Citations

AbstractWomen diagnosed with cutaneous melanoma have a survival advantage compared to men, which has been hypothesized to be due to difference in behavior and/or biology (sex hormones). It remains controversial whether this advantage is dependent on age or stage of disease. We sought to compare melanoma‐specific survival between females in pre, peri, and postmenopausal age groups to males in the same age group, adjusting for stage of disease. This is a retrospective population‐based cohort study using the Surveillance, Epidemiology, and End Results (SEER) database. Patients diagnosed from 1 January 1992 through 31 January 2011 with primary invasive cutaneous melanoma were included in our cohort. Melanoma‐specific survival was the main outcome studied. Of the 106,511 subjects that were included, 45% were female. Females in all age groups (18–45, 46–54, and ≥55) with localized and regional disease, were less likely to die from melanoma compared to males in the same age group. Among patients with localized and regional disease, the relative risk of death due to melanoma increased with advancing age at diagnosis; this increase was more pronounced among females than males. In contrast, we observed no female survival advantage among patients with distant disease and no effect of age on relative risk of death from melanoma. Females with localized and regional melanoma have a decreased risk of death compared to males within all age groups. Our data show no differences in survival between men and women with metastatic melanoma, indicating that the influence of sex on survival is limited to early stage disease but not confined to pre or perimenopausal age groups.

Abstract Training adult learners to use ultrasound in clinical practice relies on the ability of the learner to apply visuospatial concepts to the anatomy of the human body. We describe a visuospatial trainer that replicates the housing of an ultrasound transducer, through which a linear laser projects light in the same plane and orientation as the ultrasonic sound waves. We use this trainer in combination with a porcine heart dissection laboratory to teach bedside cardiac ultrasound and transthoracic echocardiography (TTE). Off-the-shelf components, including an on/off switch, a laser, and 2 ampere batteries are connected in series and placed inside the 3-dimensional (3D)–printed housing. The trainer's laser emission projects a red line that visually represents the ultrasound's field. Learners project the laser against a porcine or human heart in the orientation of the TTE window they wish to obtain and then dissect the heart in that plane, allowing for visualization of how grayscale images are obtained from 3D structures. Previous research has demonstrated that visuospatial aptitude is correlated with ultrasound procedural performance. We present this trainer and educational method as a specific training intervention that could enhance the visuospatial ability of the ultrasound learner. This visuospatial trainer and educational method present a novel process for enhancing learner understanding of 2-dimensional ultrasound images as they relate to 3D structures. Having a clear understanding of how images are generated in cross section may translate into more proficient adaptation of cardiac ultrasound and TTE.

Abstract Background: High percent mammographic density (MD), which reflects the relative fibroglandular tissue content of the breast, is one of the strongest breast cancer risk factors; however, the pathologic mediators of this risk are unknown. We hypothesize that analysis of breast tissue sections using deep learning approaches may characterize histologic features that underpin risk associated with high MD. Methods: Non-targeted H&E stained breast tissue sections of diagnostic image-guided breast biopsies were evaluated among 588 women enrolled following an abnormal mammogram in the Breast Radiology Evaluation and Study of Tissues (BREAST) Stamp Project (2007-2010). Overall volumetric percent MD for the biopsied breast and localized volumetric percent MD surrounding the biopsy site were determined for each participant. A deep convolutional neural network (CNN) model was trained to identify and quantitatively assess breast epithelial, stroma and fat tissue and their organizational and spatial arrangements. Least absolute shrinkage and selection operator (Lasso) regression was used to determine relationships between MD measures and pathological features. To ensure reliability of the model, a cross-validation strategy was employed to build and assess the performance of the fitted model. Finally, Spearman correlation coefficients were estimated to test the association between the predicted density values by each model (predicting overall or localized MD) and the actual MD measurements. We report the average and standard deviation (SD) of the correlation coefficients. Results: In an independent validation set, the CNN model was 95.5% accurate in classifying epithelial, stromal and fat tissue. The mean (SD) correlations between the predicted model and the actual measurements for overall and localized MD were 0.70 (0.06) and 0.65 (0.06) respectively. The amount of stroma identified (normalized to tissue area) had the highest selection probability (P-value) by the Lasso model and thus the strongest positive relationship with MD (P-value >0.9 for each MD measurement). In contrast, the amount of normalized epithelial tissue was not related to MD (P-value=0.01 for each MD measurement). No association was observed for the total normalized fat area with MD (P-value <0.31 for each MD measurement). In addition, the number of distributed epithelial regions was positively associated, whereas the distance between epithelial regions was inversely associated with overall MD (P-value <0.87 and 0.62, respectively). Conclusions: These results show that greater stromal tissue amount and spatial distribution patterns of epithelial regions, rather than total epithelial amounts, had the strongest relationships with elevated MD. Future work will determine the relationship of these MD features with biopsy diagnosis. Citation Format: Maeve Mullooly, Babak Ehteshami Bejnordi, Maya Palakal, Pamela M. Vacek, Donald L. Weaver, John A. Shepherd, Bo Fan, Amir Pasha Mahmoudzadeh, Jeff Wang, Jason M. Johnson, Sally D. Herschorn, Brian L. Sprague, Ruth M. Pfeiffer, Louise A. Brinton, Mark E. Sherman, Andrew Beck, Gretchen L. Gierach. Application of convolutional neural networks to breast biopsies to uncover tissue correlates of mammographic breast density [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4235. doi:10.1158/1538-7445.AM2017-4235

