bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aspirin use in robot-assisted radical prostatectomy? Systematic review and metanalysis.
Authors: Carneiro Arie , Cha Jonathan Doyun , Wroclawski Marcelo Langer , Kayano Paulo Priante , Claros Oliver Rojas , Moran Natasha Kouvaleski Saviano , Serpa Ary , Lemos Gustavo Caserta 
Published: March 2017

e553 Background: Low dose aspirin (81-100mg) used as secondary prevention in cardiovascular diseases is correlated with increased bleeding and overall complications in surgical procedures. However, the suspension of this medication can increase the risk of cerebrovascular accident and myocardial infarction. Robot-assisted radical prostatectomy (RARP) has significantly decreased the surgical morbidity and the peri-operative bleeding. Our aim was to analyze whether RARP is feasible and safe in patients with low dose aspirin intake. Methods: Systematic review of the literature using MEDLINE, ESCOPUS, Lilacs, Scielo and Cohcrane articles published until June 2016. We included prospective trials and large cohorts that evaluated patients with (Group A) or without the maintenance of aspirin (Group B). Results: 5 trials (n = 1481 men) were included. One thousand and thirteen men stopped the use of the medication and 168 kept it during the peri-operatory setting, including the procedure. For the analyses of overall complications 3 articles with 458 men were included. The overall complication rate was 19%, without statistically significant difference between groups (Group A: 10.5%; Group B: 21.8% - OR: 0.70 IC:0.31- 1.56; I2= 0%). In a sub analysis evaluating major complications (Clavien > 2), cardiovascular events were similar between groups (Group A: 10.5%; Group B: 19% OR: 0.67 IC: 0.34- 1.70; I2= 0%). There were 5 trials included to evaluate blood loss, with 1481 patients (168 Group A and 1313 Group B). The overall transfusion rate was 1.9%, without difference between groups (Group A = 3,5% and Group B = 1.7% - OR:3.24 IC:0.87- 12.06; I2= 0%). The estimate perioperative bleeding rate was significantly lower in patients using aspirin during surgery (OR:-33.74 IC:-44.99, -22.49, I2= 92%). The hospital stay length was similar between groups (OR:0 IC:-0.04, 0.04; I2= 0%). Conclusions: Low dose aspirin does not correlate with larger peri-operatory surgical morbidity, transfusion rate or hospital stay. The blood loss was lower in the aspirin intake group, but this fact should be interpreted with caution due to the high heterogeneity among studies. RARP in patients under continuous aspirin intake was feasible and safe.
Does the EPIC-26 measure five domains in English and Spanish speakers?
Authors: Mir Maria Carmen , Perera Marisa , Garin Olatz , Ferrer Montserrat , Fumadó Lluis , Punnen Sanoj , Balise Raymond R , Westrick Ashly 
Published: March 2017

e557 Background: Despite being widely used in many countries to assess health-related quality of life for patients undergoing treatment for localized prostate cancer(PC), seldom research has been done to investigate the five domain scores generated by 26 question short form of the Expanded Prostate Cancer Index Composite Short (EPIC-26). We conducted exploratory and confirmatory factor analyses searching for evidence of five unique domains of dysfunction in men being treated for PC in the US and Spain.Methods: Using two-year post treatment information, data from 400 men who were part of the original EPIC (OE) validation cohort [T1 or T2, 87% Radical Prostatectomy (RP), 10% External Beam Radiation (EBR), 3% Brachytherapy (BR)] and 450 men who were treated for prostate cancer at Institut Hospital del Mar d'Investigacions Mèdiques in Spain [33% RP, 33% EBR, 33% BR], were subjected to exploratory (EFA) and confirmatory factor analysis (CFA).Results: EFA analyses on both the OE and Spanish cohorts provides support for three, four or five factor models (accounting for approximately 83, 91 or 97% of variance in either cohort) to describe the EPIC-26 variables and weak evidence for the hormonal domain. There is evidence of separate urinary, sexual and bowel factors, but limited evidence of a separate hormonal domain. With the exception of the questions which could be described as assessing depression (lack of energy and depression and in some models weight gain), items within the hormonal domain frequently failed to consistently load onto a single factor (orthogonal communalities ranging from .22 to .27 in the OE cohort and .10 to .21 in the Spanish for hot flashes, breast tenderness and weight gain). CFA looking for the published five domain solution in the Spanish data provides mediocre support for a five factor solution (Standardized RMR = .0624, RMSEA Estimate = .07, Bentler Comparative Fit Index = .91). Conclusions: While all questions asked on the EPIC-26 are of clinical value, there is limited evidence to continue to treat the hormonal domain as a single entity. Urologists should consider looking at the questions linked to depression separately from the other hormonal questions
Angiomotin to regulate prostate cancer cell proliferation by signaling through Hippo-YAP pathway.
Authors: Shen Pengfei , Zeng Hao , Ortiz Angelica , Cheng Chien-Jui , Lee Yu-Chen , Yu Guoyu , Lin Song-Chang , Yu-Lee Li-Yuan , Lin Sue-Hwa 
Published: March 2017

