Citations

Purpose To analyze failure rate in 2‐year increments to determine if graft choice changed over time and graft failure rate. Methods A prospective 2002‐2008 database was used to identify risk factors for anterior cruciate ligament (ACL) retear. Subjects who had primary ACL retear with no history of contralateral surgery and 2‐year follow‐up were included. Subjects who underwent a multiligament reconstruction were excluded. Graft type, age, sex, smoking status, body mass index, Marx activity level at index surgery, medial and lateral meniscus status at time of ACL retear, sport played after ACL reconstruction, and clinical site were evaluated. Analysis was repeated using 2002‐2003 (early) and 2007‐2008 (late) 2‐year databases. Analysis of variance with post hoc analysis was performed to detect significant differences in age and Marx score by graft type over time. Results Two‐year follow‐up for graft failure was obtained on 2,497 of 2,692 (93%) subjects. There were 112 of 2,497 (4.5%) ACL retears identified at 2‐year follow‐up. The only predictor that changed between early/late periods was allograft use. Allograft odds ratio decreased from 13.1 to 9.5 ( P < .01). Allografts were used in older patients (31‐40 years) and with lower Marx scores (10‐8) from early to late periods. The mean age of subjects who received bone–patellar tendon–bone autografts did not significantly change over time (22.8‐23.5). The mean age of subjects who received hamstring autografts fell (27.9‐25.5). The mean age of subjects who received allografts rose significantly (31.3‐39.8, P < .01). The mean Marx score of subjects who received bone–patellar tendon–bone and hamstring autografts did not significantly change over time. The mean Marx score of subjects who received allografts decreased significantly ( P < .01). Conclusions After early recognition, allograft use in young active patients was a risk factor for retear; graft choice by surgeons changed in the late period to use of allografts in older and less‐active patients, which correlated with a significant decrease in retear risk. Level of Evidence Level III, case control study.

Abstract By regulating gene expression networks that mediate neoplastic behavior, epigenetic protein complexes are the ultimate effectors of oncogenic pathways. This hierarchical position of epigenetic pathways within the mechanisms that regulate cancer makes them ideal candidates for therapeutic targets. The current work was designed to characterize the role of the K9H3 Histone Methyltransferase (HMT) pathway in mediating oncogenic signals downstream of Aurora Kinase A (AurkA), with the goal of designing efficient combinatorial therapies against PDAC. Affinity protein purification, combined with mass spectrometry, demonstrates that HP1γ isolated from mitotic cells interacts with AurkA and the HMTs, G9a and GLP. We also find that this complex is critical for mitotic progression and cell proliferation. Congruently, treatment of PDAC cells with individual drugs against AurkA or HP1-HMT inhibits cell growth by inducing senescence, a cytostatic response. However, the combination of these agents has a synergistic effect of reducing cell growth in both, monolayer and spheroid cultures to result in a cytotoxic effect. Confocal and electron microscopy, along with cell cycle analysis, demonstrate that the cytotoxic effect of this combination is due to induction of mitotic catastrophe, a distinct form of cell death that occurs during mitosis. Molecularly, the combination of AurkA and HP1-HMT inhibition bypasses G2/M arrest with downregulation of the Chk1-Cdc25c pathway. In vivo treatment of PDAC orthotopic xenografts with the HP1-HMT inhibitor alone demonstrated reduced PDAC growth, and increased efficacy in PDAC growth reduction was observed in combination with the AurkA inhibitor over either individual treatment. Thus, our data demonstrate a novel AurkA-HP1-HMT mitotic pathway that holds promise for potential pharmacological targeting in combinatorial therapy for this malignancy. Citation Format: Angela Mathison, Ann Salmonson, Mckenna Missfeldt, Thiago de Assuncao, Jennifer Bintz, Trace Christensen, Sarah Kossak, Asha Nair, Juan Iovanna, Robert Huebert, Gwen Lomberk. Pharmacological targeting of the Aurora A and Histone 3 lysine 9 methyltransferase pathways in pancreatic cancer induces mitotic catastrophe [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 4060. doi:10.1158/1538-7445.AM2017-4060

