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Previous studies established that oral glutamine (GLN) reduced tumor development in implantable and 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer models. This finding was associated with a decrease in tumor glutathione (GSH) levels, while maintaining normal gut, blood, and breast GSH. Alterations in GSH levels contribute to the control of apoptotic and cell cycle-regulating signaling. The aim of this study was to examine the role of dietary GLN on activation of p53 and c-myc, which play critical roles in cancer development and sensitivity to radiation and chemotherapy. Mammary gland carcinomas were induced in rats by DMBA. The rats were gavaged daily with GLN or water (controls), starting 1 wk prior DMBA-application and throughout the duration of the experiment (11 wk after DMBA). Tumor DNA was examined for mutations in p53 exons 5 and 6. Protein and mRNA levels of p53, p21(WAF1/CIP1), PTEN, IGF-IR, mdm2, and c-myc in tumors of GLN-supplemented rats were compared with those of the control rats (received water). The sequencing of p53 showed that it was wild type. Increased phosphorylation of p53, as well as higher mRNA and protein levels of p21(WAF1/CIP1), PTEN, and mdm2, and lower levels of IGF-IR were detected in tumors of GLN-supplemented rats vs. controls. Both phosphorylated c-myc and c-myc mRNA levels were reduced by GLN. The up-regulation of tumor p53 signaling and down-regulation of c-myc, in addition to previously established inhibition of Akt signaling in DMBA-breast cancer model, suggest that dietary GLN could be a useful approach for increasing the effectiveness of cancer treatment. [ABSTRACT FROM AUTHOR]

Objective: Breast cancer (BC) is the leading cause of female cancer death in the world and the second leading cause of female cancer death in the U.S, Mortality from breast cancer is even higher in individuals with schizophrenia. The aim of our project was to evaluate the incidence of breast cancer in women with schizophrenia and to compare outcomes between breast cancer patients who were or were not on antipsychotics prior to diagnosis., Methods: This retrospective study used data from the TriNetX database. Women ≥18 years old diagnosed with schizophrenia were identified. The incidence of primary BC diagnosis between January 2011 and December 2023 was evaluated and stratified by ethnicity. We then conducted a retrospective cohort study to compare outcomes of women ≥18 years who did or did not use antipsychotics one year before BC diagnosis. Patients' propensity score was matched based on age, obesity, tobacco use, socioeconomic status, cancer stage, chemoradiation, axillary lymph node dissection (ALND), sentinel lymph node biopsy (SLNB), and hormone therapy use. Outcomes of interest were 5-year overall survival, recurrence, chemotherapy need, and lymphedema., Results: 1,398,475 women ≥18 years old with schizophrenia were identified. Breast cancer incidence in these patients was 0.53 ​% in 2011 and 0.53 ​% in 2022, with a peak in 2017 (1.29 ​%). Non-Hispanic patients were diagnosed with BC approximately 1.3 times more than Hispanic patients. The outcomes study included 183,062 matched patients, with 91,531 per cohort. 5-year survival with the Kaplan-Meier analysis was significantly greater in women not on antipsychotics (72 ​%) compared to those on antipsychotics (60 ​%), log-rank test p-value <0.0001. The risk of local recurrence (13.4 ​% versus 22.6 ​%, p-value <0.0001), chemotherapy need (41.2 ​% versus 48.4 ​%, p-value <0.0001), and lymphedema (7.7 ​% versus 11.5 ​%, p-value <0.0001) were also significantly lower in women who did not take antipsychotics., Conclusion: Breast cancer incidence in patients with schizophrenia identified through TriNetX has not experienced a significant uptrend or downtrend over the past decade. Non-Hispanic patients with schizophrenia have a higher incidence of BC than Hispanic patients. Matched breast cancer patients on antipsychotics at least one year prior to diagnosis had higher mortality, recurrence, chemotherapy need, and risk of lymphedema., Competing Interests: Declaration of interests The authors have no affiliation with any organization with a direct or indirect financial interest in the subject matter discussed in the manuscript. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare they have no financial interests/personal relationships which may be considered as potential competing interests., (Published by Elsevier Inc.)

Introduction: This study focuses on granulomatous mastitis (GM), a rare inflammatory condition of the breast that has been increasingly diagnosed over the recent years. This research attempts to understand the incidence and prevalence of GM and its treatments., Methods: This is a retrospective study over 9 y (January 2015-December 2023). We utilized the anonymized data collected by TriNetX Analytic Network, a global federated health research network. The database was queried for patients diagnosed with GM and 3058 patients were returned. The incidence and prevalence of GM by age, race, and ethnicity were analyzed. The most common treatments for GM (antibiotics, steroids, incision and drainage, breast excision, and methotrexate) were analyzed., Results: Hispanic and Latinos have a six-fold increased likelihood of developing GM compared to their non-Hispanic and non-Latino counterparts (0.006% compared to 0.001%). Treatment approaches reveal that antibiotics are the primary choice, while methotrexate is less commonly used. Antibiotics showed no significant differences between Hispanics and Latinos when compared to non-Hispanics and non-Latinos. Steroids showed a decreased prevalence in Hispanics and Latinos (P < 0.05). Incision and drainage showed an increased incidence in Hispanics and Latinos (P < 0.05). Excision showed no significant differences between the two groups. Methotrexate showed a higher incidence of usage among Hispanics and Latinos (P < 0.05)., Conclusions: GM has the highest incidence and prevalence among Hispanics and Latinos. Despite that, the treatments do not directly reflect these differences which underscore the need for personalized treatment strategies, particularly among Hispanic or Latino populations, and underscores the importance of further research to elucidate contributing factors to these differences., (Published by Elsevier Inc.)

