tbuckley/cabot-search huggingface dataset:
Feasibility of perioperative multi-gene panel testing (MGPT) in cancer patients eligible for hereditary genetic evaluation (GE): The PROTECT pilot.
Authors: Michael J. Hall, Elizabeth A. Handorf, Andrea Forman, Yana Chertock, Elias Obeid, Mary Beryl Daly
Journal: Journal of Clinical Oncology (2018)

1536 Background: Uptake of genetic evaluation (GE) remains limited in cancer pts. MGPT is recommended for GE of women with ovarian cancer (OC), but many will never be tested. For pts w/incident colorectal (CRC) and endometrial cancer (EC), universal mismatch repair screening (uMMR) for Lynch syndrome (LS) precedes GE and is also standard of care, but the limited scope of uMMR screening may obscure actionable mutations in non-LS genes, which are more prevalent than LS. We hypothesized that the opportunity to receive MGPT as part of GE would be favorably received by pts having cancer surgery, when relevance is highest. Additionally, to explore variation in timing/approach, we examined completion of a modified GE approach beginning w/MGPT immediately post-op (i-MGPT) vs completion of GE/MGPT when offered via a usual care (UC) pathway (MD- or self-referral). Methods: Women (F)/men (M) w/CRC (n = 20), women w/EC (n = 28) or ovarian cancer/OC (n = 6) were recruited 1-3 days pre/postop (6/2017-1/2018). Interested pts consented and were randomized to i-MGPT vs UC. Those on i-MGPT arm watched a brief pre-testing video about MGPT w/standard genetic counseling available at request. Results were phoned to i-MGPT pts; in-person counseling was encouraged for pathogenic (PV) and uncertain variants. Feasibility was measured by study consent rate (goal > 50%). Results: 56/110 (50.9%) eligible pts consented. Most (89%) reported family history (FHx) of cancer. All pts on i-MGPT arm completed GE: 11% (3/27) had actionable PVs—a BRCA2 PV in a 60F w/EC and FHx pancreas cancer; a BRIP1 PV in a 70F w/OC and FHx breast cancer; a MUTYH PV in a 52M w/CRC. On UC arm, only 40.7% (11/27) have completed GE—PVs in MSH6 (70M w/CRC) and BRCA1 (44F w/OC) were found. Another 29.6% (8/27) on the UC arm with strong cancer risks have not sought GC, including 3 pts with cancer < 50 yrs, a 54F w/OC, and a 70F w/IHC+ CRC and a strong FHx cancer. Conclusions: Perioperative I-MGPT lead to 100% completion of GE while uptake of GE on the UC arm was lower (40.7%). Of the 5 PVs discovered by MGPT, 4 were in non-LS genes. Peri-op MGPT to evaluate hereditary cancer risk is feasible in CRC, EC, and OC pts.
Efficacy and Safety of Induction Therapy With Calcineurin Inhibitors in Combination With Vedolizumab in Patients With Refractory Ulcerative Colitis
Authors: Gauthier Pellet, Carmen Stefanescu, Franck Carbonnel, Laurent Peyrin-Biroulet, Xavier Roblin, Christophe Allimant, Maria Nachury, Stephane Nancey, Jerome Filippi, Romain Altwegg, Hedia Brixi, Ginette Fotsing, Laure de Rosamel, Sarah Shili, David Laharie
Journal: Clinical Gastroenterology and Hepatology (2018)
Correlation of patient prognosis with PU.1 and JDP2 to provide potential novel prognostic/diagnostic markers in MDS.
Authors: Rachael Simpson, Alan Goddard, James Lally, Matthew Simmonds, Ciro Roberto Rinaldi
Journal: Journal of Clinical Oncology (2017)

