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Biomarker changes in patients with residual disease (RD) after neoadjuvant systemic therapy (NAT) have unclear consequences. This study examined the prevalence of biomarker [hormone receptor (HR) and HER2] change and its effect on disease-free survival (DFS) and overall survival (OS). A total of 303 patients treated with NAT from 2008 to 2016 were identified from a prospective database. Biomarker status at diagnosis was determined and retested after NAT in patients with RD. DFS and OS were compared among three groups: no biomarker change, clinically insignificant change in either ER or PR without alteration in HR status, and clinically significant change in at least one biomarker with resultant change in HR or HER2 status. Subgroups with no change and HR change were examined [HR+HER2− no change, triple negative (TN) no change, HR+HER2− to TN, TN to HR+HER2]. Overall, 61.4% of patients had RD. Of these, 32.8% had changes in at least one biomarker. At median follow up of 5.48 years, no biomarker change was associated with improved DFS compared with changes in HR or HER2 status (p = 0.043). In addition, no biomarker change (p = 0.005) and clinically insignificant changes in biomarker status (p = 0.019) were associated with improved OS compared with clinically significant changes in HR or HER2 status. Among subgroups, HR+HER2− to TN was associated with worse DFS (p = 0.029) and OS (p = 0.008) compared with HR+HER2− no change. Among those with RD, biomarker status change was common and impacted survival in subgroups of HR+ or TN disease. Retesting biomarkers after NAT has prognostic implications.

PURPOSE: The aim of this study is to characterize and compare changes in gene expression patterns of paired axillary lymph node (ALN) metastases from estrogen receptor (ER) positive and triple negative (TNBC) primary breast cancer (PBC). METHODS: Patients with stage 2-3 PBC with macrometastasis to an ALN were selected. Gene expression of 2,567 cancer-associated genes was analyzed with the HTG EdgeSeq system coupled with the Illumina Next Generation Sequencing (NGS) platform. Changes in gene expression between ER/PR positive, HER2 negative PBC and their paired ALN metastases were compared with TNBC and their paired ALN metastases. RESULTS: Fourteen pairs of ER positive and paired ALN metastasis were analyzed. Compared with the PBC, ALN metastasis had 673 significant differentially expressed genes, including 348 upregulated genes and 325 downregulated genes. Seventeen pairs of TNBC and paired ALN metastasis were analyzed. ALN metastasis had 257 significant differentially expressed genes, including 123 upregulated genes and 134 downregulated genes. When gene expression of the ALN for ER positive PBC was compared to that of TNBC, 97 genes were upregulated in both, and 115 genes were similarly downregulated. Common upregulated genes were associated with cell death, necrosis, and homeostasis. Common downregulated genes were those of migration, degradation of extracellular matrix, and invasion. CONCLUSION: Although ER positive PBC and TNBC have a distinct gene expression profiles and distinct changes from PBC to ALN metastases, a significant number of genes are similarly up- or downregulated. Understanding the role of these common genomic changes may provide clues to understanding the metastatic process itself.

Optimum tissue resection volume for patients with invasive breast cancer undergoing breast conserving surgery following neoadjuvant therapy (NAT) is not known. We compared positive margin and in-breast tumor recurrence (IBTR) between 2 groups that were created based on radiologic tumor size (RTS (cm3)) at diagnosis, RTS post-NAT, and volume of tissue resected (VTL): Pre-NAT group, patients with VTL closer to RTS at diagnosis, and post-NAT group, patients with VTL closer to post-NAT RTS. 82 patients with 84 breast cancers treated with NAT between 2007 and 2017 who had pre- and post-NAT imaging were identified from a prospectively maintained database. RTS at diagnosis, RTS post-NAT, and VTL were determined. Clinical and treatment characteristics, IBTR, and disease-free survival (DFS) were compared between pre-NAT (n = 51) and post-NAT (n = 33) groups. Compared to post-NAT patients, pre-NAT patients had smaller RTS at presentation (9.2 vs. 33.5 cm3, P < .001) and post-NAT (1.2 vs. 8.2 cm3, P = .024). At median follow-up of 4 years, there were no differences between groups in pathologic tumor size, positive margin rate, adjuvant therapy, IBTR, or DFS. Resection volumes that matched RTS on post-NAT imaging were not associated with increased positive margins or IBTR. It may be appropriate to use post-NAT imaging to guide lumpectomy volume.

Radioactive seed localization (RSL) and the Savi Scout® radar (SSR) are newer alternatives to wire-guided localization (WL) for nonpalpable breast lesions. The aim of this study was to compare three localization devices when multiple devices were used for preoperative localization for breast surgery. Between July 2017 and July 2018, 68 patients had a partial mastectomy (n = 54) or breast biopsy (n = 14) with preoperative image-guided localization using multiple wires or device placement for nonpalpable lesions. Operative timing, outcomes, and 30-day complications were evaluated. Overall, 41 patients (60%) had WL, 11 patients (16%) had RSL, and 16 patients (24%) had SSR localization. Fifty-four patients (79.4%) had localization of two lesions and 13 patients (19.1%) had localization of three lesions. Twenty-three patients (33.8%) had a lesion that was bracketed. There was no difference in retained biopsy clip among the groups (average 7.4%; p = 0.962). For operations performed in the hospital, there was no difference in operative time among the groups, with a median of 77.5 min (p = 0.705) or total perioperative time of 508 min (p = 0.210). Among operations with delayed start times, there was a longer average delay of 95.5 min in WL, compared with 42 min in SSR (p = 0.004). A greater volume of tissue was excised in the WL group (29.5 g WL vs. 15.9 g RSL vs. 12.1 g SSR; p = 0.022). There was no difference in positive margin rate and 30-day complications among groups. SSR and RSL can be used to localize multiple breast lesions, with no difference in positive margin rates or complications and less tissue excised compared with WL.

