Robert E. Heidel

Prognostic Value of Breast Cancer Subtypes, Ki‐67 Proliferation Index, Age, and Pathologic Tumor Characteristics on Breast Cancer Survival in Caucasian Women

Estrogen receptor (ER), progesterone receptor (PR), and epidermal growth factor receptor 2 (HER2) status are well‐established prognostic markers in breast cancer management. The triple negative breast carcinoma subtype (ER‐/PR‐/HER2‐) has been associated with worse overall prognosis in comparison with other subtypes in study populations consisting of ethnic minorities and young women. We evaluated the prognostic value of breast cancer subtypes, Ki‐67 proliferation index (Ki‐67PI), and pathologic tumor characteristics on breast cancer survival in Caucasian women in our institution, where greater than 90% of the total patient population is white. From 628 new invasive breast cancer cases in our data base (2000‐late 2004), 593 (94%) were identified in Caucasian women. ER/PR/HER2 breast cancer subtypes were classified based on St. Gallen International Expert Consensus recommendations from 2011. ER/PR/HER2 status and its effect on survival were analyzed using a Kaplan–Meier curve. ER/PR/HER2 status, grade, tumor‐node‐metastasis status (TNM)/anatomic stage, and age were analyzed in terms of survival in a multivariate fashion using a Cox regression. Ki‐67PI was analyzed between ER/PR/HER2 groups using the Kruskal–Wallis, Mann–Whitney U‐tests, and 2 × 5 ANOVA. Our results showed that patients with stage IIB through stage IV breast carcinomas were 2.1–16 times more likely to die than patients with stages IA‐B and IIA disease, respectively (95% CI 1.17–3.81 through 9.68–28.03, respectively), irrespective of ER/PR/HER2 subtype. Similar effect was seen with T2, N2/N3, or M1 tumors in comparison with T1, N0/N1, and M0 tumors. Chances of dying increase approximately 5% for every year increase in age. There was a significant main effect of Ki‐67PI between ER/PR/HER2 subtypes, p < .001, but Ki‐67PI could not predict survival. In summary, TNM status/anatomic stage of breast carcinomas and age are predictive of survival in our patient population of Caucasian women, but breast carcinoma subtypes and Ki‐67 proliferation index are not.

The Predictive Value of General Surgery Application Data for Future Resident Performance

OBJECTIVE The predictive value of application data for future general surgery resident performance and attrition are poorly understood. We sought to determine what variables obtained in the application process might predict future resident success. METHODS We performed an 18-year review (1990-2008) of all matched residents (n = 101) to a university program. Both categorical graduates (CG) and nongraduates (CNG) and nondesignated preliminaries matching (PM) and preliminaries nonmatching (PNM) were evaluated. We also screened for previous high-performance accomplishments outside of the medical field such as in the performing arts or collegiate athletics (SKILL). Outcome data include graduation or match status, American Board of Surgery In-service Training Examination (ABSITE), and faculty Accreditation Council for Graduate Medical Education (ACGME) core competency evaluations. RESULTS Background data from the Electronic Residency Application Service (ERAS) application between the various groups was compared with univariate analysis and logistic regression. There were significant differences between the groups on the measures of USMLE step 1 (STEP1) (p = 0.001), medical school grade point average (GPA) (p = 0.023), interview data (INTERVIEW) (p < 0.001), and ABSITE (p < 0.001). The variable of INTERVIEW had an odds ratio of 188.27 (95% confidence interval, 3.757-9435.405). Overall attrition was 23.7% (n = 24) and was evenly divided between those who left for lifestyle reasons and those who were encouraged to leave. CONCLUSIONS Within our system, INTERVIEW, USMLE STEP1, and SKILL predict successful completion of a general surgery residency. In contrast to prior reports, female sex, ethnicity, medical school grades, or Alpha Omega Alpha Honor Society (AOA) status were not significant. The variable SKILL is novel and highlights the importance of nonacademic background data. Our data indicate STEP1 is an independent predictor of resident success in general surgery and should maintain an important role in general surgery applicant screening. The ideal screening threshold is likely > 215.

Is the TNM staging system for breast cancer still relevant in the era of biomarkers and emerging personalized medicine for breast cancer - an institution's 10-year experience.