e18558 Background: PU.1 is a key transcription factor in haematopoiesis that plays important roles in various haematological malignancies. Previously, significant down-regulation of PU.1 has been reported in high risk myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML) patients. Methods: To clarify PU.1 molecular function we investigated the gene expression of PU.1 and JDP2 (c-Jun dimerization protein-2), a member of the activating protein-1 family located downstream of PU.1, in bone marrow from 12 MDS patients stratified according to IPSS-R score (6-low, 3-intermediate, 3-high risk), 1 AML patient and 10 normal controls. Samples were enriched for the mononuclear fraction by Ficoll separation. Total RNA was extracted and analysed by Real Time PCR for PU.1 and JDP2 expression relative to the housekeeping gene GAPDHusing the 2-ΔΔCT method. Results: We revealed both PU.1 and JDP2 are down regulated in MDS. In addition, our data suggests that PU.1 and JDP2 expression inversely correlates with disease, with expression of these genes consistently reducing according to IPSS-R groups. Furthermore, a positive correlation of PU.1 and JDP2expression &lt; R = O.9333, s = 0.0004 &gt; , provides additional evidence that suppression of JDP2 by PU.1 could contribute to the pathogenesis of AML. Notably, PU.1 and JDP2 do not correlate to the same extent in normal HSCs, indicating that cofactors are required for PU.1 to exert its JDP2-regulating function and that such cofactors are not present under normal conditions. To confirm that JDP2 suppression is a direct result of reduced PU.1 we performed PU.1-knockdown in K562 cells stably expressing PU.1 short interfering RNAs versus control cells. These analyses reveal only a partial reduction in JDP2 expression when analysed by RT-PCR and Western blot, suggesting a more complex regulatory mechanism. Additionally, both PU.1 and JDP2 expression was recovered by treatment with azacitidine, which is routinely used to treat MDS, suggesting an involvement in treatment response. Conclusions: PU.1 and JDP2 expression correlates with patients prognosis highlighting a potential role as new diagnostic and prognostic markers in MDS.
P2.17-08 Heart Motion in Lung Radiotherapy: How Representative Are Delineations Based on 3DCT, Average and Maximum Projection Scans?
Authors: E. Vasquez Osorio, H. Mccallum, S. Iqbal, A. Bedair, A. McWilliam, G. Price, J. Byrne, D. Cobben
Journal: Journal of Thoracic Oncology (2018)
Just Beneath the Surface
Authors: Catherine Handy Marshall, Jordan Nahas-Vigon, Reza Manesh, Allan C. Gelber
Journal: New England Journal of Medicine (2018)

A 55-year-old man presented with intermittent fevers and fatigue after returning from a 5-month visit to Pakistan. He had no night sweats, weight loss, headache, cough, diarrhea, rash, dysuria, or arthralgias.
Abstract 13304: Thrombin-activated Fibrinolysis Inhibitor in Chronic Thromboembolic Pulmonary Hypertension
Authors: Nobuhiro Yaoita, Kimio Satoh, Taijyu Satoh, Koichiro Sugimura, Shunsuke Tatebe, Saori Yamamoto, Tatsuo Aoki, Masanobu Miura, Hiroaki Shimokawa
Journal: Circulation (2015)

Introduction: The pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH) remains to be elucidated. In the present study, we examined whether fibrinolysis capacity is impaired in CTEPH patients with a special reference to thrombin-activated fibrinolysis inhibitor (TAFI) and if so, whether TAFI is also directly involved in the pathogenesis of CTEPH in mice and humans. Methods and Results: We enrolled 68 consecutive patients undergoing right heart catheterization in our hospital, including those with CTEPH (n=27), those with pulmonary arterial hypertension (PAH, n=22) and controls (non-PH, n=19). Whole blood clot-lysis assay with monteplase (100 ng/ml) showed that thrombus reduction rate was significantly reduced in CTEPH compared with PAH or controls (58.1 vs. 73.5 and 75.1%, both P&lt;0.01). Plasma clot-lysis assay showed that the clot lysis time tended to be prolonged in CTEPH compared with PAH or controls (894 vs. 652 and 720 sec, both P=0.07). Moreover, serum levels of TAFI were significantly higher in CTEPH than in PAH or controls (46.1 vs. 39.1 and 38.7 μg/ml, both P&lt;0.05), which remained unchanged even after hemodynamic improvement by percutaneous transluminal pulmonary angioplasty (49.6 vs. 50.0 μg/ml, P=0.92). The levels of TAFI released from the platelets upon stimulation by thrombin (0.05 U/ml) were significantly higher in CTEPH than in PAH or non-PH (2.7 vs. 1.7 and 1.0 folds, both P&lt;0.05). Additionally, thrombus reduction rate was significantly improved with a carboxypeptidase R (an inhibitor of activated TAFI) (62.0 vs. 73.4%, P&lt;0.01) or prostaglandin E1 (an inhibitor of activation of platelets) (62.2 vs. 70.4%, P&lt;0.01). Importantly, plasma levels of TAFI were correlated with thrombus reduction rate and improved thrombus reduction rate by an activated TAFI-inhibitor (both P&lt;0.05). Finally, we newly developed TAFI-overexpressing mice (TAFI-Tg) and found that intravenous injection of thrombin (100 units/kg) caused accelerated thrombotic obstruction of the pulmonary artery in TAFI-Tg mice compared with littermate controls (5.4±1.2 vs. 1.8±0.6 vessels/lung fields) (n=9, P&lt;0.05). Conclusions: These results provide the first evidence that TAFI plays a crucial role in the pathogenesis of CTEPH.
The molecular profile of breast cancer patients according to the presence of HER2 overexpression.
Authors: Joanna Huszno, Ewa Grzybowska, Zofia Kolosza, Karolina Tecza, Joalanta Pamula Pilat, Elzbieta Nowara
Journal: Journal of Clinical Oncology (2016)

