Assessment of Residual Cancer Burden and Event-Free Survival in Neoadjuvant Treatment for High-risk Breast Cancer: An Analysis of Data From the I-SPY2 Randomized Clinical Trial.

IMPORTANCE: Residual cancer burden (RCB) distributions may improve the interpretation of efficacy in neoadjuvant breast cancer trials. OBJECTIVE: To compare RCB distributions between randomized control and investigational treatments within subtypes of breast cancer and explore the relationship with survival. DESIGN, SETTING, AND PARTICIPANTS: The I-SPY2 is a multicenter, platform adaptive, randomized clinical trial in the US that compares, by subtype, investigational agents in combination with chemotherapy vs chemotherapy alone in adult women with stage 2/3 breast cancer at high risk of early recurrence. Investigational treatments graduated in a prespecified subtype if there was 85% or greater predicted probability of higher rate of pathologic complete response (pCR) in a confirmatory, 300-patient, 1:1 randomized, neoadjuvant trial in that subtype. Evaluation of a secondary end point was reported from the 10 investigational agents tested in the I-SPY2 trial from March 200 through 2016, and analyzed as of September 9, 2020. The analysis plan included modeling of RCB within subtypes defined by hormone receptor (HR) and ERBB2 status and compared control treatments with investigational treatments that graduated and those that did not graduate. INTERVENTIONS: Neoadjuvant paclitaxel plus/minus 1 of several investigational agents for 12 weeks, then 12 weeks of cyclophosphamide/doxorubicin chemotherapy followed by surgery. MAIN OUTCOMES AND MEASURES: Residual cancer burden (pathological measure of residual disease) and event-free survival (EFS). RESULTS: A total of 938 women (mean [SD] age, 49 [11] years; 66 [7%] Asian, 103 [11%] Black, and 750 [80%] White individuals) from the first 10 investigational agents were included, with a median follow-up of 52 months (IQR, 29 months). Event-free survival worsened significantly per unit of RCB in every subtype of breast cancer (HR-positive/ERBB2-negative: hazard ratio [HZR], 1.75; 95% CI, 1.45-2.16; HR-positive/ERBB2-positive: HZR, 1.55; 95% CI, 1.18-2.05; HR-negative/ERBB2-positive: HZR, 2.39; 95% CI, 1.64-3.49; HR-negative/ERBB2-negative: HZR, 1.99; 95% CI, 1.71-2.31). Prognostic information from RCB was similar from treatments that graduated (HZR, 2.00; 95% CI, 1.57-2.55; 254 [27%]), did not graduate (HZR, 1.87; 95% CI, 1.61-2.17; 486 [52%]), or were control (HZR, 1.79; 95% CI, 1.42-2.26; 198 [21%]). Investigational treatments significantly lowered RCB in HR-negative/ERBB2-negative (graduated and nongraduated treatments) and ERBB2-positive subtypes (graduated treatments), with improved EFS (HZR, 0.61; 95% CI, 0.41-0.93) in the exploratory analysis. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, the prognostic significance of RCB was consistent regardless of subtype and treatment. Effective neoadjuvant treatments shifted the distribution of RCB in addition to increasing pCR rate and appeared to improve EFS. Using a standardized quantitative method to measure response advances the interpretation of efficacy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01042379.

US Medical Licensing Exam Performance and American Board of Surgery Qualifying and Certifying Examinations.

