Racial Disparities in Breast Cancer Genetic Testing May be Mitigated by Counseling.

BACKGROUND: Currently, racial disparities exist in access to genetic testing. Recent developments have helped narrow the gap in accessibility. The purpose of this study was to determine whether racial disparities in genetic consultation attendance and completion of genetic testing persist, and, if so, factors that contribute to under-utilization of these resources. METHODS: A single-institution retrospective review of breast patients referred for genetic counseling between 2017 and 2019 was performed. Univariate and multivariate logistic regression evaluated factors associated with genetic counseling attendance and genetic testing. RESULTS: A total of 596 patients were referred for genetic counseling: 433 (72.7%) white; 138 (23.2%) black; and 25 (4.2%) other or unknown. In multivariate analysis, black patients, patients without breast cancer family history, and patients without a current cancer diagnosis, classified as high risk, were significantly less likely to attend their genetics appointment (p = 0.010, p = 0.007, p = 0.005, respectively). Age, insurance type, distance from facility, and need for chemotherapy did not significantly impact consult completion rate. Of the patients who completed a genetic consult, 84.4% (n = 248) had genetic testing and 17.7% (n = 44) had a pathogenic variant. For patients who attended counseling, there were no significant factors that were predictive with receipt of genetic testing. CONCLUSIONS: In this study, there was a significant association between race and attending genetic counseling. Once counseled, most patients went on to receive genetic testing, and racial disparities in testing disappeared, emphasizing the value of providing additional education about the importance and purpose of genetic testing.

A Supportive Culture Maintains General Surgery Wellness.

Social restrictions during the pandemic required creative solutions for incorporating interns into a demanding residency, building relationships, and fostering resiliency. We hypothesized that resident-driven initiatives focused on inclusion would overcome a lack of in-person events. An anonymous survey was administered to all surgery residents to assess burnout pre- and post-wellness interventions. Assessment scores were analyzed with Mann-U Whitney and Kruskal-Wallis tests. The surveys were completed by 71.6% (n = 53) and 48.6% (n = 36) of residents, respectively, and demonstrated high metrics for wellness measures. There were no significant differences on the 6-month post-assessment, suggesting interventions preserved high ratings. The PGY1 subgroup demonstrated improvement in the ability to identify a faculty mentor (P < .01) and had reduced burnout measures (P < .05). Surgical resident wellness is not dependent on department-wide gatherings; rather, resident-driven interventions in the workspace and intimate social support demonstrated an impact on wellness and reduced burnout.

The anti-proliferative effects of a frankincense extract in a window of opportunity phase ia clinical trial for patients with breast cancer.

PURPOSE: Boswellic acids, active components of frankincense, suppress tumor proliferation in vitro with a strong clinical trial safety profile in patients with inflammatory diseases. We performed a Phase Ia window of opportunity trial of Boswellia serrata (B. serrata) in patients with breast cancer to evaluate its biologic activity and safety. METHODS: Patients with invasive breast cancer were treated pre-operatively with B. Serrata (2400 mg/day PO) until the night before surgery for a median of 11 days (SD 6 days; range: 5-23 days). Paraffin-embedded sections from pretreatment diagnostic core biopsies and post-treatment surgical excisions were evaluated using a tunnel assay and immunohistochemistry staining with Ki-67 antibodies. A non-intervention retrospective control arm consisting of core and surgical tissue specimens from untreated patients was used to compare patients treated with B. Serrata. The change in proliferation and apoptosis between diagnostic core specimens and surgical specimens was compared between the control and treatment groups using a two-tailed paired t-test. RESULTS: Twenty-two patients were enrolled, of which 20 received treatment, and 18 had sufficient tissue for IHC. There was an increase in percent change in proliferation from core biopsy to surgical excision in the control group (n = 18) of 54.6 ± 21.4%. In the B. serrata-treated group there was a reduction in proliferation between core biopsy and excision (n = 18) of 13.8 ± 11.7%. This difference was statistically significant between the control and B. serrata-treated groups (p = 0.008). There was no difference in change in apoptosis. There were no serious adverse events related to the drug. CONCLUSION: Boswellia serrata inhibited breast cancer proliferation and was well-tolerated in a Phase Ia window of opportunity trial.

General surgery applicant perspectives: Two years of virtual interview experiences and supplemental application impressions.