We have previously demonstrated that TNM status and age were significant predictors of overall survival (OS) in our study population of Caucasian patients with invasive breast carcinoma (2000–2004 study period). However, estrogen receptor (ER), progesterone receptor (PR), and epidermal growth factor receptor 2 (HER2) biomarker expression was not predictive of OS when using the five‐group ER/PR/HER2 subtype classification system recommended by St. Gallen International Consensus Panel in 2011. The current study reassessed the relevance of tumor biomarkers (ER/PR/HER2) in our study population using a recently proposed biologic TNM (bTNM) classification system in which the inclusion of triple negative ER/PR/HER2 phenotype (TNP) could improve the prognostic accuracy of TNM for staging, prognosis and treatment of breast cancer patients. Seven hundred eighty‐two Caucasian women diagnosed with invasive ductal carcinoma from 1998 to 2008 were grouped according to their TNM stage and TNP versus non‐TNP ER/PR/HER2 phenotype. OS was measured comparing these categories using Kaplan Meier curves and Cox regression analysis. TNM stage (Stage II = HR 1.41, 95% CI 1.01–1.97; Stage III = HR 3.96, 95% CI 2.68–5.88; Stage IV = HR 27.25, 95% CI 16.84–44.08), and age (HR 1.05, 95% CI 1.04–1.06) were significant predictors of OS. TNP significantly worsened prognosis/survival only in higher TNM stages (Stage III = HR 3.08, 95% CI 1.88–5.04, Stage IV = HR 24.36, 95% CI 13.81–42.99), but not in lower stages (I and II). Our data support the traditional TNM staging as a continued relevant predictive tool for breast cancer outcomes and show that biomarkers primarily improve the accuracy of TNM staging in advanced stages of breast cancer. We suspect that type of ER/PR/HER2 classification system(s) (St. Gallen, TNP, etc.), characteristics of populations studied (Caucasians, minorities, etc.), and the time period chosen for a study are major factors that determine impact of biomarkers on the prognostic accuracy of TNM. We propose systematic analyses of these factors before biomarkers are fully incorporated into the TNM staging system (bTNM).

Polyprenyl Immunostimulant Treatment of Cats with Presumptive Non-Effusive Feline Infectious Peritonitis In a Field Study

Feline infectious peritonitis (FIP) is a fatal disease with no clinically effective treatment. This field study evaluated treatment with Polyprenyl Immunostimulant (PI) in cats with the non-effusive form of FIP. Because immune suppression is a major component in the pathology of FIP, we hypothesized that treatment with an immune system stimulant would increase survival times of cats with dry FIP. Sixty cats, diagnosed with dry FIP by primary care and specialist veterinarians and meeting the acceptance criteria, were treated with PI without intentional selection of less severe cases. The survival time from the start of PI treatment in cats diagnosed with dry FIP showed that of the 60 cats with dry FIP treated with PI, 8 survived over 200 days, and 4 of 60 survived over 300 days. A literature search identified 59 cats with non-effusive or dry FIP; no cat with only dry FIP lived longer than 200 days. Veterinarians of cats treated with PI that survived over 30 days reported improvements in clinical signs and behavior. The survival times in our study were significantly longer in cats who were not treated with corticosteroids concurrently with PI. While not a cure, PI shows promise in the treatment of dry form FIP, but a controlled study will be needed to verify the benefit.

Breast Cancer in Elderly Caucasian Women—An Institution-Based Study of Correlation between Breast Cancer Prognostic Markers, TNM Stage, and Overall Survival

There is still a paucity of data on how breast cancer (BC) biology influences outcomes in elderly patients. We evaluated whether ER/PR/HER2 subtype and TNM stage of invasive BC had a significant impact on overall survival (OS) in a cohort of 232 elderly Caucasian female patients (≥70 year old (y/o)) from our institution over a ten-year interval (January 1998–July 2008). Five ER/PR/HER2 BC subtypes classified per 2011 St. Gallen International Expert Consensus recommendations were further subclassified into three subtypes (traditionally considered “favorable” subtype-ER+/PR+/HER2−, and traditionally considered “unfavorable” BC subtypes: HER2+ and triple negative). OS was measured comparing these categories using Kaplan Meier curves and Cox regression analysis, when controlled for TNM stage. The majority of our patients (178/232 = 76.8%) were of the “favorable” BC subtype; 23.2% patients were with “unfavorable” subtype (HER2+ = 12% (28/232) and triple negative = 11.2% (26/232)). Although a trend for better OS was noted in HER2+ patients (68%) vs. 56% in ER+/PR+ HER2− or 58% in triple negative patients, “favorable” BC subtype was not significantly predictive of better OS (p = 0.285). TNM stage was predictive of OS (p < 0.001). These results are similar to our published studies on Caucasian BC patients of all ages in which ER/PR/HER2 status was not predictive of OS, irrespective of classification system used.

