Citations

Introduction: The increasing use of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) cytology to examine pancreatic neoplasms has led to an increase in the diagnosis of metastases to the pancreas. Renal cell carcinoma (RCC) is the most common metastasis to the pancreas. Our study examines 33 cases of metastatic RCC to the pancreas sampled by EUS-FNA from four large tertiary care hospitals. Materials and Methods: We searched the cytopathology database for RCC metastatic to the pancreas diagnosed by EUS-FNA from January 2005 to January 2015. Patient age, history of RCC, nephrectomy history, follow-up postnephrectomy, radiological impression, and EUS-FNA cytologic diagnosis were reviewed. Results: Thirty-three patients were identified. The average age was 67.5 years (range, 49–84 years). Thirty-two patients had a previous documented history of RCC. One patient had the diagnosis of pancreatic metastasis at the same time of the kidney biopsy. Thirty-one patients had been treated with nephrectomy. Twenty-seven patients were being monitored annually by computed tomography or magnetic resonance imaging. Twenty-five patients had multiple masses by imaging, but 8 patients had a single mass in the pancreas at the time of EUS-FNA. EUS-FNA of 20 cases showed classic morphology of RCC. Thirteen cases had either “atypical” clinical-radiologic features or morphologic overlaps with primary pancreatic neoplasms or other neoplasms. Cell blocks were made on all 13 cases and immunochemical stains confirmed the diagnosis. Conclusions: EUS-FNA cytology is useful for the diagnosis of metastatic RCC to the pancreas. Cytomorphology can be aided with patient history, imaging analyses, cell blocks, and immunochemical stains.

Venous thromboembolism (VTE), a disease that includes deep venous thrombosis (DVT) and pulmonary embolism (PE), is associated with high mortality, morbidity, and costs. It can result in long-term complications that include postthrombotic syndrome (PTS) adding to its morbidity. VTE affects 1/1000 patients, costs $13.5 billion annually to treat, and claims 100,000 lives annually in the US. The current standard of care for VTE is anticoagulation, though thrombolysis may be performed in patients with PE and threatened limb. This review discusses pathogenesis and medical treatment of VTE and then focuses on endovascular treatment modalities. Mechanical- and catheter-directed thrombolysis (CDT) is discussed, as well as patient selection criteria, and complications. The first prospective study (CaVenT) comparing CDT with anticoagulation alone in acute DVT, despite study shortcomings, corroborates the existing literature indicating improved outcomes with CDT. The potential of the ongoing prospective, multicenter, randomized ATTRACT trial is also highlighted.

Adolescents with postural orthostatic tachycardia syndrome (POTS) often have pain and functional impairment. This study evaluated how parental attributions of children’s symptoms relate to child functional impairment. Adolescents with chronic pain and clinical symptoms suggestive of autonomic dysfunction (fatigue, dizziness, nausea) that attended a multidisciplinary chronic pain clinic completed measures of depression, anxiety, and functioning (n = 141). Parents of 114 of these patients completed the Parent Pain Attribution Questionnaire (PPAQ), a measure indicating the extent they believe physical and psychosocial factors account for their child’s health condition. Patients were retrospectively grouped as to whether or not they had significant POTS on tilt table testing (n = 37). Greater parental attribution to physical causes was associated with increased levels of functional disability whether patients had POTS ( r = 0.45, P = .006) or not ( r = 0.25, P = .03). These results suggest that providers should advocate a more comprehensive family-oriented rehabilitative approach to treatment.