Importance: Individuals who are incarcerated represent a vulnerable group due to concerns about their ability to provide voluntary and informed consent, and there are considerable legal protections regarding their participation in medical research. Little is known about the quality of surgical care received by this population., Objective: To evaluate perioperative surgical care provided to patients who are incarcerated within the Texas Department of Criminal Justice (TDCJ) and compare their outcomes with that of the general nonincarcerated population., Design, Setting, and Participants: This cohort study analyzed data from patients who were incarcerated within the TDCJ and underwent general or vascular surgery at the University of Texas Medical Branch (UTMB) from 2012 to 2021. Case-specific outcomes for a subset of these patients and for patients in the general academic medical center population were obtained from the American College of Surgeons National Quality Improvement Program (ACS-NSQIP) and compared. Additional quality metrics (mortality index, length of stay index, and excess hospital days) from the Vizient Clinical Data Base were analyzed for patients in the incarcerated and nonincarcerated groups who underwent surgery at UTMB in 2020 and 2021 to provide additional recent data. Patient-specific demographics, including age, sex, and comorbidities were not available for analysis within this data set., Main Outcome and Measures: Perioperative outcomes (30-day morbidity, mortality, and readmission rates) were compared between the incarcerated and nonincarcerated groups using the Fisher exact test., Results: The sample included data from 6675 patients who were incarcerated and underwent general or vascular surgery at UTMB from 2012 to 2021. The ACS-NSQIP included data (2012-2021) for 2304 patients who were incarcerated and 602 patients who were not and showed that outcomes were comparable between the TDCJ population and that of the general population treated at the academic medical center with regard to 30-day readmission (6.60% vs 5.65%) and mortality (0.91% vs 1.16%). However, 30-day morbidity was significantly higher in the TDCJ population (8.25% vs 5.48%, P = .01). The 2020 and 2021 data from the Vizient Clinical Data Base included 629 patients who were incarcerated and 2614 who were not and showed that the incarcerated and nonincarcerated populations did not differ with regard to 30-day readmission (12.52% vs 11.30%) or morbidity (1.91% vs 2.60%). Although the unadjusted mortality rate was significantly lower in the TDCJ population (1.27% vs 2.68%, P = .04), mortality indexes, which account for case mix index, were similar between the 2 populations (1.17 vs 1.12)., Conclusions and Relevance: Findings of this cohort study suggest that patients who are incarcerated have equivalent rates of mortality and readmission compared with a general academic medical center population. Future studies that focus on elucidating the potential factors associated with perioperative morbidity and exploring long-term surgical outcomes in the incarcerated population are warranted.

It is on the backdrop of advances in tumor biology and systemic therapy for breast cancer, that progress in locoregional treatment has focused on management of the breast for invasive cancer, imaging for staging and therapeutic decision-making, and de-escalation in the management of the axilla., (© 2023 The Authors. Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Background: The Focused Assessment with Sonography in Trauma (FAST) exam is an important component to the evaluation of trauma patients. With advances in technology and meeting limitations due to COVID-19, remote instruction and learning have gained popularity. We sought to determine whether remote instruction of FAST exams was feasible as sustainable surgical education and a possible alternative to traditional in-person teaching., Methods: General surgery residents completed a baseline survey and skills assessment on FAST exams and were then randomized to remote or in-person instruction. The remote group participated in an instructional session with a content expert through video conference and then practiced on a simulated mannequin while the expert remotely provided feedback. The in-person group received the experience with the content expert in the room. Both groups completed a post-course survey immediately after the session and a follow-up survey and objective assessment at six-months. Results were compared with two-way analysis of variance (ANOVA)., Results: 14 residents underwent the curriculum, seven in each group. There was a significant increase in self-reported confidence when comparing pre- and immediate post-course results for both the remote and in-person groups. At six months, confidence scores remained elevated and skill assessment scores improved, although the latter did not reach significance. There was no significant difference in post-course results between the groups., Conclusions: Remote instruction of FAST exams was feasible. Pilot data demonstrated an increase in confidence and suggest outcomes that are similar to in-person instruction, which has positive implications for future remote educational and potentially clinical initiatives., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The 21-gene recurrence score (RS) is used to predict benefit from chemotherapy in hormone receptor (HR)-positive breast cancer with one to three positive lymph nodes. Prospective-retrospective studies have shown that the RS is prognostic for both systemic and locoregional recurrence in tamoxifen-treated patients. We aimed to assess whether RS could be utilized to predict a survival benefit from postmastectomy radiation therapy (PMRT)., Patients and Methods: The National Cancer Database (NCDB) was used to identify women ≤ 75 years of age with HR+, HER2-negative, T1-3, N1, M0 breast cancer who underwent mastectomy and axillary staging with available RS during the years 2010-2016. Kaplan-Meier and Cox proportional hazards models were used to identify association between treatment and overall survival (OS). Univariate and multivariate analyses were used to identify variables correlating with PMRT and OS., Results: A total of 8907 patients were identified. Of the total, 3203 (36%) patients received adjuvant PMRT and 5704 (64%) did not. Across the entire cohort, 5-year OS was 97.5% for patients receiving PMRT and 96.8% for those who did not (P = 0.063). After adjusting for all covariates, in patients with RS ≤ 25, there was no statistically significant improvement in 5-year OS with the addition of adjuvant PMRT (97.5% versus 98.1% P = 0.093). Moreover, no survival benefit was seen with axillary node dissection (P = 0.58) or with the addition of chemotherapy (P = 0.312)., Conclusions: In our cohort of patients with one to three positive nodes and a RS ≤ 25, omission of post-mastectomy radiation therapy had no impact on OS. Our results suggest that RS may be utilized in the individualized decision making on PMRT., (© 2023. Society of Surgical Oncology.)