BACKGROUND Radioactive seed localization (RSL) and the Savi scout® radar (SSR) are newer alternatives to wire-guided localization (WL) for nonpalpable breast lesions. OBJECTIVE To compare three types of localization devices used in breast conserving surgery. METHODS A total of 293 patients had a partial mastectomy (n = 194) or breast biopsy (n = 99) with preoperative image-guided localization of a single nonpalpable lesion between July 2017 to July 2018. Lesions were localized by WL, RSL, or SSR. Although all operations performed were outpatient, due to workflow differences at our institution, operations performed in the hospital operating rooms were defined as "hospital setting." Operations performed at an outpatient surgery facility without the capacity to admit patients were defined as "ambulatory." Delay in operating room start times and total perioperative times in both the hospital and ambulatory setting, localization time, explant of localization device, positive margins, volume of tissue excised, and 30-day complications were evaluated. RESULTS A total of 126 patients (43%) had WL; 59 patients (20%) had RSL; and 108 patients (37%) had SSR localization. SSR localization took longer to perform with an average time of 19 minutes, compared with 15 minutes for WL and 14 minutes for RSL (P = .020). In 93.52% of cases, the first specimen contained both the clip and localization device, which was similar among groups (P = .073). There was no difference in retained biopsy clip among the groups (average 3.4%, P = .173). For operations performed in the hospital, the time from patient arrival to the preoperative area and incision was significantly longer in the WL group with a median of 233 minutes (range 56-486), 130 minutes (range 64-294) in RSL, and 108 minutes (range 59-240) for SSR (P

Patient-reported outcome measures (PROM) are used to assess value-based care. Little is known as to whether PROM response in breast cancer reflects the diverse patient population. The BREAST-Q, a validated measure of satisfaction and quality of life, and Recovery Tracker, a postoperative assessment tool, are PROM routinely delivered to all patients undergoing breast surgery at our institution. Here we determine whether response to PROM differs by age, race, language, or disease stage.All patients who had a breast operation between January 2020 and July 2021 were requested to complete the BREAST-Q and Recovery Tracker. Non-responders did not complete the PROM at any timepoint; responders completed 1 or more. Primary outcomes included rates of non-response versus response overall.Of 6374 patients identified, 5653 (88.7%) responded to either PROM [4366/4751 (91.9%) BREAST-Q; 2746/3384 (81.1%) Recovery Tracker]. On univariate analysis, non-responders were older (60 years versus 55 years, p0.001) and more often non-English speaking (p0.001), Hispanic ethnicity (p = 0.031), and Black race (p0.001), versus responders. On multivariate analysis, non-responders were significantly more often Black race and non-English speaking (p0.001). Non-English speakers were significantly less responsive among all ethnicities and races except Black race. Although breast cancer stage did not reach significance for response, patients with malignant disease and those receiving neoadjuvant chemotherapy responded more often.Our findings demonstrate high patient engagement using 2 different PROM following breast surgery, but suggest that PROM results may not reflect the experience of the entire breast cancer population. Care process changes based solely on PROM should consider these findings to ensure that the views of the entire spectrum of patients with breast cancer are represented.

Objective Few studies examine the impact of surgical trainee involvement on tumor-free margins in breast conserving surgery (BCS). Our objective was to investigate the impact of resident and fellow involvement on positive margins rates following BCS for invasive breast cancer (BC). Design We identified female patients who had BCS for BC between January 2005 to December 2015. Setting Tertiary care hospital. Participants Around 1089 patients were identified from a prospectively maintained database. Results Of 1089 patients, mean age was 63 (range 43-99) years. Around 768 patients (70.1%) required preoperative localization, and 328 patients (29.9%) had a palpable cancer. Nonpalpable cancers had a smaller volume of specimen tissue excised (p = 0.0005) compared to palpable cancers, and no significant difference was observed in the positive margin rate between the nonpalpable group compared to the palpable group (24.7% nonpalpable vs. 25.3% palpable, p = 0.88). Nonpalpable cancer positive margin rates were 23.9% (n = 102/427) for cases performed by an attending surgeon, 25.0% (n = 15/60) with a junior resident (PGY 2-3), 28.6% (n = 8/28) with a senior resident (PGY 4-5), and 25.7% (n = 65/253) with a fellow, which were not statistically significant (p = 0.89). Palpable cancer positive margin rates were 27.6% (n = 47/170) for cases performed by an attending, 13.9% (n = 5/36) with an intern (PGY-1), 40.9% (n = 9/22) with a junior resident, 0% (n = 0/8) with a senior resident, and 23.9% (n = 22/92) with a fellow, which were also not significantly different (p = 0.07). Conclusion Resident and fellow participation in BCS for BC does not appear to impact the rate of positive margins.

Background and objective With advances in systemic therapies for breast cancer, responses to neoadjuvant chemotherapy (NAC) have increased. Pathologic complete response (pCR) after NAC is an independent prognostic factor. We examined the impact of breast and/or lymph node (LN) pCR on survival. Methods From a prospectively maintained database, 202 women were identified with LN-positive breast cancer who underwent NAC then surgery. Clinicopathologic factors and survival were compared between four groups: breast/LNs pCR, node-only pCR, breast-only pCR, and residual disease (RD). Results Forty-eight (23.8%) patients had breast/LNs pCR, 43 (21.3%) node-only pCR, 5 (2.5%) breast-only pCR, and 106 (52.5%) had RD. There was no difference in age, stage, or breast operation between groups. With a median follow-up of 48.2 months, patients with any pCR had improved disease-free survival (DFS) (HR, 0.3; 95% CI, 0.157-0.572) and OS (HR, 0.192; 95% CI, 0.057-0.652) compared with RD patients. There were no significant differences in DFS (log-rank P = .18) and OS (log-rank P = 0.12) between patients with node-only pCR, breast-only pCR, and breast/LNs pCR. Conclusion In node-positive breast cancer patients receiving NAC, any pCR was associated with improved survival vs RD. The anatomic site of pCR did not impact survival. This suggests that any favorable response to NAC has prognostic value.