Use of CPR in hemorrhagic shock, a dog model.

INTRODUCTION Cardiopulmonary resuscitation was designed for sudden cardiac events usually triggered by thrombotic phenomena. Despite this, it is routinely used in trauma resuscitations as per the American Heart guidelines. There is no data supporting the use of chest compressions in hemorrhagic shock. An evidence-based cardiopulmonary resuscitation (CPR) protocol has been developed for dogs. We sought to determine the effects and outcomes of chest compressions in hemorrhagic shock in a canine model. METHODS Eighteen dogs were randomized to three treatment groups—chest compressions only after hemorrhagic shock (CPR), CPR with fluid resuscitation after hemorrhagic shock (CPR + FLU), and fluid resuscitation alone after hemorrhagic shock (FLU). Under anesthesia, dogs were hemorrhaged until pulse was lost; they were maintained pulseless for 30 minutes and then resuscitated over 20 minutes. Vital signs and laboratory values were recorded at determined intervals. Echocardiography was performed throughout the study. Upon termination of the study, kidney, liver, heart, and brain tissue histology was evaluated for end organ damage. Statistical significance was p < 0.05 with a Bonferroni correction for multiple comparisons. RESULTS Blood loss and mean time to loss of pulse were similar between the groups. Dogs in the CPR group had significantly lower mean arterial pressure and higher pulse at all points compared to CPR + FLU and FLU (p < 0.05). Ejection fraction was lower in the CPR group at 5 and 10 minutes compared to the other groups (p < 0.05). Vital signs and laboratory results between CPR + FLU and FLU were equivalent. Two of six dogs in the CPR group died, while no dogs died in the CPR + FLU or FLU groups. Dogs in the CPR group were found to have more episodes of end organ damage. CONCLUSION There was no benefit to chest compressions in the hypovolemic animals. Chest compressions in addition to fluid did not reverse signs of shock better than fluid alone. Further research is needed to define if there is a role of CPR in the trauma patient with hemorrhagic shock.

Abstract P3-07-17: Analysis of the National cancer data base 2010-2012 oncotype DX breast cancer assay: Lessons learned

Oncotype DX (OD) 21-gene breast cancer (BC) assay is used for testing of estrogen receptor positive (ER+) early stage BC and provides a low, intermediate or high 10-year risk recurrence score (LRS, IRS, HRS) for BC. Scores are used as guidelines to predict the probability of successfully adding adjuvant chemotherapy (AC) to endocrine therapy (ET) to reduce the risk of BC recurrence. In retrospective analysis of 2 clinical trials, patients (pts) with HRS benefited from addition of AC to ET, no benefits were shown for LRS, and benefits of AC for IRS were not clear. The OD assay has been utilized since 2004, but data on the impact of using assay results in clinical practice across the US are lacking. The TAILORx and RxPONDER prospective clinical trials which are using OD scores are ongoing (results will be available in 2017 and 2022, respectively) and may help clinicians better understand the predictive capabilities of the IRS OD score. We analyzed the current impact of IRS OD score in a retrospective observational study of the National Cancer Data Base (NCDB) (which represents 75% of the US population) from 2010-2012. This time period encompasses the beginning of required recording of molecular assays and the latest data released by NCDB in 4/2015. Demographic and clinical variables of all pts with IRS results were analyzed using frequency statistics, chi-square and logistic regression analysis. Data from 24260/27995 pts with IRS and documented AC information was analyzed. 11520=47.4% pts received AC. Age ranged from 20-90 (mean 58.4, median 59 years); 99.2% were ER+ and females, 2.7% were HER2+; 6143=25.3% had T1a, T1b or T3 tumors; 19791=81.5% were N0, 3684=15.1% N1; 17950=73.6% had ≥G2 tumors and 3389=14% had lymphvascular invasion (LVI). IRS OD result had poor PPV for the administration of AC (47.4%). AC administration was significantly associated with larger tumors, LN+, LVI, high tumor grade, higher TNM stage, younger age and black race (p 0.05). Medicare pts were less likely to receive AC than ones with private insurance (p Our data analysis reveals that additional guidelines for selection of pts for OD testing and new algorithms for AC administration in the IRS subsets are needed. The authors of this abstract solicit a call to action from interested parties on behalf of the patients affected by this conundrum. Citation Format: Orucevic A, Heidel RE, Bell JL. Analysis of the National cancer data base 2010-2012 oncotype DX breast cancer assay: Lessons learned. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-17.