AbstractBackgroundSecond hematologic cancers in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) are well documented and include Hodgkin lymphoma, therapy‐related acute myeloid leukemia/myelodysplastic syndromes, and transformation to diffuse large B‐cell lymphoma. Although cutaneous T‐cell lymphoma (CTCL) has been reported in patients with CLL, the incidence and comparison to expected rates are unknown. We evaluated the incidence of CTCL among patients with CLL or other non‐Hodgkin lymphoma (NHL) subtypes using data from the Surveillance, Epidemiology, and End Results (SEER) Program.MethodsWe searched the SEER 13 registries for patients with a diagnosis of CLL and NHL between 1992 and 2008. Among patients identified, we evaluated the incidence of CTCL.ResultsAmong 31,286 patients with CLL, the incidence of CTCL was not significantly higher in men than women: 104.2 (95% CI, 50.0–191.8) and 28.1 (95% CI, 3.4–101.3) per 1,000,000 person‐years, respectively (P = 0.06). Among 97,691 patients with NHL, the incidence of CTCL was similar in men and women (97.9 [95% CI, 62.0–146.9] and 92.0 [95% CI, 56.2–142.1] per 1,000,000 person‐years, respectively; P = 0.84). The incidence of CTCL among males with CLL (standardized incidence ratio [SIR], 3.0 [95% CI, 1.4–5.5]), males with NHL (SIR, 3.7 [95% CI, 2.3–5.5]), and females with NHL (SIR, 5.9 [95% CI, 3.6–9.1]) was significantly higher than expected in the general population (all P < 0.001).ConclusionThe risk of CTCL is greater in men with CLL than in the general population. In patients with NHL, both men and women are at greater risk for CTCL than in the general population.

Females demonstrate less robust Frank‐Starling mechanism with respect to cardiac preload than males at rest. We asked whether this phenomenon would also affect cardiac performance during exercise. We hypothesized that stroke volume (SV) response to exercise would be more limited in deconditioned females such that cardiac output would be mainly rate dependent, compared with males. We conducted a chart audit of clinical exercise tests performed by adolescents with chronic fatigue. Oxygen uptake () was measured breath‐by‐breath at rest and during cycle ergometry, while cardiac output was measured by acetylene rebreathing at rest plus 2‐3 subthreshold workloads. SV response was analyzed in two ways: after normalization for body surface area (SV index, SVI) and as percentage change from resting values. Among 304 adolescents (78% females) with chronic fatigue, 189 (80%) of 236 females and 52 (76%) of 68 males were deconditioned (peakO2 <90% predicted). Heart rate trajectory during exercise was steeper for unfit than fit females, 70 vs 61 beat·min−1 per L·min−1 , (P=.003); but not for males, 47 vs 42 beat·min−1 per L·min−1 (P=.23). The highest measured SVI did not differ between unfit vs fit females (42.8 vs 41.5 mL·m−2, P=.39) while fit males showed larger SV during exercise than their unfit peers (highest SVI 55.9 vs 48.0 mL·m−2, P=.014). Both qualitative and quantitative sex differences exist in SV responses to exercise among chronically fatigued adolescents, suggesting volume loading may be more efficacious in girls.