BACKGROUND: Program directors use US Medical Licensing Exam (USMLE) scores as criteria for ranking applicants. First-time pass rates of the American Board of Surgery (ABS) Qualifying (QE) and Certifying (CE) Examinations have become important measures of residency program quality. USMLE Step 1 will become pass/fail in 2022. STUDY DESIGN: American Board of Surgery QE and CE success rates were assessed considering multiple characteristics of highly ranked (top 20) applicants to 22 general surgery programs in 2011. Chi-square, t-test, Wilcoxon Rank sum, linear and logistic regression were used, as appropriate. RESULTS: The QE and CE first attempt pass rates were 96% (235/244) and 86% (190/221), respectively. QE/CE success was not significantly associated with sex, race, research experience, or publications. Alpha Omega Alpha (AΩA) status was associated with success on the index CE (98% vs 83%; p = 0.008). Step 1 and Step 2 Clinical Knowledge (CK) scores of surgeons who passed QE on their first attempt were higher than scores of those who failed (Step 1: 233 vs 218; p = 0.016); (Step 2CK: 244 vs 228, p = 0.009). For every 10-point increase in Step 1 and 2CK scores, the odds of passing CE on the first attempt increased 1.5 times (95% CI 1.12, 2.0; p = 0.006) and 1.5 times (95% CI 1.11, 2.02, p = 0.008), respectively. For every 10-point increase in Steps 1 and 2CK scores, the odds of passing the QE on the first attempt increased 1.85 times (95% CI 1.11, 3.09; p = 0.018) and 1.86 times (95% CI 1.14, 3.06, p = 0.013), respectively. CONCLUSIONS: USMLE Step 1 and Step 2 CK examination scores correlate with American Board of Surgery QE and CE performance and success. The USMLE decision to transition Step 1 to a pass/fail examination will require program directors to identify other factors that predict ABS performance for ranking applicants.

Moral determinants of health: An overview of disparities in healthcare.

Healthcare disparities are a serious problem that shorten the lives of many Americans, even after accounting for social, cultural, and economic factors and correcting for confounders such as the lack of medical insurance and access to healthcare, black Americans and other minority groups receive worse medical care and experience worse outcomes as a result. Healthcare does not occur in a vacuum; surgeons cannot serve our patients' needs isolated in a bubble and cocooned from larger societal concerns. Although disparities rooted in race likely have the greatest negative effects on our patients' health, plenty of groups exist that have not historically received equal opportunities and acceptance within the surgical world. Despite now accounting for more than one half of all medical graduates, women remain underrepresented in leadership positions, and the gender pay gap has remained significant in all branches of medicine. It will require active, multifaceted, and sustained effort to increase diversity, equity, and inclusion in academic surgery. We have described the steps that can be taken within surgical departments and in national surgical societies to recruit, retain, and foster a diverse surgical workforce and to develop a more inclusive culture within surgery and surgical training.

Lived Experiences of Surgical Residents During the COVID-19 Pandemic: A Qualitative Assessment.

OBJECTIVE: As the COVID-19 pandemic dynamically changes our society, it is important to consider how the pandemic has affected the training and wellness of surgical residents. Using a qualitative study of national focus groups with general surgery residents, we aim to identify common themes surrounding their personal, clinical, and educational experiences that could be used to inform practice and policy for future pandemics and disasters. DESIGN: Six 90-minute focus groups were conducted by a trained qualitative researcher who elicited responses on six predetermined topics. De-identified transcripts and audio recordings were later analyzed by two independent researchers who organized responses to each topic into themes. SETTING: Focus groups were conducted virtually and anonymously. PARTICIPANTS: General surgery residents were recruited from across the country. Demographic information of potential participants was coded, and subjects were randomly selected to ensure a diverse group of participants. RESULTS: The impact of the COVID-19 pandemic on residents' clinical, educational, and personal experiences varied depending on the institutional response of the program and the burden of COVID-19 cases geographically. Many successes were identified: the use of telehealth and virtual didactics, an increased sense of camaraderie amongst residents, and flexibility in scheduling. Many challenges were also identified: uncertainty at work regarding personal protective equipment and scheduling, decreased case volume and educational opportunities, and emotional trauma and burnout associated with the pandemic. CONCLUSIONS: These data gathered from our qualitative study highlight a clear, urgent need for thoughtful institutional planning and policies for the remainder of this and future pandemics. Residency programs must ensure a balanced training program for surgical residents as they attempt to master the skills of their craft while also serving as employed health care providers in a pandemic. Furthermore, a focus on wellness, in addition to clinical competency and education, is vital to resident resilience and success in a pandemic setting.

