bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decreasing length of hospital stay following radical cystectomy using multimodal enhanced recovery protocol.
Authors: Djaladat Hooman , Ahmadi Hamed , Schuckman Anne , Daneshmand Siamak 
Published: February 2017

313 Background: To evaluate a peri-operative protocol to expedite recovery and decrease length of stay (LOS) without increasing readmission and complication rates after cystectomy for bladder cancer. Methods: From 5/2012 to 8/2013, a peri-operative protocol used in 126 unselected consecutive patients who underwent open cystectomy for bladder cancer with prospective follow-up. The enhanced recovery after surgery (ERAS) protocol focused on avoiding bowel prep and NGT, early feeding, minimizing narcotics and use of a μ-opioid antagonist. Exclusion was any adjunct surgery (10), previous diversion (2) and prolonged intubation (4). Time to bowel movement (BM) and regular diet, LOS, 30-day readmission and complication rates were captured. The outcomes of interest were compared to a historical cohort. Results: A total of 110 (84 male) patients were included. Median age was 69 y/o (range, 31-90). 40 (36%) patients were ≥ 75 y/o and 75 (68%) patients underwent continent diversion. 90 (82%) patients had BM and 87 (79%) were advanced to regular diet by postop day (POD) 2. Median LOS was 4 days and 63/110 (57%) discharged at or before POD 4. Five patients needed NGT due to ileus. Most common 30-day complications were anemia requiring transfusion (19%), UTI (13%) and dehydration (9%), with the latter two also being the most common etiologies for readmission. Major complications (≥ Clavian grade III) were seen in 15 (13%) patients and were significantly higher in patients ≥75 y/o than younger (22% vs. 8%; P=0.05). There was no difference in other measured outcomes with respect to age (≥75 vs. <75 y/o) and type of diversion (continent vs. incontinent). Conclusions: Our current ERAS protocol resulted in significant reduction in time to BM and LOS without increasing early readmission and complication rates. [Table: see text]
The high incidence of vascular thromboembolic events (VTE) in advanced urothelial cancer (UC) patients (pts) treated with carboplatin (Cb): Analysis of treatment with gemcitabine (G)/cb (GCb), gcb/bevacizumab (GCbBev), or gemcitabine/cisplatin (GCis).
Authors: Tully Christopher Michael , Apolo Andrea Borghese , Zabor Emily C. , Regazzi Ashley Marie , Ostrovnaya Irina , Rosenberg Jonathan E. , Bajorin Dean F. 
Published: February 2017

316 Background: VTE occur in ~13% of pts receiving Cis-based therapy for UC. Cb-based therapy is considered less thrombogenic but no definitive data exist to support this conclusion. While Bev added to chemotherapy (Ch) increases VTE in other tumors, VTE impact when added to UC Ch is unknown. This study evaluated the incidence of and etiologic factors for VTE in UC pts treated with GCb, GCbBev and GCis. Methods: UC pts treated from 6/2006 to 6/2010 on a GCbBev protocol were analyzed prospectively. Planned therapy was 6 cycles of GCbBev then Bev alone; pts who had ≥ 3 cycles were included. Similar UC pts treated with GCb or GCis during the same time were retrospectively evaluated. Type of VTE and potential contributing clinical factors were collected. VTE was defined as pulmonary embolism, vascular thrombosis, myocardial infarction or cerebral vascular accident. Associations with Ch regimen were tested using Fisher’s exact test or linear regression. Factors associated with VTE were analyzed using conditional logistic regression stratified by Ch regimen. Results: 198 pts were analyzed. VTE occurred in 13/51 (26%) GCbBev pts, 22/92 (24%) GCb pts, and 8/55 (15%) GCis pts. Age (≤65 vs >65; p<0.001), having had a prior cystectomy (p<0.001), mass near pelvic vessels (p=0.027), Khorana risk group (p=0.025) and anti-platelet therapy (p=0.036) were significantly associated with the Ch regimen reflecting cohort-specific differences. Type of Ch was not associated with any VTE (p=0.3) or type of VTE (arterial vs venous) (p=0.11). Having had a prior cystectomy was associated with increased risk of VTE (OR 2.2, 95% CI 1.0-5.0, p=0.047). Conclusions: This is the largest series reporting VTE in Cb-treated UC pts; the VTE rate of 24% (95% CI 17, 32%) is higher than expected. Bev does not appear to increase this risk. VTE in Cis-treated pts (15%) was similar to prior reports. The finding that pts with advanced UC are at high risk of VTE regardless of the specific platinum agent warrants further study of Cb therapy-related risk and analysis for contributing factors including prior pelvic surgery.
