Citations

Secretory carcinoma is a special-type breast carcinoma underpinned by a recurrent t(12;15)(p13;q25) translocation resulting in ETV6-NTRK3 gene fusion. Immunohistochemistry (IHC) using a pan-TRK antibody has been recently shown to help identify NTRK rearrangements in other tumor types. The purpose of this study was to assess the diagnostic utility of pan-TRK IHC in secretory carcinoma of the breast. Pan-TRK IHC was performed using a rabbit monoclonal antibody on whole sections of 24 breast secretory carcinomas and tissue microarray sections of other breast carcinoma types (n=203) and histologic mimics (n=15). Cases were assessed for staining intensity and localization. The 24 patients with secretory carcinoma had a median age of 44 years and a median tumor size of 1.0 cm. ETV6 fluorescence in situ hybridization was positive in all cases tested (n=20). Twenty-three cases (95.8%) showed staining with pan-TRK, which was exclusively nuclear in 19, primarily nuclear with weak cytoplasmic staining in 3, and primarily cytoplasmic with focal nuclear staining in 1. The nuclear staining was diffuse in 17 and at least focally strong in 17. The only pan-TRK negative case was a core biopsy with limited tumor. Among the 203 nonsecretory carcinomas, 21 (10.3%) showed focal, weak nuclear staining in <5% of tumor cells and 1 (0.5%) showed focal membranous staining. All histologic mimics were negative. In conclusion, diffuse and/or at least focally strong nuclear pan-TRK staining is a sensitive and specific marker for secretory carcinoma of the breast.

Purpose To report the return‐to‐duty rate and surgical outcomes in a military population after mini‐open arthroscopic‐assisted surgery for femoroacetabular impingement (FAI) in an effort to affirm its efficacy. Methods A retrospective review of consecutive active‐duty patients receiving mini‐open arthroscopic‐assisted surgery for FAI between 2007 and 2011 was performed. Patients younger than 18 years, non–active‐duty patients, and patients with prior hip surgery were excluded. Demographic, radiographic, and duty‐status data were collected. The primary outcome measure was a return to duty. Outcome scores were obtained in a proportion of the cohort, including the modified Harris Hip Score, Single Assessment Numeric Evaluation score, Western Ontario and McMaster Universities Osteoarthritis Index score, patient satisfaction score, and Veterans RAND 12 (VR‐12) score. All patients had achieved a minimum of 1 year of follow‐up at the time of assessment. All P values for significance were set at .05 or lower. Results Of 182 patients (average age, 30.4 years), 156 (86%) were available for follow‐up with return‐to‐duty data at an average of 2.8 years (range, 1‐6 years). Of the patients, 78% returned to full duty (53%) or returned to duty with restrictions (25%). Outcome scores were available for 101 of 182 patients (55%) with duty rates similar to the total cohort (81% who returned to duty: 58% with no restrictions and 23% with restrictions). Return to duty correlated with improved outcomes compared with those who were medically discharged with respect to the modified Harris Hip Score (68.2 vs 54.5, P < .03), Single Assessment Numeric Evaluation score (48.2 vs 25.3, P < .02), and VR‐12 physical (39.7 vs 33.2, P < .05) and VR‐12 mental (54.5 vs 43.4, P < .005) scores. Conclusions Mini‐open arthroscopic‐assisted surgery for FAI is successful in returning most service members to duty at short‐term follow‐up. Return correlates with improved outcome scores, although previously reported minimally clinical important difference and patient acceptable symptomatic state threshold values were not uniformly achieved. Level of Evidence Level IV, retrospective case series.

