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Nipple aspiration in diagnosis of breast cancer.

It has been shown that early detection of breast cancer saves lives. Mammography and physical examination are currently the most commonly utilized screening methods for breast cancer. Research is being carried out to optimize these screening methods, as well as to develop new techniques. This review summarizes the findings of the research focusing on the diagnostic techniques involving the breast ductal system to date. These tests include nipple fluid cytology, nipple fluid tumor markers, ductogram, and ductoscopy.

Biomarkers, Tumor↗

Presence of carotenoid, an anticarcinogenic marker, in nipple aspirates postlactation.

Case-controlled studies have identified a protective effect of lactation against breast cancer; however, little is known about the nature of this protective mechanism. The purpose of this study was to examine postweaned, nipple aspirate fluid (NAF) from women, ages 18 to 45, for carotenoid, a known antioxidant and anticarcinogenic marker, and compare carotenoid availability in NAF with that reported in colostrum. Women who had lactated at least 6 months and weaned for at least 6 months were recruited into the study A prestudy and poststudy serum prolactin level was obtained. NAF was obtained through a nipple aspirator method. Total carotenoid ranged from 0.4 to 4.0 microg/mL, with a mean level of 1.9+/-1.2 (SD). Women who had weaned earlier (<12mo) had significantly more carotenoids than those who had lactated longer (>12mo) (P = 0.04). These levels were similar to those known to occur in colostrum. This research elucidates possible mechanisms of the protective effect of lactation on the microenvironment of the breast.

Adolescent↗

Prolonged electrical stimulation of the nipples evokes intermittent milk ejection in the anaesthetised lactating rat.

Intermittent and continuous electrical stimulation of the nipples elicited milk-ejection responses in the lactating rat. The responses occurred intermittently, with similar amplitudes and periodicity as those seen in suckled rats. The responses were always associated with synchronization of the electroencephalogram (EEG), but some rats with synchronized EEG activity did not milk eject during stimulation. Since continuous stimulation also resulted in intermittent milk ejection it seems unlikely that the periodicity of the reflex in suckled rats depends upon changes in the intensity of sensory stimulation. The techniques of nipple stimulation may be a useful method with which to study neural pathways and other phenomena such as gating involved in oxytocin release and milk ejection. The success of the technique depends on a variety of factors such as parameters of the stimulation and state of anaesthesia.

Anesthesia↗

The effects of neonatal capsaicin treatment on the sensory innervation of the nipple and on the milk ejection reflex in the rat.

Much of the sensory innervation of the nipple is provided by fibers of small calibre (A delta and C). In order to determine the contribution of unmyelinated C-fibers to this innervation and to the physiology of lactation, mammary afferents were studied in rats that had succeeded in lactating after neonatal treatment with capsaicin, a neurotoxin which selectively destroys C-fibers. After subcutaneous injection of horseradish peroxidase-wheat germ agglutinin (HRP-WGA) into the nipple of capsaicin-treated lactating rats, cell counts and surface area estimates of peroxidase-labelled and unlabelled cells were made in the corresponding dorsal root ganglia (DRG) and compared to values obtained in untreated lactating females that had received similar tracer injections. The segmental distribution of HRP-labelled primary sensory neurons in the capsaicin-treated rats was similar to that in untreated controls, but the number of labelled cells was significantly reduced at each segmental level. This reduction reflected a marked decrease in C-fibers, since there was a striking reduction in the number of small HRP-labelled and unlabelled cell bodies in the DRG and unmyelinated fibers in the dorsal roots. Peroxidase labelling within the dorsal horn of capsaicin-treated rats was also substantially diminished. About 40% of the females that had been treated neonatally with capsaicin gave birth and lactated. Although the average weight gain of their litters was retarded with respect to that of litters of untreated controls, the milk ejection reflex appeared to function normally.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Halux pulp composite graft in nipple reconstruction.

We present a nipple reconstruction method that uses a composite graft of a constant halux's prominence. This technique, which has advantages over nipple reconstruction with toe pulp free grafts, has produced good results.

Female↗

Detection of c-erbB-2 gene amplification in nipple discharge by means of polymerase chain reaction.

In a patient with non-palpable breast carcinoma, c-erbB-2 gene amplification was detected by means of polymerase chain reaction (PCR) in the small number of breast carcinoma cells present in nipple discharge. Amplification of the c-erbB-2 gene is more frequent in carcinoma in situ than in invasive types. Detection by a PCR-based method may help diagnose non-palpable breast carcinoma with nipple discharge. Since this gene amplification is related to high proliferation, it might provide useful preoperative information regarding intraductal carcinoma of comedo type and predict responses to chemotherapy.

Adult↗

Treatment of the postoperative inverted nipple with or without asymmetry of the areola.