The American College of Surgeons Oncology Group (ACOSOG) Z1071 and Sentinel Neoadjuvant (SENTINA) trials of sentinel node biopsy for node-positive breast cancer treated with neoadjuvant chemotherapy (NAC) demonstrated false-negative rates that varied on the basis of surgical technique. This study evaluated trends in axillary operations before and after publication of these trials. This study analyzed patients from National Cancer Database (NCDB) with clinical T0 through T4, N1 and N2, M0 breast cancer who received NAC from 1 January 2012 to 31 December 2015 and sentinel lymph node biopsy (SNB) or axillary lymph node dissection (ALND). The patients were divided into the following groups: SNB, ALND, and (SNB + ALND). Of the 32,036 evaluable patients identified in this study. 5565 had SNB, 19,930 had ALND, and 6541 had SNB + ALND. Compared with the ALND group, the SNB group was younger, had more invasive ductal cancers, and had lower clinical T- and N-stage disease (p

For women with breast cancer in whom multiple Oncotype DX

585 Background: The use of neoadjuvant chemotherapy (NAC) in patients with early-stage breast cancer (EBC) increases the opportunity for genomic testing which can help predict treatment response and optimize outcomes. MammaPrint (MP) classifies tumors as having a Low Risk (LR) or High Risk (HR) of distant recurrence. MP with BluePrint (BP), a molecular subtyping assay, categorize tumors as Luminal A (MP LR), Luminal B (MP HR), HER2, or Basal-Type. Our recent analysis comparing matched pre- and post-NAC tumors found 25% of pre-NAC Luminal B tumors changed to Luminal A post-NAC, which corresponded with improved 5-year outcomes compared with patients who remained Luminal B. Here, we report differential gene expression (DGE) and pathway analyses in these matched tumors that may distinguish the different responses. Methods: Among the patients with EBC who received NAC at Cedars Sinai Medical Center between 2007-2016, 38 with residual disease (RD) had paired pre- and post-NAC tissues. In patients with Luminal tumors, 8 were Luminal B pre- and post-NAC (HR/HR), and 7 were Luminal B pre-NAC but changed to Luminal A post-NAC (HR/LR). Limma R package was used for quantile normalization and DGE analyses. Differentially expressed genes (DEG) with < 0.05 false discovery rate and > 2-fold change were considered significant. Functional pathway enrichment was performed using Metascape. Results: Within HR/LR tumors, a DGE analysis identified 104 DEGs in post-NAC tissues relative to pre-NAC, with changes in cell cycle/proliferation pathways. Interestingly, there was a more robust transcriptional change in HR/HR tumors, with 956 DEGs between post- and pre-NAC samples, with enrichment of extracellular matrix organization, angiogenesis, and wound healing pathways. Notably, immune pathway enrichment was in both HR/LR and HR/HR groups, although the nature of enrichment differed. Immune deconvolution identified significant increases in activated myeloid dendritic cells (DC) and CD8+ T cells in HR/LR but not in HR/HR post-NAC tumors, suggestive of a host immune response. Conclusions: Although post-NAC RD correlates with poor prognosis, even in Luminal tumors, these data suggest gene expression profiling may distinguish a subset with good prognosis. Using matched samples, we assessed the transcriptional differences in tumors that changed MP risk (HR/LR) with tumors that stayed MP HR post-NAC (HR/HR). Overall, HR/HR tumors had a larger transcriptional response with metastatic-related pathway enrichment. Given these patients with HR/HR tumors displayed worse outcomes, pathway changes may indicate resistance and patients may need additional therapy. Differential changes in immune cells between HR/HR and HR/LR tumors were also observed. The activated immune response in HR/LR tumors may be a biomarker for therapy response and improved outcome and will be the focus of further evaluation.

NCCN guidelines discourage the use of staging imaging for newly diagnosed patients with early breast cancer (BC). When performed, incidental radiologic findings of uncertain significance are often encountered. The purpose of this study was to compare incidental findings seen on staging imaging with distant recurrence in patients undergoing neo-adjuvant chemotherapy (NAC). 396 patients with BC who had NAC from 2008 to 2016 were identified from a prospectively maintained data base. Staging imaging was reviewed. Of 396 patients with BC treated with NAC, patients with a positive PET/CT for metastatic disease (n = 36, 9.1%), those that did not undergo staging imaging (n = 49, 12.4%), or those that did not have a reported incidental finding (n = 49, 12.4%) were excluded from analysis. Of the 262 patients who met criteria, mean age was 50 years (range: 26-88). 201 (76.7%) patients had stage I-II cancer, and 61 (23.3%) patients had stage III cancer. Overall, 146 (55.7%) patients had an incidental finding on imaging. 90 (34.4%) patients had one finding, 42 (16.0%) patients had two, and 14 (5.3%) patients had three or more findings. The majority of incidental findings were seen in the ovary/uterus (29.7%), followed by lung (18.4%), liver (10.3%), and bone (9.0%). 5 (3.4%) patients had additional imaging performed. At mean follow-up of 3.7 years (range: 0.7-10.8), 43 (15.6%) patients had a distant recurrence. Of these patients, only 5 (1.9%) patients had distant metastasis in the same organ that was initially thought to be an incidental finding. Our results suggest that breast cancer patients with incidental findings on preoperative staging imaging are unlikely to be indicative of sites for future metastasis.