ObjectiveSystemic lupus erythematosus (SLE) and other autoimmune diseases cause significant morbidity. Identifying populations at risk of developing SLE is essential for curtailing irreversible inflammatory damage. The aim of this study was to identify factors associated with transition to classified disease that would inform our understanding of the risk of SLE.MethodsPreviously identified blood relatives of patients with SLE, who had <4 American College of Rheumatology (ACR) classification criteria for SLE at baseline, were enrolled in this follow‐up study (n = 409 unaffected relatives). Participants provided detailed family, demographic, and clinical information, including the SLE‐specific portion of the Connective Tissue Disease Screening Questionnaire (SLE‐CSQ). Serum and plasma samples were tested for the presence of lupus‐associated autoantibodies and 52 soluble mediators. Generalized estimating equations (GEEs) were applied to identify factors predictive of disease transition.ResultsOf the 409 unaffected relatives of SLE patients, 45 (11%) had transitioned to classified SLE at follow‐up (mean time to follow‐up 6.4 years). Relatives who transitioned to SLE displayed more lupus‐associated autoantibody specificities and higher SLE‐CSQ scores (P < 0.0001) at baseline than did relatives who did not transition. Importantly, those who had developed SLE during the follow‐up period also had elevated baseline plasma levels of inflammatory mediators, including B lymphocyte stimulator, stem cell factor (SCF), and interferon‐associated chemokines (P ≤ 0.02), with concurrent decreases in the levels of regulatory mediators, transforming growth factor β (TGFβ), and interleukin‐10 (P ≤ 0.03). GEE analyses revealed that baseline SLE‐CSQ scores or ACR scores (number of ACR criteria satisfied) and plasma levels of SCF and TGFβ, but not autoantibodies, were significant and independent predictors of SLE transition (P ≤ 0.03).ConclusionPreclinical alterations in levels of soluble mediators may predict transition to classified disease in relatives of SLE patients. Thus, immune perturbations precede SLE classification and can help identify high‐risk relatives for rheumatology referral and potential enrollment in prevention trials.

ObjectiveWe investigated the relationships between glucocorticoid use, disease activity, and changes in body mass index (BMI) in patients with antineutrophil cytoplasmic antibody–associated vasculitis (AAV).MethodsWe analyzed AAV patients enrolled in the Rituximab in AAV trial. Glucocorticoid use, BMI, and disease activity were measured regularly during the trial period. We performed mixed‐effects regressions to examine the associations of time‐dependent cumulative average glucocorticoid use and disease activity with changes in BMI over time, while adjusting for potential confounders.ResultsThe mean ± SD baseline BMI of the 197 patients enrolled was 28.8 ± 6.3 kg/m2. Patients with newly diagnosed AAV tended to have a lower mean ± SD BMI than those with relapsing disease (28.0 ± 5.7 kg/m2 versus 29.6 ± 6.8 kg/m2) and higher disease activity (mean ± SD Birmingham Vasculitis Activity Score for Wegener's Granulomatosis 8.7 ± 3.3 versus 7.4 ± 2.7). The most significant change in BMI occurred during the first 6 months of the trial (mean ± SD increase of 1.1 ± 2.2 kg/m2; P < 0.0001). Disease activity improvement, glucocorticoid exposure, and randomization to rituximab were each independently associated with an increase in BMI (P < 0.001 for all analyses).ConclusionOur findings suggest that changes in BMI, as well as glucocorticoid exposure, are independently associated with improvements in disease activity in AAV. Rituximab may also have effects on BMI independent of its impact on disease activity.

Abstract Background: The precise mechanism by which the immune system is adversely affected in cancer patients remains poorly understood, but the accumulation of immunosuppressive/protumorigenic myeloid-derived suppressor cells (MDSCs) is thought to be a prominent mechanism contributing to immunologic tolerance of malignant cells in epithelial ovarian cancer (EOC). To this end, we hypothesized genetic variation in MDSC pathway genes would be associated with survival after EOC diagnoses. Methods: We measured the hazard of death due to EOC within 10 years of diagnosis, overall and by invasive subtype, attributable to SNPs in 24 genes relevant in the MDSC pathway in 10,751 women diagnosed with invasive EOC. Versatile Gene-based Association Study and the admixture likelihood method were used to test gene and pathway associations with survival. Results: We did not identify individual SNPs that were significantly associated with survival after correction for multiple testing (P &lt; 3.5 × 10−5), nor did we identify significant associations between the MDSC pathway overall, or the 24 individual genes and EOC survival. Conclusions: In this well-powered analysis, we observed no evidence that inherited variations in MDSC-associated SNPs, individual genes, or the collective genetic pathway contributed to EOC survival outcomes. Impact: Common inherited variation in genes relevant to MDSCs was not associated with survival in women diagnosed with invasive EOC. Cancer Epidemiol Biomarkers Prev; 26(3); 420–4. ©2016 AACR.