Background: Preoperative localization is necessary for nonpalpable breast lesions. A novel procedure, fluoroscopic intraoperative neoplasm and node detection (FIND), obviates the preoperative painful and potentially expensive localization by using intraoperative visualization of the standard clip placed during diagnostic biopsy. We hypothesized FIND would improve negative margin rates., Study Design: This is an IRB-approved retrospective study (September 2016 to March 2021). Electronic chart review identified breast and axillary node procedures using wire localization (WL) or FIND. Primary outcome was margin status. Secondary outcomes included re-excision rate, specimen weight, surgery time, and axillary node localization rate., Results: We identified 459 patients, of whom 116 (25.3%) underwent FIND and 343 (74.7%) WL. Of these, 68.1% of FIND and 72.0% of WL procedures were for malignant lesions. Final margin positivity was 5.1% (4 of 79) for FIND and 16.6% (41 of 247) for WL (p = 0.008). This difference lost statistical significance on multivariable logistic regression (p = 0.652). Re-excision rates were 7.6% and 14.6% for FIND and WL (p = 0.125), with an equivalent mean specimen weight (p = 0.502), and mean surgery time of 177.5 ± 81.7 and 157.1 ± 66.8 minutes, respectively (mean ± SD; p = 0.022). FIND identified all (29 of 29) targeted axillary nodes, and WL identified only 80.1% (21 of 26) (p = 0.019)., Conclusions: FIND has lower positive margin rates and a trend towards lower re-excision rates compared with WL, proving its value in localizing nonpalpable breast lesions. It also offers accurate localization of axillary nodes, valuable in the era of targeted axillary dissection. It is a method of visual localization, using a skill and equipment surgeons already have, and saves patients and medical systems an additional schedule-disruptive, painful procedure, especially valuable when using novel localization devices is cost-prohibitive., (Copyright © 2023 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background/aim: Gastric linitis plastica (LP) is a rare type of gastric tumor with limited data. We sought to investigate the clinical characteristics, treatment modalities, and outcomes utilizing a national database., Patients and Methods: The National Cancer Database (NCDB) was reviewed for LP of the stomach from 2004 to 2017. Kaplan-Meier analysis and Cox proportional hazards model were utilized to evaluate overall survival and predictors of survival., Results: Out of 222,488 gastric cancer cases, 896 patients with histologically confirmed primary gastric LP were included. Patients were predominantly white (78.5%), female (51.9%) and presented at advanced stage disease (stage 4=69%). A total of 369 (41.2%) patients underwent surgical resection, 520 (58.0%) received chemotherapy and 158 (17.6%) received radiation therapy. The mean OS (overall survival) of the entire cohort was 16.9 months with 1-year and 5-year OS rates of 33% and 5%, respectively. Mean OS for the patients receiving surgery with chemotherapy and/or radiation, surgery alone, chemotherapy and/or radiotherapy alone, and no treatment was 28.4, 17.1, 12.3, and, 8.1 months, respectively (p<0.001). On multivariate cox-regression analysis, advanced-stage disease (stage IV) (p<0.001), no surgical resection (p<0.001), and no receipt of chemotherapy (p<0.001) were associated with increased hazards of death. Over time, the proportion of patients receiving surgical resection (30.7% from 48.3%) and radiation therapy decreased (13.8% from 20.6%) and the use of chemotherapy increased (63.9% from 54.8%)., Conclusion: Gastric LP is associated with a poor prognosis. Multimodal therapy including surgical resection and systemic therapy in the neoadjuvant setting seems to provide the best long-term outcomes., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: There is a growing body of evidence to support tears as a non-traditional biological fluid in clinical laboratory testing. In addition to the simplicity of tear fluid processing, the ability to access key cancer biomarkers in high concentrations quickly and inexpensively is significantly enhanced. Tear fluid is a dynamic environment rich in both proteomic and genomic information, making it an ideal medium for exploring the potential for biological testing modalities., Methods: All protocols involving human subjects were reviewed and approved by the University of Arkansas IRB committee (13-11-289) prior to sample collection. Study enrollment was open to women ages 18 and over from October 30, 2017-June 19, 2019 at The Breast Center, Fayetteville, AR and Bentonville, AR. Convenience sampling was used and samples were age/sex matched, with enrollment open to individuals at any point of the breast health continuum of care. Tear samples were collected using the Schirmer strip method from 847 women. Concentration of selected tear proteins were evaluated using standard sandwich ELISA techniques and the resulting data, combined with demographic and clinical covariates, was analyzed using logistic regression analysis to build a model for classification of samples., Results: Logistic regression analysis produced three models, which were then evaluated on cases and controls at two diagnostic thresholds and resulted in sensitivity ranging from 52 to 90% and specificity from 31 to 79%. Sensitivity and specificity variation is dependent on the model being evaluated as well as the selected diagnostic threshold providing avenues for assay optimization., Conclusions and Relevance: The work presented here builds on previous studies focused on biomarker identification in tear samples. Here we show successful early classification of samples using two proteins and minimal clinical covariates., (© 2022. The Author(s).)

