Mammography screening is associated with more favourable breast cancer tumour characteristics and better overall survival: case-only analysis of 3739 Asian breast cancer patients.

BACKGROUND: Early detection of breast cancer (BC) through mammography screening (MAM) is known to reduce mortality. We examined the differential effect that mammography has on BC characteristics and overall survival and the sociodemographic determinants of MAM utilization in a multi-ethnic Asian population. METHODS: This study included 3739 BC patients from the Singapore Breast Cancer Cohort (2010-2018). Self-reported sociodemographic characteristics were collected using a structured questionnaire. Clinical data were obtained through medical records. Patients were classified as screeners (last screening mammogram ≤ 2 years before diagnosis), non-screeners (aware but did not attend or last screen > 2years), and those unaware of MAM. Associations between MAM behaviour (MB) and sociodemographic factors and MB and tumour characteristics were examined using multinomial regression. Ten-year overall survival was modelled using Cox regression. RESULTS: Patients unaware of screening were more likely diagnosed with late stage (ORstage III vs stage I (Ref) [95% CI]: 4.94 [3.45-7.07], p < 0.001), high grade (ORpoorly vs well-differentiated (reference): 1.53 [1.06-2.20], p = 0.022), nodal-positive, large size (OR>5cm vs ≤2cm (reference): 5.06 [3.10-8.25], p < 0.001), and HER2-positive tumours (ORHER2-negative vs HER2-positive (reference): 0.72 [0.53-0.97], p = 0.028). Similar trends were observed between screeners and non-screeners with smaller effect sizes. Overall survival was significantly shorter than screeners in the both groups (HRnon-screeners: 1.89 [1.22-2.94], p = 0.005; HRunaware: 2.90 [1.69-4.98], p < 0.001). Non-screeners and those unaware were less health conscious, older, of Malay ethnicity, less highly educated, of lower socioeconomic status, more frequently ever smokers, and less physically active. Among screeners, there were more reported personal histories of benign breast surgeries or gynaecological conditions and positive family history of breast cancer. CONCLUSIONS: Mammography attendance is associated with more favourable BC characteristics and overall survival. Disparities in the utility of MAM services suggest that different strategies may be needed to improve MAM uptake.

Oncoplastic breast-conserving surgery for women with primary breast cancer.