BACKGROUND: We sought to evaluate the unique benefits and challenges the virtual recruitment and interviewing platform had on general surgery residency applicants. METHODS: Applicants who interviewed for a categorical position at our institution during the 2021 and 2022 Match season were contacted to participate in the anonymous online survey focused on applicant behavior related to the virtual interview format. Data were analyzed using chi-square and paired t-tests. RESULTS: A response rate of 56.7 â€‹% (n â€‹= â€‹135) was achieved. Applicants accepted a median of 17 (IQR 13-20) interviews in 2021 and 15 (IQR 11-19) interviews in 2022. More than half (54 â€‹%) of applicants indicated they applied to more programs, and 53 â€‹% accepted more interviews, because of the virtual format. The greatest advantages of the virtual interviews as cited by applicants were saving money (96.3 â€‹%), saving time (49.6 â€‹%), and avoiding travel risks (43.7 â€‹%). The top limitations of virtual interviews were less exposure to current residents and faculty (61.5 â€‹%), to the city or location of the program (58.5 â€‹%), and difficultly comparing programs (57.8 â€‹%). The 2022 Match cycle included use of the supplemental application; however, 85 â€‹% of applicants did not feel that the supplemental improved their overall application. Some applicants (20 â€‹%) who "signaled" programs did not receive an interview offer from any of the programs they signaled. CONCLUSION: The transition to virtual interviews saved applicants time and money but limited their exposure. Future efforts to maintain virtual interviews will need to be balanced against the intangible benefit of human interaction and observing a program's culture.

The impact of nurse navigation on timeliness to treatment for benign high-risk breast pathology.

PURPOSE: High-risk breast pathology is a breast cancer risk factor for which timely treatment is crucial. Nurse navigation programs have been implemented to minimize delays in patient care. This study evaluated nurse navigation in terms of timeliness to surgery for patients with high-risk breast pathology. METHODS: This was a single-institution, retrospective review of patients with identified high-risk breast pathology undergoing lumpectomy between January 2017 and June 2019. Patients were stratified into cohorts based on periods with and without nurse navigation. Preoperative and postoperative time to care as well as demographic and tumor characteristics were compared using univariate and multivariate analysis. RESULTS: 100 patients had assigned nurse navigators and 29 patients did not. Nurse navigation was associated with reduced time from referral to date of surgery (DOS) by 16.9 days (p = 0.003). Patients > 75 years had a shorter time to first appointment (p = 0.03), and patients with Medicare insurance had a reduced time from referral to DOS (p = 0.005). 20% of all patients were upstaged to cancer on final surgical pathology. CONCLUSION: Nurse navigation was significantly associated with decreased time to care for patients with high-risk breast pathology undergoing lumpectomy. We recommend nurse navigation programs as part of a comprehensive approach for patients with high-risk breast pathology.

Factors Associated With Receipt of Molecular Testing and its Impact on Time to Initial Systemic Therapy in Metastatic Non-Small Cell Lung Cancer.

BACKGROUND: Despite recommendations for molecular testing irrespective of patient characteristics, differences exist in receipt of molecular testing for oncogenic drivers amongst metastatic non-small cell lung cancer (mNSCLC) patients. Exploration into these differences and their effects on treatment is needed to identify opportunities for improvement. PATIENTS AND METHODS: We conducted a retrospective cohort study of adult patients diagnosed with mNSCLC between 2011 and 2018 using PCORnet's Rapid Cycle Research Project dataset (n = 3600). Log-binomial, Cox proportional hazards (PH), and time-varying Cox regression models were used to ascertain whether molecular testing was received, and time from diagnosis to molecular testing and/or initial systemic treatment in the context of patient age, sex, race/ethnicity, and multiple comorbidities status. RESULTS: The majority of patients in this cohort were ≤ 65 years of age (median [25th, 75th]: 64 [57, 71]), male (54.3%), non-Hispanic white individuals (81.6%), with > 2 comorbidities in addition to mNSCLC (54.1%). About half the cohort received molecular testing (49.9%). Patients who received molecular testing had a 59% higher probability of initial systemic treatment than patients who were yet to receive testing. Multiple comorbidity status was positively associated with receipt of molecular testing (RR, 1.27; 95% CI 1.08, 1.49). CONCLUSION: Receipt of molecular testing in academic centers was associated with earlier initiation of systemic treatment. This finding underscores the need to increase molecular testing rates amongst mNSCLC patients during a clinically relevant period. Further studies to validate these findings in community centers are warranted.