Surgery, radiation, and chemotherapy have all been used to de-escalate the treatment of breast cancer patients. Despite its impact on local recurrence, systemic endocrine therapy (ET) has yet to be de-escalated, even though it has substantial adverse effects and a lower quality of life (QoL) over 5-10 years. The 21-gene recurrence score (RS) and MammaPrint have been used to identify subgroups of younger patients whose long-term survival is unaffected by adjuvant ET. Local treatment only, with de-escalation of long-term systemic ET for patients aged 50-69 with RS < 11, appears not to impact OS and should have an anticipated improvement in QoL., (© 2022. Society of Surgical Oncology.)

Background: Current screening options for colorectal cancer (CRC) are either invasive (colonoscopy) or have lower sensitivity to identify pre-malignant lesions (fecal immunochemical test). We proposed to identify protein profiles in tears of patients with both pre-malignant polyps and CRC; these profiles could have potential as a noninvasive screening test., Method: Colonoscopy patients were divided into "high risk" group (CRC and tubular adenomatous polyp) and "low risk" (normal and hyperplastic polyps). Tear fluids from patients were analyzed by Liquid Chromatography Mass Spectrometry/Mass Spectrometry. The data were analyzed for protein expression, protein-protein interaction and gene set enrichment., Results: The results showed 80 proteins (18 up-regulated and 62 down-regulated) significantly differentiated in "high-risk" compared to "low-risk"; Twenty-eight of these show protein-protein interactions, 9 of which were associated with pathways demonstrated to be altered in CRC patients., Conclusion: Our pilot data, though limited, demonstrated tear protein profiling could distinguish the groups of patients with and without colon lesions., (Published by Elsevier Inc.)

Background: Invasive lobular carcinoma (ILC) is traditionally considered less responsive to chemotherapy. Although the Oncotype recurrence score (RS) has been validated to identify high-risk patients who benefit from chemotherapy, some studies have questioned its relevance in patients with ILC. The objective of this study was to better characterize potential use of the RS in these patients., Methods: The National Cancer Database was used to identify women with stage I through III, T1 through T3, N0 or N1, hormone receptor-positive, HER2-negative ILC or invasive ductal carcinoma (IDC) who had an available RS between 2010 and 2016. Multivariable Cox regression was used to model the effect of variables on 5-year overall survival (OS). The Kaplan-Meier method was used to estimate OS according to the RS, nodal status, and chemotherapy., Results: In total, 15,763 patients with ILC and 100,070 with IDC were identified. The mean age of patients with ILC and IDC was 59.2 ± 9.1 and 57.2 ± 9.8, respectively. A lower percentage of patients with ILC versus those with IDC had a high RS, defined as >25 (6.6% vs 16.0%; P < .0001). ILC patients with a high RS who had N0 or N1 disease received approximately 10% less chemotherapy compared with similar patients who had IDC. The results indicated that the RS had statistically significant prognostic value for patients with ILC. In addition, an absolute OS advantage was correlated with the receipt of chemotherapy by patients with ILC who had a high RS with N0 or N1 disease., Conclusions: Patients with ILC who have a high RS are treated less often with chemotherapy compared with similar patients who have IDC. Nevertheless, the RS has a prognostic as well as a predictive value in ILC, with an association between OS benefit and chemotherapy receipt in patients who have ILC with a high RS, especially if they have N1 disease., Lay Summary: Invasive lobular carcinoma (ILC) is a subtype of breast cancer comprising about 15% of cases. The Oncotype recurrence score (RS) is a genetic test of breast tumors that helps predict which patients might benefit from chemotherapy. Some have doubted the relevance of the RS for patients with ILC. In this study, the authors show that the RS is relevant for patients who have ILC. The RS has the potential of predicting the risk of recurrence and identifying patients with ILC who might benefit from chemotherapy., (© 2022 American Cancer Society.)

The changing expression levels of ocular proteins in response to systemic disease has been well established in literature. In this study, we examined the ocular proteome to identify protein biomarkers with altered expression levels in women diagnosed with breast cancer. Tear samples were collected from 273 participants using Schirmer strip collection methods. Following protein elution, proteome wide trypsin digestion with Liquid chromatography/tandem mass spectrometry (LC-MS/MS) was used to identify potential protein biomarkers with altered expression levels in breast cancer patients. Selected biomarkers were further validated by enzyme linked immunosorbent assay (ELISA). A total of 102 individual tear samples (51 breast cancer, 51 control) were analyzed by LC-MS/MS which identified 301 proteins. Spectral intensities between the groups were compared and 14 significant proteins (p-value <0.05) were identified as potential biomarkers in breast cancer patients. Three biomarkers, S100A8 (p-value = 0.0069, 7.8-fold increase), S100A9 (p-value = 0.0048, 10.2-fold increase), and Galectin-3 binding protein (p-value = 0.01, 3.0-fold increase) with an increased expression in breast cancer patients were selected for validation using ELISA. Validation by ELISA was conducted using 171 individual tear samples (75 Breast Cancer and 96 Control). Similar to the observed LC-MS/MS results, S100A8 (p-value <0.0001) and S100A9 (p-value <0.0001) showed significantly higher expression in breast cancer patients. However, galectin-3 binding protein had increased expression in the control group. Our results provide further support for using tear proteins to detect non-ocular systemic diseases such as breast cancer. Our work provides crucial details to support the continued evaluation of tear samples in the screening and diagnosis of breast cancer and paves the way for future evaluation of the tear proteome for screening and diagnosis of systemic diseases., Competing Interests: This investigation has resulted in the achievement of the following patent. Class, I. P. C., and AG01N3072FI USPC. Daily et al. Methods of Detecting Cancer, US 10,451,625 B2, issued October 22, 2019. AED and PR are employees of Namida Lab Inc. AED is an inventor on the patent and serves as the Vice President of Product Development and Innovation. AED owns shares of Namida Lab Inc. PR serves as the Research and Development Scientist at Namida Lab Inc. SH and VSK are on the clinical advisory board of Namida Lab Inc.