e23150 Background: Overexpression of the oncogene HER2/neu (c-erbB-2) occurs in up to 30% of breast cancers and is correlated with worse survival, especially in node-positive patients. The aim of this study was to evaluate the association between genes such as BRCA1, BRCA2, CHEK2, NOD2, TP53 and HER2 overexpression in breast cancer patients (pts). Methods: We reviewed the medical records of 118 breast cancer patients with HER2 positive tumors (HER2 overexpression or amplification) who were treated with trastuzumab in COI. The control group (129 patients) was chosen from breast cancer pts with HER2 negative tumors. Mutation profile was assessed by PCR technique. We evaluated the presence of BRCA1 (c.5266dupC), (c.68_69delAG), (c.181T > G), (c.4034delA), BRCA2 (c.9403delC), (c.5946delT), CHEK2 (c.470T > C), (c.1100delC) and NOD2(c.3016_3017insC), polymorphism TP53 (c.[215G > C]). In statistical analysis Fisher’s exact test were used for categorical variables to determine differences between groups. Results: In the group with HER2 overexpression 15 (13%) pts were mutation carriers. The most commonly detected mutation was 215G > C TP53. It was observed in 8 (6.8%) of pts. Six (5.1%) pts were CHEK2 mutation carriers (4% I157T carriers and 0.8% 1100delC carriers). Only one woman had 3020insC NOD2 mutation. No one in analyzed group had BRCA1/2 mutation. In control group (HER2 negative pts) 83 (64%) pts were mutation carriers. The most commonly detected mutations in this group were BRCA1/2 (n = 43; 33%) and CHEK2 (n = 38; 29%), (28.7% I157T carriers and 0.8% 1100delC) carriers. Only 2 (1.6%) pts had polymorphism TP53. No one of them has NOD2 mutation and 215G > C TP53. Polymorphism TP53 was detected more frequently in HER2 positive group than in HER2 negative pts (6.8% vs 1.6%), p = 0.05. CHEK2 mutation was present more often in pts without HER2 overexpression (29.5% vs 5.1%), p = 0.0001. Conclusions: HER2 overexpression in breast cancer tumor was associated with the presence of 215G > C TP53 polimorfizm. In the group of pts with HER2 negative tumor BRCA1/2 and CHEK2 mutations were more often observed than in HER2 positive tumors. Further studies on a larger group of patients are necessary.
Injury, dysbiosis, and filaggrin deficiency drive skin inflammation through keratinocyte IL-1α release
Authors: Nathan K. Archer, Jay-Hyun Jo, Steven K. Lee, Dongwon Kim, Barbara Smith, Roger V. Ortines, Yu Wang, Mark C. Marchitto, Advaitaa Ravipati, Shuting S. Cai, Carly A. Dillen, Haiyun Liu, Robert J. Miller, Alyssa G. Ashbaugh, Angad S. Uppal, Michiko K. Oyoshi, Nidhi Malhotra, Sabine Hoff, Luis A. Garza, Heidi H. Kong, Julia A. Segre, Raif S. Geha, Lloyd S. Miller
Journal: Journal of Allergy and Clinical Immunology (2018)
Lympho-platelets relationship as a prognostic factor for advanced colorectal cancer.
Authors: Eduardo Richardet, Rocio Paola Villavicencio, Luciana Paola Acosta, Matias Molina, Luciano Dicalbo, Martin Eduardo Richardet
Journal: Journal of Clinical Oncology (2018)

