Citations

e14048 Background: Cancer associated macrophage like cells (CAMLs), a circulating stromal cell subtype, has been shown as an independent prognostic indicator of survival in late stage metastatic breast cancer when cells enlarge to ≥50µm. However, no study has evaluated the clinical relationship between changes in CAML size and their ability to predict treatment response. While CAMLs are prognostic for progression, we hypothesized that monitoring changes in CAMLs after initiation of therapy may be predictive for responsiveness of new treatment regimens. Methods: A prospective 12 months blind multi-institutional pilot study was undertaken to evaluate CAMLs before, and after, induction of a new line of investigational therapy based on CT scans. Patients with progressive metastatic breast cancer (n = 29) who had failed at least 2 prior therapies were recruited. A baseline (BL) blood sample was taken prior to induction of a new therapy and a 2nd sample (T1) taken after initiation (~30 days). Blood was filtered by CellSieve filtration.The quantities and sizes of CAMLs were analyzed based on PFS hazard ratios (HRs) by censored univariate analysis. Results: CAMLs were found in 97% of BL samples and 93% of T1 samples. At first CT scan, after the assigned dose of investigational treatment, 17 of 29 patients had clinical progression with 14/17 (82%) patients having an increased CAML size and 3/17 (18%) having a decreased CAML size. The remaining 12 of 29 patients saw clinically stable, or regression, of disease with 10/12 (83%) having decreased CAML size and 2/12 (17%) having increased CAML size. Overall CAML size change after therapy induction was 83% accurate at predicting response or progression based on CT scans. Further, patients with increasing CAML size at T1 had a 4 month mPFS vs 10 month mPFS for decreasing CAMLs, with a lower 12 month PFS HR = 3.7 (95%CI = 1.5-10.1, p = 0.020). Conclusions: Our data suggests that in metastatic breast cancer, monitoring CAMLs changes over the first 30 days of treatment accurately predicts responsiveness of disease to new treatments. Further, we suggests using blood sampling may increase the clinical value of blood based diagnostics by rapidly predicting the benefit of subsequent therapies.

In 2011, we initiated a sentinel surveillance network to assess changes in Clostridioides (formerly Clostridium ) difficile antimicrobial susceptibility to fidaxomicin from 6 geographically dispersed medical centers in the United States. This report summarizes data from 2013 to 2016. C. difficile isolates or toxin-positive stools from patients were referred to a central laboratory. Antimicrobial susceptibility was determined by agar dilution. CLSI, EUCAST, or FDA breakpoints were used, where applicable.

Abstract Background: This analysis aimed to determine if associations of prediagnostic mammographic percent breast density, absolute dense area, and absolute non-dense area and risk of breast cancer vary according to the subsequent breast tumors biomarker status. Methods: We included 1,154 postmenopausal women diagnosed with breast cancer between June 1, 1989, and June 30, 2004, and 2,078 matched controls from the Nurses' Health Study I and II. Percent breast density, absolute dense and non-dense areas were estimated from digitized film mammograms using computer assisted thresholding techniques. Density measures were modeled as quartiles. Information on estrogen receptor (ESR1 [ER]), progesterone receptor (PGR [PR]), and human epidermal growth factor receptor 2 (ERBB2 [HER2]) status was obtained from pathology reports and medical records, and if missing, from immunostains performed on paraffin sections of tumor tissue microarrays (TMAs). Other biomarkers assessed on TMAs were androgen receptor (AR), cytokines 5/6 (KRT5/KRT6 [CK5/6]), epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGFA [VEGF]), and cyclooxygenase 2 (PTGS2 [COX2]). Information on breast cancer risk factors was obtained prospectively from biennial questionnaires before the date of cancer diagnosis for cases and matched controls. Polychotomous logistic regression was used to assess associations of the three breast density measures with tumor subtypes based on the status of selected tissue markers. Results: Breast cancer risk was positively associated with percent density and absolute dense area and inversely associated with absolute non-dense area (p for trend<0.0001 for all). The associations of percent density with breast cancer risk did not statistically significantly differ by the status of any of the markers. However, we found stronger positive associations for absolute dense area and KRT5/KRT6- and EGFR- tumors as compared to respective marker-positive tumors (4th vs. 1st quartile: OR=2.99 for KRT5/KRT6- vs. OR=0.92 for KRT5/KRT6+ tumors, p-heterogeneity <0.001; OR=3.06 for EGFR- vs. OR=1.08 for EGFR+ tumors, p-heterogeneity=0.001). Stronger inverse associations of absolute non-dense area with breast cancer risk were found for ESR1- as compared to ESR1+ tumors, and for AR+, KRT5/KRT6+, and EGFR+ tumors as compared to respective marker-negative tumors (4th vs. 1st quartile: OR=0.21 for ESR1- vs. OR=0.59 for ESR1+ tumors, p-heterogeneity <0.0001; OR=0.22 for AR+ vs. OR=0.42 for AR- tumors, p-heterogeneity=0.04; OR=0.21 for KRT5/KRT6+ vs. OR=1.14 for KRT5/KRT6- tumors, p-heterogeneity<0.01; OR=0.37 for EGFR+ vs. OR=1.11 for EGFR- tumors, p-heterogeneity<0.01). There were no differences in associations of the density measures with breast cancer by status of other markers evaluated. Conclusions: The findings suggest that some mammographic density measures are differentially associated with the risk of subsequent breast tumor subtypes. Citation Format: Lusine Yaghjyan, Andreas Pettersson, Graham Colditz, Laura Collins, Stuart Schnitt, Andrew Beck, Bernard Rosner, Celine Vachon, Rulla Tamimi. Mammographic breast density and subsequent risk of breast cancer in postmenopausal women according to the status of selected tissue markers: A case-control study. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr PR09.