Targeting protein tyrosine phosphatases for CDK6-induced immunotherapy resistance.

Elucidating the mechanisms of resistance to immunotherapy and developing strategies to improve its efficacy are challenging goals. Bioinformatics analysis demonstrates that high CDK6 expression in melanoma is associated with poor progression-free survival of patients receiving single-agent immunotherapy. Depletion of CDK6 or cyclin D3 (but not of CDK4, cyclin D1, or D2) in cells of the tumor microenvironment inhibits tumor growth. CDK6 depletion reshapes the tumor immune microenvironment, and the host anti-tumor effect depends on cyclin D3/CDK6-expressing CD8+ and CD4+ T cells. This occurs by CDK6 phosphorylating and increasing the activities of PTP1B and T cell protein tyrosine phosphatase (TCPTP), which, in turn, decreases tyrosine phosphorylation of CD3ζ, reducing the signal transduction for T cell activation. Administration of a PTP1B and TCPTP inhibitor prove more efficacious than using a CDK6 degrader in enhancing T cell-mediated immunotherapy. Targeting protein tyrosine phosphatases (PTPs) might be an effective strategy for cancer patients who resist immunotherapy treatment.

Step 1 is Pass/Fail, Now What? Can Clinical Clerkship Grades be Used as a Reliable Metric to Screen General Surgery Residency Applicants?

INTRODUCTION: For decades, the three-digit United States Medical Licensing Exam Step 1 score has been used to competitively evaluate and compare candidates during the residency application process. Starting in 2022, however, all Step 1 scores will be converted to pass/fail. A different quantitative measure will likely gain importance in its stead, one such being clerkship performance grades. This study aims to determine the consistency of class rank and distribution of clerkship grades reported by medical schools for applicants to a general surgery program. METHODS: Candidates' Medical Student Performance Evaluation letters from 141 unique US allopathic medical schools were reviewed for student overall class rank, the number of grading tiers in each clerkship, and the percent achieving honors criteria in each clerkship from the 2020 application cycle. Comparative analysis was performed by region and medical school prestige. RESULTS: Most medical schools rank students using a four-tier system (e.g., fail, pass, high pass, and honors). A third of schools do not provide an overall class rank of students (34.7% of schools); this was most prevalent in the Northeast and Western regions. Schools in the Central US more often rank their students in five tiers compared to the South (P < 0.01). The percent of students that achieve the highest grading tier varies across the core clerkships (mean 37.1%, range 6.5%-78%); an average of 34.5% of students meet the highest honors tier in their Surgery clerkship. Students at US News and World Report Top 20 medical schools are more likely to receive the highest honors tier, across all core clerkships and overall class rank, than students at schools outside the Top 20 (P < 0.05). CONCLUSIONS: In the absence of the United States Medical Licensing Exam Step 1 score, the variability in clerkship grading tiers and overall class rank will likely pose a challenge to residency programs' ability to stratify desirable applicants. Further transparency and standardization may be required to compare students objectively and fairly from medical schools across the country.

The Perioperative Patient Experience During COVID-19.

BACKGROUND: Access to elective surgical procedures has been impacted by the COVID-19 pandemic. METHODS: We sought to understand the patient experience by developing and distributing an anonymous online survey to those who underwent non-emergency surgery at a large academic tertiary medical center between March and October 2020. RESULTS: The survey was completed by 184 patients; the majority were white (84%), female (74.6%), and ranged from 18 to 88 years old. Patients were likely unaware of case delay as only 23.6% reported a delay, 82% of which agreed with that decision. Conversely, 44% felt that the delay negatively impacted their quality of life. Overall, 82.7% of patients indicated high satisfaction with their care. African American patients more often indicated a "neutral" vs "satisfactory" hospital experience (P < .05) and considered postponing their surgery (P < .01). Interestingly, younger patients (<60) were more likely than older (≥60) patients to note anxiety associated with having surgery during the pandemic (P < .01), feeling unprepared for discharge (P < .02), not being allowed visitors (P < .02), and learning about the spread of COVID-19 from health care providers (P < .02). DISCUSSION: These results suggest that patients are resilient and accepting of changes to health care delivery during the current pandemic; however, certain patient populations may have higher levels of anxiety which could be addressed by their care provider. These findings can help inform and guide ongoing and future health care delivery adaptations in response to care disruptions.