Abstract BACKGROUND One study has investigated postoperative growth rates following subtotal resection of petroclival meningiomas utilizing linear measurements, which are insensitive to the multidimensional complex growth of meningiomas, to estimate tumor volume. OBJECTIVE To describe petroclival meningioma growth patterns following less-than-complete resection utilizing volumetric analysis and to identify variables associated with tumor progression. METHODS Patients with surgically resected WHO grade I petroclival meningiomas were retrospectively reviewed (1999-2015). Image analysis software was utilized to perform volumetric analyses of tumor size and growth on serial MRI studies. The impact of preoperative and postoperative variables on tumor growth after subtotal resection was analyzed. An increase in tumor volume of at least 20% was defined as “tumor growth.” RESULTS Twenty-three patients had immediate preoperative and serial postoperative MRI studies available for review. The mean preoperative tumor volume was 20.9 cm 3 (range 0.4-54.6). The mean extent of resection was 75.5% (range 31.5%-100.0%). At a mean follow-up of 24.8 mo, 12 tumors (66.7%) exhibited radiological tumor growth, while 6 tumors did not change in size. The median annual volumetric growth rate was 2.82 cm 3 /yr (range –0.34 to 10.1). Extent of resection and immediate postoperative tumor volume were significantly correlated with the annual volumetric growth rate following resection. At last follow-up, 3 (13%) patients required further intervention. CONCLUSION The majority of petroclival meningiomas exhibit growth following subtotal resection. Extent of resection is strongly associated with risk for disease progression following surgery.

INTRODUCTION: Postpartum hemorrhage is the leading cause of maternal mortality worldwide. There are multiple known risk factors, including induction of labor. METHODS: A retrospective cohort study was completed with review of nulliparous women undergoing labor induction at term, from July 2006 to May 2011. Baseline maternal variables and risk factors for postpartum hemorrhage were assessed. All combinations of methods of induction were sequential rather than concurrent. The need for additional uterotonics (beyond routine oxytocin) was used as a surrogate for postpartum hemorrhage. Variables were evaluated for an association with additional uterotonic use based on fitting logistic regression models. RESULTS: A total of 785 women were included in the study. Additional uterotonics were required for 84/785 (11%) of women. Based on univariate analysis, only birth weight and presence of meconium were significantly (p < 0.05) associated with additional uterotonic use, while method of induction approached statistical significance (p=0.06). The mean (SD) birth weight was 3668 (584) vs. 3463 (500) grams in those with and without additional uterotonic use. Multivariate analysis showed an increased risk of additional uterotonics with higher birth weight (adjusted odds ratio (aOR) 1.44 per 500 gram increase in birth weight; 95% CI 1.15, 1.82) and use of Foley plus oxytocin (aOR 4.40; 95% CI 1.36, 14.23). CONCLUSION: In our model, higher birth weight and induction method of Foley followed by oxytocin were associated with increased need for additional uterotonics. This data adds detail to previous studies that have broadly identified induction of labor as a risk factor for postpartum hemorrhage.