Due to the low incidence of male breast cancer (BC), there are few studies evaluating outcomes. We evaluated the clinicopathologic features and outcomes of male BC. Male patients with BC from January 2006 to December 2018 were identified. Of 49 patients, mean age was 64 (range 33-94) years. Of the 27 (55.1%) patients who had genetic testing, 9 (33.3%) had a Breast Cancer gene (BRCA) 1 or 2 mutation. The majority of patients had a mastectomy (n = 43/49, 87.8%) and had invasive ductal carcinoma (n = 47/49, 95.9%). 20 patients (n = 20/43, 46.5%) had positive lymph nodes. 41 (n = 41/47, 87.2%) patients had estrogen receptor positive disease. The majority of patients were pathologic stage 2 (n = 21/46, 45.7%), followed by stage 1 (n = 15/46, 32.6%), stage 3 (n = 6/46, 13.0%), and stage 4 (n = 4/46, 8.7%). Eight patients had the 21-gene recurrence score performed. Of patients with stage 1-3 BC, 10 (n = 10/43, 23.3%) patients had recurrence. With median follow-up of 4.1 (range .6-10.6) years, 5-year overall survival was 82.9% and 5-year disease-free survival was 65.9%. In conclusion, our cohort of patients with male BC had a high incidence of BRCA mutations and most commonly had high-grade estrogen positive stage 2 tumors. Breast conserving surgery was utilized in 4% of patients and genomic testing utilized in 55% of patients.

Aim Pedestrian fatalities commonly involve alcohol. We sought to characterize alcohol intoxication among pedestrians struck by vehicles and examine correlations between admission time and injury severity. Methods The Los Angeles County Trauma and Emergency Medicine Information System database was reviewed for pedestrians struck by vehicles over a 16-year period starting January 2000. Subjects aged ≥18 years with available time and day of admission were selected. Patients with available blood alcohol content (BAC) were analyzed and those with positive (+) BAC (≥ 0.01%) were compared with those with negative (−) BAC. The primary outcome was mortality. Result 35 840 patients met criteria, with 12 122 (33.8%) tested for BAC. 71.2% were (+) BAC. The proportion of (+) BAC pedestrians peaked at 02:00 (48.9% of admitted pedestrians, 88.5% of BAC tested pedestrians). Patients with a (+) BAC were more likely hypotensive (3.5% vs 2.7%, P = .019) and admitted with a Glasgow Coma Scale ≤ 8 (9.4% vs 7.1%, P < .001). Overall mortality was 4.6%. Those admitted from 06:00 to 11:00 had the highest odds of mortality in (+) BAC patients (4.7%, adjusted odds ratio 3.16, adjusted P < .001). Conclusion Pedestrians struck by vehicles during late hours are commonly intoxicated. These findings could help legislators to implement changes and strategies to decrease the risk and burden of injury in intoxicated pedestrians.

Biomarker changes in patients with residual disease (RD) after neoadjuvant systemic therapy (NAT) have unclear consequences. This study examined the prevalence of biomarker [hormone receptor (HR) and HER2] change and its effect on disease-free survival (DFS) and overall survival (OS).A total of 303 patients treated with NAT from 2008 to 2016 were identified from a prospective database. Biomarker status at diagnosis was determined and retested after NAT in patients with RD. DFS and OS were compared among three groups: no biomarker change, clinically insignificant change in either ER or PR without alteration in HR status, and clinically significant change in at least one biomarker with resultant change in HR or HER2 status. Subgroups with no change and HR change were examined [HR+HER2- no change, triple negative (TN) no change, HR+HER2- to TN, TN to HR+HER2].Overall, 61.4% of patients had RD. Of these, 32.8% had changes in at least one biomarker. At median follow up of 5.48 years, no biomarker change was associated with improved DFS compared with changes in HR or HER2 status (p = 0.043). In addition, no biomarker change (p = 0.005) and clinically insignificant changes in biomarker status (p = 0.019) were associated with improved OS compared with clinically significant changes in HR or HER2 status. Among subgroups, HR+HER2- to TN was associated with worse DFS (p = 0.029) and OS (p = 0.008) compared with HR+HER2- no change.Among those with RD, biomarker status change was common and impacted survival in subgroups of HR+ or TN disease. Retesting biomarkers after NAT has prognostic implications.

Radioactive seed localization (RSL) and the Savi ScoutThe aim of this study was to compare three localization devices when multiple devices were used for preoperative localization for breast surgery.Between July 2017 and July 2018, 68 patients had a partial mastectomy (n = 54) or breast biopsy (n = 14) with preoperative image-guided localization using multiple wires or device placement for nonpalpable lesions. Operative timing, outcomes, and 30-day complications were evaluated.Overall, 41 patients (60%) had WL, 11 patients (16%) had RSL, and 16 patients (24%) had SSR localization. Fifty-four patients (79.4%) had localization of two lesions and 13 patients (19.1%) had localization of three lesions. Twenty-three patients (33.8%) had a lesion that was bracketed. There was no difference in retained biopsy clip among the groups (average 7.4%; p = 0.962). For operations performed in the hospital, there was no difference in operative time among the groups, with a median of 77.5 min (p = 0.705) or total perioperative time of 508 min (p = 0.210). Among operations with delayed start times, there was a longer average delay of 95.5 min in WL, compared with 42 min in SSR (p = 0.004). A greater volume of tissue was excised in the WL group (29.5 g WL vs. 15.9 g RSL vs. 12.1 g SSR; p = 0.022). There was no difference in positive margin rate and 30-day complications among groups.SSR and RSL can be used to localize multiple breast lesions, with no difference in positive margin rates or complications and less tissue excised compared with WL.

