Nipple‐sparing Mastectomy and Sub‐areolar Biopsy: To Freeze or not to Freeze? Evaluating the Role of Sub‐areolar Intraoperative Frozen Section

Use of nipple‐sparing mastectomy (NSM) for risk‐reduction and therapeutic breast cancer resection is growing. The role for intraoperative frozen section of the nipple‐areolar complex remains controversial. Records of patients undergoing NSM at our institution from 2006 to 2013 were reviewed. Records from 501 nipple‐sparing mastectomies were reviewed (216 therapeutic, 285 prophylactic). Of the 480 breasts with sub‐areolar biopsies, 307 had intraoperative frozen sections and 173 were evaluated with permanent paraffin section only. Among the 307 intraoperative frozen sections, 12 biopsies were positive on permanent paraffin section (3.9% or 12/307). Of the 12 positive permanent biopsies, five were false negative and the remaining seven concordant intraoperatively. Sensitivity and specificity of sub‐areolar frozen section were 0.58 and 1, respectively. Positive sub‐areolar biopsies consisted primarily of ductal carcinoma in situ (62% or 13/21). The nipples or nipple‐areolar complex were resected in a separate procedure following mastectomy (10/21), intraoperatively following frozen section results (7/21) or during second‐stage breast reconstruction (3/21; 1 additional scheduled). Only 30% (6/20) of resected specimens had abnormal residual pathology. Intraoperative frozen section is highly specific and moderately sensitive for the detection of positive sub‐areolar biopsies in NSM. Its use can help guide intraoperative reconstructive planning. The presence of positive sub‐areolar biopsies in both contralateral and high‐risk prophylactic mastectomy specimens emphasizes the need to perform sub‐areolar biopsies in all nipple‐sparing mastectomies.     

Intramammary lymph nodes and breast cancer: a marker for disease severity, or just another lymph node?

BACKGROUND: Axillary lymph node status is still considered the most significant prognostic factor for breast cancer outcome, and treatment decisions are based on the presence or absence of nodal disease. Intramammary lymph nodes (IMLNs) can be a site of regional spread. Is this a marker for more aggressive disease? METHODS: We reviewed the cancer center pathology database from 1991 to 2005 for all cases of breast cancer with IMLNs. RESULTS: IMLNs were identified in 64 breast cancer patients, with metastatic spread in 20 patients, and benign IMLNs described in 44 patients. Positive IMLNs were associated with more aggressive disease, including higher rates of invasive versus noninvasive cancers (5% ductal carcinoma-in-situ [DCIS] with positive IMLNs vs. 23% with negative IMLNs), lymphovascular invasion (55% vs. 11%), and a higher rate of axillary lymph node involvement (72% vs. 18%). Patients with positive IMLNs were also more likely to undergo mastectomy (75% vs. 54%). CONCLUSIONS: IMLN metastases are a marker for disease severity; recognition of this may influence choice of adjuvant therapy. The presence of metastatic disease in an IMLN is associated with a high rate of axillary nodal involvement, and should mandate axillary dissection. Preoperative lymphoscintigraphy may help identify these extra-axillary metastases.     

Biomarkers of Exposure to Phthalate Mixtures and Adverse Birth Outcomes in a Puerto Rico Birth Cohort

Background: Humans are exposed to complex mixtures of phthalate chemicals from a range of consumer products. Previous studies have reported significant associations between individual phthalate metabolites and pregnancy outcomes, but mixtures research is limited.Objectives: We used the Puerto Rico Testsite for Exploring Contamination Threats longitudinal pregnancy cohort to investigate associations between phthalate metabolite mixtures and pregnancy outcomes.Methods: Women (n=462 carrying females, n=540 carrying males) provided up to three urine samples throughout gestation (median 18, 22, and 26 wk), which were analyzed for 13 phthalate metabolites. Pregnancy outcomes including preterm birth (PTB), spontaneous PTB, small and large for gestational age (SGA, LGA), birth weight z-score, and gestational age at delivery were abstracted from medical records. Environmental risk scores (ERS) were calculated as a weighted linear combination of the phthalates from ridge regression and adaptive elastic net, which are variable selection methods to handle correlated predictors. Birth outcomes were regressed on continuous ERS. We assessed gestational average and visit-specific ERS and stratified all analyses by fetal sex. Finally, we used Bayesian kernel machine regression (BKMR) to explore nonlinear associations and interactions between metabolites.Results: Differences in metabolite weights from ridge and elastic net were apparent between birth outcomes and between fetal sexes. An interquartile range increase in gestational average phthalate ERS was associated with increased odds of PTB [male oddsratio(OR)=1.56; 95% confidence interval (CI): 1.08, 2.27; female OR=1.91; 95% CI: 1.23, 2.98], spontaneous PTB (male OR=2.32; 95% CI: 1.46, 3.68; female OR=2.00; 95% CI: 1.04, 3.82), and reduced gestational age at birth (male β=−0.39 wk, 95% CI: −0.62, −0.15; female β=−0.29 wk, 95% CI: −0.52, −0.05). Analyses by study visit suggested that exposure at ∼22 wk (range 20–24 wk) was driving those associations. Bivariate plots from BKMR analysis revealed some nonlinear associations and metabolite interactions that were different between fetal sexes.Discussion: These results suggest that exposure to phthalate mixtures was associated with increased risk of early delivery and highlight the need to study mixtures by fetal sex. We also identified various metabolites displaying nonlinear relationships with measures of birth weight. https://doi.org/10.1289/EHP8990     

