The impact of cosmetic breast implants on breastfeeding: a systematic review and meta-analysis

Background: Cosmetic breast augmentation (breast implants) is one of the most common plastic surgery procedures worldwide and uptake in high income countries has increased in the last two decades. Women need information about all associated outcomes in order to make an informed decision regarding whether to undergo cosmetic breast surgery. We conducted a systematic review to assess breastfeeding outcomes among women with breast implants compared to women without. Methods: A systematic literature search of Medline, Pubmed, CINAHL and Embase databases was conducted using the earliest inclusive dates through December 2013. Eligible studies included comparative studies that reported breastfeeding outcomes (any breastfeeding, and among women who breastfed, exclusive breastfeeding) for women with and without breast implants. Pairs of reviewers extracted descriptive data, study quality, and outcomes. Rate ratios (RR) and 95% confidence intervals (CI) were pooled across studies using the random-effects model. The Newcastle-Ottawa scale (NOS) was used to critically appraise study quality, and the National Health and Medical Research Council Level of Evidence Scale to rank the level of the evidence. Results: Three small, observational studies met the inclusion criteria. The quality of the studies was fair (NOS 4-6) and the level of evidence was low (III-2 - III-3). There was no significant difference in attempted breastfeeding (one study, RR 0.94, 95%CI 0.76, 1.17). However, among women who breastfed, all three studies reported a reduced likelihood of exclusive breastfeeding amongst women with breast implants with a pooled rate ratio of 0.60 (95%CI 0.40, 0.90). Conclusions: This systematic review and meta-analysis suggests that women with breast implants who breastfeed were less likely to exclusively feed their infants with breast milk compared to women without breast implants.NHMRC, Dr Albert McKern Research Scholarshi

The impact of cosmetic breast implants on breastfeeding: a systematic review and meta-analysis

Background: Cosmetic breast augmentation (breast implants) is one of the most common plastic surgery procedures worldwide and uptake in high income countries has increased in the last two decades. Women need information about all associated outcomes in order to make an informed decision regarding whether to undergo cosmetic breast surgery. We conducted a systematic review to assess breastfeeding outcomes among women with breast implants compared to women without. Methods: A systematic literature search of Medline, Pubmed, CINAHL and Embase databases was conducted using the earliest inclusive dates through December 2013. Eligible studies included comparative studies that reported breastfeeding outcomes (any breastfeeding, and among women who breastfed, exclusive breastfeeding) for women with and without breast implants. Pairs of reviewers extracted descriptive data, study quality, and outcomes. Rate ratios (RR) and 95% confidence intervals (CI) were pooled across studies using the random-effects model. The Newcastle-Ottawa scale (NOS) was used to critically appraise study quality, and the National Health and Medical Research Council Level of Evidence Scale to rank the level of the evidence. Results: Three small, observational studies met the inclusion criteria. The quality of the studies was fair (NOS 4-6) and the level of evidence was low (III-2 - III-3). There was no significant difference in attempted breastfeeding (one study, RR 0.94, 95%CI 0.76, 1.17). However, among women who breastfed, all three studies reported a reduced likelihood of exclusive breastfeeding amongst women with breast implants with a pooled rate ratio of 0.60 (95%CI 0.40, 0.90). Conclusions: This systematic review and meta-analysis suggests that women with breast implants who breastfeed were less likely to exclusively feed their infants with breast milk compared to women without breast implants.NHMRC, Dr Albert McKern Research Scholarshi

Parathyroidectomy for patients with secondary hyperparathyroidism in a changing landscape for the management of end-stage renal disease

Background: The landscape of patients with end-stage renal disease is changing with the increasing availability of kidney transplantation. In the near future, a less aggressive approach to treat secondary hyperparathyroidism might be beneficial. We report outcomes of parathyroidectomy for end-stage renal disease-related hyperparathyroidism comparing the outcomes of limited, subtotal, and total parathyroidectomy. Methods: We performed a retrospective analysis of prospectively collected data. Patients were divided into 3 parathyroidectomy subgroups: limited ( Results: In total, 195 patients were included for analysis of whom 13.8% underwent limited parathyroidectomy, 46.7% subtotal parathyroidectomy, and 39.5% total parathyroidectomy. Preoperative parathyroid hormone levels (pg/mL) were 471 (210-868), 1,087 (627-1,795), and 1,070 (475-1,632) for the limited, subtotal, and total parathyroidectomy groups, respectively (P < .001). A decrease in serum parathyroid hormone was seen in all groups; however, postoperative levels remained greater in the limited parathyroidectomy group compared to the subtotal and total parathyroidectomy groups (P < .001). Serum calcium, phosphate, and alkaline phosphatase levels decreased in all groups to within the reference range. In the limited parathyroidectomy group, persistent disease and recurrence occurred more frequently (P = .02 and P = .07, respectively). Conclusion: Subtotal parathyroidectomy is the optimal strategy in an era with an increasing availability of kidney transplantation and improved regimens of dialysis. In this changing practice, the approach to parathyroid surgery, however, might shift to a less aggressive and patient-tailored approach. (C) 2020 Elsevier Inc. All rights reserved

