammography is an useful modality for differentiating breast lesions and has potential for evaluating intraductal lesions with nipple discharge.

Adult↗

PubMed1998

Supernumerary nipples: prevalence, size, sex and side predilection -- a prospective clinical study.

UNLABELLED: The purpose of the following clinical study was to determine the prevalence, size, sex and side predilection of supernumerary nipples. Out of 502 patients, 28 (5.6%) exhibited a supernumerary nipple of small (only areola with diameter less than 30% of normal areola) or middle size (areola with nipple, diameter 30%-50% of normal areola). The male/female ratio was 20/8 and left/right side ratio 15/7 in males and 5/4 in females. CONCLUSION: A supernumerary areola or a supernumerary areola with nipple is a frequent finding. There is a higher prevalence for the left side and male gender.

Adolescent↗

PubMed2005

Breast duct microendoscopy in nipple discharge: microbrush improves cytology.

BACKGROUND: Breast duct microendoscopy is a new technique that allows direct visualization of the mammary ductal epithelia and has the potential to provide greater accuracy in the diagnosis of benign and malignant breast conditions. We have already established the feasibility of BDME on mastectomy specimens and in patients both under general and local anesthesia. It was the aim of this study to investigate the use of BDME in patients with pathological nipple discharge and to explore the feasibility of using an endoluminal microbrush to take cytology samples from specific lesions. MATERIALS AND METHODS: Breast duct microendoscopy was offered to all patients undergoing surgery for nipple discharge. Surgery included microdochectomy (younger women) and total duct excision (especially in postmenopausal women). The microbrush was used to collect samples whenever an endoluminal papilloma was seen on endoscopy. The results of microbrush cytology samples were compared to ductal lavage samples. RESULTS: Fifty consecutive patients undergoing microdochectomy or total duct excision for nipple discharge had breast microendoscopy (28 general, and 22 under local anesthesia). Thirty-one patients had microdochectomy and nineteen had total duct excision. Visualiza- tion of discharging ducts was accomplished in 100% cases. Endoluminal abnormalities were seen in 33 (66%) patients and dilated ducts were seen in 17 patients. Among the 33 patients, 15 had single papilloma, 3 multiple papilloma and 15 inflammation (erythema, fronds, adhesions). Seven out of eight patients with an intraductal papillorna who had microbrush cytology showed papillary cells whereas only 2 out of 11 patients who had ductal lavage were positive for papillary cells. Thus the sensitivity of the brush cytology technique for the diagnosis of papilloma was 87.5% and the sensitivity of ductal lavage 18% (p = 0.0055). CONCLUSION: Breast duct microendoscopy is an effective way of establishing the etiology of nipple discharge. The microbrush increases the sensitivity of cytology significantly.

Breast Diseases↗

PubMed1998

Syringomatous adenoma of the nipple: report of a case.

We report herein a rare case of syringomatous adenoma (SA) of the nipple. Only 22 cases of SA of the nipple have been documented in the world literature, and to the best of our knowledge this is the first case to be reported in Japan. The patient was a 68-year-old woman who presented with a painful mass in the right subareolar region of over 15 years' duration. Clinical examination including needle biopsy indicated a high possibility of carcinoma; however, the final histopathological diagnosis after mastectomy proved to be SA. SA is a benign locally infiltrating neoplasm of the nipple which shares many clinicopathological features with adenoma of the nipple. Both lesions sometimes show deceptive clinicopathological findings, causing then to be easily confused with carcinomas. However, SA can be distinguished by its unique histological appearance resembling sweat duct, or syringomatous, tumors and locally infiltrating growth, which is probably responsible for its misleading clinical findings and higher rate of recurrence. Surgeons should be aware of the possibility of diagnosing this extremely rare tumor, and the appropriate treatment.

Adenoma↗

PubMed2004

Supernumerary nipples and renal malformations: a family study.