Background Firearm violence results in the death of thousands of children in the US annually. The effects of firearm legislation on gun violence are published but widely contested. Materials and Methods The Kid's Inpatient Database from 2000 to 2009 were queried to capture hospitalizations of children diagnosed with a firearm-related injury. Cases were categorized into five levels of firearm legislation strictness by Brady State Scorecard. Trends of injuries were explored in terms of legislative strength, age, and race. Results 27,566 children analyzed in the study. Most were adolescents aged 15–19 (87.3%), male (89.7%), and black (53.7%). The proportion of accidental injuries increased relative to state law leniency (R2 = 0.90), with highest percentage in lenient states (33.2%) compared to strict (16.7%). The proportion of suicide attempts were higher in states with lenient laws (4.4%) compared to strict (1.3%). Accidents were inversely related to age (59.3% in ages 0–4 compared to 22.0% in adolescents), while assaults were positively related to age (31.6% in ages 0–4 compared to 66.6% in adolescents). Whites were most likely to present with accidental injuries (44.6%), and Blacks and Hispanics with assaults (68.2% and 75.6%). Race (p = 0.009), age (p Conclusions Firearm-related injuries types in hospitalized children are associated with age, race, and state level legislation. Accidents are most prevalent in young children, Whites, and states with lenient gun laws, while suicide attempts are more common in adolescents, Whites, and states with lenient gun laws. Suicide attempts are also associated with the greatest odds of in-hospital mortality. To address firearm violence, consideration should be given to legislation that promote safe gun storage behaviors and restrict firearm accessibility to children.

PURPOSE: Few studies examine the genomics of axillary lymph node (ALN) metastasis in triple negative breast cancer (TNBC). The aim was to characterize and compare gene expression patterns of primary breast cancers and paired ALN metastases. METHODS: Patients with stage 2–3 ER/PR negative, HER2 negative TNBC with ALN macrometastasis without neoadjuvant therapy were selected. Tumor-specific area was isolated from breast and ALN tissue sections. Gene expression of 2,567 cancer-associated genes was analyzed with the HTG EdgeSeq system coupled with Illumina Next Generation Sequencing (NGS). RESULTS: 17 pairs of TNBC and autologous ALN metastasis were analyzed. Compared with the primary, ALN metastasis had 257 statistically significant differentially expressed genes, including 123 upregulated genes and 134 downregulated genes. Notably, there was an upregulation of anti-apoptosis and survival signaling genes (BIRC3, TCL1A, FLT3, VCAM1) in the ALN metastasis. There was also an upregulation of chemotaxis genes (CCL19, CCL21, CXCL13, TNFSF11). The most striking feature is the downregulation of genes known to regulate cell microenvironment interaction (MMP2, MMP 3, MMP 7, MMP 11, MMP14, COL1A1, COL1A2, COL3A1, COL5A1, COL5A2, COL6A6, COL11A1, COL17A1). CONCLUSION: In TNBC, ALN metastases have a distinct gene expression profile. Genes associated with anti-apoptosis, survival responses, and chemotaxis are upregulated, and genes associated with regulation of extracellular matrix are downregulated when compared to autologous primary cancer. TNBC cells metastatic to lymph nodes undergo a change in order to metastasize and survive in the new microenvironment, which may lead to insights into the metastatic process

Flat Epithelia Atypia (FEA) is a proliferative lesion of the breast where cells demonstrate columnar change and cytologic atypia. This lesion has been identified as distinct from the classic atypical hyperplasias (AH). While many patients undergo excisional biopsy, management of FEA identified on core needle biopsy (CNB) is controversial, and the rate of associated ductal carcinoma in situ (DCIS) or invasive cancer is not well defined. The aim of this study was to determine the upstage rate of FEA diagnosed by CNB. We identified patients from a prospectively maintained data base who had FEA diagnosed by CNB from 01/2010 to 07/2015. Patient variables collected included age at presentation, imaging findings, pathologic findings following surgical excision, and subsequent development of breast cancer. Of 132 patients, 62 (n = 62/132, 47.0%) patients had FEA associated with DCIS and invasive ductal carcinoma (IDC) on CNB and were excluded from analysis. Of the remaining 70 patients, median age was 52 (range 31-84) years. Thirty-two (45.7%) patients had FEA plus AH, 4 (5.7%) patients had FEA plus lobular carcinoma in situ (LCIS), and 34 (48.6%) patients had FEA alone or with another non-pathologic finding (pure FEA). Two (6.3%) patients with FEA plus AH had DCIS or IDC on subsequent excisional biopsy. Of the 34 patients with pure FEA who underwent excisional biopsy, only one (2.9%) was found to have IDC. Twenty-two (64.7%) patients with pure FEA who underwent excisional biopsy presented with calcifications on mammography. None of these patients had cancer on excisional biopsy, and 10 (45.5%) patients had AH (3 ADH, 3 ALH, and 4 both ALH and ADH). Twelve (n = 12/34, 35.3%) patients with pure FEA underwent CNB for a mass or asymmetry noted on imaging. Of these 12 patients, 9 (75.0%) had benign findings on excisional biopsy, two (16.7%) patients had AH, and one (8.3%) patient had IDC. Median follow-up was 4.6 years (IQR 3.1-6.5 years). Three (4.3%) patients subsequently developed IDC, two of which were in the contralateral breast. FEA is often found in combination with ADH and ALH as well as carcinoma on CNB. In our study, pure FEA was upstaged to cancer in only 2.9% of patients. Mammographic findings unlikely predict upstaging to malignancy. These findings suggest that excisional biopsy may not be warranted in patients with pure FEA and could be managed with close imaging surveillance.