Surgery alone for papillary thyroid microcarcinoma is less costly and more effective than long term active surveillance

Background: Papillary thyroid microcarcinoma is a subtype of thyroid cancer that may be managed with active surveillance rather than immediate surgery. Active surveillance decreases complication rates and may decrease health care costs. This study aims to analyze complication rates of thyroid surgery, papillary thyroid microcarcinoma recurrence, and survival rates. Additionally, the costs of surgery versus hypothetic active surveillance for papillary thyroid microcarcinoma are compared in an Australian cohort. Methods: Papillary thyroid microcarcinoma patients were included from a prospectively collected surgical cohort of patients treated for papillary thyroid cancer between 1985 and 2017. The primary outcomes were the complications of thyroid surgery, recurrence-free survival, overall survival, and cost of surgical treatment and active surveillance. Results: In a total of 349 patients with papillary microcarcinoma with a median age of 48 years (range, 18–90 years), the permanent operative complications rate was 3.7%. Postoperative radioactive iodine did not decrease recurrence-free survival (P = .3). The total cost of surgical treatment was $10,226 Australian dollars, whereas hypothetic active surveillance was at a yearly cost of$756 Australian dollars. Estimated cost of surgical papillary thyroid microcarcinoma treatment was equivalent to the cost of 16.2 years of active surveillance. Conclusion: Surgery may have a long-term economic advantage for younger Australian patients with papillary thyroid microcarcinoma who are likely to require more than 16.2 years of follow-up in an active surveillance scheme

MET-receptor targeted fluorescent imaging and spectroscopy to detect multifocal papillary thyroid cancer

Purpose: Multifocal disease in PTC is associated with an increased recurrence rate. Multifocal disease (MD) is underdiagnosed with the current gold standard of pre-operative ultrasound staging. Here, we evaluate the use of EMI-137 targeted molecular fluorescence-guided imaging (MFGI) and spectroscopy as a tool for the intra-operative detection of uni- and multifocal papillary thyroid cancer (PTC) aiming to improve disease staging and treatment selection. Methods: A phase-1 study (NCT03470259) with EMI-137 was conducted to evaluate the possibility of detecting PTC using MFGI and quantitative fiber-optic spectroscopy. Results: Fourteen patients underwent hemi- or total thyroidectomy (TTX) after administration of 0.09 mg/kg (n = 1), 0.13 mg/kg (n = 8), or 0.18 mg/kg (n = 5) EMI-137. Both MFGI and spectroscopy could differentiate PTC from healthy thyroid tissue after administration of EMI-137, which binds selectively to MET in PTC. 0.13 mg/kg was the lowest dosage EMI-137 that allowed for differentiation between PTC and healthy thyroid tissue. The smallest PTC focus detected by MFGI was 1.4 mm. MFGI restaged 80% of patients from unifocal to multifocal PTC compared to ultrasound. Conclusion: EMI-137-guided MFGI and spectroscopy can be used to detect multifocal PTC. This may improve disease staging and treatment selection between hemi- and total thyroidectomy by better differentiation between unifocal and multifocal disease. Trial registration: NCT03470259.</p

Intraoperative MET-receptor targeted fluorescent imaging and spectroscopy for lymph node detection in papillary thyroid cancer:novel diagnostic tools for more selective central lymph node compartment dissection