AbstractThere is limited evidence guiding management of medial collateral ligament (MCL) avulsions or functional disruptions distal to the medial joint line. This study aims to determine outcomes of a series of patients with grade III distal MCL injuries managed with acute surgical repair. Patients with grade III, distal MCL injuries, with or without multiligament involvement were identified. Demographic, clinical examination, and midterm patient-reported outcomes (PRO) data were collected. Clinical follow-up included physical examination and ligamentous stress testing at a minimum of 6 months. PROs included Lysholm's knee scoring scale, Tegner's activity score, and subjective International Knee Documentation Committee (IKDC) scores at minimum of 2 years follow-up. Of the 24 eligible patients, outcomes data were available for 20 (83%). Of the 20 included patients, 16 had a concomitant anterior cruciate ligament (ACL) injury, 3 had ACL and posterior cruciate ligament (PCL) injuries, and 1 had an isolated MCL injury. Mean time from injury to surgery was 5 weeks. At mean clinical follow-up of 20.3 months, all patients showed valgus stability and satisfactory range of motion (ROM). Anteroposterior stability was normal in all but one patient who demonstrated a 2+ posterior drawer but with firm end points. At a mean follow-up of 5.7 years for PROs, mean Lysholm's score was 91.5 (standard deviation [SD] = 12.2), median Tegner's activity score was 7 (range, 4–9), and mean subjective IKDC score was 88.8 (SD: 9.9). The surgical repair of grade III distal MCL injuries delivered satisfactory clinical and functional outcomes. Future comparative studies with larger patient samples are needed.

Abstract Double radial tears of the lateral meniscus are rare injuries that typically occur in the setting of an acute anterior cruciate ligament rupture. Full‐thickness radial tears of the meniscus body and root render the meniscus nonfunctional from a loss of hoop stress resistance. Repair of these tears can normalize contact pressures in the lateral compartment and delay arthritic changes. We describe our technique for repairing a lateral meniscus body radial tear and concomitant posterior root tear, via inside‐out suture repair and transtibial suture repair, respectively. This investigation was performed at Mayo Clinic. Technique Video video See video under supplementary data.

SUMMARY Volumetric laser endomicroscopy (VLE) uses optical coherence tomography (OCT) for real-time, microscopic cross-sectional imaging. A US-based multi-center registry was constructed to prospectively collect data on patients undergoing upper endoscopy during which a VLE scan was performed. The objective of this registry was to determine usage patterns of VLE in clinical practice and to estimate quantitative and qualitative performance metrics as they are applied to Barrett's esophagus (BE) management. All procedures utilized the NvisionVLE Imaging System (NinePoint Medical, Bedford, MA) which was used by investigators to identify the tissue types present, along with focal areas of concern. Following the VLE procedure, investigators were asked to answer six key questions regarding how VLE impacted each case. Statistical analyses including neoplasia diagnostic yield improvement using VLE was performed. One thousand patients were enrolled across 18 US trial sites from August 2014 through April 2016. In patients with previously diagnosed or suspected BE (894/1000), investigators used VLE and identified areas of concern not seen on white light endoscopy (WLE) in 59% of the procedures. VLE imaging also guided tissue acquisition and treatment in 71% and 54% of procedures, respectively. VLE as an adjunct modality improved the neoplasia diagnostic yield by 55% beyond the standard of care practice. In patients with no prior history of therapy, and without visual findings from other technologies, VLE-guided tissue acquisition increased neoplasia detection over random biopsies by 700%. Registry investigators reported that VLE improved the BE management process when used as an adjunct tissue acquisition and treatment guidance tool. The ability of VLE to image large segments of the esophagus with microscopic cross-sectional detail may provide additional benefits including higher yield biopsies and more efficient tissue acquisition. Clinicaltrials.gov NCT02215291

Purpose To compare patellar bone socket and cortical surface fixation techniques for isolated medial patellofemoral ligament (MPFL) reconstruction and determine whether there was a difference in (1) complication rates, including fracture of the patella; (2) redislocation rates; or (3) patient‐reported outcomes. Methods A literature search was conducted following Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. We included patients who underwent isolated MPFL reconstruction for recurrent patellar instability. Patients with confirmed concomitant or prior ipsilateral knee procedures, multiligament injury, or less than 3 months of follow‐up were excluded. Risk‐of‐bias assessment was performed using the Methodological Index for Non‐randomized Studies (MINORS) system. Studies were classified by surgical technique (patellar bone socket group [group S] vs cortical fixation group [group F]), and complications, redislocations, and patient‐reported outcomes were collected. Results A total of 29 studies yielded 981 patients with MPFL reconstruction for inclusion. Of the patients, 620 underwent a patellar bone socket technique and 361 underwent a cortical fixation technique. Patients ranged in age from 11 to 68 years. Patellar fracture rates ranged from 0% to 17% in group S and were 0% in all group F studies. Mean Kujala scores ranged from 83.5 to 93.6 in group S and from 84.4 to 94.5 in group F. Mean Lysholm scores ranged from 84.6 to 91.7 in group S and from 83.5 to 95 in group F. Redislocation rates ranged from 0% to 21% in group S and from 0% to 13% in group F. Although heterogeneous in nature, complication rates ranged from 0% to 28% in group S and from 0% to 4% in group F. Conclusions MPFL reconstruction techniques with patellar bone sockets showed a larger range of complication rates than cortical fixation techniques, although overall, complications remained uncommon. Clinically, the bone socket group had comparable postoperative redislocation rates and patient outcomes to the group treated with cortical fixation techniques. Level of Evidence Level IV, systematic review of Level I through IV studies.