Abstract Background: Pathologic complete response (pCR) is an established prognostic biomarker for aggressive HER2+ breast cancer (BC). Improving pCR rates may identify new therapies that improve survival. Pertuzumab (P) has established survival benefit in the metastatic setting, and received accelerated approval in the neoadjuvant setting when combined with trastuzumab (H) and docetaxel(D) as part of a complete treatment regimen for early breast cancer. We tested its ability, when combined with standard therapy (paclitaxel, T, and H) to improve pCR (ypT0ypN0) over TH in the adaptively randomized, phase II, I-SPY 2 neoadjuvant trial. Methods: Enrolled patients (pts) had invasive BC ?2.5 cm in HER2-positive subsets. Pts were adaptively randomized to control (TH, qwk x 12) or THP (P, q3wk x 4) followed by doxorubicin/cyclophosphamide (AC) x 4 and surgery. To compare THP to TH we utilized all control pts accrued over the course of the trial, adjusting for potential differences due to time period treated, which were informed by the several other treatment arms that have been in the trial. Adaptive assignment to the experimental arms was based on current Bayesian probabilities of superiority over control. “Graduation” by signature and futility stopping were based upon Bayesian predictive probability of success in a 2-arm, N = 300 phase III randomized 1:1 trial of THP vs. TH with pCR endpoint. Results: THP met the predictive probability criterion and graduated in 3 signatures: all HER2+, HER2+/HR+, and HER2+/HR- (See Table 1). Final accrual: 44 THP and 31 TH. Safety data will be shown. Conclusions: I-SPY 2's standing platform trial efficiently evaluates agents in biomarker-defined pt subsets. THP -&gt; AC substantially improves pCR rates over standard TH -&gt; AC in all 3 HER2+ signatures, including HR+ and HR- subsets. APHINITY, a trial of adjuvant pertuzumab with a primary outcome of invasive disease-free survival, is ongoing. Table 1Signature*Estimated pCR Rate (95% probability interval)Signature*THPControl (TH)Probability THP Is Superior to ControlPredictive Probability of Success in Phase IIIHER2+54% (38%-70%)22% (5%-39%)99.8%96%HER2+/HR+44% (24%-63%)17% (0%-34%)99%91%HER2+/HR-74% (53%-95%)33% (6%-59%)99.8%98%*HR = Hormone Receptor Citation Format: Meredith Buxton, Angela M. DeMichele, Stephen Chia, Laura van't Veer, Jo Chien, Anne Wallace, Henry Kaplan, Julie Lang, Douglas Yee, Claudine Isaacs, Stacy Moulder, Kathy Albain, Judy Boughey, Kathleen Kemmer, Barbara Haley, Susan Minton, Andres Forero, Rita Nanda, Anthony Elias, Larissa Korde, Rebecca Viscuzi, Hope Rugo, Richard Schwab, Fraser Symmans, Melissa Paoloni, Nola Hylton, Michael Hogarth, Julia Lyandres, Jane Perlmutter, Ashish Sanil, Christina Yau, Laura Esserman, Don Berry, I-SPY 2 TRIAL Investigators. Efficacy of pertuzumab/trastuzumab/paclitaxel over standard trastuzumab/paclitaxel therapy for HER2+ breast cancer: Results from the neoadjuvant I-SPY 2 TRIAL. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT106.