Radioactive seed localization (RSL) and the Savi scoutTo compare three types of localization devices used in breast conserving surgery.A total of 293 patients had a partial mastectomy (n = 194) or breast biopsy (n = 99) with preoperative image-guided localization of a single nonpalpable lesion between July 2017 to July 2018. Lesions were localized by WL, RSL, or SSR. Although all operations performed were outpatient, due to workflow differences at our institution, operations performed in the hospital operating rooms were defined as "hospital setting." Operations performed at an outpatient surgery facility without the capacity to admit patients were defined as "ambulatory." Delay in operating room start times and total perioperative times in both the hospital and ambulatory setting, localization time, explant of localization device, positive margins, volume of tissue excised, and 30-day complications were evaluated.A total of 126 patients (43%) had WL; 59 patients (20%) had RSL; and 108 patients (37%) had SSR localization. SSR localization took longer to perform with an average time of 19 minutes, compared with 15 minutes for WL and 14 minutes for RSL (P = .020). In 93.52% of cases, the first specimen contained both the clip and localization device, which was similar among groups (P = .073). There was no difference in retained biopsy clip among the groups (average 3.4%, P = .173). For operations performed in the hospital, the time from patient arrival to the preoperative area and incision was significantly longer in the WL group with a median of 233 minutes (range 56-486), 130 minutes (range 64-294) in RSL, and 108 minutes (range 59-240) for SSR (P .001). There was no difference in operative time among the groups with a median of 51 minutes (range 17-122) (P = .108). There was, however, significantly longer perioperative time of 469 minutes (range 210-926) in the WL group compared with 399 minutes (range 240-871) for RSL and 381 minutes (range 232-711) for SSR (P ≤ .001). For the ambulatory setting, although there was no difference in operating time among the groups (median 50 minutes, range 18-127, P = .715), only the RSL showed a decreased perioperative time compared to WL (WL 356 vs RSL 275, P .001; SSR 279, p = NS). A total of 131 patients (44.7%) had same day localizations. Among operations with delayed start times, there was a longer average delay of 85 minutes (range 1-304) for WL group compared with 69 minutes (range 13-219) in RSL and 53 minutes (range 0-228) in SSR (P .001). There was no difference among the three groups in positive margin rate, volume of tissue excised, and 30-day complications.Nonwire localization devices are associated with reduced overall perioperative time compared to wire localization, with few complications.

Guidelines of the American Society of Clinical Oncology (ASCO), the National Comprehensive Cancer Network (NCCN), and the European Society for Medical Oncology (ESMO) discourage the use of imaging to stage newly diagnosed early breast cancer (stages 1 and 2). This study aimed to evaluate preoperative staging imaging rates among patients with stage 1 or 2 breast cancer treated with neoadjuvant chemotherapy (NAC). From a prospectively maintained database, 303 patients with stage 1 or 2 breast cancer who had NAC from 2008 to 2016 were identified. The main outcome measures were the rate and outcomes of staging imaging performed. The mean age of the 303 patients with stage 1 or 2 breast cancer was 51 years (range, 26–87 years). Of these 303 patients, 278 (92.4%) had invasive ductal cancer. 90 (30.2%) had estrogen receptor (ER)-positive disease, 79 (26.5%) had triple-negative disease, and 127 (42.6%) had human epidermal growth factor receptor 2 (HER2)-positive disease. Staging positron emission tomography (PET) or computed tomography (CT) scan was performed for 258 patients (85.2%), brain imaging for 94 patients (31%), bone scans for 117 patients (38.6%), and all three for 48 patients (15.8%). As a result, 15 patients (4.9%) with a positive PET/CT scan were upstaged to stage 4 breast cancer. No difference was observed among the ER-positive (p = 1.000), HER2-positive (p = 0.259), or triple-negative (p = 0.369) receptor profiles of the patients upstaged to stage 4 disease. One patient (1.1%) had positive brain imaging. Five patients (4.3%) had a positive bone scan, and three of these patients (60%) had bone metastasis also shown on the PET/CT scan. Despite guideline recommendations, a high rate of preoperative staging imaging is completed for patients with clinical stage 1 or 2 breast cancer who receive NAC, with few positive results.

565 Background: Sentinel lymph node (SLN) biopsy guides breast cancer treatment and prognostication. To date, there have been few studies examining the genetics of SLN metastasis in triple negative breast cancer (TNBC). The aim of this study is to characterize and compare gene expression patterns of primary breast cancers and autologous matched SLN metastases. Methods: Patients with stage 2-3 ER/PR negative, HER2 negative TNBC with macrometastasis to the SLN who did not have neoadjuvant therapy were selected. The tumor-specific area was isolated from breast and SLN paraffin embedded tissue sections. Gene expression of a panel of 2567 cancer-associated genes was analyzed with the HTG EdgeSeq system coupled with the Illumina Next Generation Sequencing (NGS) platform. Results were validated with RNA-scope assays for RNA in situ detection. Results: 18 pairs of TNBC and matched SLN metastasis were analyzed for 2567 genes. Compared with the primary TNBC, SLN metastasis had 34 statistically significant upregulated genes and 31 downregulated genes. SLN metastasis had at least a 5-fold change (FC) in upregulation in 3 genes and downregulation in 3 genes, compared to primary TNBC [Table]. Notably, there was an upregulation of anti-apoptosis and survival signaling genes (i.e. BIRC3) in the SLN metastasis. There was also an upregulation of chemotaxis genes (CCL13, CXCL19, CXCL21, CXCR5, TNFSF11, p