e559 Background: Angiomotin (AMOT) is a family of proteins found to be a component of the apical junctional complex of vertebrate epithelial cells and is recently found to play important roles in neurofibromatosis type 2 (NF-2). Whether AMOT plays a role in prostate cancer (PCa) is unknown. Methods: Purified GST-AMOTp80 was used as immunogen for antibody generation. Real-time PCR, western blot and immunohistochemistry were used to identify the expression of AMOT. To study the function of AMOT, retroviral vector were constructed, also shRNA was used to knockdown AMOT in cells. Cell migration and invasion assays were performed by using transwell chambers. Nuclear and cytoplasmic protein fractions were prepared by using NE-PER reagents (Pierce). The SPSS 19.0 software was used for statistical analysis. Chi-square test and t test were used for the comparisons between groups. Results: AMOT is expressed as two isoforms, AMOTp80 and AMOTp130, which has a 409 aa N-terminal domain that is absent in AMOTp80. Both AMOTp80 and AMOTp130 are expressed in LNCaP and C4-2B4, but at a low to undetectable level in PC3 cells. Further study showed that AMOTp130 and AMOTp80 have distinct functions in PCa cells. We found that AMOTp80 functioned as a tumor promoter by enhancing PCa cell proliferation while AMOTp130 did not. Mechanistic studies showed that AMOTp80 signaled through the Hippo pathway by promoting the nuclear translocation of YAP, resulting in an increased expression of YAP target protein BMP4. Moreover, inhibition of BMP receptor activity by LDN-193189 abrogates AMOTp80-mediated cell proliferation. Conclusions: Together, this study reveals a novel mechanism whereby the AMOTp80-Merlin-MST1-LATS-YAP-BMP4 pathway leads to AMOTp80-induced tumor cell proliferation.
Effect of incorporation of preoperative CT scan on bladder doses and irradiated volume in postprostatectomy radiation therapy (pPRT).
Authors: Akhtari Mani , Yuan Denley Ming Kee , Endres Eugene C. , Tran Bao Minh , Swanson Todd A. 
Published: March 2017

e561 Background: pPRT increases local control, biochemical progression free survival, and even overall survival in patients with adverse features undergoing prostatectomy. The Radiation Therapy Oncology Group (RTOG) consensus definition of the clinical target volume (CTV) in 2010 was based on patterns of failure and anatomy without consideration of pre-operative imaging. This results in large volumes of bladder in the treatment field. Our study evaluates whether incorporation of pre-operative prostate volume can reduce the post-operative CTV and minimize dose to adjacent normal tissue. Methods: We reviewed records of all patients with available pre-operative pelvic CT scans treated at our institution with pPRT. The pre-operative CT scan was fused to the simulation CT. Post-operative CTV (CTV1) was delineated based on RTOG guidelines. A separate CTV (CTV2) was constructed, based on the intact prostate and proximal seminal vesicles. Plans were constructed for each CTV and doses to rectum, bladder, and penile bulb calculated, as well as concordance between the two CTVs and planning target volumes (PTVs). Paired student’s t-test was used to calculate difference between doses in the two different plans. Results: 10 patients’ plans were analyzed. Dosimetric parameters are shown in table 1. Volume of the bladder receiving 65 Gy or higher (V65) was significantly higher in CTV1. As would be expected, there were no significant differences in dose to either the rectum or penile bulb. Additionally, there was on average only 39% overlap between the CTVs and 60% between the PTVs in the two plans. Conclusions: Utilization of the pre-operative pelvic CT scan can aid in more accurate delineation of the CTV/PTV in prostate bed radiation therapy and decrease the bladder dose. As many patients at risk for pPRT have had this imaging performed preoperatively, in accordance with guidelines, incorporation of this data appears prudent. These findings need to be validated in a larger cohort. [Table: see text]
Impact of castration resistant status on overall survival for prostate cancer patients treated with radical prostatectomy.
Authors: Fujita Naoki , Koie Takuya , Yamamoto Hayato , Imai Atsushi , Tobisawa Yuki , Yoneyama Tohru , Hatakeyama Shingo , Yoneyama Takahiro , Hashimoto Yasuhiro , Ohyama Chikara 
Published: March 2017