Postoperative inversion of the nipple is a possible complication in reduction mammoplasty, especially when a tendency toward inversion exists prior to surgery. A technique for correction is presented, leaving no more scars than the peri-areolar scar corresponding to the nipple transposition. Dermal flaps are used to prevent recurrence. Any asymmetry in the location of the areolas or excessively high position can be corrected simultaneously.

Breast↗

Correction of the inverted nipple.

A simple procedure for correction of inverted nipples is described. The key to the method is the preparation of 2 deepithelized dermal flaps after supplementing the volume of tissue beneath the nipple, and preventing recurrence of the deformity with slings.

Breast↗

Nipple reconstruction with muscle flap.

The authors present a new technique for nipple reconstruction using muscle flaps obtained from muscles situated deep in the retromammary costal region. In the case illustrated, the muscle used was the rectus abdominal muscle, previously transposed for reconstruction in a patient mastectomized more than three years ago. The resulting nipple salience as well as the areolar area were covered with a skin graft obtained from the medial thigh donor site.

Abdominal Muscles↗

Nipple aspirate fluids in adult nonlactating women--lactose content, cationic Na+, K+, Na+/K+ ratio, and coloration.

The presence of lactose in nipple secretions is considered biochemical evidence of breast secretory activity, and has been reported to occur more frequently in white compared to brownish or green colored breast fluid. We studied lactose, Na+, and K+ concentrations, the Na+/K+ ratio, and the coloration of nipple aspirate fluid (NAF) from 49 nonpregnant women. A significant relationship was found between the concentrations of lactose, Na+, and K+, and age and the coloration of NAF. Lactose was present in 22/49 (44.8%) of the NAF samples and declined with age from 100% positivity in women less than or equal to 29 years to 29% in those less than or equal to 35 years. In NAF of deep yellow, brown and green colorations, only traces of lactose were found. Na+ and K+ increased with age and with darker colorations compared to white, pale yellow, or colorless NAF. Lactose was present in NAF samples from both parous and nulliparous younger women, indicating that the breasts of many nonpregnant women respond to prolactin stimulation; hence, lactose may provide a simple marker indicating active physiologic secretory activity of the breast. As reported previously, NAF of darker coloration, containing elevated levels of cholesterol, cholesterol oxidation products, and other substances, suggests retention and impaired reabsorption of these and other products of secretion. Because of the secretion and temporary retention by the breast glands of chemical substances of exogenous and endogenous origin, including mutagens and carcinogens, lactose concentration and coloration of NAF may be useful as markers of secretion and reabsorption in future physiologically based clinical and epidemiologic studies of the pathogenesis of breast disease.

Adult↗

Duct endoscopy and endoscopic biopsy in the evaluation of nipple discharge.

Microdochectomy is usually performed on patients with nipple discharge caused by intraductal proliferative lesions, such as intraductal papilloma and carcinoma. But this operation often sacrifices large amounts of normal mammary gland even when the lesion is a benign intraductal papilloma a few millimeters in diameter. We have developed duct endoscopy for the mammary duct system, and have reliably performed biopsies for intraductal proliferative lesions intraductally. From June 1989 to April 1990, we examined 22 cases by duct endoscopy, and performed endoscopic biopsy in 16 cases. The method of endoscopic biopsy is as follows. First, a bougie is inserted, without anesthesia other than Xylocaine jelly, into the orifice of the duct to enlarge it. Second, the outer cylinder and the inner needle are inserted; then the inner needle is removed, and the endoscope is inserted. After examination, the outer cylinder is moved up to the lesion to be biopsied and the endoscope is taken out. Then a sample is taken into the outer cylinder by aspiration. We diagnosed 10 cases of benign lesion and 5 cases of malignant lesion by cytological and/or histological examination. In conclusion, endoscopic biopsy, aided by duct endoscopy, is a useful and harmless diagnostic procedure in the evaluation of nipple discharge.

Biopsy↗

A comparison of MR imaging, galactography and ultrasonography in patients with nipple discharge.

BACKGROUND: The aim of this study is to assess the usefulness of three-dimensional contrast-enhanced magnetic resonance (MR) imaging, compared with galactography and ultrasonography(US). METHODS: Fifty-five patients with bloody nipple discharge were investigated retrospectively. All patients were examined by galactography, ultrasonography and MR imaging. These three sets of findings were compared with the histopathological results from 16 intraductal biopsies, 3 excisional biopsies, 24 microdochectomies and 12 mastectomies. RESULTS: Contrast enhanced MR imaging demonstrated all malignant lesions including ductal carcinoma in situ (DCIS). Four cases of DCIS were not visualized by ultrasonography and three malignant lesions were missed by galactography. In the MR study, segmental clumped enhancement (positive predictive value =100 %), and focal mass with smooth border (negative predictive value =87.5 %) were the statistically significant predictive factors. CONCLUSIONS: Among the three modalities, contrast-enhanced three-dimensional MR imaging demonstrated the location and distribution of the lesions most clearly, especially in cases of ductal carcinoma in situ. It has the potential to be a useful diagnostic tool for patients with nipple discharge.