PURPOSE: Patients undergoing prophylactic central compartment dissection (PCLND) for papillary thyroid cancer (PTC) are often overtreated. This study aimed to determine if molecular fluorescence-guided imaging (MFGI) and spectroscopy can be useful for detecting PTC nodal metastases (NM) and to identify negative central compartments intraoperatively. METHODS: We used a data-driven prioritization strategy based on transcriptomic profiles of 97 primary PTCs and 80 normal thyroid tissues (NTT) to identify tumor-specific antigens for a clinically available near-infrared fluorescent tracer. Protein expression of the top prioritized antigen was immunohistochemically validated with a tissue microarray containing primary PTC (n = 741) and NTT (n = 108). Staining intensity was correlated with 10-year locoregional recurrence-free survival (LRFS). A phase 1 study (NCT03470259) with EMI-137, targeting MET, was conducted to evaluate safety, optimal dosage for detecting PTC NM with MFGI, feasibility of NM detection with quantitative fiber-optic spectroscopy, and selective binding of EMI-137 for MET. RESULTS: MET was selected as the most promising antigen. A worse LRFS was observed in patients with positive versus negative MET staining (81.9% versus 93.2%; p = 0.02). In 19 patients, no adverse events related to EMI-137 occurred. 0.13 mg/kg EMI-137 was selected as optimal dosage for differentiating NM from normal lymph nodes using MFGI (p < 0.0001) and spectroscopy (p < 0.0001). MFGI identified 5/19 levels (26.3%) without NM. EMI-137 binds selectively to MET. CONCLUSION: MET is overexpressed in PTC and associated with increased locoregional recurrence rates. Perioperative administration of EMI-137 is safe and facilitates NM detection using MFGI and spectroscopy, potentially reducing the number of negative PCLNDs with more than 25%. CLINICAL TRIAL REGISTRATION: NCT03470259

BRAF V600E Status Sharply Differentiates Lymph Node Metastasis-associated Mortality Risk in Papillary Thyroid Cancer

[Context]: How lymph node metastasis (LNM)-associated mortality risk is affected by BRAF V600E in papillary thyroid cancer (PTC) remains undefined. [Objective]: To study whether BRAF V600E affected LNM-associated mortality in PTC. [Design, Setting, and Participants]: We retrospectively analyzed the effect of LNM on PTC-specific mortality with respect to BRAF status in 2638 patients (2015 females and 623 males) from 11 centers in 6 countries, with median age of 46 [interquartile range (IQR) 35-58] years and median follow-up time of 58 (IQR 26-107) months. [Results]: Overall, LNM showed a modest mortality risk in wild-type BRAF patients but a strong one in BRAF V600E patients. In conventional PTC (CPTC), LNM showed no increased mortality risk in wild-type BRAF patients but a robustly increased one in BRAF V600E patients; mortality rates were 2/659 (0.3%) vs 4/321 (1.2%) in non-LNM vs LNM patients (P = 0.094) with wild-type BRAF, corresponding to a hazard ratio (HR) (95% CI) of 4.37 (0.80-23.89), which remained insignificant at 3.32 (0.52-21.14) after multivariate adjustment. In BRAF V600E CPTC, morality rates were 7/515 (1.4%) vs 28/363 (7.7%) in non-LNM vs LNM patients (P < 0.001), corresponding to an HR of 4.90 (2.12-11.29) or, after multivariate adjustment, 5.76 (2.19-15.11). Adjusted mortality HR of coexisting LNM and BRAF V600E vs absence of both was 27.39 (5.15-145.80), with Kaplan-Meier analyses showing a similar synergism. [Conclusions]: LNM-associated mortality risk is sharply differentiated by the BRAF status in PTC; in CPTC, LNM showed no increased mortality risk with wild-type BRAF but a robust one with BRAF mutation. These results have strong clinical relevance.This work was supported partly by the following funding at the individual participating centers: Polish National Center of Research and Development MILESTONE Project—molecular diagnostics and imaging in individualized therapy for breast, thyroid and prostate cancer, grant No. STRATEGMED2/267398/4/ NCBR/2015 (Poland, AC, BJ); Grants No. PID2019-105303RB-I00 (AEI from MICINN), GCB14142311CRES (AECC Foundation), and B2017/BMD-3724 TIRONET2-CM (Spain; PS and GR-E); Grant No. AZV 16-32665A and MH CZ-DRO (Institute of Endocrinology-EU, 00023761) (Czech Republic; BB, VS); NIH/ National Institute on Aging Grant No. 5R03AG042334-02 (LY); and grants from the Qingdao Science and Technology Project for People’s Livelihood No.13-1-3-58-nsh (China; FW) and the Innovative Platform Project of Qingdao No.12-1-2-15-jch (China; YW)

Association of the Genomic Profile of Medullary Thyroid Carcinoma with Tumor Characteristics and Clinical Outcomes in an International Multicenter Study