Biologic activity of dasatinib administered as neoadjuvant therapy preceding radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC).
Authors: Knudsen Beatrice , Hahn Noah M. , Daneshmand Siamak , Posadas Edwin M. , Muhanty Sambit , Lerner Seth P. , Sonpavde Guru 
Published: February 2017

324 Background: Dasatinib (D) is an oral tyrosine kinase inhibitor of Src mediated signaling, and has demonstrated promising preclinical anti-tumor activity in bladder cancer with activated Src (Sonpavde G, Mol Cancer Ther, 2010). We previously reported the feasibilty of neoadjuvant D before RC for MIBC in a phase II trial (Hahn NM, ASCO, 2012). Here, we report correlative tumor tissue studies. Methods: A phase II trial (N=25) was conducted to assess the safety and biologic activity of neoadjuvant D in cT2-T4a, N0, M0 bladder cancer patients (pts) unsuitable for or willing to forego platinum-based neoadjuvant therapy. Patients received D 100 mg po once daily for 28 +/- 7 days followed by RC 8-24 hours after the last dose. Correlative studies evaluated tissues from baseline biopsy and RC for expression of phosphorylated (p) SRC family kinases (SFK) by immunohistochemistry (IHC). pSFK expression was scored on a scale from 0 - 3 by 2 pathologists. Results: The study completed accrual with enrollment of 25 patients. Both baseline and RC tumor were available and adequate for correlative studies in 14 cases. In 5 additional cases, carcinoma was available for baseline or RC tumor only. All pre- and post-treatment tissue samples demonstrated positive staining by IHC in inflammatory cells, which were used as the internal positive control. In all cases, the cancer cells were positive before treatment and the staining decreased after treatment. In 6 cases there was no detectable staining after treatment. In 9 cases (66%), pSFK levels decreased by 2 units from 2.5-3 pre-treatment to 0.5-1 post-treatment. In 5 cases, levels declined <2 units and of these, 2 demonstrated weak staining before treatment (0.5 and 1).In a separate tissue microarray from 20 RC specimens, 15 (75%) bladder cancers demonstrated pSFK expression, while all 40 control kidney and prostate cancers were negative. Conclusions: Neoadjuvant D demonstrated biologic activity in MIBC with marked decrease of pSFK in 66% of cases, while the remaining showed smaller decreases. This study also demonstrates frequent and high expression of pSFK at baseline in MIBC, suggesting that evaluation of D may be justified in a broad population.
Radical cystectomy versus trimodality bladder-preserving therapy for muscle-invasive bladder cancer among elderly (80-84 years old) patients.
