bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of (18F) FDG-PET-CT for preoperative lymph-node staging of bladder cancer.
Authors: van Essen Julius , Grosse Joachim , Pfister David J. K. P. , Epplen Robin , Heidenreich Axel 
Published: February 2017

275 Background: Radical cystectomy with extended pelvic lymphadenectomy (EPLA) is the treatment of choice for muscle-invasive bladder cancer. For preoperative staging computed tomography and magnetic resonance imaging of the abdomen and the small pelvis are most commonly used in daily routine.Since the aforementioned methods, have a low sensitivity to detect local lymph node metastasis (LNM) we have prospectively evaluated the role of FDG – PET/CT for locoregional staging. Methods: In 27 patients (n = 27) with known invasive urothelial carcinoma or squamous cell carcinoma of the bladder a staging FDG – PET - CT was performed 1-2 days prior to radical cystectomy with EPLA. Subsequently, the results of the histopathological work-up of lymph node specimens and their anatomical localisations were correlated to the FDG-PET/CT findings. Total of 452 lymph nodes were removed, on average ≈ 16.7 per patient. Results: In 3/27 (11.1%) patients LNM were detected in histopathology. 2 patients showed one positive lymph node, 1 patient had two LNM. In two of these patients, the FDG-PET/CT showed an increased enrichment of FDG in projection to the corresponding histologically positive LN. One false negative and one false positive result of FDG-PET/CT were found. Calculated based on the patient population, the following statistics were calculated: Sensitivity (SENS) 66%, specificity (SPEC) 95.8%, positive predictive value (PPV) 66%, negative predictive value (NPV) 95.8%. Related to the absolute number of LN (n = 452), the following numbers were calculated: SENS 75% SPEC 98.7, PPV 37.5%, NPV 99.7%. Conclusions: To date, few studies have been conducted with regard to FDG-PET/CT and its role in locoregional staging. The reported specificity and NPV was between 86% and 100%, sensitivity and PPV were between 50% and 100%. Our results demonstrate specificity and NPV values of larger than 90% and make FDG-PET/CT a valuable staging tool to potentially identify patients with negative nodes in whom EPLA could be safely ommitted. Curently, routine use of PET CT scans can not be recommended and it is currently tested in a prospective multicenter study including a larger patient cohort.
Alterations in the PI3K/Akt signaling pathway and association with outcome in invasive high-grade urothelial cancer (UC).
Authors: Balar Arjun Vasant , Iyer Gopa , Al-Ahmadie Hikmat , Janakiraman Manickam , Ostrovnaya Irina , Regazzi Ashley Marie , Garcia-Grossman Ilana Rebecca , Pendse Deepa , Bochner Bernard , Bajorin Dean F. , Milowsky Matthew I. , Solit David B. 
Published: February 2017

277 Background: Activating mutations in PIK3CA have been associated with improved outcomes in patients (pts) with breast cancer (Kalinsky, Clin Cancer Res 2009). Molecular profiling of invasive high-grade UC demonstrates that PI3K/Akt pathway alterations occur in up to 15% of cases. The prognostic value of PI3K/Akt pathway alterations in invasive UC is unknown. Methods: Clinically annotated archival frozen surgical specimens from 95 pts (94 cystectomies, 1 nephroureterectomy) with high-grade invasive UC were genotyped for mutations in all coding exons of PIK3CA, PIK3R1, TSC1, PTEN and the AKT isoforms using high-throughput Sanger sequencing. Copy number alterations were examined using an Agilent 1M oligonucleotide array. Clinical variables including time to recurrence (TTR) and overall survival (OS) were correlated with the presence of mutations or copy number events in PIK3CA, PIK3R1, TSC1, PTEN and the AKT isoforms. Results: Specimens from 95 pts (71 M; 24 F) with a median age of 71 years (41-88) were evaluated. 34 (36%) received neoadjuvant chemotherapy and 75 (79%) were prior smokers. 4 pts (4%) had Stage 0, 11 (12%) had Stage I, 15 (16%) had Stage II, 33 (35%) had Stage III and 32 (34%) had Stage IV disease at surgery. The median follow-up was 31.5 months. Alterations (mutations or copy number gains/losses) in PI3K/Akt signaling pathway genes were identified in 26 (27%) specimens and were associated with a trend toward longer TTR, hazard ratio 0.53 (95%CI 0.24, 1.14) (p=0.08). Conclusions: Alterations in PI3K/Akt signaling in pts with invasive UC may be associated with an improvement in outcome similar to that observed in breast cancer. Further analysis in a large independent tumor set is ongoing.
Prognostic value of extranodal extension and other lymph node parameters in patients with upper tract urothelial carcinoma.
Authors: Cha Eugene K. , Fajkovic Harun , Jeldres Claudio , Chromecki Thomas F. , Rink Michael , Margulis Vitaly , Novara Giacomo , Lotan Yair , Raman Jay D. , Kassouf Wassim , Bensalah Karim , Weizer Alon Z. , Roscigno Marco , Pycha Armin , Ficarra Vincenzo , Montorsi Francesco , Scherr Douglas , Shariat Shahrokh F. 
Published: February 2017