Introduction and Importance: Large chest wall defects in the context of breast cancer or its sequelae can be challenging to address. Oncoplastic techniques have been demonstrated to be safe and feasible options for immediate reconstruction. We describe the use of dual fasciocutaneous flaps for coverage following resection of a large chest wall mass in an area with a remote history of radiation therapy., Case Presentation: A 67-year-old woman with a distant history of bilateral mastectomies and adjuvant chemoradiation for Stage IIB triple negative invasive ductal carcinoma presented with an enlarging left chest wall mass and chronic wound. The mass was excised with adequate margins, and the resulting defect was reconstructed with two locoregional fasciocutaneous flaps. Pathology returned negative for malignancy and follow-up demonstrated viable flaps that were healing well., Clinical Discussion: Fasciocutaneous flaps are one of many techniques for breast reconstruction and offer advantages of a relatively superficial dissection, shorter operative time, and decreased risk of functional impairment. They are consequently an attractive option for patients with multiple comorbidities and high risk of perioperative complications. Historically used for immediate reconstruction at the time of oncologic resection, we present its successful use decades after the index cancer operation to manage a chest wall defect secondary to radiation injury., Conclusions: Oncoplastic reconstruction with dual fasciocutaneous flaps is a feasible option for a large chest wall defect in the setting of previous radiation., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The use of robotics in colorectal surgery has been steadily increasing, however, reported longer operative times and increased cost has limited its widespread adoption. We investigated the cost of elective colorectal surgery based on type of anatomic resection and the impact of a standardized protocol for robotic colectomies. A retrospective review was conducted of 279 elective colectomies at a single institution between 2013 and 2017. Clinical outcomes and detailed cost data were compared based on open, laparoscopic, or robotic surgical approach and stratified by anatomic resection. Robotic, laparoscopic and open colectomy rates were 35, 34 and 31%, respectively. While total costs were similar in robotic and laparoscopic surgery, anatomic resection stratification showed that low anterior resection (LAR) was significantly cheaper ($14,093 vs $17,314). When a standardized surgical protocol was implemented for robotic colectomies, significant reductions in operative times, length of stay, total cost, and operative cost were observed. Robotic surgery may be most cost effective for elective LAR compared to laparoscopic or open approaches. A standardized surgical protocol for robotic surgery may help reduce costs by reducing operative times, operating rooms expenditure, and lengths of stay., (© 2021. The Author(s), under exclusive licence to Springer-Verlag London Ltd. part of Springer Nature.)

Introduction: Breast surgical oncology is a defined sub-specialty of general surgery that focuses on the surgical management of breast disease and malignancy within a multidisciplinary context. The fellowship directors (FD) that lead these programs have been selected for their abilities. As programs do research to ensure proper training for the next generation of breast surgical oncologists, we wanted to look into the FDs responsible for their training., Methods: The Breast Surgical Oncology care program list was compiled via the Society of Surgical Oncology and American Society of Breast Surgeons Accredited programs ( n  = 60). The demographic information that was of interest included, but was not limited to, gender, age, ethnicity/background, past residency training, past fellowship training, year graduated from residency and fellowship, year since graduation to FD appointment, time at institution till FD appointment, and Hirsch index (h-index)., Results: Data were collected on all 60 FDs. The average age of FDs was 52 years old, 27% of FDs are men and 73% of FDs are women. The average H-index, number of publications, and number of citations were 19, 67, and 2648, respectively. The mean graduation year from residency was 2003, and from fellowship was 2006; with a mean of 9 years post fellowship graduation until becoming an FD. The most frequently attended residency was Rush ( n  = 4), and the most common fellowships were Memorial Sloan Kettering ( n  = 8), MD Anderson Cancer Center ( n  = 7), and John Wayne Cancer Institute ( n  = 4). Nine of the FDs stayed at the same institution after doing both residency and fellowship there (15%)., Conclusion: This is the first study to examine the demographics of those in FD positions in Surgical Breast Oncology, which is a relatively young fellowship. We found that FDs in Breast Surgical Oncology are defined by their high output of research. This qualification may be why the average age, and the number of years to FD are higher compared to other specialties where this research has been undertaken. Initial evaluation of FDs suggest more diversity in this field is needed. Further insight into the leaders training our next generation of surgeons is warranted., Competing Interests: Conflict of interestThe authors did not receive support from any organization for the submitted work., (© The Author(s), under exclusive licence to Association for Surgical Education 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: The number of involved lymph nodes negatively affects prognosis in breast cancer patients. Nevertheless, current staging and treatment recommendations do not distinguish between patients with single versus multiple lymphatic micrometastases. In this study, we aim to better characterize these patients., Methods: The National Cancer Database was retrospectively queried to identify 486,800 women with stage I-III, estrogen receptor-positive/progesterone receptor-positive/human epidermal growth factor receptor 2-negative (ER+/PR+/HER2-) breast cancer and nodal status of N0, N1mi with 1 (Nmic1) or more (Nmic > 1) involved nodes, and N1 with 1 involved node (N1.1), from 2010 to 2016. Patients with different nodal statuses were compared regarding treatment characteristics, survival, and benefit from chemotherapy by their 21-gene recurrence score (RS)., Results: Of the 23,072 N1mi patients, 88.3% were Nmic1 and 11.7% were Nmic > 1. Nmic > 1 patients were younger, had larger and higher-grade tumors, with more lymphovascular invasion, and were more commonly treated by axillary dissection, radiation, and chemotherapy than Nmic1 patients. In that, they were comparable with N1.1 patients. Five-year survival of Nmic > 1 patients (88.1%) was worse than Nmic1 patients (90.1%; p = 0.02), but similar to N1.1 patients (87.9%). Nmic1, Nmic > 1, and N1.1 patients with RS 11-25 exhibited a < 2% absolute survival benefit associated with chemotherapy. With RS > 25, Nmic > 1 patients showed a 3.5% benefit, similar to Nmic1 (4.8%) and lower than N1.1 (10.9%) patients., Conclusions: Nmic > 1 breast cancer patients have worse prognoses than Nmic1 patients, similar to N1.1 patients. Our data suggest those patients with RS 11-25 have minimal benefit from chemotherapy. These findings should be taken into account when discussing prognosis and considering chemotherapy in patients with lymphatic micrometastases., (© 2021. Society of Surgical Oncology.)