Authors: Hatakeyama Shingo , Yamamoto Hayato , Okamoto Akiko , Imai Atsushi , Yoneyama Takahiro , Hashimoto Yasuhiro , Koie Takuya , Ohyama Chikara 
Published: February 2017

340 Background: Management of muscle-invasive bladder cancer (MIBC) in elderly patients is issue of vital importance. The aim of the present study was to compare the oncological outcome of radical cystectomy to trimodality bladder preservation therapy. Methods: Between 1996 and 2013, we treated consecutive 419 patients with MIBC. Of these, we identified 44 patients with MIBC (cT2-4aN0M0) aged 80-84 years. We retrospectively reviewed the clinical charts of these patients. All patients received maximally safe transurethral resection of the bladder tumor before definitive therapy. The patients were categorized according to the treatment options into 2 cohorts; radical cystectomy cohort (RCx, n = 22), or radiotherapy with chemotherapy cohort (Trimodality, n = 22). All patients in trimodality cohort received at least 2 courses of gemcitabine plus carboplatin chemotherapy. Each patient was evaluated every 3-6 months by blood test, urine cytology, and computed tomography. Overall survival (OS), progression free survival (PFS) was estimated by Kaplan-Meier method. Multivariate analysis was used to identify independent factors to predict OS or PFS. Results: There were no significant differences in patient backgrounds between the groups, except for ECOG performance status (ECOG-PS), Charlson comorbidity index (CCI) and eligibility for cisplatin. The mean ECOG-PS, CCI and the number of cisplatin-unfit patients were significant higher in trimodality cohort (p = 0.001, p = 0.034, and p = 0.003, respectively). There were no significant differences in OS and PFS between the groups. On multivariate analysis, ECOG-PS >1 was the independent prognostic factors for OS and PFS. Conclusions: Trimodality bladder preservation therapy for MIBC in elderly patients is comparable to those who received radical cystectomy. For patients with MIBC who are non-cystectomy candidates, or select patients who are motivated to keep their native bladders, trimodality bladder preservation therapy should recognized as an effective alternative to radical cystectomy, and be considered.
Trends in the utilization of diagnositics for upper-tract urothelial carcinoma.
Authors: Vemana Goutham , Bhayani Sam , Baty Jack , Vetter Joel , Strope Seth A. 
Published: February 2017

348 Background: The evolution and adoption of better endoscopes and imaging allow for improved diagnostic capacity for upper tract urothelial cancer (UTUC). We evaluated the changes in diagnostic modalities used to establish a diagnosis of UTUC. Additionally, we assessed how these changes affected the stage of patients receiving definitive surgery. Methods: Using linked SEER-Medicare data from 1992-2009, we identified patients between the age of 66-90 who underwent surgical treatment for UTUC. Among this cohort we assessed the types of diagnostics: endoscopy, computed tomography urogram (CTU), magnetic resonance urography (MRU), intravenous pyelogram (IVP), and retrograde pyelogram (RGP), used to evaluate their disease. Additionally, we dichotomized the final stage at surgery as lower stage disease (Ta, CIS, or unknown stage) or higher-stage disease (T1 or greater). Tests for trend were calculated for the five diagnostic modalities. Logistic regression models were fit to determine the impact of diagnostic modalities on stage at surgery. Results: We found a downward trend in utilization of IVP and RPG over time (p < 0.001, p = 0.011) with IVP having largest decline in use. Endoscopy, CTU and MRU all demonstrated increased utilization over time (p <0.0001). The incidence of lower stage disease was not found to be changing over time (p = 0.123). Logistic regression analysis demonstrated that among modern use (2000-2009), only the use of endoscopy and IVP were associated with smaller tumors (CI 1.310-1.996, CI 1.150-1.720). Conclusions: Modern diagnostics (endoscopy, CTU, MRU) have supplanted traditional methods of establishing a diagnosis of UTUC. Although these newer adopted technologies have a greater sensitivity in diagnosis of UTUC, only the use of endoscopy prior to definitive management has been associated with the diagnosis of smaller tumors.
Heterogeneity of circulating tumor cells isolated from bladder cancer patients using ApoStream and biomarkers of epithelial-mesenchymal transition.