Introduction High-dose vancomycin is increasingly prescribed for critically ill trauma patients at risk for methicillin-resistant Staphylococcus aureus pneumonia. Although trauma patients have multiple known risk factors for acute kidney injury (AKI), a link between vancomycin and AKI or mortality has not been established. We hypothesize that high vancomycin trough concentration (VT) after trauma is associated with AKI and increased mortality. Methods This was a retrospective analysis from a single institution Level I trauma center. Data were reviewed for all adult trauma patients who were admitted between 2006 and 2010. Patients were included if they received intravenous vancomycin, had serum creatinine levels before and after vancomycin administration, and had at least one recorded VT. Patients were stratified by VT into four groups: VT1 = 0–10 mg/L, VT2 = 10.1–15 mg/L, VT3 = 15.1–20 mg/L, VT4 >20 mg/L. Multivariable logistic regression was performed to determine the association between VT, AKI, and mortality. Results Of the 6781 trauma patients reviewed, 263 (3.9%) fit inclusion criteria. Ninety-seven (36.9%) patients developed AKI and 25 (9.5%) died. AKI and mortality increased progressively with VT. Ninety-one patients (34.6%) had troughs >20 mg/L and VT4 was independently associated with AKI (AOR 4.7, P Conclusion AKI is common in trauma patients who receive intravenous vancomycin. A supratherapeutic trough level of >20 mg/L is an independent predictor of AKI and mortality in trauma patients.

The aim of this study was to assess how increasing age affects mortality in trauma patients with Glasgow Coma Scale (GCS) 3. The Los Angeles County Trauma System Database was queried for all patients aged 20 to 99 years admitted with GCS 3. Mortality was 41.8 per cent for the 3306 GCS 3 patients. Mortality in the youngest patients reviewed, those in the third decade, was 43.5 per cent. After logistic regression analysis, patients in the third decade had similar mortality rates to patients in the sixth (adjusted OR, 0.88; CI, 0.68 to 1.14; P = 0.33) and seventh decades (adjusted OR, 0.96; CI, 0.70 to 1.31; P = 0.79). A significantly lower mortality rate, however, was noted in the fifth decade (adjusted OR, 0.76; CI, 0.61 to 0.95; P = 0.02). Conversely, significantly higher mortality rates were noted in the eighth (adjusted OR, 1.93; CI, 1.38 to 2.71; P = 0.0001) and combined ninth/tenth decades (adjusted OR, 2.47; CI, 1.71 to 3.57; P < 0.0001). Given the high survival in trauma patients with GCS 3 as well as continued improvement in survival compared with historical controls, aggressive care is indicated for patients who present to the emergency department with GCS 3.

Hyperglycemia after traumatic brain injury (TBI) is an independent predictor of mortality. Insulin deficiency, as opposed to elevated blood glucose, might be the reason for increased mortality. TBI patients with diabetes mellitus (DM) were analyzed to determine how insulin deficiency affects mortality after TBI.NTDB version 7 was queried for patients with isolated moderate to severe TBI (head abbreviated injury score [AIS]≥3 with AIS≤3 for other body regions). Demographics and outcomes were compared between TBI patients with insulin-dependent DM (IDDM), noninsulin-dependent DM (NIDDM), and those without DM. Logistic regression analysis was used to investigate the relationship between mortality and DM.Overall, 51,585 patients with isolated moderate to severe TBI were analyzed. Mortality was 14.4% and 8.2% in patients with and without DM, respectively (p0.0001). Although head AIS scores were similar, patients with DM had a statistically higher Glasgow coma scale (GCS) at presentation compared with patients without DM (GCS score 12.4 vs. GCS score 10.9; p0.0001). After multivariable logistic regression analysis, DM was an independent predictor for mortality (odds ratio 1.5, confidence interval 1.29-1.74, p0.0001). When comparing TBI patients with IDDM to NIDDM, mortality was 17.1% for IDDM and 13.0% for NIDDM (p=0.025).DM is a significant predictor for mortality after moderate to severe TBI. Insulin deficiency is a likely contributor to increased mortality after TBI as IDDM patients have higher mortality than NIDDM patients who have higher mortality than no-DM patients.

This protocol introduces researchers to a new model for large-scale bone repair utilizing the mouse rib. The procedure details the following: preparation of the animal for surgery, opening the thoracic body wall, exposing the desired rib from the surrounding intercostal muscles, excising the desired section of rib without inducing a pneumothorax, and closing the incisions. Compared to the bones of the appendicular skeleton, the ribs are highly accessible. In addition, no internal or external fixator is necessary since the adjacent ribs provide a natural fixation. The surgery uses commercially available supplies, is straightforward to learn, and well-tolerated by the animal. The procedure can be carried out with or without removing the surrounding periosteum, and therefore the contribution of the periosteum to repair can be assessed. Results indicate that if the periosteum is retained, robust repair occurs in 1 - 2 months. We expect that use of this protocol will stimulate research into rib repair and that the findings will facilitate the development of new ways to stimulate bone repair in other locations around the body.

BACKGROUND Coagulation abnormalities in critically ill surgical patients cause confusion in administration of venous thromboembolism (VTE) prophylaxis. Pharmaceutical VTE prophylaxis is often withheld because of presumed increased risk for bleeding and assumption that these patients would not benefit from it. Coagulopathic critically ill surgical patients are at risk for VTE and should be treated with chemical prophylaxis. METHODS A retrospective review was performed of all coagulopathic patients (international normalized ration >1.5 or platelets