e15667 Background: Mature platelets have a greater capacity to produce TGFβ, which promotes metastasis, since it increases the ability to invade. Some studies observed that the increase in platelets was related to lower survival.The lympho-platelets relationship (LPR) has been identified as a prognostic factor in ovarian, breast and lung cancers with a cut-off value of 190. However, the data are insufficient about the RLP in colorectal cancer Methods: We analyzed 96 medical records. The cut-off point for the RLP 190. OS was analized by Kaplan-Meier statistical method. Multivariate and univariate analyses were performed using as independent variables: right and left colon cancer, and obesity Results: The OS was 19.04 months. 51 patients presented a LPR pretreatment > 190, with an OS of 17.72 vs 45 patients had LPR < 190 with an OS of 21.08 months , p: 0.0075. Patients with BMI > 25 had an OS of 18.04 vs. 19.75 m vs BMI < 25, (p = 0.18). The LPR > 190, patients with BMI > 25 had an OS of 17.8 vs 18.04 months for patients with BMI < 25, (p = 0.147). Women had an OS of 18.71 vs 19.67m among men (p = 0.47). Women with RLP > 190 had an OS of 18.26 vs. 17.28 months in male patients, (p: 0.37). The OS for patients with right vs left was 18.25 vs 20.08 respectively. Patients with right tumor with RLP > 190 had an OS of 16.57 vs 18,68m with left colon tumor(p: 0.47). The OS of patients with 1 metastatic site at diagnosis was 19.57 vs 19.03 months for 2 or more metastatic sites, (p = 0.97). Patients with 1 metastasis site with RLP > 190 had a OS of 20.56 vs. 18.71m in patients with more than 2 sites of metastasis, (p: 0.0057). Conclusions: It was found that OS and metastatic sites are significantly associated with poor prognosis in patients with a greater lymphoplatelets relationship. Therefore, we could consider this relationship as a prognostic factor in our patients with advanced colorectal cancer
Non-adherence and health outcomes in women treated with oral endocrine therapy for breast cancer.
Authors: Daniel M. Geynisman, Kuang-Yi Wen, Amir Goren
Journal: Journal of Clinical Oncology (2016)

6563 Background: Non-adherence (nAdh) with oral selective estrogen receptor modulators (SERMs) or aromatase inhibitors (AIs) in women with breast cancer (BC) is common. Understanding the impact of nAdh on health outcomes can inform effective interventions. Methods: We analyzed US 2010-2015 National Health and Wellness Survey data to assess nAdh to SERMs and AIs and health outcomes based on SF-12v2/SF-36v2 health status, including SF-6D health utilities, WPAI productivity measures, resource use, and self-reported diagnosis of depression. Morisky Medication Adherence Scale was used to assess adherence (Adh) (0 vs. 1+ nAdh behaviors). Bivariate comparisons across Adh vs. nAdh groups comprised pairwise t tests for continuous variables and Chi square tests for categorical variables. Multivariable, generalized linear models examined the association of nAdh with health outcomes. Results: 679 women receiving SERMs (n = 222) or AIs (n = 457) were included. Mean age was 62 years, most were insured (92%) and white (84%); 25% were non-adherent, with more nAdh among those taking SERMs (31% vs. 22%, p < 0.05). In bivariate comparisons, nAdh vs. Adh behavior was associated with significantly lower age (58 vs. 63 years) and more non-white (23% vs. 14%), employed, smoking, and non-exercising respondents, all p < .05. In multivariable models, adjusting for aforementioned differences, nAdh vs. Adh behavior was associated with lower health utilities (b = -0.035, 95% CI -0.057 to -0.012, p = 0.002, estimated mean = 0.703 vs. 0.738, respectively), lower mental health status (b = -4.06, 95% CI -5.79 to -2.33, p < 0.001, mean = 47.9 vs. 52.0), increased odds of depression (OR = 1.75, 95% CI 1.10 to 2.79, p = 0.019, mean = 19.4% vs. 12.1%), and higher rates of activity impairment (RR = 1.25, 95% CI 1.03 to 1.52, p = 0.027, mean = 28.7% vs. 23.0%). nAdh was not associated with greater hospitalization or emergency room visits in the prior 6 months. Conclusions: Self-reported nAdh to SERMs and AIs in women with BC was common and associated with statistically significant decrements in health utilities and mental health status and increased activity impairment. Developing patient-centered adherence-promoting interventions is critically needed.
Tissue acquisition for diagnosis of biliary strictures using peroral cholangioscopy or endoscopic ultrasound-guided fine-needle aspiration
Authors: Yun Lee, Jong Moon, Hyun Choi, Hee Kim, Hyun Lee, Tae Lee, Moon Choi, Sang-Woo Cha, Young Cho, Sang-Heum Park
Journal: Endoscopy (2018)