Associations of Metabolic and Obstetric Risk Parameters with Timing of Lactogenesis II

Lactogenesis II is the onset of copious milk production following parturition. Delayed onset of lactogenesis II (DLII) often contributes to poorer lactation performance, which may adversely affect maternal and child health. The present study aims to identify the metabolic and obstetric risk factors for DLII in a secondary analysis of a prospective cohort study following pregnant women through postpartum. We defined the onset of lactogenesis II as delayed if it occurred ≥72 h postpartum. Multiple logistic regression analyses were conducted to evaluate the associations of metabolic and obstetric variables with DLII. Median onset of lactogenesis II was 72.4 h (IQR 60.4–91.6) postpartum, and 55.4% (98 of 177) of women experienced DLII. Time to first breast contact ≥ 2 h postpartum compared to ≤1 h postpartum was associated with DLII (OR 2.71 95% CI 1.12–6.53) with adjustment for age, race, pregravid BMI, primiparity, and mode of delivery, while metabolic variables were not significantly associated with DLII. In this comprehensive examination of potential metabolic and obstetric parameters, earlier timing of putting the infant to the breast remained significantly associated with earlier onset of milk coming in after consideration of the other potential risk factors. Obstetrical practices, including putting the baby to the breast later, may have an important impact on the timing of lactation, and interventions are needed to address this concern.     

Effects of hypoxic-ischemic encephalopathy and whole-body hypothermia on neonatal auditory function: a pilot study

We assessed the effects of hypoxic-ischemic encephalopathy (HIE) and whole-body hypothermia therapy on auditory brain stem evoked responses (ABRs) and distortion product otoacoustic emissions (DPOAEs). We performed serial assessments of ABRs and DPOAEs in newborns with moderate or severe HIE, randomized to hypothermia ( N = 4) or usual care ( N = 5). Participants were five boys and four girls with mean gestational age (standard deviation) of 38.9 (1.8) weeks. During the first week of life, peripheral auditory function, as measured by the DPOAEs, was disrupted in all nine subjects. ABRs were delayed but central transmission was intact, suggesting a peripheral rather than a central neural insult. By 3 weeks of age, peripheral auditory function normalized. Hypothermia temporarily prolonged the ABR, more so for waves generated higher in the brain stem but the effects reversed quickly on rewarming. Neonatal audiometric testing is feasible, noninvasive, and capable of enhancing our understanding of the effects of HIE and hypothermia on auditory function.     

The effect of chorionic villus sampling on the fraction of cell-free fetal DNA in maternal plasma

Objective: This study aims to assess whether the fraction of cell-free fetal DNA (cffDNA) is different at 24?h or 7 days after chorionic villus sampling (CVS), compared to subjects that do not undergo CVS.

Methods: Pregnant women undergoing CVS for genetic testing and matched subjects undergoing first trimester combined screening alone were enrolled between 11^0/7 and 13^6/7 weeks gestation. The fractions of cffDNA were compared before the procedure, 24?h after and 7 days after between CVS patients and ultrasound-only patients.

Results: Forty-five women underwent CVS and 45 had ultrasound alone. The women undergoing CVS were, on average, older (36.8 years versus 28.5 years, p=0.001) and had a higher baseline fraction of cffDNA than women in the comparison group (11.4% versus 9.8%, p=0.033). Both groups had a decrease in the mean fraction of cffDNA after 24?h. After 7 days, the trend of the mean fraction of cffDNA continued to decline in the CVS group but began to trend toward an increase in the ultrasound only group.

Conclusions: CVS does not significantly increase the fraction of cell free fetal (placental) DNA in the maternal plasma. A downward trend in cffDNA in maternal plasma is seen at 24?h and 7 days following CVS compared to baseline.     

Review of axillary lesions,emphasising some distinctive imaging and pathology findings

The axilla is often included on mammography, ultrasound (US), CT and MRI. Axillary masses can arise from any of the tissue components present in this region including breast parenchyma. Aetiologies include: lymphadenopathy due to inflammation, malignancy and degenerative causes; soft tissue tumours such as haemangioma, lymphangioma, peripheral nerve sheath tumours and lipomas; post‐surgical complications such as seroma, lymphocoele and haematoma; lesions arising in accessory breast tissue such as fibroadenoma and carcinoma. Some of these entities have distinctive imaging appearances knowledge of which can be helpful in suggesting the correct diagnosis.     

Differential proteome analysis of diabetes mellitus type 2 and its pathophysiological complications

The prevalence of Diabetes Mellitus Type 2 (DM 2) is increasing every passing year due to some global changes in lifestyles of people. The exact underlying mechanisms of the progression of this disease are not yet known. However recent advances in the combined omics more particularly in proteomics and genomics have opened a gateway towards the understanding of predetermined genetic factors, progression, complications and treatment of this disease. Here we shall review the recent advances in proteomics that have led to an early and better diagnostic approaches in controlling DM 2 more importantly the comparison of structural and functional protein biomarkers that are modified in the diseased state. By applying these advanced and promising proteomic strategies with bioinformatics applications and bio-statistical tools the prevalence of DM 2 and its associated disorders i-e nephropathy and retinopathy are expected to be controlled.