Heckman, Michael G.

Objective: High GATA2 expression has been associated with an increased risk of poor clinical outcomes after radical prostatectomy; however, this has not been studied in relation to risk of biochemical recurrence (BCR) after salvage radiation therapy (SRT) for recurrent prostate cancer after radical prostatectomy. Our aim was to evaluate the association between protein expression levels of GATA2 in primary prostate cancer tumour samples and the risk of BCR after SRT. Methods: 109 males who were treated with SRT were included. The percentage of cells with nuclear staining and GATA2 staining intensity were both measured. These two measures were multiplied together to obtain a GATA2 H-score (range 0–12) which was our primary GATA2 staining measure. Results: In unadjusted analysis, the risk of BCR was higher for patients with a GATA2 H-score >4 (hazard ratio = 2.04, p = 0.033). In multivariable analysis adjusting for SRT dose, pre-SRT PSA, pathological tumour stage and Gleason score, this association weakened substantially (hazard ratio = 1.45, p = 0.31). This lack of an independent association with BCR appears to be the result of correlations between GATA2 H-score >4 and higher pre-SRT PSA (p = 0.021), higher Gleason score (p = 0.044) and more severe pathological tumour stage (p = 0.068). Conclusion: Higher levels of GATA2 expression appear to be a marker of prostate cancer severity; however, these do not provide independent prognostic information regarding BCR beyond that of validated clinicopathological risk factors. Advances in knowledge: A higher GATA2 expression level appears to be correlated with known measures of prostate cancer severity and therefore is likely not an independent marker of outcome after SRT.

Poly(GP) proteins are a promising pharmacodynamic marker for developing and testing therapeutics for treating C9ORF72 -associated amyotrophic lateral sclerosis.

541 Background: A long wait-time for colectomy for colon cancer should theoretically affect survival but, to date, the association between delay to colectomy and survival remains unresolved. Methods: We studied 4,692 patients who underwent colectomy for colon cancer between 1990 and 2012. Wait-time was defined as the number of days between diagnosis and colectomy. Cox regression models were used to estimate all-cause mortality across wait-time categories. Multivariable analyses were controlled for clinicopathologic variables and Charlson comorbidity index. Results: The number of patients in the wait-time group of 1-28 days was 3,950 (84.2%), 29-84 days was 681 (22.7%), and >84 days was 61 (1.3%). A wait-time of 29-84 days was not associated with an increased risk of death (HR=1.13; p=0.056) when compared to a wait-time of 1-28 days. Though a wait-time >84 days represented a small group, it was associated with an increased risk of death (HR=1.60; p=0.013). For patients with stage I and II disease, wait-times of 29-84 days (HR =1.44; p=0.0001) and >84 days (adjusted HR=2.24; p=0.0007) were associated with an increased risk of mortality. Conclusions: A wait-time for colon cancer surgery of up to 12 weeks is likely safe for most patients. However, those suspected to have early-stage colon cancer may benefit from less of delay. These data provide a framework to address concerns over prolonged wait-times and can direct efforts for timely surgical intervention in patients with colon cancer. [Table: see text]

88 Background: There is not yet a consensus on the efficacy and safety of IMRT for the treatment of patients with esophageal carcinomas. We report on our experience with outcomes and toxicity with IMRT for these patients. Methods: Fifty-five patients with esophageal carcinoma were treated with IMRT at our institution from 12/2008 and 12/2014. Medical records were retrospectively reviewed. All patients received concurrent chemotherapy (majority 5-FU with oxaliplatin). Thirty-one (56%) patients underwent surgery. Fifty (91%) received 50.4 Gy in 28 fractions. Seventy-three percent of cases were adenocarcinoma. Regions include mid-thoracic (15%), lower thoracic (64%), and GE junction (22%). Clinical uT-stages were as follows: T1 (2%), T2 (20%), T3 (69%), and T4a (5%). Clinical N-stages were as follows: N0 (33%), N1 (53%), N2 (13%), and N3 (2%). Results: Median follow-up for all patients was 15 months (1.5 - 64.5) and 25.5 months (1.5 - 64.5) for patients who were alive at follow-up (n = 31). Fifty-one (93%) patients completed RT. Of the 31 patients who underwent surgery, 9 (29%) were found to have a complete pathologic response. Site of first recurrence was local (n = 2, 4%), regional (n = 3, 6%), and distant (n = 14, 26%). At 12 and 24 months, overall survival was 72% and 58%, freedom from recurrence was 78% and 65%, and freedom from distant recurrence was 78% and 68%. On univariate analysis, improved OS was noted with patients who underwent surgery (RR 0.29) or were cN0 (RR 0.27). Twenty eight patients (51%) experienced > / = CTCAE v.4grade 3 acute toxicity; notable were hematologic (n = 14, 25%), esophagitis (n = 6, 11%), acute coronary event (n = 1, 2%), and post-chemoRT pneumonia (n = 1, 2%). Fifteen patients (31%) experienced > grade 3 late toxicity; notable were esophageal stricture (n = 7, 14%), post-op pneumonia (n = 3, 6%), post-CRT pneumonia (n = 2, 4%), and COPD exacerbation (n = 1, 2%). Conclusions: Patient receiving IMRT with concurrent chemotherapy for esophageal carcinomas have good LC rates, with or without surgery. Majority of patients are able to finish treatment with acceptable rates of late toxicity. Patient who underwent surgery or were cN0 had better OS.