Abstract Background Although endoscopic retrograde cholangiopancreatography (ERCP) is a first-line diagnostic modality for suspected malignant biliary stricture (MBS), the diagnostic yield of ERCP-based tissue sampling is insufficient. Peroral cholangioscopy-guided forceps biopsy (POC-FB) and endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) are evolving as reliable diagnostic procedures for inconclusive MBS. This study aimed to evaluate the usefulness of a diagnostic approach using POC-FB or EUS-FNAB according to the stricture location in patients with suspected MBS. Methods Consecutive patients diagnosed with suspected MBS with obstructive jaundice and/or cholangitis were enrolled prospectively. ERCP with transpapillary forceps biopsy (TPB) was performed initially. When malignancy was not confirmed by TPB, POC-FB using a SpyGlass direct visualization system or direct POC using an ultraslim endoscope was performed for proximal strictures, and EUS-FNAB was performed for distal strictures as a follow-up biopsy. Results Among a total of 181 patients, initial TPB showed malignancy in 122 patients, and the diagnostic accuracy of initial TPB was 71.8 % (95 % confidence interval [CI] 65.3 % – 78.4 %]. Of the 59 patients in whom TPB was negative for malignancy, 32 had proximal biliary strictures and underwent successful POC. The remaining 27 patients had distal strictures and underwent successful EUS-FNAB. The accuracy of malignancy detection using POC-FB for proximal biliary strictures and EUS-FNAB for distal biliary strictures was 93.6 % (95 %CI 84.9 %−100 %) and 96.3 % (95 %CI 89.2 %−100 %), respectively. The overall diagnostic accuracy for the combination of TPB with either POC-FB for proximal strictures and EUS-FNAB for distal strictures was 98.3 % (95 %CI 95.9 %−100 %) and 98.4 % (95 %CI 95.3 %−100 %), respectively. Conclusions An approach using POC-FB or EUS-FNAB according to the stricture location may be useful in the diagnosis of suspected MBS.
Pathophysiology and Individualized Treatment of Hypothalamic Obesity Following Craniopharyngioma and Other Suprasellar Tumors: A Systematic Review
Authors: Laura van Iersel, Karen E Brokke, Roger A H Adan, Lauren C M Bulthuis, Erica L T van den Akker, Hanneke M van Santen
Journal: Endocrine Reviews (2018)

The development of hypothalamic obesity (HO) following craniopharyngioma (CP) and other suprasellar tumors leads to reduced patient quality of life. No treatment algorithms are currently available for management of HO. Depending on which hypothalamic nuclei are destroyed, the pathophysiologic mechanisms and clinical symptoms that contribute to HO differ among patients. Herein, we review the contribution of the hypothalamus to the pathophysiologic mechanisms and symptoms underlying CP-associated HO. Additionally, we performed a systematic search of MEDLINE and Embase to identify all intervention studies for weight management in patients with CP or other suprasellar tumors published until September 2017. The search yielded 1866 publications, of which 40 were included. Of these 40 studies, we identified four modalities for intervention (i.e., lifestyle, dietary, pharmacotherapeutic, or surgical) within six clinical domains (i.e., psychosocial disorders, hyperphagia, sleep disturbances, decreased energy expenditure, hyperinsulinemia, and hypopituitarism). We used the findings from our systematic review, in addition to current knowledge on the pathophysiology of HO, to develop an evidence-based treatment algorithm for patients with HO caused by CP or other suprasellar tumors. Although the individual effects of the HO interventions were modest, beneficial individual effects may be achieved when the pathophysiologic background and correct clinical domain are considered. These two aspects can be combined in an individualized treatment algorithm with a stepwise approach for each clinical domain. Recently elucidated targets for HO intervention were also explored to improve future management of HO for patients with CP and other suprasellar tumors.
Diagnostic value of DNA aneuploidy for urothelial carcinoma.
Authors: Pei Zhang, Chao Zhao Liang, Jun Li
Journal: Journal of Clinical Oncology (2017)