We describe a family with supernumerary nipples and kidney and urinary tract malformations. The proband is a 59-year-old man with a supernumerary nipple and recently identified hypoplastic kidney, bladder diverticulum, and hypotonic bladder. His mother also has a supernumerary nipple and a recently identified hypoplastic kidney. Of his three children, all male, one has a supernumerary nipple but has not been evaluated for a kidney or urinary tract malformation. This familial disorder is discussed.

Abnormalities, Multiple↗

PubMed2004

Changes in testicular and nipple volume related to age and seasonality in Japanese macaques (Macaca fuscata), especially in the pre- and post-pubertal periods.

We investigated, longitudinally and cross-sectionally, age and seasonal change in both the testis and nipple volume of Japanese macaques (Macaca fuscata) in relation to concentration profiles of gonadal steroids: testosterone (T) in males and progesterone (P) in females. Testicular volume (TV) and nipple volume (NV) showed rapid growth at puberty, 4.5 and 3.5 years of age in males and females, respectively, but in both sexes there were precocious individuals. The testis as a whole matures at about 10 years of age. TV change is closely related to T concentration profile. The pattern of TV change is composed of maturation and seasonal effects, with individual variation evident mainly in the latter. Some individuals show a simple pattern consisting of one peak in the breeding season (from summer to winter) and one trough in the non-breeding season. Other individuals exhibit a more complicated pattern composed of two or more peaks and troughs before and during the breeding season. The nipple matures at about 7 years but it is difficult to determine the exact maturational age as there are many confounding factors relating to NV. NV shows seasonal fluctuations similar to that of TV. Many animals have periods of substantial growth whereas others do not. The NV in adults from 10 to 25 years does not appear to change much with age, but animals older than 25 years of age have significantly smaller nipples. Seasonal fluctuation in NV mirrors that of the P level. Considered to be controlled by estrogen and P, the NV is a good indicator of the physiological status of reproduction, with its peak about 2 weeks earlier than that of P, that is, at the mid-follicular phase. NV and P level show a similar pattern in pregnancy; from conception, indicated by a P peak, NV and P concentration first decrease, then they increase until peri-parturition and slowly decrease again until the next breeding season.

Aging↗

PubMed2005

Nipple-sparing mastectomy in association with intra operative radiotherapy (ELIOT): A new type of mastectomy for breast cancer treatment.

BACKGROUND: Breast-conserving surgery has become the standard approach for about 80% of patients treated for primary breast cancer in most centres. However, mastectomy is still required in case of multicentric and/or large tumours or where recurrences occur after conservative treatment. When a total mastectomy is performed, the removal of the nipple areola complex (NAC) is a strongly debated issue. In fact, although removal of the NAC greatly increases the patient's sensation of mutilation, and the risk of tumor involvement of the areola is reported as a very variable percentage, NAC excision still remains the standard treatment. PATIENTS AND METHODS: From March 2002 to September 2003, 106 nipple sparing mastectomies (NSM) were peformed in 102 patients, 63% of whom had invasive carcinoma and 37% of whom had in situ carcinoma. Four patients underwent bilateral surgery. In all cases, a large or multicentric tumour and/or diffuse microcalcifications, clinically distant from the NAC, were present. During surgery, the tissue under the areola was routinely sampled to exclude the presence of tumor. If disease-free at the frozen sections, the NAC was spared and a NSM was performed. Additionally, a total dose of 16 Gy of radiotherapy (ELIOT) was delivered intraoperatively in the region of the NAC. All the patients underwent an immediate plastic breast reconstruction. RESULTS: In eleven patients (10.4%), the breast tissue under the areola resulted infiltrated at the definitive histological examination: in 10 cases a single or multiple foci of in situ carcinoma and in one case an invasive component were present. Eleven patients (10.4%) developed a superficial skin areolar slough followed by spontaneous healing, and 5 patients (4.7%) lost their NAC due to total necrosis. Among these, one patient had a poor cosmetic result on the NAC with asymmetrical location and required further surgical removal and reconstruction with tattoo and local flap in a better position. When rating the results from 0 (bad) to 10 (excellent), on average, the colour of the areola was rated 9/10, the sensitivity of nipple 3/10, the overall aesthetic result was rated 8/10 by both the surgeon and the patients. Early radiodystrophy (pigmentation) was observed in eight cases (7.5%). After an average follow up of 13 months, one local recurrence, located under the clavicula, far from the NAC, was observed. The preliminary results of the psychological study show a very high satisfaction with the preservation of the nipple (97.6 %), with younger women expressing a higher satisfaction than older counterparts. CONCLUSIONS: In selected cases, NSM with ELIOT of NAC has so far permitted good local control of the disease and satisfactory cosmetic results. Wider surgical experience is required to minimise the risk of leaving tumor cells in the region of the spared NAC and a longer follow up is necessary to evaluate the long term tumor recurrence rate at the NAC.