e562 Background: We estimated the natural history and predictive factors of oncological outcomes in patients with prostate cancer (PCa) after radical prostatectomy (RP). Methods: In this retrospective study, we reviewed the clinical and pathological records of 1083 PCa patients who underwent RP and bilateral pelvic lymphadenectomy with or without neoadjuvant therapy between July 1996 and December 2014 at Hirosaki University. All patients were followed-up by assessing serum prostate-specific antigen (PSA) and testosterone levels every 3 months for 5 years and every 6 months thereafter. The endpoint was the oncological outcomes after surgery. Univariate analyses were performed using the Kaplan-Meier and log-rank methods, and the multivariate analysis was performed using a Cox proportional hazard model. Results: The 5-year and 10-year overall survival rates were 98.5 % and 92.0 %, respectively. At the end of the study, 226 patients (20.8%) showed biochemical recurrence and 28 patients (2.6%) had developed castration-resistant Pca (CRPC). The patients with CRPC were significantly poor prognosis compared with those without CRPC (P < 0.01). On multivariate analysis, although preoperative variables were no significant differences, only CRPC was significantly associated with OS. Conclusions: RP was shown to provide excellent long-term survival with OS at 10 years. In addition, a small proportion of the patients treated with RP had CRPC and died of Pca within 10 years. Development to castration resistant status may have critical impact on OS.
MILGa-01: A first-in-human study assessing the safety and tolerability of chMIL-38 in metastatic prostate, bladder, and pancreatic cancers.
Authors: Gurney Howard , Sabanathan Dhanusha , Gillatt David , Poursoultan Pirooz , Ho Shon Kevin , Walsh Brad , Velonas Vicki , Thurecht Kristofer , Campbell Douglas 
Published: March 2017

e565 Background: Metastatic or recurrent cancer continues to be a challenge in patients with urogenital and pancreatic cancers despite the development of newer anti-androgen therapies. MIL-38 is an IgG1 murine monoclonal antibody directed against Glypican-1 (GPC-1). The proteoglycan GPC-1 is upregulated in prostate, pancreatic and bladder cancer cell lines. Targeting of tumor xenografts and lack of adverse events in pre-clinical models suggest chimeric MIL-38 (chMIL-38) is a good candidate for both radioimmunotherapy and antibody-drug conjugate development. Methods: Patients with known metastatic prostate and pancreatic cancer were injected with a single dose of MILGa drug (1mg, 250MBq dose) and imaged with whole body gamma camera scans and SPECT/CT at 30 minutes, 6 h, 24 h, 48 h, 72 h (if required) and 144h post infusion. Blood and urine samples for pharmacokinetic, biomarker studies, cancer markers and hematology and biochemistry analysis were collected at each time point. Dosimetry analysis of tumour images was performed to determine the relative accumulation of MILGa in different organs. Results: To date one pancreatic cancer patient and one prostate cancer patient with metastatic disease have been infused with the MILGa drug. The drug was safe and well tolerated in both patients with no infusion reactions or drug-related adverse events. Tracer uptake was observed in the liver, with mild tracer uptake in the spleen, skeletal system and kidneys. Significant MILGa targeting was seen in Patient 2 24 hours post infusion onwards with uptake in the right foot (right calcaneum and cuneiform bones). SPECT/CT at 24 hours confirmed uptake was in the bone, not in the joint space or soft tissue. Conclusions: MILGa has shown a promising safety profile to date with indication of tumour targeting in metastatic prostate cancer. Additional data from this study may permit the selection and evaluation of potentially sensitive tumor types to be studied for further therapeutic and diagnostic studies. Clinical trial information: ACTRN12616000787482.
Refill gaps and dose reductions in patients treated with abiraterone acetate plus prednisone (AA+P) or enzalutamide (ENZ).
Authors: Pilon Dominic , Behl Ajay S. , Emond Bruno , Xiao Yongling , Lefebvre Patrick , Kane Christopher J. 
Published: March 2017