Authors: Dinney Colin P. N. , Melnikova Vladislava O. , Pretzsch Shanna M. , Garza Miguel , Wu Weiguo , Davis Darren W. , Anderes Kenna Lynn 
Published: February 2017

349 Background: Elucidating the molecular pathways that drive the progression of metastatic bladder cancer (BC) from local disease to metastatic may provide insight into prognosis and potentially treatment. The frequency of detection of circulating tumor cells (CTCs) in metastatic BC patients is only 30% using EpCAM based methods. Reports have shown that EpCAM based methods detect only a fraction of CTCs and miss the heterogeneous subpopulations of CTCs related to epithelial to mesenchymal transition (EMT). EMT is a hallmark of cellular invasion and metastasis and CTCs undergoing EMT may have prognostic value in BC if reliable detection and characterization methods were developed. Here we used ApoStream, a novel antibody-free CTC isolation device to isolate CTCs and perform molecular characterization. Methods: Blood samples from 13 early stage or metastatic BC patients were collected and processed using ApoStream. Isolated cells were immunophenotyped using a multiplexed immunofluorescence assay for CK, CD45, DAPI, uroplakin, vimentin and Twist. Laser scanning cytometry analysis was applied to identify subsets of CK+CD45-DAPI+ or CK-CD45-DAPI+ cells for the expression and distribution of uroplakin, vimentin and Twist. Urovysion FISH analysis was performed on CTCs from 6 BC patients. Results: CK+CD45- DAPI+ cells were detected in 4/13 (31%) of patients with vimentin detected in this subset. CK-CD45-DAPI+ cells were detected in 9/12 (75%) of patients with Twist expression detected in this subset. Uroplakin expression was not detected. Chromosomal abnormalities were detected in CK-CD45-DAPI+ cells isolated from the blood of 3/6 (50%) BC patients. Conclusions: ApoStream isolated cells from the blood of BC patients with phenotypic and genotypic characteristics of CTCs. The CK+/-CD45-DAPI+ Twist and vimentin phenotype indicates a population of circulating cells with relevant biomarkers of EMT and may represent an important population of CTCs mediating disease progression. Detection of chromosomal abnormalities on non-canonical CTCs highlights heterogeneity and underscores the need for expanded definitions of CTCs in BC.
Evaluation of the neutrophil-lymphocyte ratio (NLR) during neoadjuvant chemotherapy (NC) for muscle-invasive bladder cancer (MIBC) and correlation with pathologic response to treatment.
Authors: Seah Jo-An , Leibowitz-Amit Raya , Atenafu Eshetu G. , Alimohamed Nimira , Joshua Anthony Michael , Knox Jennifer J. , Sridhar Srikala S. 
Published: February 2017

351 Background: Cancer associated inflammation, as measured by markers such as NLR, appears to impact on outcome. In MIBC, an elevated NLR> 2.5 prior to radical cystectomy (RC) is associated with a poorer prognosis (Gondo, 2011). We evaluated the pattern of change in NLR before (pre-NC), during (mid-NC) and after NC (pre-RC) and correlated this with pathological outcomes, to determine if NLR is of predictive value in this setting. Methods: AllMIBC pts treated with NC and RC between Jan 2005 – April 2013 were evaluated. Standard demographic, disease-related and biochemical parameters (Hb, LDH, albumin) and NLR were analyzed with univariate and multivariable logistic regression. The continuous variable pre-RC NLR was dichotomized using a cut-off of 2.5 based on area under the receiver-operator-curve analysis. Generalized linear mixed model was used to account for the time trend and co-linearity when assessing NLR change between pts who achieved pathological response (pathR) and non-responders. Results: Twenty-three patients were evaluable. Age, gender, ECOG, smoking, clinical stage, and hydronephrosis did not significantly predict for pathR. Pre-NC and mid-NC NLR did not predict for pathR. Pre-RC NLR <2.5 showed a trend towards association with pathR (p=0.05). The pattern of NLR change between responders and non-responders was significantly different (p=0.039). Non-responders exhibited a transient decrease in NLR during NC, followed by an increase in NLR pre-RC above its baseline; responders exhibited a sustained decrease in NLR which remained suppressed until RC (Figure: http://bit.ly/1bYC2wR). Conclusions: While there was no significant difference in pre-NC NLR between responders and non-responders, there was a significant difference in the pattern of NLR change during NC. We speculate that a sustained decrease in inflammatory burden during NC, as manifested by NLR, is associated with pathR. Despite limitations of a small retrospective study, our results may have potential translational and clinical implications.