ABSTRACTBackgroundMutations in the leucine‐rich repeat kinase 2 gene (LRRK2) are the most common genetic cause of Parkinson's disease (PD). Unexpectedly, tau pathology has been reported in a subset of LRRK2 mutation carriers.MethodsTo estimate the frequency of pathogenic LRRK2 mutations and to evaluate the association of common LRRK2 variants with risk of primary tauopathies, we studied 1039 progressive supranuclear palsy (PSP) and 145 corticobasal degeneration patients from the Mayo Clinic Florida brain bank and 1790 controls ascertained at Mayo Clinic. Sanger sequencing of LRRK2 exons 30, 31, 35, and 41 was performed in all patients, and genotyping of all 17 known exonic variants with minor allele frequency >0.5% was performed in patients and controls.ResultsLRRK2 mutational screening identified 2 known pathogenic mutations (p.G2019S and p.R1441C), each in 1 PSP patient, the novel p.A1413T mutation in a PSP patient and the rare p.R1707K mutation in a corticobasal degeneration patient. Both p.A1413T and p.R1707K mutations were predicted damaging by at least 2 of 3 prediction programs and affect evolutionary conserved sites of LRRK2. Association analysis using common LRRK2 variants only showed nominal association of the p.L153L variant with PSP.ConclusionsOur study confirms the presence of pathogenic and potentially pathogenic LRRK2 mutations in pathologically confirmed primary tauopathies, albeit with low frequency. In contrast to PD, common LRRK2 variants do not appear to play a major role in determining PSP and corticobasal degeneration risk. © 2016 International Parkinson and Movement Disorder Society.

Background: Bone marrow aspirate concentrate (BMAC) is increasingly used as a regenerative therapy for musculoskeletal pathological conditions despite limited evidence-based support. Hypothesis: BMAC will prove feasible, safe, and efficacious for the treatment of pain due to mild to moderate degenerative joint disease of the knee. Study Design: Randomized controlled trial; Level of evidence, 2. Methods: In this prospective, single-blind, placebo-controlled trial, 25 patients with bilateral knee pain from bilateral osteoarthritis were randomized to receive BMAC into one knee and saline placebo into the other. Fifty-two milliliters of bone marrow was aspirated from the iliac crests and concentrated in an automated centrifuge. The resulting BMAC was combined with platelet-poor plasma for an injection into the arthritic knee and was compared with a saline injection into the contralateral knee, thereby utilizing each patient as his or her own control. Safety outcomes, pain relief, and function as measured by Osteoarthritis Research Society International (OARSI) measures and the visual analog scale (VAS) score were tracked initially at 1 week, 3 months, and 6 months after the procedure. Results: There were no serious adverse events from the BMAC procedure. OARSI Intermittent and Constant Osteoarthritis Pain and VAS pain scores in both knees decreased significantly from baseline at 1 week, 3 months, and 6 months ( P ≤ .019 for all). Pain relief, although dramatic, did not differ significantly between treated knees ( P > .09 for all). Conclusion: Early results show that BMAC is safe to use and is a reliable and viable cellular product. Study patients experienced a similar relief of pain in both BMAC- and saline-treated arthritic knees. Further study is required to determine the mechanisms of action, duration of efficacy, optimal frequency of treatments, and regenerative potential. Registration: ClinicalTrials.gov record 12-004459.

AbstractBackground/AimsInadequate bowel preparations can necessitate early repeat of colonoscopy and increased healthcare costs. Established risk factors for suboptimal bowel preparation are known, yet data are lacking in the specific subgroup of patients with decompensated cirrhosis. The primary aim of this study was to reduce inadequate bowel preparation rates in patients with decompensated cirrhosis undergoing evaluation for liver transplant via a quality improvement initiative targeting patient education.MethodsA total of 121 patients undergoing evaluation at our institution prior to implementation of the quality improvement initiative and 91 patients undergoing evaluation after implementation were included. The initiative was an educational intervention via a 6‐minute colonoscopy and split‐prep bowel preparation educational video during the initial liver transplantation evaluation visit for all patients with scheduled colonoscopy.ResultsInadequate bowel preparation was observed in 36 patients (29.8%) in the pre‐intervention period compared to 29 patients (31.9%) in the post‐intervention period. This corresponded to a lack of a significant difference in both single‐variable analysis and multivariable analysis. Of note, there was a significantly higher rate of inadequate bowel preparation as ascites worsened (P=.028).ConclusionPatient educational video failed to improve bowel preparations in patients undergoing colonoscopy with decompensated cirrhosis.