e572 Background: Recently available treatmentssuch as AA+P or ENZ have improved survival and quality of life for patients with metastatic castrate resistant prostate cancer (mCRPC). However, drug-drug interactions, intolerance or toxicities can potentially lead to dose reductions or treatment interruption. This study assessed refill gaps and dose reduction events in patients treated with AA+P or ENZ. Methods: The MarketScan databases (03/2012-10/2015) were used to conduct a retrospective analysis. Patients initiated on AA+P or ENZ (index date) after 09/2012 with ≥ 6 months of continuous eligibility prior to index date and ≥ 1 diagnosis for prostate cancer were included. Inverse probability of treatment weighting (IPTW) was used to adjust for observed baseline confounders between groups. Weighted Kaplan-Meier (KM) rates and Cox proportional hazard models were used to compare the occurrence of refill gaps ( ≥ 14, ≥ 30, or ≥ 60 days) or dose reductions (i.e., relative dose intensity [RDI] ≤ 80%, and ≤ 85%) between groups. RDI was calculated as the ratio of the delivered dose intensity (total delivered dose divided by the period over which the total dose was measured) to the standard dose intensity as recommended in the package insert for AA+P or ENZ. Results: A total of 2,540 AA+P and 1,265 ENZ patients were identified. IPTW resulted in balanced baseline demographic, comorbidities, and disease characteristics. At 12 months post-index, patients initiated on ENZ were more likely to have an RDI ≤ 80% or ≤ 85% or to have a refill gap ≥ 30 or ≥ 60 days when compared to patients initiated on AA+P (Table). Conclusions: This study showed that mCRPC patients treated with ENZ were more likely to experience a refill gap and to reduce their treatment dose than patients treated with AA+P. [Table: see text]
A probabilistic threshold analysis of metformin (Met) with enzalutamide (Enza) to determine the cost and added efficacy needed to make such a combination theray cost-effective (CE).
Authors: Hill Jordan , Venner Peter , Paulden Mike , McCabe Christopher , North Scott A. , Danielson Brita Lavender , Usmani Nawaid 
Published: March 2017

e577 Background: Enza has become known for its' effectiveness in treating patients with metastatic castrate-resistant prostate cancer. However, Enza is expensive (~$3175/month) and unlikely to be CE at any willingness to pay (WTP) threshold from $0-$125 000/quality-adjusted life years (QALYs). Met is inexpensive (~$8.00/month) and recently two large population-based studies of prostate cancer (PCa) demonstrated that diabetics taking Met had improved PCa specific and overall survival compared to those not taking Met. As a result we theorized that there must be a cost of Enza and a specific added effect Met could provide that would make Met a CE adjuvant therapy to Enza even though it is not currently used as such. Methods: We constructed a Markov-based decision analytic model and performed a probabilistic threshold analysis to narrow in on several combinations of costs of Enza and added efficacies needed to make Enza + Met a CE combination therapy at different WTP thresholds. Costs, utilities, and transition probabilities were derived from existing literature. Effectiveness was measured using QALYs. Costs and QALYs were considered over a lifetime horizon and discounted at 5% per annum. Results: At a WTP threshold of $50 000/QALY Enza + Met is unlikely to be CE no matter the cost decrement or added efficacy applied to the model. At a WTP threshold of $75 000/QALY Met is also unlikely to be CE unless the price of Enza could drop to $1934/month and Met could also add 1% to the efficacy of Enza. At Enza's current cost and a WTP threshold of $100 000, Enza + Met could be CE barring Met adds 0.621% to the number of patients still on treatment at 36 months. Conclusions: Enza + Met is unlikely to be CE at WTP thresholds of $50 000/QALY or $75 000/QALY unless there is a significant price drop for Enza; these results make sense because a therapy that is considered not CE at these WTP thresholds by itself is unlikely to be CE with a theoretical adjuvant therapy that would hold a patient on such a treatment for even longer. Our results show that the only way for Enza + Met to be CE is through the theoretical overall survival benefit of Met as the price of Enza is unlikely to drop any time soon.
3D-microdevice for the in vivo capture of cancer-associated circulating cells.
Authors: Cayron Hélène , Jiménez Zenteno Alejandro Kayum , Esteve Aurore , Sanson Sylvain , Vieu Christophe , Malavaud Bernard Andre , Cerf Aline 
Published: March 2017