Preoperative pitfalls: Prediction of pathologic lymph node status in patients undergoing neoadjuvant chemotherapy and radical cystectomy.
Authors: Espiritu Patrick , Luchey Adam , Lin Hui-Yi , Yue Binglin , Lockhart Jorge , Pow-Sang Julio , Spiess Philippe E. , Sexton Wade Jeffers , Poch Michael Adam 
Published: February 2017

352 Background: Category 1 evidence supports neoadjuvant chemotherapy (NC) prior to radical cystectomy (RC) in patients with muscle invasive urothelial carcinoma of the bladder (UC). In addition, patients with clinical node (cN) positive disease may undergo RC after consolidative chemotherapy. Pathologic node (pN) positive disease at the time of radical cystectomy for UC portends a poor prognosis but is often challenging to predict. The purpose of this study was to investigate clinical predictors of pN positive disease in patients receiving NC followed by RC. Methods: After IRB approval, a retrospective analysis was performed on all patients who underwent neoadjuvant chemotherapy followed by RC from 2001-2013. Chi-square, Fisher’s exact, and logistic regression analyses were performed to analyze relationships between preoperative variables including clinical grade, stage, lymphovascular invasion, histologic variance, concomitant carcinoma in−situ, cycles of NC, smoking status with pN status. Overall survival (OS) and progression free survival (PFS) analysis was performed using Kaplan-Meier methodology. Results: 158 patients met inclusion criteria for the study. Fifty-five (35%) patients had pN positive disease at the time of RC. Of all of the preoperative variables assessed, cN positive disease was the only factor associated with pN positive disease (p <0.001). Of the 129 patients with cN negative disease 36 (28%) patients had pN positive disease. Six patients (32%) who were cN positive were pN negative at RC. Overall survival for the cohort was 30 months. Compared to pN negative disease, patients with pN positive disease had a worse PFS (p <0.01) and OS (p <0.01). Compared to non−organ confined (≥ pT3) pN positive disease, patients with organ confined (≤pT2) pN positive tumors had an improved PFS (p<0.01) and OS (p<0.01). Conclusions: Clinical node status is the only preoperative variable associated with pN status at the time of RC for patients receiving NC. A large percentage of patients who are cN negative will be pN positive at RC. As expected, patients who are pN positive had poor PFS and OS compared to pN negative patients.
Response to second-line chemotherapy (Ctx) in advanced urothelial carcinoma: A pooled retrospective analysis of the correlation between objective response rate (ORR) and progression-free survival (PFS) and overall survival (OS).
Authors: Jayaram Anuradha , Teo MinYuen , McDermott Raymond S. 