Assessment of simple indices based on a single fasting blood sample as a tool to estimate beta-cell function after total pancreatectomy with islet autotransplantation - a prospective study.

We investigated six indices based on a single fasting blood sample for evaluation of the beta-cell function after total pancreatectomy with islet autotransplantation (TP-IAT). The Secretory Unit of Islet Transplant Objects (SUITO), transplant estimated function (TEF), homeostasis model assessment (HOMA-2B%), C-peptide/glucose ratio (CP/G), C-peptide/glucose creatinine ratio (CP/GCr) and BETA-2 score were compared against a 90-min serum glucose level, weighted mean C-peptide in mixed meal tolerance test (MMTT), beta score and the Igls score adjusted for islet function in the setting of IAT. We analyzed values from 32 MMTTs in 15 patients after TP-IAT with a follow-up of up to 3 years. Four (27%) individuals had discontinued insulin completely prior to day 75, while 6 out of 12 patients (50%) did not require insulin support at 1-year follow-up with HbA1c 6.0% (5.5-6.8). BETA-2 was the most consistent among indices strongly correlating with all reference measures of beta-cell function (r = 0.62-0.68). In addition, it identified insulin independence (cut-off = 16.2) and optimal/good versus marginal islet function in the Igls score well, with AUROC of 0.85 and 0.96, respectively. Based on a single fasting blood sample, BETA-2 score has the most reliable discriminant value for the assessment of graft function in patients undergoing TP-IAT.

White Paper: SSAT Commitment to Workforce Diversity and Healthcare Disparities.

The Society for Surgery of the Alimentary Track (SSAT) is committed to diversity and inclusiveness of its membership, promotion of research related to healthcare disparities, cultural competency of practicing gastrointestinal surgeons, and cultivation of leaders with unique perspectives. The SSAT convened a task force to assess the current state of diversity and inclusion and recommend sustainable initiatives to promote these goals. Working through the current committee structure of the Society, and by establishing a permanent Diversity and Inclusion liaison committee, the SSAT will maintain its commitment and strive towards diversity of thought and inclusiveness on every level to improve the well-being and betterment of its membership and the patients they serve.

Geriatric assessment improves prediction of surgical outcomes in older adults undergoing pancreaticoduodenectomy: a prospective cohort study.

OBJECTIVE: To prospectively evaluate the additional value of geriatric assessment (GA) for predicting surgical outcomes in a cohort of older patients undergoing a pancreaticoduodenectomy (PD) for pancreatic tumors. BACKGROUND: Older patients are less often referred for possible PD. Standard preoperative assessments may underestimate the likelihood of significant adverse outcomes. The prospective utility of validated GA has not been studied in this group. METHODS: PD-eligible patients were enrolled in a prospective outcome study. Standard preoperative assessments were recorded. Elements of validated GA were also measured, including components of Fried's model of frailty, the Vulnerable Elders Survey (VES-13), and the Short Physical Performance Battery (SPPB). All postoperative adverse events were recorded, systematically reviewed, and graded using the Clavien-Dindo system by a surgeon blinded to the GA results. Multivariate regression analyses were conducted. RESULTS: Seventy-six older patients underwent a PD. Significant unrecognized vulnerability was identified at the baseline: Fried's "exhaustion" (37.3%), SPPB <10 (28.5%), and VES-13 >3 (15.4%). Within 30 days of PD, 46% experienced a severe complication (Clavien-Dindo grade ≥III). In regression analyses controlling for age, the body mass index, the American Society of Anesthesiologists score, and comorbidity burden, Fried's "exhaustion" predicted major complications [odds ratio (OR) = 4.06; P = 0.01], longer hospital stays (ß = 0.27; P = 0.02), and surgical intensive care unit admissions (OR = 4.30; P = 0.01). Both SPPB (OR = 0.61; P = 0.04) and older age predicted discharge to a rehabilitation facility (OR = 1.1; P < 0.05) and age correlated with a lower likelihood of hospital readmission (OR = 0.94; P = 0.02). CONCLUSIONS: Controlling for standard preoperative assessments, worse scores on GA prospectively and independently predicted important adverse outcomes. Geriatric assessment may help identify older patients at high risk for complications from PD.