Background: There are many risk factors for shoulder and elbow injuries in professional baseball pitchers. The elbow carrying angle has not been studied as a potential risk factor. Purpose/Hypothesis: The aim of this study was to determine whether elbow carrying angle is a risk factor for shoulder or elbow injuries in professional baseball pitchers. We hypothesized that pitchers with a higher elbow carrying angle would be less likely to sustain an injury during the season than pitchers with a lower elbow carrying angle. Study Design: Cohort study; Level of evidence, 2. Methods: All professional pitchers for a single baseball club during the 2018 season had the carrying angle of both elbows measured at spring training by a single examiner. The pitchers were followed prospectively throughout the season. Shoulder and elbow injuries were recorded prospectively. Results: A total of 52 pitchers (21 [40%] Major League Baseball and 31 [60%] Minor League Baseball) were included. During the season, 23 (44%) pitchers became injured. The mean carrying angle in the throwing arm was 12.5° ± 4.2° versus 9.9° ± 2.8° in the nonthrowing arm ( P < .001). Comparing the injured and noninjured groups, there were no differences in level of play ( P = .870), throwing hand dominance ( P = .683), batting hand dominance ( P = .554), throwing-side carrying angle ( P = .373), nonthrowing-side carrying angle ( P = .773), or side-to-side difference in carrying angle ( P = .481). Conclusion: The elbow carrying angle was not associated with an injury risk during a single season in professional baseball pitchers.

Abstract Background: Smoking has been associated with colorectal cancer (CRC) risk; but limited evidence has shown the association between smoking and molecular subtypes of CRC. Methods: We analyzed 9,422 CRC cases and 9,950 controls from 10 observational studies. Multinomial logistic regression analysis was performed to assess the association between sex-study-specific quartiles of pack years of smoking and risk of CRC molecular subtypes, using non-smokers as reference group, adjusting for age, sex, and study. Known oncogenic mutations in four somatic colorectal tumor markers were assessed individually and in combination, including BRAF mutations, KRAS mutations, CpG island methylator phenotype (CIMP), and microsatellite instability (MSI) status. Case-only analysis was also performed to estimate heterogeneity in risk of molecular subtypes of CRC. Results: Compared with controls, higher pack years of smoking were statistically significantly associated with increased CRC risk when stratified, individually, by all four markers, and the associations got stronger with higher quartiles pack years (p-trend&lt;0.001). Associations between smoking and CRC risk also differed significantly among molecular subtypes. Compared to nonsmokers, the risk of BRAFmut CRC was 83% higher for smokers within the highest quartile of pack-years (OR=1.83; 95% CI: 1.50, 2.25), and 29% higher for BRAFwt CRC (OR=1.29; 95% CI: 1.17, 1.43; Ratio of ORs (ROR)=1.45; 95% CI: 1.18, 1.17; p=3.45x10-4). Similarly, heavy pack-years of smoking was associated with almost two times higher risk of CIMP-high CRC (OR=1.93; 95% CI: 1.60, 2.31), but only 33% higher risk of CIMP-low/negative CRC (OR=1.33; 95% CI: 1.19, 1.48; ROR=1.49; 95% CI: 1.24, 1.79; p=1.72x10-5). The association between smoking and CRC was also stronger in MSI-high tumors (ORMSI-H=1.65; 95% CI: 1.36, 2.00; ORMSI-L/MSS=1.37; 95% CI: 1.23, 1.52; ROR=1.22; 95% CI: 1.00, 1.48; p=0.046). In contrast, the association between smoking and CRC risk was stronger for KRASwt (OR=1.43; 95% CI: 1.27, 1.60), than KRASmut tumors (OR=1.18; 95% CI: 1.02, 1.37; ROR=0.83; 95% CI: 0.71, 0.97; p =0.016). When combining tumor markers, smoking was found to be significantly associated with higher risk of colorectal tumors from the serrated pathway. Conclusion: In this largest study with a total of 19,372 subjects, we found that heavier pack years of smoking was associated with increased risk of all CRC molecular subtypes. Smokers with heavier pack-years of smoking had particularly higher risk of CRC subtypes with BRAF mutation and CIMP-high, suggesting smoking may be particularly involved in the development of these subtypes of colorectal tumor. Citation Format: Xiaoliang Wang, Efrat Amitay, Barbara L. Banbury, Hermann Brenner, Daniel D. Buchanan, Peter T. Campbell, Jenny Chang-Claude, Steven J. Gallinger, Graham G. Giles, Tabitha A. Harrison, John L. Hopper, Mark A. Jenkins, Yi Lin, Reiko Nishihara, Polly A. Newcomb, Shuji Ogino, Lori C. Sakoda, Robert E. Schoen, Martha L. Slattery, Steven N. Thibodeau, Bethany Van Guelpen, Michael O. Woods, Li Hsu, Michael Hoffmeister, Ulrike Peters. Smoking is associated with risks of molecular subtypes of colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 630.