Published: February 2017

354 Background: Second-line ctx for advanced urothelial carcinoma (UC) constitutes a substantial unmet need. A commonly used endpoint in phase II studies is ORR, however it is unclear whether this translates to a benefit in OS and PFS. We previously examined pooled OS, PFS, ORR and DCR in second line ctx in advance UC. We now are now determining whether increased ORR correlates with improved PFS and OS. Methods: Published second-line studies were identified from PubMed between 1997- 2012 and were reviewed for data extraction. Pearson correlation coefficient was used to determine correlation between ORR and OS and PFS. Results: 25 prospective studies of second-line ctx for progressive advanced UC were identified (22 non-randomised, 3 randomised) (n= 1,297). The majority of studies (88%) were phase II. 12 studies investigated combination regimens and 13 studies monotherapy. All studies allowed adjuvant and primary chemotherapy as first-line but only 7 studies reported median time from last chemotherapy. The range of reported response rates were 1% - 29%. ORR is moderately correlated to PFS (r= 0.42 {0.01 - 0.71} p = 0.04) and OS (r=0.67 {0.39 - 0.84} p = <0.01) in the entire cohort. When we compared the combination regimens to monotherapy the ORR was 27.7% versus 12.3% (p<0.01). The reported response rate for monotherapy was 8.6% - 27.7% and there was no correlation between ORR and PFS (r=0.26 {-0.37 - 0.72} p=0.42) and OS (r = 0.35 {-0.25 - 0.76} p=0.24). Conversely with combination regimens, response rates were 7% - 60% and ORR strongly correlated to PFS (r= 0.78 {0.40 - 0.93} p =<0.001) and OS (r=0.80 {0.43 - 0.94}, p=<0.001). Conclusions: The analysis revealed that ORR translated to a survival benefit. In second line ctx for advanced UC, responses to combination therapy only yielded a survival benefit. This may be appropriate approach in patients with a good performance status.
Vinflunine maintenance therapy versus best supportive care after platinum combination in advanced bladder cancer: A phase II, randomized, open label, study (MAJA study, SOGUG 2011-02)—Interim analysis on safety.
Authors: Polo Susana Hernando , Gonzalez del Alba Aranzazu , Perez-Valderrama Begoña , Villa Guzman José Carlos , Climent Miguel Angel , Lainez Nuria , Font Albert , Duran Ignacio , Mellado Begoña , Castellano Daniel , García-Donas Jesús , Virizuela Juan Antonio , Leon Luis , LLorente Maria del Mar , Domenech Montserrat , Morales Rafael , Gallardo Enrique , Puente Javier , Maciá Sonia , Bellmunt Joaquim 
Published: February 2017

359 Background: Vinflunine (VFL) is a novel microtubule inhibitor currently approved by EMA as treatment after platinum progression, in metastasic bladder cancer. We evaluated whether maintenance vinflunine delays progression after response to CT. Methods: Multicenter, randomized, open label, proof-of-concept study that is being performed in 21 institutions members of the Spanish Oncology Genitourinary Group (SOGUG). Subjects are randomized to receive (arm A) VFL 320 mg/m2 (280mg/m2 for patients with PS=1, age ≥ 75 years, prior pelvic radiotherapy or creatinine clearance Cr <60ml/min) every 21 days plus best supportive care (BSC) vs. (arm B) BSC alone until disease progression. Main inclusion criteria: Subjects ≥18 and< 80 years of age with histological diagnosis of transitional cell carcinoma of the urothelial tract and measurable disease whith radiological response or stabilization after 4 to 6 cy of a cisplatin-containing doublet for metastasic/advanced disease (carboplatin allowed on cy 5-6). Primary objective: progression free survival (PFS). A sample size of 86 patients allocated in a 1:1 ratio is planned. Recruitment started on April 2012. A pharmacogenomic translational study will be conducted. Results: To September 2013, 46 pts have been enrolled, 20 in the VFL+BSC group, 26 in the BSC group. We present the results of the interim analysis including data from first 25 patients who have completed at least 2 cycles. Median age 65.6 years (range 54-77); PS 0/1, 44%/56%; CrCl <60 ml/min 16%; liver metastasis 16%; prior pelvic RT 8%. Primary tumour location: bladder 76%, upper urinary tract 20%, urethra 4%. Pure transitional cells 84%. Metastatic/locoregional disease, 72% / 28%. We analyzed 63 cy in the chemotherapy arm. Most common G3/4 (% cycles) AEs on vinflunine were constipation (12.7%), neutropenia (7.9%), fatigue (4.8%), myalgia (3.2%). One death was reported due to dyspnea, not related to the treatment. No febrile neutropenia was reported at the time of the analysis. Conclusions: Maintenance with vinflunine presented an acceptable security profile leading to trial continuation. Clinical trial information: 2011-001271-39.