General surgery applicants report the impact of virtual interviews on their rank list and match.

Purpose: The transition to an all-virtual application cycle for General Surgery Match 2021 significantly altered interview day and the interactions of applicants with residency programs. We sought to evaluate the impact of a virtual match cycle on applicants' rank list and Match results. Methods: We surveyed applicants who were offered an interview for a categorical general surgery residency position at our institution during the 2021 match season. Voluntary anonymous surveys were sent after the rank list deadline and again after the Match. Results: Out of 108 interviewees, 43 completed the survey (40%). Median age was 26, and 61% of respondents were male and 82% white, which skewed from our diverse interview pool. They completed a median of 17 interviews. 69% felt they had sufficient exposure to make their rank list, and this group reached statistically significant higher confidence in their decisions when compared with those who endorsed not having enough exposure to the residency programs (58% vs 42%, p = 0.02). Applicants cited the most influential interview day factors to be their interview with faculty and the virtual social with residents. Least important was their ability to assess the hospital facility. Among seven different program factors, comradery between faculty and residents (31%) and perceived happiness of the residents (18.6%) were most often selected most influential. Only 56% reported ranking all programs at which they interviewed. After submitting their rank list, 59% of applicants stated they had not visited the city of their top ranked program; however, post-match surveys revealed only 44% matched to a program in a city unknown to them. 57% of applicants stated they reached out to their top choice program with additional questions, but only 47% matched at one of those institutions. Conclusions: Even in the constraints of the virtual interviews, most applicants felt they had sufficient exposure to programs to make their rank list. Applicants were willing to highly rank cities they had never visited and to reach out to programs but were ultimately less successful matching at those programs. Understanding what factors and communications most impact applicants and programs may lead to a more successful Match. Supplementary Information: The online version contains supplementary material available at 10.1007/s44186-022-00071-8.

Prognostic factors for residual occult disease in shave margins during partial mastectomy.

PURPOSE: Shave margins have been shown to decrease positive final margins in partial mastectomy. We investigated prognostic factors associated with residual disease in shave margins. METHODS: Patients with invasive breast carcinoma and ductal carcinoma in situ (DCIS) who had circumferential shave margins excised during lumpectomy were abstracted from a retrospective database from 2015 to 2018. We defined residual occult disease (ROD) as either (1) residual disease in a shave margin when the initial lumpectomy specimen had negative margins or (2) residual disease in a shave margin that did not correspond with the positive lumpectomy margin. We identified the frequency of ROD and conducted logistic regression analysis to identify associated prognostic factors. RESULTS: 166 Patients (139 invasive carcinoma, 27 DCIS) were included with median follow-up of 28 months (9-50 months). Residual occult disease existed in 34 (24.5%) with invasive carcinoma and 8 (29.6%) with DCIS. In univariate analyses of the invasive group, invasive lobular carcinoma and a positive initial, non-corresponding lumpectomy margin were predictive of ROD (OR 3.63, p = 0.04, OR 3.48, p = 0.003 respectively). In multivariate analysis, a positive lumpectomy margin remained significant, p = 0.007. No variables were associated with ROD in DCIS. CONCLUSION: Residual occult disease was shown to be a frequent event in this analysis of lumpectomy with circumferential shave margins. Having a positive initial lumpectomy margin was predictive of ROD in a non-corresponding margin. Surgeons should consider not being selective in their shave margins or margin of re-excision if shave margins were not obtained in their initial surgery.

A Multifaceted Approach to Opioid Education, Prescribing, and Disposal for Patients with Breast Cancer Undergoing Surgery.