Background: In 2017, the American Society of Breast Surgeons (ASBrS) published expert panel recommendations for patients at risk for breast cancer-related lymphedema (BCRL) and those affected by BCRL. This study sought to determine BCRL practice patterns., Methods: A survey was sent to 2975 ASBrS members. Questions evaluated members' clinical practice type, practice duration, and familiarity with BCRL recommendations. Descriptive statistics, the chi-square test, and Fisher's exact test were used., Results: Of the ASBrS members surveyed, 390 (13.1%) responded. Most of the breast surgeons (58.5%, 228/390) indicated unfamiliarity with recommendations. Nearly all respondents (98.7%, 385/390) educate at-risk patients. Most (60.2%, 234/389) instruct patients to avoid venipuncture, injection or blood pressure measurements in the at-risk arm, and 35.6% (138/388) recommend prophylactic compression sleeve use during air travel. Nearly all (97.7%, 380/389) encourage those at-risk to exercise, including resistance exercise (86.2%, 331/384). Most do not perform axillary reverse mapping (ARM) (67.9%, 264/389) or a lymphatic preventive healing approach (LYMPHA) (84.9%, 331/390). Most (76.1%, 296/389) screen at-risk patients for BCRL. The most frequently used screening tools include self-reported symptoms (81%, 255/315), circumferential tape measure (54%, 170/315) and bioimpedance spectroscopy (27.3%, 86/315). After a BCRL diagnosis, most (90%, 351/390) refer management to a lymphedema-certified physical therapist. For affected patients, nearly all encourage exercise (98.7%, 384/389). Many (49%, 191/390) refer affected patients for consideration of lymphovenous bypass or lymph node transfer., Conclusion: Most respondents were unfamiliar with the ASBrS expert panel recommendations for patients at risk for BCRL and those affected by BCRL. Opportunities exist to increase awareness of best practices and to acquire ARM and LYMPHA technical expertise., (© 2021. Society of Surgical Oncology.)