A Mathematical Model to Predict Length of Stay in Pediatric ATV Accident Victims

BACKGROUND Children under age 12 y represent 15% of all-terrain vehicle (ATV)-related deaths, and those under 16 y old represent >36% of deaths nationwide. In recent years, this has accounted for an increasing proportion of pediatric trauma victims and longer hospitalizations secondary to worsened injuries. We believe it is possible to create a simple mathematical model that can be used to predict hospital length of stay. METHODS A retrospective review of the trauma registry was performed for all pediatric patients who were involved in ATV accidents from January 2000 to December 2009. Four hundred twenty pediatric patients were identified. A model to predict for total LOS in pediatric patients involved in ATV accidents was constructed. SPSS ver. 17 (SPSS Inc., Chicago, IL) was utilized to conduct all statistical analyses. Statistical significance of regression coefficients was assumed at a P < 0.05 level. RESULTS We performed a hierarchical multiple regression analysis to build a model that would predict for total length of stay (LOS). A logarithmic transformation was employed on LOS as a dependent variable due to skewness. In Step 1, ISS accounted for a 25% increase in shared variance in LOS (P < 0.001). In Step 2, Glasgow Coma Score (GCS) accounted for 4.3% more variance in LOS (P < 0.001). Finally, in Step 3, the presence of a closed head injury further increased (3.6%) the amount of shared variance in the model (P < 0.001). The final model accounts for 32.9% of the shared variance in total LOS. When using the logarithmic transformation, the final model is: Total LOS = 1.00 + 0.05 injury severity score (ISS) - 0.06 (GCS) + 0.35 closed head injury (CHI). CONCLUSION Based on our data and statistical analysis, we found it was possible to create a mathematical model that could predict hospital LOS in pediatric ATV accident victims.

Librarians Promoting Changes in the Health Care Delivery System through Systematic Assessment

ABSTRACT Patient engagement in health care decisions largely depends on a patient’s health literacy and the health literacy attributes of the health care organization. Librarians have an established role in connecting patients with health information in the context of their care. However, librarians can play a larger role in helping to make changes in their organization’s health literacy attributes. This article discusses one medical library’s process of leading systematic assessment of their organization’s health literacy attributes. Included in this discussion is the institutional support, timeline, assessment tool, the results for five areas of health literacy, marketing and the event-planning process to disseminate results. The systematic assessment process described employs the Health Literacy Environment of Hospitals and Health Centers document, which provides assessment tools for Print Communication, Oral Communication, Navigation, Technology, and Policies and Protocols.

Walking to recovery: the effects of missed ambulation events on postsurgical recovery after bowel resection

Background Early ambulation after surgery is demonstrated to reduce complications and decreases patient length of stay (LOS) as part of an enhanced recovery after surgery (ERAS) program. This study hypothesizes that missed and refused ambulation attempts prolong patient LOS. Methods From January 2014 to December 2016, all patients admitted to one ward who had undergone bowel resection surgery were assigned a dedicated ambulation team with the goal of ambulating 3 times per day. Clinical data was collected prospectively. Statistical analysis of ambulation frequency, percentage of ambulation sessions completed and overall LOS was performed to test the hypothesis. Results A total of 127 patients were analyzed for mean age, breakdown of laparoscopic/open procedures/pre-surgery ambulation status. The median LOS (mLOS) for all patients was 4.3 days. When ambulation was not offered for a 24-hour period, the mLOS increased from 3.6 to 6.6 days (P<0.001). When a patient refused to ambulate at any time, the mLOS increased from 4.0 to 4.7 days (P=0.004). There was a significant association between completed ambulation attempts and mLOS (r=-0.536, P<0.001). Increasing narcotic use (r=0.548, P<0.001) including the use of a patient-controlled analgesia (PCA) (r=0.213, P=0.011) increased mLOS. Conclusions Ambulation participation is a critical component of an enhanced bowel resection pathway. Non-compliance is associated with an increased LOS. Optimizing pain control, minimizing narcotics, and ensuring adequate ambulation resources also contribute to decreased LOS.