e16007 Background: The incidence and mortality of urologic cancer are increasing in China and worldwide. Early diagnosis is the key to improve survival. DNA-Image-Cytometry (DNA-ICM) is to assist in the early microscopical diagnosis and grading of various types of tumors, measuring the DNA-contents of their cells. This study investigates the role of DNA aneuploidy in improving diagnostic sensitivity and specificity for urothelial carcinoma. Methods: 274 voided urine samples (204 cases from patients with urothelial carcinomas and 70 cases from patients with benign urinary system diseases) were analyzed with DNA-ICM and liquid-based cytology (LBC) .Fresh urine samples were collected in the morning of the analysis. Sedimented cell-preparations were obtained through centrifugation (cytospins) for DNA-ICM. The sensitivity and specificity of DNA ICM and LBC were calculated by comparing with the pathology in cells with moderate and severe dysplasia. Results: Sensitivity of DNA-ICM was 70.3% which was much higher than that of liquid-based cytology (27.2%)(P &lt; 0.01). Specificity of DNA-ICM was 100% while specificity of LBC was 98.6%. The sensitivity of DNA-ICM in upper urinary tract urothelial cell carcinoma(UTCUs) were 68.75%, lower than 75.00% in bladder urothelial cell carcinomas, there was no significant differences between them(P &gt; 0.01). Conclusions: DNA single cell cytometry represents a highly relevant tool in the objective identification of urothelial carcinoma with a sufficient sensitivity and specificity. Enhancing its extended use as an adjuvant strategy for the early screening of the urothelial carcinoma during routine analyses is benefical. DNA-ICM is an effective screening method for urothelial cancer. Its use to monitor the treatment should be further validated in larger series.
Posttraumatic stress disorder: from diagnosis to prevention
Authors: Xue-Rong Miao, Qian-Bo Chen, Kai Wei, Kun-Ming Tao, Zhi-Jie Lu
Journal: Military Medical Research (2018)

Posttraumatic stress disorder (PTSD) is a chronic impairment disorder that occurs after exposure to traumatic events. This disorder can result in a disturbance to individual and family functioning, causing significant medical, financial, and social problems. This study is a selective review of literature aiming to provide a general outlook of the current understanding of PTSD. There are several diagnostic guidelines for PTSD, with the most recent editions of the DSM-5 and ICD-11 being best accepted. Generally, PTSD is diagnosed according to several clusters of symptoms occurring after exposure to extreme stressors. Its pathogenesis is multifactorial, including the activation of the hypothalamic–pituitary–adrenal (HPA) axis, immune response, or even genetic discrepancy. The morphological alternation of subcortical brain structures may also correlate with PTSD symptoms. Prevention and treatment methods for PTSD vary from psychological interventions to pharmacological medications. Overall, the findings of pertinent studies are difficult to generalize because of heterogeneous patient groups, different traumatic events, diagnostic criteria, and study designs. Future investigations are needed to determine which guideline or inspection method is the best for early diagnosis and which strategies might prevent the development of PTSD.
A Large Rheumatoid Nodule Mimicking Hepatic Malignancy
Authors: Claudia Campani, Maria Guido, Stefano Colagrande, Francesca Bartoli, Umberto Arena, Fabio Marra
Journal: Hepatology (2018)

Campani, Claudia; Guido, Maria; Colagrande, Stefano; Bartoli, Francesca; Arena, Umberto; Marra, Fabio Author Information