Adults with cancer are at risk of restricted functioning in work, usual activities, life roles, and quality of life both during and after cancer treatment. Herein, the authors discuss unique opportunities to examine how cancer rehabilitation, delivered as part of cancer and survivorship care, might help to achieve the quadruple aim of better patient health, better patient experience, and lower cost for patients who receive services, as well as improving the work life of clinicians and staff.

Abstract Rationale Less invasive, nonsurgical approaches are needed to treat severe emphysema. Objectives To evaluate the effectiveness and safety of the Spiration Valve System (SVS) versus optimal medical management. Methods In this multicenter, open-label, randomized, controlled trial, subjects aged 40 years or older with severe, heterogeneous emphysema were randomized 2:1 to SVS with medical management (treatment) or medical management alone (control). Measurements and Main Results The primary efficacy outcome was the difference in mean FEV1 from baseline to 6 months. Secondary effectiveness outcomes included: difference in FEV1 responder rates, target lobe volume reduction, hyperinflation, health status, dyspnea, and exercise capacity. The primary safety outcome was the incidence of composite thoracic serious adverse events. All analyses were conducted by determining the 95% Bayesian credible intervals (BCIs) for the difference between treatment and control arms. Between October 2013 and May 2017, 172 participants (53.5% male; mean age, 67.4 yr) were randomized to treatment (n = 113) or control (n = 59). Mean FEV1 showed statistically significant improvements between the treatment and control groups—between-group difference at 6 and 12 months, respectively, of 0.101 L (95% BCI, 0.060–0.141) and 0.099 L (95% BCI, 0.048–0.151). At 6 months, the treatment group had statistically significant improvements in all secondary endpoints except 6-minute-walk distance. Composite thoracic serious adverse event incidence through 6 months was greater in the treatment group (31.0% vs. 11.9%), primarily due to a 12.4% incidence of serious pneumothorax. Conclusions In patients with severe heterogeneous emphysema, the SVS shows significant improvement in multiple efficacy outcomes, with an acceptable safety profile. Clinical trial registered with www.clinicaltrials.gov (NCT01812447).

Abstract Objective To assess the negative predictive value (NPV) of breast MRI in detecting residual disease after neoadjuvant chemotherapy (NAC) in women with invasive breast cancer, overall and by tumor subtype. Methods An institutional review board approved retrospective study from January 2010 through December 2016 identified patients with invasive breast cancer who achieved complete MRI response to NAC, defined as the absence of residual enhancement in the tumor bed above background parenchymal enhancement. During the study period, it was our routine practice to assign a BI-RADS 1 or 2 assessment to these cases. The NPV was defined as the ability of a complete MRI response to predict pathologic complete response (pCR) at final surgical pathology. Statistical analyses were performed using a Fisher exact test. Results Among 244 patients who underwent MRI to assess NAC response, 38 (16%) were determined to have complete MRI response by the interpreting radiologist. Of these, 20/38 (53%) had pCR. Complete MRI response did not significantly predict pCR for the total group (P &lt; 0.9). However, NPVs significantly varied by molecular subtype (P &lt; 0.004). True negative MRIs by tumor subtype were 2/10 (20%) for hormone receptor (HR)+/HER2–, 3/10 (30%) for HR+/HER2+, 6/8 (75%) for HR–/HER+, and 9/10 (90%) for triple negative (TN) subtypes. Complete MRI response significantly predicted pCR for only the TN subtype (NPV 90%; P &lt; 0.02). Conclusions In patients with complete MRI response, 53% had pCR. While MRI lacks sufficient NPV to obviate the need for surgical excision, it may add prognostic value for certain molecular subtypes. The TN subtype demonstrated the highest NPV.