BACKGROUND: Oncoplastic breast-conserving surgery (O-BCS) involves removing the tumour in the breast and using plastic surgery techniques to reconstruct the breast. The adequacy of published evidence on the safety and efficacy of O-BCS for the treatment of breast cancer compared to other surgical options for breast cancer is still debatable. It is estimated that the local recurrence rate is similar to standard breast-conserving surgery (S-BCS) and also mastectomy, but the aesthetic and patient-reported outcomes may be improved with oncoplastic techniques. OBJECTIVES: Our primary objective was to assess oncological control outcomes following O-BCS compared with other surgical options for women with breast cancer. Our secondary objective was to assess surgical complications, recall rates, need for further surgery to achieve adequate oncological resection, patient satisfaction through patient-reported outcomes, and cosmetic outcomes through objective measures or clinician-reported outcomes. SEARCH METHODS: We searched the Cochrane Breast Cancer Group's Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (via OVID), Embase (via OVID), the World Health Organization's International Clinical Trials Registry Platform and ClinicalTrials.gov on 7 August 2020. We did not apply any language restrictions. SELECTION CRITERIA: We selected randomised controlled trials (RCTs) and non-randomised comparative studies (cohort and case-control studies). Studies evaluated any O-BCS technique, including volume displacement techniques and partial breast volume replacement techniques compared to any other surgical treatment (partial resection or mastectomy) for the treatment of breast cancer. DATA COLLECTION AND ANALYSIS: Four review authors performed data extraction and resolved disagreements. We used ROBINS-I to assess the risk of bias by outcome. We performed descriptive data analysis and meta-analysis and evaluated the quality of the evidence using GRADE criteria. The outcomes included local recurrence, breast cancer-specific disease-free survival, re-excision rates, complications, recall rates, and patient-reported outcome measures. MAIN RESULTS: We included 78 non-randomised cohort studies evaluating 178,813 women. Overall, we assessed the risk of bias per outcome as being at serious risk of bias due to confounding; where studies adjusted for confounding, we deemed these at moderate risk. Comparison 1: oncoplastic breast-conserving surgery (O-BCS) versus standard-BCS (S-BCS) The evidence in the review found that O-BCS when compared to S-BCS, may make little or no difference to local recurrence; either when measured as local recurrence-free survival (hazard ratio (HR) 0.90, 95% confidence interval (CI) 0.61 to 1.34; 4 studies, 7600 participants; very low-certainty evidence) or local recurrence rate (HR 1.33, 95% CI 0.96 to 1.83; 4 studies, 2433 participants; low-certainty evidence), but the evidence is very uncertain due to most studies not controlling for confounding clinicopathological factors. O-BCS compared to S-BCS may make little to no difference to disease-free survival (HR 1.06, 95% CI 0.89 to 1.26; 7 studies, 5532 participants; low-certainty evidence). O-BCS may reduce the rate of re-excisions needed for oncological resection (risk ratio (RR) 0.76, 95% CI 0.69 to 0.85; 38 studies, 13,341 participants; very low-certainty evidence), but the evidence is very uncertain. O-BCS may increase the number of women who have at least one complication (RR 1.19, 95% CI 1.10 to 1.27; 20 studies, 118,005 participants; very low-certainty evidence) and increase the recall to biopsy rate (RR 2.39, 95% CI 1.67 to 3.42; 6 studies, 715 participants; low-certainty evidence). Meta-analysis was not possible when assessing patient-reported outcomes or cosmetic evaluation; in general, O-BCS reported a similar or more favourable result, however, the evidence is very uncertain due to risk of bias in the measurement methods. Comparison 2: oncoplastic breast-conserving surgery (O-BCS) versus mastectomy alone O-BCS may increase local recurrence-free survival compared to mastectomy but the evidence is very uncertain (HR 0.55, 95% CI 0.34 to 0.91; 2 studies, 4713 participants; very low-certainty evidence). The evidence is very uncertain about the effect of O-BCS on disease-free survival as there were only data from one study. O-BCS may reduce complications compared to mastectomy, but the evidence is very uncertain due to high risk of bias mainly resulting from confounding (RR 0.75, 95% CI 0.67 to 0.83; 4 studies, 4839 participants; very low-certainty evidence). Data on patient-reported outcome measures came from single studies; it was not possible to meta-analyse the data. Comparison 3: oncoplastic breast-conserving surgery (O-BCS) versus mastectomy with reconstruction O-BCS may make little or no difference to local recurrence-free survival (HR 1.37, 95% CI 0.72 to 2.62; 1 study, 3785 participants; very low-certainty evidence) or disease-free survival (HR 0.45, 95% CI 0.09 to 2.22; 1 study, 317 participants; very low-certainty evidence) when compared to mastectomy with reconstruction, but the evidence is very uncertain. O-BCS may reduce the complication rate compared to mastectomy with reconstruction (RR 0.49, 95% CI 0.45 to 0.54; 5 studies, 4973 participants; very low-certainty evidence) but the evidence is very uncertain due to high risk of bias from confounding and inconsistency of results. The evidence is very uncertain for patient-reported outcome measures and cosmetic evaluation. AUTHORS' CONCLUSIONS: The evidence is very uncertain regarding oncological outcomes following O-BCS compared to S-BCS, though O-BCS has not been shown to be inferior. O-BCS may result in less need for a second re-excision surgery but may result in more complications and a greater recall rate than S-BCS. It seems that O-BCS may give better patient satisfaction and surgeon rating for the look of the breast, but the evidence for this is of poor quality, and due to lack of numerical data, it was not possible to pool the results of different studies. It seems O-BCS results in fewer complications compared with surgeries involving mastectomy. Based on this review, no certain conclusions can be made to help inform policymakers. The surgical decision for what operation to proceed with should be made jointly between clinician and patient after an appropriate discussion about the risks and benefits of O-BCS personalised to the patient, taking into account clinicopathological factors. This review highlighted the deficiency of well-conducted studies to evaluate efficacy, safety and patient-reported outcomes following O-BCS.

Protection levels of N95-level respirator substitutes proposed during the COVID-19 pandemic: safety concerns and quantitative evaluation procedures.