Purpose: The prognostic importance of RET and RAS mutations and their relationship to clinicopathologic parameters and outcomes in medullary thyroid carcinoma (MTC) need to be clarified. Experimental Design: A multicenter retrospective cohort study was performed utilizing data from 290 patients with MTC. The molecular profile was determined and associations were examined with clinicopathologic data and outcomes. Results: RET germ line mutations were detected in 40 patients (16.3%). Somatic RET and RAS mutations occurred in 135 (46.9%) and 57 (19.8%) patients, respectively. RETM918T was the most common somatic RET mutation (n = 75). RET somatic mutations were associated with male sex, larger tumor size, advanced American Joint Committee Cancer (AJCC) stage, vascular invasion, and high International Medullary Thyroid Carcinoma Grading System (IMTCGS) grade. When compared with other RET somatic mutations, RETM918T was associated with younger age, AJCC (eighth edition) IV, vascular invasion, extrathyroidal extension, and positive margins. RET somatic or germ line mutations were significantly associated with reduced distant metastasis-free survival on univariate analysis, but there were no significant independent associations on multivariable analysis, after adjusting for tumor grade and stage. There were no significant differences in outcomes between RET somatic and RET germ line mutations, or between RETM918T and other RET mutations. Other recurrent molecular alterations included TP53 (4.2%), ARID2 (2.9%), SETD2 (2.9%), KMT2A (2.9%), and KMT2C (2.9%). Among them, TP53 mutations were associated with decreased overall survival (OS) and disease-specific survival (DSS), independently of tumor grade and AJCC stage. Conclusions: RET somatic mutations were associated with high-grade, aggressive primary tumor characteristics, and decreased distant metastatic-free survival but this relationship was not significant after accounting for tumor grade and disease stage. RETM918T was associated with aggressive primary tumors but was not independently associated with clinical outcomes. TP53 mutation may represent an adverse molecular event associated with decreased OS and DSS in MTC, but its prognostic value needs to be confirmed in future studies

Characteristics of contralateral carcinomas in patients with differentiated thyroid cancer larger than 1 cm

Purpose: Traditionally, total thyroidectomy has been advocated for patients with tumors larger than 1 cm. However, according to the ATA and NCCN guidelines (2015, USA), patients with tumors up to 4 cm are now eligible for lobectomy. A rationale for adhering to total thyroidectomy might be the presence of contralateral carcinomas. The purpose of this study was to describe the characteristics of contralateral carcinomas in patients with differentiated thyroid cancer (DTC) larger than 1 cm. Methods: A retrospective study was performed including patients from 17 centers in 5 countries. Adults diagnosed with DTC stage T1b-T3 N0-1a M0 who all underwent a total thyroidectomy were included. The primary endpoint was the presence of a contralateral carcinoma. Results: A total of 1

MET-receptor targeted fluorescent imaging and spectroscopy to detect multifocal papillary thyroid cancer

Purpose: Multifocal disease in PTC is associated with an increased recurrence rate. Multifocal disease (MD) is underdiagnosed with the current gold standard of pre-operative ultrasound staging. Here, we evaluate the use of EMI-137 targeted molecular fluorescence-guided imaging (MFGI) and spectroscopy as a tool for the intra-operative detection of uni- and multifocal papillary thyroid cancer (PTC) aiming to improve disease staging and treatment selection. Methods: A phase-1 study (NCT03470259) with EMI-137 was conducted to evaluate the possibility of detecting PTC using MFGI and quantitative fiber-optic spectroscopy. Results: Fourteen patients underwent hemi- or total thyroidectomy (TTX) after administration of 0.09 mg/kg (n = 1), 0.13 mg/kg (n = 8), or 0.18 mg/kg (n = 5) EMI-137. Both MFGI and spectroscopy could differentiate PTC from healthy thyroid tissue after administration of EMI-137, which binds selectively to MET in PTC. 0.13 mg/kg was the lowest dosage EMI-137 that allowed for differentiation between PTC and healthy thyroid tissue. The smallest PTC focus detected by MFGI was 1.4 mm. MFGI restaged 80% of patients from unifocal to multifocal PTC compared to ultrasound. Conclusion: EMI-137-guided MFGI and spectroscopy can be used to detect multifocal PTC. This may improve disease staging and treatment selection between hemi- and total thyroidectomy by better differentiation between unifocal and multifocal disease