e579 Background: Circulating tumor cells (CTCs) are cancer cells that have detached from a tumor and have entered into the blood circulation at a very low concentration (D. Shook, Mech. Dev., Nov 2003). CTCs have a strong prognostic value, as their number has been correlated to overall survival in different metastatic cancers (J. S. de Bono, Clin. Cancer Res., Oct 2008). Considering the rareness of CTCs in blood, capturing them in vitro is very challenging. CTCs being mainly larger and less deformable than most of blood cells, ISET was the first system exploiting their physical traits using a filtration membrane to enrich 10mL blood samples (G. Vona, Am. J. Pathol., Jan 2000). However, placing the trapping system directly within the bloodstream would increase the amount of blood screened and ensure no sampling bias. To our knowledge, the only system developed for in vivo capture of CTCs relies on an immunologic detection targeting CTCs with specific epithelial-cell adhesion molecules (N. Saucedo-Zeni, Int. J. Oncol., Oct 2012). The major drawback of this technique is the selection bias induced, given the strong heterogeneity of antigen expression profiles in CTC population as confirmed by several studies. Methods: Our device combines the advantages of in vivo capture and physical trapping of CTCs. A polymeric 3D net-like microdevice is fabricated using a Direct Laser Writing technique (Nanoscribe) and integrated onto a Nitinol guidewire to be introduced into the basilic vein through a routine 20G catheter. To optimize the design, we conducted simulation studies and in vitro assays using a fluidic platform reproducing in vivo conditions. Results: We succeeded in capturing PC3 human prostate cancer cells from 20 mL healthy donor blood spiked with 1,000 PC3 cells in 2 minutes, demonstrating the capability to capture CTCs in conditions close to those found in vivo, in terms of pressure and flow rate and without any additional treatment or dilution of the blood. Conclusions: This device could facilitate treatment personalization and follow-up. Its versatility should render it transposable to the capture of single or clustered CTCs, derived from all types of cancer and, by extension, to other circulating cellular and molecular biomarkers.
Physiological evidence of DNA damage by carcinogens known to be present in charred and processed meats (PhIP DNA adducts) in a small cohort of patients with prostate cancer.
Authors: Weight Christopher J. , Xiao Shun , Guo Jingshu , Hwa Byeong , Villalta Peter , Tejpaul Resha , Krishna Suprita , Murugan Paari , Turesky Robert 
Published: March 2017

e580 Background: Epidemiologic studies have reported an association between frequent consumption of well-done cooked meats and prostate cancer (PC) risk. Charred red meat and cooked processed meats are known to contain heterocyclic aromatic amine (HAA) carcinogens, such as 2-amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP) the most mass abundant HAA, and are linked to PC development in a rodent model. However, unambiguous physiochemical markers of DNA damage from these meat-derived carcinogens have not been identified in human samples to support the paradigm of HAA induced human prostate carcinogenesis. Methods: Thirty-five men with biopsy proven intermediate to high-risk PC underwent radical prostatectomy at University of Minnesota from Dec 2015-Aug 2016. After prostatectomy, both tumor bearing tissue and non-tumor bearing adjacent fresh tissue was analyzed for DNA adducts using a highly sensitive nano-LC-Orbitrap mass spectrometry method. We also analyzed formalin fixed paraffin embedded (FFPE) tissues from each patient. Results: Median age of the men with PC was 65 (range 45-78). Pathology demonstrated the following Gleason Scores (GS) and pathologic staging: GS = 6 in 1 patient (2.8%), GS = 7 in 28 patients (80%) and GS = 8-10 in 6 patients (17%) and 16 men (46%) were stage 2 and 19 men were stage 3 (54%). The PhIP DNA adduct was identified in 11 out of 35 patients, at levels ranging from 2 to 120 adducts per 109 nucleotides. PhIP DNA adducts also were recovered quantitatively from FFPE tissues. Conclusions: Our data provide support to the epidemiological observations implicating PhIP as a DNA damaging agent that may contribute to the etiology of PC in humans. FFPE tissues can be used as a tissue source in DNA-adduct biomarker research using our mass spectrometry method