OBJECTIVE: The COVID-19 pandemic has precipitated widespread shortages of filtering facepiece respirators (FFRs) and the creation and sharing of proposed substitutes (novel designs, repurposed materials) with limited testing against regulatory standards. We aimed to categorically test the efficacy and fit of potential N95 respirator substitutes using protocols that can be replicated in university laboratories. SETTING: Academic medical centre with occupational health-supervised fit testing along with laboratory studies. PARTICIPANTS: Seven adult volunteers who passed quantitative fit testing for small-sized (n=2) and regular-sized (n=5) commercial N95 respirators. METHODS: Five open-source potential N95 respirator substitutes were evaluated and compared with commercial National Institute for Occupational Safety and Health (NIOSH)-approved N95 respirators as controls. Fit testing using the 7-minute standardised Occupational Safety and Health Administration fit test was performed. In addition, protocols that can be performed in university laboratories for materials testing (filtration efficiency, air resistance and fluid resistance) were developed to evaluate alternate filtration materials. RESULTS: Among five open-source, improvised substitutes evaluated in this study, only one (which included a commercial elastomeric mask and commercial HEPA filter) passed a standard quantitative fit test. The four alternative materials evaluated for filtration efficiency (67%-89%) failed to meet the 95% threshold at a face velocity (7.6 cm/s) equivalent to that of a NIOSH particle filtration test for the control N95 FFR. In addition, for all but one material, the small surface area of two 3D-printed substitutes resulted in air resistance that was above the maximum in the NIOSH standard. CONCLUSIONS: Testing protocols such as those described here are essential to evaluate proposed improvised respiratory protection substitutes, and our testing platform could be replicated by teams with similar cross-disciplinary research capacity. Healthcare professionals should be cautious of claims associated with improvised respirators when suggested as FFR substitutes.

Partial Breast Reconstruction with Lateral Chest Wall Perforator Flap to Facilitate Breast Conservation in Breast Cancer: First 100 Cases with Cancer Outcomes at 8 Years Follow-Up and the Lessons Learned.

BACKGROUND: This is a prospective cohort study of partial breast reconstruction (PBR) with a lateral chest wall perforator flap (LCWPF) to facilitate breast conservation surgery (BCS) for women undergoing surgery for breast cancer. The study was undertaken to study the clinical and cancer outcomes. METHODS: Patients diagnosed with ductal carcinoma in situ (DCIS) or breast cancer who consented to undergo BCS with PBR with LCWPF were included in the study. A prospective database has been maintained to collect information on clinico-pathological features, complications, and follow-up. Patients were asked to complete an anonymised PROM questionnaire over the years. The hospital electronic records were interrogated for women who have completed 5 years follow-up to assess for development of recurrence/events. RESULTS: A total of 105 patients underwent PBR with LCWPFs between 2011 and 2018. Of these, 74% underwent cancer resection and PBR as one operation whilst 26% underwent PBR as a two-stage approach. The median tumor size on pre-op imaging was 30 mm for the one-stage approach and 39.5 mm for the two-stage approach (p-value=0.003). The complication rates were low and the re-operation rate for close margins was 10%, with 4% eventually requiring mastectomy. Good-to-excellent esthetic outcomes were reported in more than 80% of cases by patients and clinicians. The local recurrence rate (LR) was 2%, distant recurrence rate 10.5%, disease free survival (DFS) 86%, distant disease-free survival (DDFS) 89% and overall survival (OS) 94.8% at 4.5 years median follow-up. This procedure provides an effective oncological approach, avoiding mastectomy with a good-to-excellent cosmetic outcome. The follow-up data establishes the safety of this approach. DISCUSSION: This is the first published series of recurrence and survival data in patients undergoing PBR. We intend to continue with data collection to assess long-term outcomes beyond 10 years. The authors would recommend consideration of this technique to facilitate BCS and avoid mastectomy. REGISTRATION: Not applicable.

Quantitative Fit Tested N95 Respirator-Alternatives Generated With CT Imaging and 3D Printing: A Response to Potential Shortages During the COVID-19 Pandemic.