Objective: To identify subgroups of hormone receptor-positive (HR+) breast cancer patients that might not benefit from adding endocrine therapy (ET) to their local treatment., Background: De-escalation in breast cancer treatment has included surgery, radiation, and chemotherapy and has often focused on older patient populations. Systemic ET has yet to be de-escalated, though it carries serious side-effects, decreasing quality of life over 5 to 10 years. We hypothesize the 21-gene recurrence score (RS) could identify subgroups of younger patients whose long-term survival is unaffected by adjuvant ET., Methods: The National Cancer Database was used to identify women aged ≥50, with HR+, HER2-negative tumors, ≤3 cm in size, N0 status, and a RS≤25, who underwent breast-conserving surgery in 2010 to 2016. Kaplan-Meier and Cox proportional hazards models were used to identify association between treatment and overall survival (OS)., Results: Of the 45,217 patients identified, 80.6% were 50 to 69 years old. 42,632 (94.3%) patients received ET and 2585 (5.7%) did not. The 5-year OS was 96.4% for patients receiving ET and 93.1% for those who did not (P < 0.001). After adjusting for all covariates, patients aged 50 to 69 with RS < 11 showed no statistically significant improvement in OS when adding ET to surgery, with or without radiation (P = 0.40). With RS 11 to 25, there was a significant improvement of OS with ET plus radiation (P < 0.001)., Conclusions: Local treatment only, with de-escalation of long-term ET, for patients aged 50 to 69 with RS < 11, seems not to impact OS and should have an anticipated quality of life improvement. Prospective studies investigating this approach are warranted., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The Surgical Council on Resident Education (SCORE) curriculum is aligned with the American Board of Surgery (ABS) objectives. Our program adopted the SCORE curriculum in 2015 after poor ABS In-Training Examination (ABSITE) performance and lowest quartile ABS Certifying Exam (CE) and Qualifying Exam (QE) first-time pass rates. We examined the association of SCORE use with ABSITE performance and ABS board exam first-time pass rate., Study Design: At a single institution, a retrospective review of surgery residents' SCORE metrics and ABSITE percentile was conducted for academic years 2015 to 2019. Metrics analyzed on the SCORE web portal were mean total minutes and total visits per resident for all residents using SCORE that year. First-time pass rates of the ABS QE and CE were examined from 2013 to 2019. Chi-square and linear regression analysis were performed, and a 95% level of confidence was assumed (alpha = 0.05)., Results: Yearly data from categorical general surgery residents showed a significant increase in total minutes, total visits, and ABSITE percentile. Combined first time pass rates for the ABS QE and CE significant increased from 70.8% in 2013 to 2015 to 93.9% in 2016 to 2019 (p = 0.018)., Conclusions: Increased longitudinal use of the SCORE curriculum was associated with programmatic improvements in ABSITE performance and ABS board exam first-time pass rate., (Copyright © 2021 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: The 21-gene recurrence score assay (RS) has not been prospectively validated to predict adjuvant chemotherapy benefit in hormone receptor-positive (HR+), HER2-negative (HER2-), node-positive breast cancer patients. Nevertheless, de-escalation based on RS has been demonstrated and partially advocated by retrospective data. The purpose of this study was to identify subgroups of node-positive patients with low to intermediate RS who still benefit from adjuvant chemotherapy., Methods: The National Cancer Database was used to identify 28,591 women with stage I-III, T1-T3, N1, HR+, HER2- breast cancer and a RS ≤ 25 between 2010 and 2016. Univariate and multivariate analyses were used to identify variables correlating with chemotherapy use and 5-year survival. Subgroup analysis was performed to discern patients in whom the use of adjuvant chemotherapy correlated with better survival., Results: A 35% decline in chemotherapy use was observed from 2010 to 2016. Patients with younger age, higher RS, larger tumors and more positive lymph nodes, and those treated by mastectomy, axillary lymph node dissection and radiation, were more likely to receive chemotherapy. Chemotherapy use was associated with an improved 5-year survival (HR = 1.63, 95% CI 1.28-2.07). Upon subgroup analysis, this association was lost in patients > 70 years and those with a RS ≤ 11, while patients ≤ 70 with a RS of 12-25 treated with chemotherapy had an absolute 5-year survival advantage of 3.0% (HR = 1.91, 95% CI 1.42-2.57)., Conclusion: Clinicians should be cautious when considering omission of adjuvant chemotherapy in patients ≤ 70 years, with HR+, HER2-, N1 tumors and a RS 12-25, at least until the results of the anticipated RxPONDER trial become available.

Background: General Surgery residencies use protected education time in various fashions in order to optimize content quality and yield for their learners. This knowledge is tested annually with the American Board for Surgery In-Training Examination (ABSITE) exam and is used to evaluate several aspects of a resident. We hypothesized that using a jeopardy game in educational conference would encourage residents to engage in self-learning and improve ABSITE scores at a single institution., Materials and Methods: At a single institution, during protected education conference, residents played an hour-long surgical jeopardy game every 7 wk to summarize high yield topics discussed during the previous 6 wk of didactic learning. A 5-point Likert survey was completed by general surgery residents to discern the utility of the game format for learning. The ABSITE category scores were also evaluated from the year before and the year after the game was implemented., Results: Twenty-four general surgery residents took the survey with >80% agreeing that the jeopardy format was either a fun or an effective way to learn general surgery topics. Additionally, over 80% of residents thought the game format helped with retention of knowledge. ABSITE categories that had a jeopardy session improved from 65.9% to 70.4% correct (P = 0.0003). ABSITE categories that did not have dedicated jeopardy had a non-significant increase in scores (67.7%-69.9%, P = 0.1)., Conclusions: Implementing surgical jeopardy as a component of educational conferences in general surgery resident training is correlated with improvement of ABSITE scores. Surgical jeopardy may be easily adopted and implemented to stimulate self-directed learning for residents., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The association between proximity to oil refineries and cancer rate is largely unknown. We sought to compare the rate of cancer (bladder, breast, colon, lung, lymphoma, and prostate) according to proximity to an oil refinery in Texas., Methods: A total of 6 302 265 persons aged 20 years or older resided within 30 miles of an oil refinery from 2010 to 2014. We used multilevel zero-inflated Poisson regression models to examine the association between proximity to an oil refinery and cancer rate., Results: We observed that proximity to an oil refinery was associated with a statistically significantly increased risk of incident cancer diagnosis across all cancer types. For example, persons residing within 0-10 (risk ratio [RR] = 1.13, 95% confidence interval [CI] = 1.07 to 1.19) and 11-20 (RR = 1.05, 95% CI = 1.00 to 1.11) miles were statistically significantly more likely to be diagnosed with lymphoma than individuals who lived within 21-30 miles of an oil refinery. We also observed differences in stage of cancer at diagnosis according to proximity to an oil refinery. Moreover, persons residing within 0-10 miles were more likely to be diagnosed with distant metastasis and/or systemic disease than people residing 21-30 miles from an oil refinery. The greatest risk of distant disease was observed in patients diagnosed with bladder cancer living within 0-10 vs 21-30 miles (RR = 1.30, 95% CI = 1.02 to 1.65), respectively., Conclusions: Proximity to an oil refinery was associated with an increased risk of multiple cancer types. We also observed statistically significantly increased risk of regional and distant/metastatic disease according to proximity to an oil refinery., (© The Author(s) 2020. Published by Oxford University Press.)