Recent evidence suggests a survival advantage in trauma patients who receive controlled or hypotensive resuscitation volumes. This study examines the threshold crystalloid volume that is an independent risk factor for mortality after trauma.This study analyzed prospectively collected data from a Level I Trauma Center between January 2000 and December 2008. Demographics and outcomes were compared in elderly (≥70 years) and nonelderly (70 years) trauma patients who received crystalloid fluid in the emergency department (ED) to determine a threshold volume that was an independent predictor for mortality.A total of 3,137 patients who received crystalloid resuscitation in the ED were compared. Overall mortality was 5.2%. Mortality among the elderly population was 17.3% (41 deaths), whereas mortality in the nonelderly population was 4% (116 deaths). After multivariate logistic regression analysis, fluid volumes of 1.5 L or more were significantly associated with mortality in both elderly (odds ratio [OR]: 2.89, confidence interval [CI] [1.13-7.41], p=0.027) and nonelderly patients (OR: 2.09, CI [1.31-3.33], p=0.002). Fluid volumes up to 1 L were not associated with significantly increased mortality. At 3 L, mortality was especially pronounced in the elderly (OR: 8.61, CI [1.55-47.75] p=0.014), when compared with the nonelderly (OR=2.69, CI [1.53-4.73], p=0.0006).ED volume replacement of 1.5 L or more was an independent risk factor for mortality. High-volume resuscitations were associated with high-mortality particularly in the elderly trauma patient. Our finding supports the notion that excessive fluid resuscitation should be avoided in the ED and when required, operative intervention or intensive care admission should be considered.

The clinical need for methods to repair and regenerate large cartilage and bone lesions persists. One way to make new headway is to study skeletal regeneration when it occurs naturally. Cartilage repair is typically slow and incomplete. However, an exception to this observation can be found in the costal cartilages, where complete repair has been reported in humans but the cellular and molecular mechanisms have not yet been characterized. In this study, we establish a novel animal model for cartilage repair using the mouse rib costal cartilage. We then use this model to test the hypothesis that the perichondrium, the dense connective tissue that surrounds the cartilage, is a tissue essential for repair. Our results show that full replacement of the resected cartilage occurs quickly (within 1 to 2 months) and properly differentiates but that repair occurs only in the presence of the perichondrium. We then provide evidence that the rib perichondrium contains a special niche that houses chondrogenic progenitors that possess qualities particularly suited for mediating repair. Label-retaining cells can be found within the perichondrium that can give rise to new chondrocytes. Furthermore, the perichondrium proliferates and thickens during the healing period and when ectopically placed can generate new cartilage. In conclusion, we have successfully established a model for hyaline cartilage repair in the mouse rib, which should be useful for gaining a more detailed understanding of cartilage regeneration and ultimately for developing methods to improve cartilage and bone repair in other parts of the skeleton.

Underage drinking and driving is a national safety issue. We hypothesized students would have lenient thoughts and behaviors about drinking and driving. The aim of our study was to assess current adolescent behavior and attitudes on alcohol use and driving.A survey of 40 multiple choice questions was administered to 11th and 12th grade students at an urban, public high school in Los Angeles, California.Of the 1282 upper class students, 302 completed the survey (127 eleventh graders and 175 twelfth graders; 31% response rate). Overall, 64.2% reported having used alcohol. Significantly more 12th graders than 11th graders had consumed alcohol (71.4% versus 54.3%; P = 0.002); irrespective of gender. Binge drinking was reported by 8.6% of students (11.4% 12th graders vs. 4.7% 11th graders; P = 0.06). Nearly one-half (49.7%) of students indicated they disapproved of binge drinking. Students were more willing to discuss alcohol issues with peers (63.2%) than parents (44.0%) or teachers/counselors (19.5%; P =0.001). Most students (88.1%) indicated they would not drive when they had consumed one to two drinks.Greater than 60% of respondents reported having used alcohol. Students expressed strong concern about alcohol-impaired driving. Binge drinking appears prevalent in high school-aged individuals and increases with age. The lack of communication between students and adults on the topic of alcohol offers opportunity for improvement. Since the number of young drivers injured in alcohol-related crashes remains unacceptably high, more effective prevention strategies are necessary.

The standard practice of irrigation and debridement (ID) of open fractures within 6 hours of injury remains controversial.To prospectively evaluate the effect of the time from injury to the initial ID on infectious complications.A total of 315 patients who were admitted to a level 1 trauma center with open extremity fractures from September 22, 2008, through June 21, 2011, were enrolled in a prospective observational study and followed up for 1 year after discharge (mean [SD] age, 33.9 [16.3] years; 79% were male; and 78.4% were due to blunt trauma). Demographics, mechanism of injury, time to ID, operative intervention, and incidence of local infectious complications were documented. Patients were stratified into 4 groups based on the time of ID (6 hours, 7-12 hours, 13-18 hours, and 19-24 hours after injury). Univariate and multivariable analysis were used to determine the effect of time to ID on outcomes.Development of local infectious complications at early (30 days) or late (30 days and1 year) intervals from admission.The most frequently injured site was the lower extremity (70.2%), and 47.9% of all injuries were Gustilo classification type III. There was no difference in fracture location, degree of contamination, or antibiotic use between groups. All patients underwent ID within 24 hours. Overall, 14 patients (4.4%) developed early wound infections, while 10 (3.2%) developed late wound infections (after 30 days). The infection rate was not statistically different on univariate (6 hours, 4.7%; 7-12 hours, 7.5%; 13-18 hours, 3.1%; and 19-24 hours, 3.6%; P = .65) or multivariable analysis (6-hour group [reference], P = .65; 7- to 12-hour group adjusted odds ratio [AOR] [95% CI], 2.1 [0.4-10.2], P = .37; 13- to 18-hour group AOR [95% CI], 0.8 [0.1-4.5], P = .81; 19- to 24-hour group AOR [95% CI], 1.1 [0.2-6.2], P = .90). Time to ID did not affect the rate of nonunion, hardware failure, length of stay, or mortality.In this prospective analysis, time to ID did not affect the development of local infectious complications provided it was performed within 24 hours of arrival.