Adult↗

Free nipple reduction mammaplasty with a horizontal scar in high-risk patients.

Women with extremely large and ptotic breasts have many complaints and difficulties during daily life. Conventional reduction mammaplasty techniques are not convenient because the presence of excess tissue beneath and over a long pedicle may cause nipple-areola complex necrosis. These patients mostly have systemic health problems so they benefit from a shorter operative procedure. The amputation method is an option providing rapid surgical operation time and little blood loss but it may lead to a flat, unaesthetic breast with poor projection. In this paper we present an alternative amputation with the use of a backfolded dermoglandular flap and free nipple graft. The inferior pole is amputated. The deepithelialized breast tissue is left on the superior pedicle extending below the 7-cm vertical limb mark. This deepithelialized tissue is tucked to give more central mound projection. The aesthetic outcomes, such as well-rounded breasts with good projection and a hidden scar at the submammary sulcus, have led us to perform this technique, which was first described by the Mansteins in 1997.

Adult↗

Increasing projection in patients undergoing free nipple graft reduction mammoplasty.

Reduction mammoplasty in patients with gigantomastia has traditionally been performed by a technique involving free nipple grafting. These patients usually have only a small amount of breast tissue above the inframammary fold and therefore this type of procedure has often left patients with an insufficient amount of superior pole projection. I have performed free nipple grafting in three patients with gigantomastia using a technique that utilizes two deepithelialized pedicles to increase projection. This technique is simple to perform, does not significantly lengthen the operative time, and results in a breast that provides significant projection.

Female↗

Paget's disease of the nipple diagnosed by MRI.

BACKGROUND: Paget's disease of the breast is a rare manifestation of breast carcinoma. CASE REPORT: The patient presented with a red lesion of the left nipple-areola complex. Breast physical examination, ultrasonography and mammography were normal bilaterally. Magnetic resonance imaging (MRI) correctly depicted Paget's disease of the nipple. Before surgery the patient underwent biopsy of the lesion that showed Paget's disease of the breast associated with an underlying ductal carcinoma in situ. The patient underwent left mastectomy and unilateral axillary lymph node dissection. The patient refused the breast-conserving surgery because she was afraid that she could have a recurrence of the carcinoma. Microscopy of the lesion confirmed the MRI diagnosis. CONCLUSION: MRI was very useful and accurate to diagnose Paget's disease of the breast without palpable mass, ultrasonographic and mammographic findings.

Breast Neoplasms↗

Paget's disease versus Toker cell hyperplasia in a supernumerary nipple.

We report the second case of mammary Paget's disease arising in a supernumerary nipple of a 29-year-old woman. The epithelium of the nipple was infiltrated by large cells with abundant and pale-staining cytoplasm. The nuclei had a vesicular chromatin pattern and identifiable nucleoli. The cells were strongly immunoreactive with KL1, CEA and EMA, but did not show reactivity with PS100, HMB45, or erb-B2. The pathogenesis of Paget cells is unclear. In our case, the lesion showed nearly all the clinical, histological and histochemical characteristics of Paget's disease, though without involvement of mammary gland epithelium and underlying carcinoma. The possibility of an intraepidermal origin, either by transformation from epidermal keratinocytes or by derivation from intraepidermal precursor cells, has to be considered. The differential diagnosis against Toker cell hyperplasia is also discussed.

Adult↗

A strong association between body fat mass and protein profiles in nipple aspirate fluid of healthy premenopausal non-lactating women.

Fluid can be aspirated from the nipples of most non-lactating women. This nipple aspirate fluid (NAF) is a potential source for the discovery of new breast cancer biomarkers. NAF has two distinct protein profiles. Type I NAF is similar to the fluid associated with cystic disease of the breast, whereas type II NAF is enriched in milk-associated proteins. The prevalence of these two profiles differs in healthy women and in breast cancer patients. This study investigated the relationship of these two NAF profiles to reproductive history, body composition, diet, and levels of lipids, steroids and thyroid hormones in healthy premenopausal women (age 30-40 years) who had regular menstrual cycles and normal mammograms and were not taking contraceptive medications. On average, women with the type I NAF profile were older, had more years since last childbirth, were less likely to have breastfed their babies and had higher dietary saturated fat intake, body mass index, body fat mass, and levels of plasma low density lipoproteins than women with the type II profile (P <0.05). Using multiple logistic regression, type I NAF was predicted independently (P <0.05) by higher body fat mass [Odds Ratio (OR) = 3.0; 95% Confidence Interval (CI): 1.5-6.1], more years since last childbirth (OR = 2.6; 95% CI: 1.3-5.2) and a higher percentage of calories from saturated fat (OR = 4.1; 95% CI: 1.1-14.6). These results suggest that protein profiles of NAF might be influenced by amounts or types of dietary and body fat, but further study of the relationship of the two profiles to breast cancer risk is needed.

Adipose Tissue↗