A Microcosm of Disparities in Breast Cancer: Comparison Between a Private Hospital and a Safety-Net County Hospital Within Los Angeles County.

BACKGROUND: Breast cancer survival is improving due to early detection and treatment advances. However, racial/ethnic differences in tumor biology, stage, and mortality remain. The objective of this study was to analyze presumed disparities at a local level. METHODS: Breast cancer patients at a county hospital and private hospital from 2010 to 2012 were retrospectively reviewed. Demographic, clinical, pathologic, and surgical data were collected. Comparisons were made between hospital cohorts and between racial/ethnic groups from both hospitals combined. RESULTS: 754 patients were included (322 from county hospital and 432 from private hospital). All patients were female. The median age was 54 years at county hospital and 60 years at private hospital (P < .0001). Racial/ethnic minorities comprised 85% of county hospital patients vs. 12% of private hospital patients (P < .0001). County hospital patients had a higher grade, clinical/pathologic stage, HER2-positive rate, and mastectomy rate. Compared to other racial/ethnic groups, non-Hispanic white women were more likely to have lower grade and ER-positive tumors. Hispanic/Latina women were younger and were more likely to have HER2-positive tumors. Both Hispanic/Latina and non-Hispanic black women presented at higher clinical stages and were more likely to undergo neoadjuvant chemotherapy and mastectomy. DISCUSSION: At county hospital compared to private hospital, the proportion of racial/ethnic minorities was higher, and patients presented at younger ages with more aggressive tumors and more advanced disease. The racial/ethnic disparities that were identified locally are largely consistent with those identified in national database studies. These marked differences at hospitals within a diverse city highlight the need for further research into the disparities.

N-myristoyltransferase-1 is necessary for lysosomal degradation and mTORC1 activation in cancer cells.

N-myristoyltransferase-1 (NMT1) catalyzes protein myristoylation, a lipid modification that is elevated in cancer cells. NMT1 sustains proliferation and/or survival of cancer cells through mechanisms that are not completely understood. We used genetic and pharmacological inhibition of NMT1 to further dissect the role of this enzyme in cancer, and found an unexpected essential role for NMT1 at promoting lysosomal metabolic functions. Lysosomes mediate enzymatic degradation of vesicle cargo, and also serve as functional platforms for mTORC1 activation. We show that NMT1 is required for both lysosomal functions in cancer cells. Inhibition of NMT1 impaired lysosomal degradation leading to autophagy flux blockade, and simultaneously caused the dissociation of mTOR from the surface of lysosomes leading to decreased mTORC1 activation. The regulation of lysosomal metabolic functions by NMT1 was largely mediated through the lysosomal adaptor LAMTOR1. Accordingly, genetic targeting of LAMTOR1 recapitulated most of the lysosomal defects of targeting NMT1, including defective lysosomal degradation. Pharmacological inhibition of NMT1 reduced tumor growth, and tumors from treated animals had increased apoptosis and displayed markers of lysosomal dysfunction. Our findings suggest that compounds targeting NMT1 may have therapeutic benefit in cancer by preventing mTORC1 activation and simultaneously blocking lysosomal degradation, leading to cancer cell death.

Unconscious Bias in Speaker Introductions at a Surgical Oncology Meeting: Hierarchy Reigns Over Gender.

BACKGROUND: Recent reviews of medical conferences have shown that women were less likely to receive a formal introduction compared with men. We examined speaker introductions at the Society of Surgical Oncology (SSO) annual meeting to determine whether similar biases exist within our organization. METHODS: An observational study of video-archived speaker introductions at the 2018 and 2019 SSO annual meetings was conducted. Professional address was defined as professional title followed by full name or last name. Multivariable logistic regression was used to identify factors associated with form of address. RESULTS: There were 499 speaker introductions reviewed. Speakers included 290 (58%) men and 238 (49%) post-graduate trainees (residents and fellows). A non-professional form of address was used to introduce 148 (30%) speakers and was most often used for post-graduate trainees (33%). Full professors were more likely than junior faculty to introduce speakers with a non-professional form of address (37% of full professors vs 18% of assistant professors, p < 0.001). In multivariable regression analysis these findings persisted. Trainees were 2.8 times more likely to receive a non-professional form of address (p = 0.003). Use of a non-professional introduction did not significantly vary by the speaker's nor the introducer's gender. CONCLUSIONS: Residents and fellows were more likely to receive a non-professional form of address, and the likelihood of this increased with rising seniority of the introducer. The manner of speaker introduction did not vary by gender in our organization. More research is needed to explore the influence of these disparities on academic advancement for the next generation of surgical oncologists.

Lipomatous Soft Tissue Masses: Challenging the Paradigm of Routine Preoperative Biopsy.

BACKGROUND: Lipomatous masses are the most common soft tissue tumors. While the majority are benign lipomas, it is important to identify those masses that are malignant prior to excision. Current guidelines recommend core needle biopsy (CNB) for all lipomatous masses larger than 3-5 cm. The objective of this study was to determine if routine preoperative CNB based on mass size is necessary, or if radiographic features can guide the need for CNB. MATERIALS AND METHODS: Patients who underwent excision of extremity or truncal lipomatous masses at a single institution from October 2014 to July 2017 were retrospectively reviewed. By protocol, preoperative imaging was routinely obtained for all masses larger than 5 cm. High-risk radiographic features (intramuscular location, septations, nonfat nodules, heterogeneity, and ill-defined margins) and surgical pathology were evaluated to determine patients most likely to benefit from preoperative CNB. RESULTS: Of 178 patients, 2 (1.1%) had malignant tumors on surgical pathology. All masses smaller than 5 cm were benign and, if imaging was obtained, had two or fewer high-risk radiographic features. Both of the patients with malignant tumors had masses larger than 5 cm, preoperative imaging that showed at least four high-risk radiographic features, and underwent CNB prior to excision. CONCLUSIONS: The overall rate of malignancy is very low. The results of this study suggest that lipomatous masses smaller than 5 cm without concerning clinical characteristics do not require preoperative imaging or CNB. Conversely, lipomatous masses larger than 5 cm should undergo routine MRI with subsequent CNB if multiple high-risk radiographic features are present.

Factors associated with general surgery residents' decisions regarding fellowship and subspecialty stratified by burnout and quality of life.

BACKGROUND: Although most surgery residents pursue fellowships, data regarding those decisions are limited. This study describes associations with interest in fellowship and specific subspecialties. METHODS: Anonymous surveys were distributed to 607 surgery residents at 19 US programs. Subspecialties were stratified by levels of burnout and quality of life using data from recent studies. RESULTS: 407 (67%) residents responded. 372 (91.4%) planned to pursue fellowship. Fellowship interest was lower among residents who attended independent or small programs, were married, or had children. Residents who received AOA honors or were married were less likely to choose high burnout subspecialties (trauma/vascular). Residents with children were less likely to choose low quality of life subspecialties (trauma/transplant/cardiothoracic). CONCLUSIONS: Surgery residents' interest in fellowship and specific subspecialties are associated with program type and size, AOA status, marital status, and having children. Variability in burnout and quality of life between subspecialties may affect residents' decisions.