Abstract Photon-counting computed tomography (PCCT) uses a photon counting detector to count individual photons and allocate them to specific energy bins by comparing photon energy to preset thresholds. This enables simultaneous multi-energy CT with a single source and detector. Phantom studies were performed to assess the spectral performance of a research PCCT scanner by assessing the accuracy of derived images sets. Specifically, we assessed the accuracy of iodine quantification in iodine map images and of CT number accuracy in virtual monoenergetic images (VMI). Vials containing iodine with five known concentrations were scanned on the PCCT scanner after being placed in phantoms representing the attenuation of different size patients. For comparison, the same vials and phantoms were also scanned on 2nd and 3rd generation dual-source, dual-energy scanners. After material decomposition, iodine maps were generated, from which iodine concentration was measured for each vial and phantom size and compared with the known concentration. Additionally, VMIs were generated and CT number accuracy was compared to the reference standard, which was calculated based on known iodine concentration and attenuation coefficients at each keV obtained from the U.S. National Institute of Standards and Technology (NIST). Results showed accurate iodine quantification (root mean square error of 0.5 mgI/cc) and accurate CT number of VMIs (percentage error of 8.9%) using the PCCT scanner. The overall performance of the PCCT scanner, in terms of iodine quantification and VMI CT number accuracy, was comparable to that of EID-based dual-source, dual-energy scanners.

PEComas represent a family of uncommon mesenchymal tumors composed of “perivascular epithelioid cells” with a distinct immunophenotype that typically shows both myogenic and melanocytic differentiation. The PEComa family includes angiomyolipoma (AML), clear cell “sugar” tumor of the lung and extra pulmonary sites, lymphangioleiomyomatosis and clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres. Very rarely, PEComas may arise in the skin. Primary cutaneous PEComas typically display a dermal proliferation of epithelioid cells with pale, clear, or granular pink cytoplasm arranged in nests and trabecula with an intervening arborizing network of delicate capillaries. Primary cutaneous PEComas have a lower frequency of myogenic marker expression than their deep soft tissue and visceral counterparts. They also often express strong diffuse CD10, leading to potential confusion with metastatic renal cell carcinoma. Most cases behave indolently. We report 5 additional cases of this rare entity. All showed classic histologic features and expression of either HMB‐45 and/or Melan‐A/MART‐1. Four cases were tested for myogenic markers (2 were positive & 2 were negative). Three cases were tested for CD10 (all 3 were positive). All of our cases with clinical follow‐up behaved indolently. Table 1 provides a summary of findings for all 5 cases in our series.

Purpose: The use of social media, in particular Twitter, has substantially increased among health care stakeholders in the field of hematology and oncology, with an especially sharp increase in the use of Twitter during times of major national meetings. The most attended meeting in the oncology field is the ASCO annual meeting. Little is known about the detailed metrics involved in the use, volume, and impact of Twitter during the ASCO annual meeting. Methods: We conducted a retrospective review of tweets during the ASCO annual meetings from 2011 to 2016. The total data set encompassed 190,732 tweets from 39,745 authors over six consecutive ASCO meetings from 2011 to 2016 (inclusive). Tweets, all publically available, were collected by Nephrology On-Demand Analytics. Results: The number of individual authors increased from 1,429 during the 2011 ASCO meeting to 15,796 during the 2016 ASCO meeting, an 11-fold increase over the total 5-year period. There was a notable increase in tweets from the 2011 ASCO meeting (n = 7,746) to the 2016 ASCO meeting (n = 72,698), a nine-fold increase during the study period. The most commonly tweeted term or topic changed over time, generally reflecting the breakthroughs of each designated year; these terms were “melanoma” for both the 2011 and 2012 ASCO meetings; “breast cancer” for the 2013 ASCO meeting; “lung cancer” for the 2014 ASCO meeting; and “ImmunOnc” or “immunotherapy/immuno-oncology” for both the 2015 and 2016 ASCO meetings. Conclusion: The use of Twitter among health care stakeholders during the ASCO meeting has markedly increased over time, demonstrating the increasing role of social media in the dissemination of findings at the most highly attended hematology and oncology conference of the year.