BACKGROUND: Standardized prescribing practices are recommended to decrease opioid abuse, however, data regarding the handling and disposal of leftover narcotics are lacking. This quality improvement project and analysis evaluated implementation of standardized prescribing, opioid education, and a narcotic disposal system. METHODS: This initiative was implemented over a 1-y period among patients who underwent breast surgery. The project included the following: 1) implementation of standardized prescribing, 2) voluntary and anonymous survey analysis, and 3) preoperative education regarding risks of opioids, charcoal disposal bag distribution, and follow-up survey to assess use and use of intervention. RESULTS: Preintervention surveys were completed by 53 patients, and 60% (n = 32) underwent lumpectomy. Narcotic prescriptions were filled by 90%; median number of pills taken was 3 (range 0-24), however 93% felt that a non-narcotic was more effective. Eighty three percentage of patients had unused pills, and 58% kept these pills in an unlocked cabinet. Postintervention surveys were completed by 66 patients, and 48% (n = 32) underwent lumpectomy. Narcotic prescriptions were filled by 88%, median number of pills taken was 4 (range 0-40), and 89% of patients had pills leftover. Sixty seven percentage of patients found the education handout useful and charcoal bag use was reported by 37% (n = 17). The median postoperative pain control satisfaction score was 4.5 (5-point Likert scale, 1 = very dissatisfied, 5 = very satisfied) on both preintervention and postintervention surveys. CONCLUSIONS: This study, which included standardized prescribing parameters, opioid education, and implementation of a disposal method, was found to be feasible, beneficial, and did not compromise postoperative pain control.

Resident-Driven Wellness Initiatives Improve Resident Wellness and Perception of Work Environment.

BACKGROUND: Resident burnout is associated with increased adverse patient events and increased incidence of resident depression and suicide when compared to the general population. We hypothesized that resident-driven assessment and implementation of wellness measures would allow implementation of desired interventions and facilitate improvement in wellness. METHODS: A wellness intervention team was established to address resident wellness and job satisfaction. A needs assessment to determine desired interventions as well as a three-part anonymous 5-point Likert scale survey was developed and distributed to general surgery residents. Following implementation of three measures, a postintervention survey was administered at 6 and 15 mo to the same cohort. Analysis of variance test was used to evaluate for significant difference between preintervention and postintervention surveys. RESULTS: Three interventions were implemented: two protected weekday personal days per year, modernization of resident workspace, and additional meal funds. There were statistically significant changes in perceptions of wellness opportunities (3.14 versus 3.88 and 3.7; P < 0.05), time for wellness (2.53 versus 3.42 and 3.2; P < 0.05), work/life balance satisfaction (2.86 versus 3.71 and 3.41; P < 0.05), and improved quality of life (2.67 versus 3.3 and 3.0; P < 0.05) in both 6-mo and 15-mo postintervention responses. CONCLUSIONS: Implementation of resident-selected wellness measures was found to influence overall resident satisfaction and improved perception of the working environment. Several scores of wellness items showed sustained improvement at 15 mo. These results suggest that resident-driven wellness interventions can positively affect working conditions for residents.

High Mitotic Rate Predicts Sentinel Lymph Node Involvement in Thin Melanomas.

BACKGROUND: Indications for sentinel lymph node (SLN) biopsy in the population with thin melanoma have frequently changed over time. The objective of our study was to evaluate T1 melanoma pathologic features predictive of SLN positivity with a primary focus on identifying a specific mitotic value that is most predictive of lymph node disease. Further detailed predictive features would help physicians select patients with thin melanoma for SLN biopsy. METHODS: The Surveillance, Epidemiology, and End Results database was queried for all patients diagnosed with trunk or extremity cutaneous melanoma with ≤1 mm depth who underwent SLN biopsy between the years of 2010 and 2013. Patient demographics and tumor characteristics including depth, mitotic rate (MR), ulceration, and tumor location were evaluated. MR was dichotomized at multiple cut points to identify the ideal number of mitosis for MR as a predictor of SLN status. Multivariable logistic regression analyses were performed to identify the factors affecting nodal positivity and the impact of MR threshold. Kaplan-Meir curves were used for overall survival (OS) analysis. RESULTS: Factors significantly associated with SLN positivity in the entire cohort included MR (P < 0.001, OR 1.24, 95% CI 1.18-1.31), tumor location (P = 0.017, OR 1.48, 95% CI 1.07-2.05), and ulceration (P < 0.001, OR 2.01, 95% CI 1.39-2.93,). An MR ≥ 4 was significant for SLN positivity (P = 0.049, OR 1.08, 95% CI 1.01-1.38). Mean OS was 46.7 mo for MR < 4 compared with 43.2 mo for MR ≥ 4 (P < 0.001). CONCLUSIONS: MR ≥ 4 was significant and associated with SLN positivity in thin melanomas and asulceration. Thus, MR ≥ 4 should be considered as an indication for SLN biopsy in thin melanoma.