Breast Neoplasms↗

PubMed1988

Nipple development and pup-induced prolactin release in male rats treated prenatally with the antiandrogen flutamide.

While maternal female rats display increases in circulating prolactin (PRL) concentrations in response to pup exposure, parental male rats fail to show such an increase. One possible explanation for the lack of an acute PRL response in parental male rats is that males do not have nipples and therefore do not receive stimuli from the pups comparable to those experienced by parental female rats. To examine the contribution of nipple presence and possible stimulation, i.e. suckling, in this sexually differentiated endocrine response, male rats were exposed from days 12-15 of gestation to the antiandrogen flutamide. As adults, flutamide-exposed males had nipples. These males and a group of control males were castrated in adulthood and treated with a 21-day hormone regimen (estradiol and progesterone) that effectively stimulates parental behavior in adult rats. Following hormone treatment, mammary tissue from one set of flutamide-treated males was examined histologically to assess nipple and mammary gland development and responsiveness of these tissues to hormonal stimulation. Additional sets of flutamide-treated and control animals were tested for parental behavior. These latter animals were implanted with indwelling atrial cannulae on day 4 of parental behavior and subsequently bled on day 6 in the absence of young and on day 8 after presentation of young. PRL concentrations did not change in either the flutamide-treated or control parental males bled in the presence or absence of young.(ABSTRACT TRUNCATED AT 250 WORDS)

Anilides↗

PubMed2005

Nipple-areolar pigmentation: histology and potential for reconstitution in breast reconstruction.

The makeup of nipple-areolar skin, in terms of its melanin and melanocyte content has not previously been established. This histological information is required if pigmentation of the reconstructed nipple-areola is to be successful in post-mastectomy breast reconstruction. We describe examination of 200 parallel sections of nipple-areolar skin of 20 women using histochemical (Masson-Fontana) and immunohistochemical (Mel-5) techniques, evaluated using quantitative image analysis. The amount of melanin present per length of basement membrane was 2.14 times higher in areolar skin than breast skin. The ratio of melanocytes to keratinocytes was 1:9.7 in areolar skin vs. 1:14.7 in breast skin. We also describe a cell culture and skin construct method using autologous human serum without toxic growth promoting additives, which could be used in the clinical setting of nipple-areolar reconstruction.

Analysis of Variance↗

PubMed2006

Reconstruction of the nipple-areola complex: an update.

Along with continuing progress in reconstructive surgery of the breast numerous techniques of nipple-areola reconstruction have been developed. With time and experience some methods have been discredited to historical significance only while others have evolved to widely accepted concepts used by surgeons all over the world, which in turn contributed new ideas and modifications. In addition to those favourite techniques others are reserved as second-line alternatives in specific situations. The principle criterion for a pleasing nipple-areola complex is symmetry regarding several parameters: colour, texture, size, and projection. The purpose of this manuscript is to review and discuss the concepts and techniques of nipple-areola reconstruction that have evolved over the past decades. Furthermore, those principles and techniques are pointed out that fulfil best the criteria of an ideal nipple-areola complex with emphasis on different techniques of breast reconstruction and individual conditions of the patient.

Esthetics↗

PubMed2006

Nipple sparing subcutaneous mastectomy: sixty-six months follow-up.