RATIONALE AND OBJECTIVE: Three-dimensional (3D) printing allows innovative solutions for personal protective equipment, particularly in times of crisis. Our goal was to generate an N95-alternative 3D-printed respirator that passed Occupational Safety and Health Administration (OSHA)-certified quantitative fit testing during the COVID-19 pandemic. MATERIALS AND METHODS: 3D printed prototypes for N95 solutions were created based on the design of commercial N95 respirators. Computed tomography imaging was performed on an anthropomorphic head phantom wearing a commercially available N95 respirator and these facial contour data was used in mask prototyping. Prototypes were generated using rigid and flexible polymers. According to OSHA standards, prototypes underwent subsequent quantitative respirator fit testing on volunteers who passed fit tests on commercial N95 respirators. RESULTS: A total of 10 prototypes were 3D printed using both rigid (n = 5 designs) and flexible materials (n = 5 designs), Prototypes generated with rigid printing materials (n = 5 designs) did not pass quantitative respirator fit testing. Three of the five prototypes with flexible materials failed quantitative fit testing. The final two prototypes designs passed OSHA-certified quantitative fit tests with an overall mean fit factor of 138 (passing is over 100). CONCLUSION: Through rapid prototyping, 3D printed N95 alternative masks were designed with topographical facial computed tomography data to create mask facial contour and passed OSHA-certified quantitative respiratory testing when flexible polymer was used. This mask design may provide an alternative to disposable N95 respirators in case of pandemic-related shortages. Furthermore, this approach may allow customization for those that would otherwise fail fit testing on standard commercial respirators.

The Results of Surveillance Imaging After Breast Conservation Surgery and Partial Breast Reconstruction With Chest Wall Perforator Flaps; A Qualitative Analysis Compared With Standard Breast-Conserving Surgery for Breast Cancer.

INTRODUCTION: Partial breast reconstruction (PBR) using chest wall perforator flaps (CWPF) allows for excision of tumors in the outer quadrant of the breast in women with small to moderate non-ptotic breasts resulting in a good aesthetic outcome. There are limited data available in the literature regarding long-term follow-up and the effect of CWPF on subsequent surveillance mammographic interpretation and recall rates. A retrospective audit with qualitative analysis of initial mammograms was performed to assess this. PATIENTS AND METHODS: This retrospective analysis of a prospectively maintained database included all consecutive patients who underwent either PBR with CWPF or wide local excision (WLE) between January 2013 and December 2014 by a single surgeon in a tertiary referral center. Qualitative analysis of the postoperative mammograms was performed after review by 2 blinded radiologists. RESULTS: Thirty-six patients were included in the study, 18 in each arm. The CWPF group was younger and had larger tumor size anticipated on preoperative imaging, which correlated with larger specimens excised. Both groups were comparable with respect to tumor pathological characteristics. Comparing the first postoperative mammograms, both groups were similar in features reported such as calcifications, fat necrosis, volume loss, and radiotherapy changes. During the follow-up period (median 4 years), 138 surveillance mammograms were performed. One patient was recalled for further imaging in the CWPF group. There was no significant difference in the need for diagnostic imaging and biopsy between the groups. CONCLUSION: Patients who underwent PBR using CWPF had similar features on postoperative surveillance mammograms compared with that post WLE.

Objective assessment of clinical, oncological and cosmetic outcomes following volume replacement in patients undergoing oncoplastic breast-conserving surgery: protocol for a systematic review.

INTRODUCTION: Oncoplastic breast surgery allows the excision of larger tumours without compromising cosmetic outcome and can be broadly divided into volume displacement and volume replacement techniques. Although oncoplastic surgery has rapidly gained acceptance and is now widely practised, evidence is still lacking especially in patients who underwent volume replacement techniques. As it is a relatively new technique that has been described in the literature in the recent years, a summary of evidence from this literature can help clinicians to understand the clinical, oncologicalandcosmetic outcomes of such procedures. METHODS AND ANALYSIS: All original studies including randomised controlled trials, cohort studies, case-control studies and case series involving more than 10 women undergoing partial breast reconstruction using a volume replacement technique will be included. The primary objective is to evaluate the clinical, oncological and cosmetic outcomes following volume replacement in patients undergoing oncoplastic breast-conserving surgery. The secondary objective is to review the patient-reported outcomes (PROMs) associated with oncoplastic breast surgery to help identify any unmet needs and to consider refining the existing PROMs to suit women undergoing volume replacement surgery.A comprehensive literature search, eligibility assessment and extraction of data will be conducted by two trained teams acting independently. Data will be extracted and stored in a database with standardised extraction fields to facilitate easy and consistent data entry. Heterogeneity will be assessed using the Cochrane tests. ETHICS AND DISSEMINATION: This systematic review requires no ethical approval. It will be published in a peer-reviewed journal, and it will also be presented at nationalandinternational conferences. PROSPERO REGISTRATION NUMBER: CRD42017075700; Pre-results.