What is Elective Oncologic Surgery in the Time of COVID-19? A Literature Review of the Impact of Surgical Delays on Outcomes in Patients with Cancer.

BACKGROUND: The impact of the COVID-19 pandemic has spread beyond those infected with SARS-CoV-2. Its widespread consequences have affected cancer patients whose surgeries may be delayed in order to minimize exposure and conserve resources. METHODS: Experts in each surgical oncology subspecialty were selected to perform a review of the relevant literature. Articles were obtained through PubMed searches in each cancer subtype using the following terms: delay to surgery, time to surgery, outcomes, and survival. RESULTS: Delays in surgery > 4 weeks in breast cancer, ductal carcinoma in situ, T1 pancreatic cancer, ovarian cancer, and pediatric osteosarcoma, negatively impacted survival. Studies on hepatocellular cancer, colon cancer, and melanoma (Stage I) demonstrated reduced survival with delays > 3 months. CONCLUSION: Studies have shown that short-term surgical delays can result in negative impacts on patient outcomes in multiple cancer types as well as in situ carcinoma. Conversely, other cancers such as gastric cancer, advanced melanoma and pancreatic cancer, well-differentiated thyroid cancer, and several genitourinary cancers demonstrated no significant outcome differences with surgical delays.

Comparing Standardized and Parent-Reported Motor Outcomes of Extremely Preterm Infants.

Extremely preterm infants are at increased risk of motor impairment. The Canadian Neonatal Follow-Up Network (CNFUN) afforded an opportunity to study the outcomes of extremely preterm children. The purpose of this study was to compare 18-month corrected age (CA) motor outcomes of extremely preterm infants with parent-reported functional outcomes at 3 years CA. CNFUN data of 1376 infants were used to conduct chi-square analyses to compare Bayley-III motor scores (composite, gross, and fine motor) at 18 months CA with parent-reported Ages and Stages Questionnaire motor scores (gross and fine motor) at 3 years CA. The correlation of motor scores at 18-months CA with parent-reported gross and fine motor scores at 3 years CA was also examined. We found that 1 in 5 infants scoring within or above the average range on the Bayley-III had parent-reported functional fine and gross motor difficulties at 3 years CA. Bayley-III scores were only moderately correlated with functional motor outcomes. Results of the study suggest that the Bayley-III at 18 months CA was able to detect the majority of infants with motor problems, but not all; therefore, ongoing follow-up of extremely preterm infants is required. The Bayley-III motor composite score has greater clinical utility compared to sub-scale scores.

Advanced glycation end products are elevated in estrogen receptor-positive breast cancer patients, alter response to therapy, and can be targeted by lifestyle intervention.

PURPOSE: Lifestyle factors associated with personal behavior can alter tumor-associated biological pathways and thereby increase cancer risk, growth, and disease recurrence. Advanced glycation end products (AGEs) are reactive metabolites produced endogenously as a by-product of normal metabolism. A Western lifestyle also promotes AGE accumulation in the body which is associated with disease phenotypes through modification of the genome, protein crosslinking/dysfunction, and aberrant cell signaling. Given the links between lifestyle, AGEs, and disease, we examined the association between dietary-AGEs and breast cancer. METHODS: We evaluated AGE levels in bio-specimens from estrogen receptor-positive (ER+) and estrogen receptor-negative (ER-) breast cancer patients, examined their role in therapy resistance, and assessed the ability of lifestyle intervention to reduce circulating AGE levels in ER+ breast cancer survivors. RESULTS: An association between ER status and AGE levels was observed in tumor and serum samples. AGE treatment of ER+ breast cancer cells altered ERα phosphorylation and promoted resistance to tamoxifen therapy. In a proof of concept study, physical activity and dietary intervention was shown to be viable options for reducing circulating AGE levels in breast cancer survivors. CONCLUSIONS: There is a potential prognostic and therapeutic role for lifestyle derived AGEs in breast cancer. Given the potential benefits of lifestyle intervention on incidence and mortality, opportunities exist for the development of community health and nutritional programs aimed at reducing AGE exposure in order to improve breast cancer prevention and treatment outcomes.