LBA8003 Background: PemC and PCB are regimens used for first-line treatment of advanced NS-NSCLC. The primary objective was to compare progression-free survival without Grade 4 toxicity (G4PFS) between two vs three drug regimen arms. Methods: Patients ≥18 years, Stage IV NS NSCLC, AJCC (v7.0), and ECOG PS 0/1 were enrolled. Patients were randomized (1:1); received 4 cycles of induction (PemC: Pem, 500 mg/m2 and C, AUC = 6; PCB: P, 200 mg/m2, C, AUC = 6, and B, 15 mg/kg) followed by Pem (PemC Arm) or B (PCB Arm) maintenance therapy in the absence of progressive disease or discontinuation. Secondary endpoints were PFS, overall survival (OS), overall response rate (ORR), and disease control rate (DCR). The study was powered for G4PFS; assuming hazard ratio (HR) of 0.75; there was 80% power to detect superiority of PemC over PCB with a 2-sided type I error of 0.10. Efficacy data were analyzed by intent-to-treat principle using the log-rank test for time-to-event variables, and an exact test for ORR and DCR. Safety data were evaluated using CTCAE v3 for patients who received ≥1 dose of study treatment. Results: Patients were randomized to PemC (N = 182) or PCB (N = 179). Baseline factors were balanced between arms: median age 66/66 years; % female 42/42; % PS=0, 47/47; % stage IV M1a 29/30; for PemC vs PCB, median G4PFS (months) was 3.91/2.86 (HR = 0.85, 90% CI 0.7, 1.04, p = 0.176); PFS and OS had HR = 1.06 (95% CI 0.84, 1.35), p = 0.610, and HR = 1.07 (95% CI 0.83, 1.36), p = 0.616, respectively. The ORR (%) 23.6/ 27.4 and DCR (%) 59.9/57.0 were for PemC vs PCB, respectively. Significantly more drug-related grade 3/4 anemia (18.7% vs 5.4%), and thrombocytopenia (24.0% vs 9.6%) were seen on PemC; significantly more grade 3/4 neutropenia (48.8% vs 24.6%) and grade 1/2 alopecia (28.3 % vs 8.2%) were seen on PCB. Conclusions: PemC was not superior to PCB in G4PFS; no difference in PFS or OS was observed for the two- vs three-drug regimens. There were no unexpected toxicities; the toxicity profiles demonstrated distinctions by arm, and both regimens demonstrated tolerability. Clinical trial information: NCT00948675.

PURPOSE: A significant number of patients with stage T1 bladder carcinoma are at risk for cancer progression. We sought to identify factors associated with cancer progression in a series of patients with stage T1 bladder carcinoma treated with a contemporary therapeutic approach. PATIENTS AND METHODS: The study population consisted of 83 consecutive patients in whom stage T1 bladder carcinoma was diagnosed at the Mayo Clinic between 1987 and 1992. All patients underwent transurethral resection of the bladder (TURB) and had histologic confirmation of the diagnosis. The mean age was 71 years (range, 47 to 94 years). The male-to-female ratio was 3.9:1. The mean length of follow-up was 5.2 years (range, 1 day to 10.4 years). The depth of lamina propria invasion in the TURB specimens was measured with an ocular micrometer. Cancer progression was defined as the development of muscle-invasive or more advanced stage carcinoma, distant metastasis, or death from bladder cancer. RESULTS: The overall 5- and 7-year progression-free survival rates were 82% and 80%, respectively. The depth of invasion in the TURB specimens was associated with cancer progression (hazards ratio, 1.6 for doubling of depth of invasion; 95% confidence interval, 1.03 to 2.4; P = .037). The 5-year progression-free survival rate for patients with depth of invasion of ≥ 1.5 mm was 67%, compared with 93% for those with depth of invasion of less than 1.5 mm (P = .009). No other variable, including age, sex, tobacco use, alcohol use, the presence of carcinoma-in-situ, histologic grade, lymphocytic infiltration, or muscularis mucosae invasion, was associated with cancer progression. CONCLUSION: The depth of invasion in the TURB specimens, measured with a micrometer, is predictive of cancer progression in patients with stage T1 bladder carcinoma.

A large cohort consisting of all children born to mothers from community provides ‘natural’ selection into different exposures and is a powerful resource for epidemiological research. A large population-based birth cohort with detailed systematic information already recorded, as part of longitudinal medical care, historical and current school data, detailed birth certificate data and all three resources available for every member of the birth cohort, are extremely rare. Our population-based birth cohort consists of all children born between 1976 and 2000 to mothers residing in Olmsted County, Minnesota, at the time of child's birth (N=39 890). In this paper, we provide a comprehensive report of the method describing the identification, the characteristics and longitudinal follow-up of each child (and family members) from the birth cohort, wealth of complementary resources of data and study measures and designs (retrospective, combined retrospective/prospective). In the last decade or so, we obtained scientific and clinically needed answers for incidence rates, potential risk/protective factors, treatment, comorbidities, outcomes, cost/usage and potential biases (that are always assessed and clinically interpreted) of many developmental learning and behavioural disorders (DLBDs) including learning and attention-deficit/hyperactivity disorders, intellectual disability, speech-language impairment and autism spectrum disorder. Many current and future questions related to DLBDs are remaining to be answered. The Olmsted County Birth Cohort (OCBC) is an example of a comprehensive, contemporary epidemiological research model for the development of similar research infrastructures, and its current and future results are important for replication and comparison with other population-based retrospective and prospective birth cohort studies.