AIM: Validation of oncological and reconstructive efficacy of nipple sparing subcutaneous mastectomy. METHODS: We enrolled 50 patients on behalf of Humanitas Centro Catanese di Oncologia fulfilling appropriate reconstructive and oncological criteria to undergo nipple sparing subcutaneous mastectomy. We preferably selected women with medium size-small breast affected by early stage breast cancer peripherally located with intra-operative negative frozen section of the major ducts. RESULTS: fourty-six patients were alive after a mean follow-up of 5.5 years. We observed a single case of local recurrence in the nipple successfully treated with local excision. Five patients presented metastatic disease. One is currently alive, 4 died because of progressive disease. CONCLUSIONS: Our study supports other findings regarding safety and efficacy of nipple sparing subcutaneous mastectomy for selected patients.

Adult↗

PubMed2003

Nipple reconstruction in Asian females using banked cartilage graft and modified top hat flap.

Nipple reconstruction is usually the final stage of breast reconstruction and there are over 50 articles that describe different techniques. The majority of methods use local soft tissue as local flaps but they face the disadvantage of reduction in nipple projection after the initial two months. This is particularly troublesome in Asian females who may have wider nipples with prominent projection but small areola surface area. We developed a method to correct this problem using cartilage graft harvested during the initial breast reconstruction operation and banked beneath the skin flap. Using the modified 'top hat' flap, we found that no excess soft tissue is required to compensate for the reduction. We have used this method in 25 cases of nipple reconstruction and have obtained satisfactory result in projection.

Asia↗

PubMed1996

Vertical scar breast reduction with medial flap or glandular transposition of the nipple-areola.

Vertical scar breast reduction is a well accepted technique which we believe improves the shape and projection of the breast and leaves no horizontal scars. Lassus and Lejour described superiorly based nipple flaps; we describe a medially based flap or glandular transposition of the nipple in small reductions. Fifty-seven consecutive patients are presented. Thirty-three patients had medial transposition of the nipple-areola with a mean resection of 608 g (range 220-1250 g). Twenty-four patients had a glandular transposition of the nipple-areola, with a mean resection of 380 g (range 220-600 g); transposition of the areola should be less than 5 cm in this group. After a short learning curve, the complications have been few and minor.

Adult↗

PubMed1996

An anatomical study of the nerve supply of the breast, including the nipple and areola.

There are widely differing accounts in the literature of the origin, course, and distribution of the nerves to the breast and especially to the nipple and areola. This, together with our own findings at operation, led us to investigate whether the accounts are inaccurate or the nerve supply is very variable or both. 15 breast specimens from dissecting room cadavers, 12 female and 3 male, were dissected to study the nerve supply of the breast in detail. In the female, the breast received its innervation from the lateral and anterior cutaneous branches of the second to the sixth intercostal nerves and from the supraclavicular nerves. On the lateral side in the 12 females, branches from the third (9/12), fourth (12/12) and fifth (4/12), and on the medial side branches from the second (3/12), the third (6/12), the fourth (4/12) and the fifth (2/12) intercostal nerves were traced to a plexus under the areola. Branches from the sixth intercostal nerve supplied the lower part of the breast but there was no direct branch to the nipple. The nerves to the nipple lay in the superficial fascia and passed through the subdermal tissue of the areola to form a plexus under it. The extent of the contribution by each nerve was variable, and it differed even on the left and right of the same cadaver. The nerve often described as passing through the inferolateral part of the breast to reach the nipple is a deep branch from the anterior division of the fourth lateral cutaneous nerve. This was present in 11/12 of the female breasts but it is not the only nerve to reach the plexus under the areola as sometimes claimed. The male breast had a similar nerve supply but the nerves were lying close together, whereas in a female breast they are spread out more widely.

Aged↗

PubMed1985

Hyperkeratosis of the nipple and areola.

Hyperkeratosis of the nipple and areola is a rare condition. We report two cases of hyperkeratosis of the nipple and areola occurring in men with no underlying endocrinopathy or synthetic estrogenic drug therapy. Both patients demonstrated prompt resolution of the hyperkeratosis of the nipples with a keratolytic gel. Because our cases were not associated with ichthyosis or epidermal nevus, they best fit into the category of nevoid hyperkeratosis of the nipples.

Aged↗