Background: General surgery resident performance on the American Board of Surgery In-Service Training Exam (ABSITE) has been used to predict American Board of Surgery (ABS) passage rates, selection for remediation programs, and ranking of fellowship applicants. We sought to identify electronic resource study habits of general surgery residents associated with successful test scores., Study Design: A single-institution, retrospective review of general surgery resident use of 2 electronic study resources, Surgical Council on Resident Education (SCORE) and TrueLearn (TL), were evaluated for the 7 months before the 2019 ABSITE. Metrics included TL question performance, SCORE use, and a survey about other reading sources. These metrics were evaluated in 3 ABSITE percentile groupings: ≥80 th , 31 st to 79 th , and ≤30 th ., Results: The ≥80 th and 31 st to 79 th percentile groups scored higher on TL questions, at 69% and 67.7%, respectively, compared with 61.4% for the ≤30 th percentile group (p < 0.03). The ≥80 th percentile group spent on average 14.6 minutes/day on SCORE compared with 5.0 minutes/day and 4.7 minutes/day for the 31 st to 79 th and ≤30 th percentile groups, respectively (p < 0.04). The ≥80 th percentile group spent 34.8 minutes/session (77 sessions) compared with 19.2 minutes/session (49 sessions) and 20.7 minutes/session (43 sessions) in the 31 st to 79 th and ≤30 th percentile groups, respectively (p = 0.009)., Conclusions: Our nomogram incorporates time spent accessing an electronic content-based resource, SCORE, and performance on an electronic question-based resource as a novel method to provide individualized feedback and predict future ABSITE performance., (Published by Elsevier Inc.)

Dysregulation of calcium homeostasis is a major mechanism of doxorubicin (DOX)-induced cardiotoxicity. Treatment with DOX causes activation of sarcoplasmic reticulum (SR) ryanodine receptor (RYR) and rapid release of Ca 2+ in the cytoplasm resulting in depression of myocardial function. The aim of this study was to examine the effect of dantrolene (DNT) a RYR blocker on both the cardiotoxicity and antitumor activity of DOX in a rat model of breast cancer. Female F344 rats with implanted MAT B III breast cancer cells were randomized to receive intraperitoneal DOX twice per week (12 mg/kg total dose), 5 mg/kg/day oral DNT or a combination of DOX + DNT for 3 weeks. Echocardiography and blood troponin I levels were used to measure myocardial injury. Hearts and tumors were evaluated for histopathological alterations. Blood glutathione was assessed as a measure of oxidative stress. The results showed that DNT improved DOX-induced alterations in the echocardiographic parameters by 50%. Histopathologic analysis of hearts showed reduced DOX induced cardiotoxicity in the group treated with DOX + DNT as shown by reduced interstitial edema, cytoplasmic vacuolization, and myofibrillar disruption, compared with DOX-only-treated hearts. Rats treated with DNT lost less body weight, had higher blood GSH levels and lower troponin I levels than DOX-treated rats. These data indicate that DNT is able to provide protection against DOX cardiotoxicity without reducing its antitumor activity. Further studies are needed to determine the optimal dosing of DNT and DOX in a tumor-bearing host., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Metaplastic breast cancer (MBC) is a rare, aggressive variant of breast cancer that has been associated with poor clinical outcomes, as has triple-negative breast (TNBC) cancer. Limited studies compare the clinical characteristics and prognosis of MBC to TNBC. This study uses a large, contemporary US cancer database to compare clinical characteristics and survival outcomes for patients with MBC to those with TNBC., Methods: The National Cancer Database was queried for women with cT1-4N1-3M0 MBC or TNBC diagnosed between 2004 and 2013 and treated with definitive surgery. Chi-squared analysis was performed to determine differences between the cohorts. Kaplan-Meier curves compared overall survival (OS), and Cox regression determined patient factors associated with OS., Results: Altogether, 55,847 patients met the inclusion criteria; 50,705 (90.8%) had TNBC and 5,142 (9.2%) had MBC. Most patients had no comorbid conditions (82%), N0 disease (71%), poorly differentiated histology (77%), received chemotherapy (87%), and received radiation therapy (60%). Amongst all patients, patients with TNBC disease were observed to have greater OS than those with MBC (5-year OS 72.0% vs 55.8%, p < 0.001). The greater observed OS for patients with TNBC persisted when controlling for stage and when comparing propensity score matched cohorts. On Cox regression, lower age, T1 status, N0 status, chemotherapy, TNBC disease, and radiation therapy (RT) were associated with improved OS., Conclusions: MBC had an association with poorer OS compared to TNBC, while RT and chemotherapy receipt were associated with improved OS for patients regardless of stage. Further studies are needed to corroborate the conclusions herein., Competing Interests: Declaration of competing interest The authors have no conflicts of interest. There was no funding for this study. Ethical approval was not required for the present manuscript., (Copyright © 2019 Elsevier Ltd. All rights reserved.)