Enzyme-Sensitive and Amphiphilic PEGylated Dendrimer-Paclitaxel Prodrug-Based Nanoparticles for Enhanced Stability and Anticancer Efficacy.

In this study, we prepared a smart polymeric vehicle for the hydrophobic drug paclitaxel (PTX) that allowed a maximum steady-state circulation and a fast intracellular release in tumors. PTX was linked to the Janus PEGylated (PEG = poly(ethylene glycol)) peptide dendrimer via an enzyme-sensitive linker glycylphenylalanylleucylglycine tetrapeptide by efficient click reaction, resulting in Janus dendritic prodrug with 20.9% PTX content. The prodrug self-assembled into nanoscale particles with appropriate nanosizes, compact morphology, and negative surface charge. In addition to high stability during circulation, as demonstrated by protein adsorption assays and drug release studies in the cancer's intracellular environment, the nanoparticles were able to quickly release the drug intact in its original molecular structure, as verified via high-performance liquid chromatography and mass spectrometry analyses. Compared to free PTX, the enzyme-responsive feature of nanoparticles promoted higher cytotoxicity against 4T1 cancer cells and much lower cytotoxicity against normal cells. The nanoparticles accumulated in the tumor and were retained for an extended period of time, as confirmed by fluorescence imaging. Therefore, these nanoparticles exhibited significantly enhanced antitumor efficiency in the 4T1 breast cancer model as indicated by the observed inhibition of angiogenesis and proliferation as well as induction of apoptosis. Moreover, the nanoparticles reduced the occurrence of side effects, particularly dose-limited toxicities, as monitored by body weight and hematological features. Hence, our Janus PEGylated dendrimer-PTX prodrug-based nanoparticles may potentially serve as nanoscale vehicles for breast cancer therapy.

Training improves laparoscopic tasks performance and decreases operator workload.

BACKGROUND: It has been postulated that increased operator workload during task performance may increase fatigue and surgical errors. The National Aeronautics and Space Administration-Task Load Index (NASA-TLX) is a validated tool for self-assessment for workload. Our study aims to assess the relationship of workload and performance of novices in simulated laparoscopic tasks of different complexity levels before and after training. METHODS: Forty-seven novices without prior laparoscopic experience were recruited in a trial to investigate whether training improves task performance as well as mental workload. The participants were tested on three standard tasks (ring transfer, precision cutting and intracorporeal suturing) in increasing complexity based on the Fundamentals of Laparoscopic Surgery (FLS) curriculum. Following a period of training and rest, participants were tested again. Test scores were computed from time taken and time penalties for precision errors. Test scores and NASA-TLX scores were recorded pre- and post-training and analysed using paired t tests. One-way repeated measures ANOVA was used to analyse differences in NASA-TLX scores between the three tasks. RESULTS: NASA-TLX score was lowest with ring transfer and highest with intracorporeal suturing. This was statistically significant in both pre-training (p < 0.001) and post-training (p < 0.001). NASA-TLX scores mirror the changes in test scores for the three tasks. Workload scores decreased significantly after training for all three tasks (ring transfer = 2.93, p < 0.001, precision cutting = 3.74, p < 0.001, intracorporeal suturing = 2.98, p < 0.001). CONCLUSION: NASA-TLX score is an accurate reflection of the complexity of simulated laparoscopic tasks in the FLS curriculum. This also correlates with the relationship of test scores between the three tasks. Simulation training improves both performance score and workload score across the tasks.

Mediastinal parathyroid adenomas and their surgical implications.

Primary hyperparathyroidism is a relatively common problem encountered by any endocrine surgical unit. Ectopic parathyroid adenomas have been known to be a common cause of persistent hyperparathyroidism after surgery. A common site of the missed ectopic gland will be that in the mediastinum. However, with the increasing improvement in available imaging, it is likely that this can be diagnosed preoperatively. The surgical approach to the mediastinal parathyroid has also changed vastly over the last decade from maximally invasive to minimally invasive with minimal complications. We provide a review on the entity of mediastinal parathyroid adenomas and their surgical implications.