Ethical management of conflict of interest: proposed standards for academic surgical societies.

BACKGROUND: A significant increase in industry support of professional medical associations coupled with data suggesting that gifts from industry have significant clinical influence have prompted calls from the Institute of Medicine and physician leaders to identify and manage conflicts of interest that stem from financial support of professional medical associations by industry. STUDY DESIGN: A joint task force of members appointed by the Association for Academic Surgery and the Society of University Surgeons was convened in July 2009. Recommendations were developed regarding management of all potential conflicts of interest that can arise within the context of an academic surgical society, with specific focus on relationships with industry. Task force members reached consensus around each recommendation and the guidelines were subsequently adopted by the Executive Councils of both societies. RESULTS: The committee identified 4 primary areas of need for transparent and definitive management of conflict of interest: 1) individual society activities, including general budget support, society endorsements, and journal affiliation; 2) individual personnel conflicts such as society leadership and standards for disclosure of conflict; 3) meeting activities including budgetary support, program committee associations, and abstract review process; and 4) foundation support and research and travel awards. The resulting guidelines aim to protect the societies and their membership from undue bias that may undermine the credibility and mission of these associations. CONCLUSIONS: Policy guidelines to mitigate conflict of interest are necessary to protect the integrity of the work of academic surgical societies and their fiduciary duty to members and patients. Guidelines created and adopted by the Association for Academic Surgery and Society of University Surgeons form an effective model for academic surgical societies and their members.

Ten years of the Immune Tolerance Network: an integrated clinical research organization.

The U.S. National Institutes of Health Roadmap and the U.S. Food and Drug Administration's Critical Path Initiative have endorsed the establishment of large academic clinical research networks as part of the solution to the growing divide between increased R&D spending and the lagging number of new drugs making it to market. Clearly, the role of these networks as translational science incubators that complement industry-sponsored programs is laudable and much-needed. However, the path to success for such organizations is less clear. Here, drawing on the experiences of the Immune Tolerance Network, a multidisciplinary clinical research network founded in 1999, we discuss some of the barriers inherent in developing such consortia and offer firsthand insight into the planning, resources, and organizational infrastructure required for a successful research program.

The cost effectiveness of laparoscopic versus open gastric bypass surgery.

BACKGROUND: Over the last decade, laparoscopic gastric bypass (LGBP) has been proven to be a safe and well-tolerated approach to the Roux-en-Y gastric bypass, despite its increased cost when compared to the open approach (OGBP). This increased expense has led many to question whether LGBP is a cost effective alternative to OGBP. The aim of this study is to determine which approach is most cost effective, considering costs associated with the operation itself, perioperative complications, and income lost during convalescence. METHODS: A PubMed search of the National Library of Medicine online journal database was conducted. Studies that met predetermined criteria for selection were included in the analyses of patient demographics, perioperative complications, length of hospital stay, excess weight loss, and time to recovery. Data on 6,425 OGBP and 5,867 LGBP patients were used to compare the outcomes associated with each approach. RESULTS: Significant differences were found in the perioperative complication profiles, time to recovery, and overall expense of the two approaches. OGBP was associated with an increased incidence of major perioperative complications, especially extraintestinal complications, and greater perioperative mortality. LGBP was associated with shorter hospital stays, increased incidence of intestinal complications, and a 2.25% incidence of conversion to OGBP. Patient demographics and percent excess weight loss (%EWL) at 3 years follow-up were found to be similar with both OGBP and LGBP. CONCLUSION: LGBP is a cost effective alternative to OGBP for surgical weight loss. Despite the increased cost of LGBP, patients suffer fewer expensive and lifethreatening perioperative complications.