281 Background: The aim of the current study was to assess the prognostic value of extranodal extension (ENE) and other lymph node (LN) parameters in a large multicenter cohort of patients with LN metastasis (LNM) following radical nephroureterectomy (RNU). Methods: Retrospective analysis of 222 patients with LNM treated with RNU for upper tract urothelial carcinoma (UTUC) without neoadjuvant therapy. Microscopically, each LN metastasis was evaluated for presence of ENE. Results: The median number of LNs removed, number of positive LNs, and LN density were 4 (IQR: 8), 2 (IQR: 2), and 51.3% (IQR: 71.7%), respectively. Overall, 110 patients (49.5%) had ENE. Presence of ENE was associated with more advanced pT stage (p=0.026). In multivariable analyses, ENE was associated with disease recurrence (p=0.01) and cancer-specific mortality (p=0.013). LN density, when stratified by 30% cutoff, was associated with disease recurrence and cancer-specific mortality (p=0.048 and p=0.049) in univariable, but not in multivariable analyses. Addition of ENE to a multivariable model including pT stage and tumor architecture improved predictive accuracy for disease recurrence from 70.3% to 74.5% (p<0.001). Addition of ENE to a multivariable model including age, pT stage, and tumor architecture improved predictive accuracy for cancer-specific mortality from 70.6% to 74.4% (p<0.001). Conclusions: ENE is a powerful predictor of clinical outcomes in UTUC patients with LNM. While other LN parameters seem to have limited clinical value, ENE could help risk stratify UTUC patients with LNM for better counseling and clinical trial design.
Prognostic impact of expression Notch-1 in invasive bladder transitional cell carcinoma.
Authors: Yousif Nasser Ghaly , Deb Abdallah Ali , Al-Matwari Majid , Mousa Husham J. 
Published: February 2017

299 Background: Notch signal pathway plays a fundamental role in mediator of tumorigenesis, either as a tumor promoter or suppressor, depending on cellular context and expression levels; we investigated the prognosis of invasive bladder transitional cell carcinoma patients with over-expression of Notch-1. Methods: Tumor tissue samples from 78 resected patients with invasive bladder transitional cell carcinoma were obtained, and immunohistochemistry was used to evaluate the expression of the molecular markers Notch-1 and Jagged-1. To further confirm the immunohistochemical results tissue samples were subjected to RT-PCR and Western blot analysis, staining evaluation results were analyzed statistically in relation to various clinicopathological characters. Kaplan–Meier and Cox proportional hazards regression methods were used to assess associations of Notch-1 expression with invasive bladder transitional cell carcinoma survival. Results: Survival time in patients with high expression of Notch-1 and Jagged-1 was significantly shorter than that in patients with low expression p=0.009 and more recurrence p=0.01, in multivariate analysis, Notch1 expression was proved to be an independent predictor of prognosis; (hazard ratio Notch-1 was 1.93 (95% CI, 1.02-3.03; P =0.014), expression was not related to patient sex or age. Conclusions: Notch-1 expression is associated with tumor progression, indicating that Notch-1 may be involved in the carcinogenesis and progression of invasive bladder transitional cell carcinoma. These findings also suggest that Notch-1 may be a potential diagnostic marker and therapeutic target in patients.
Comparative effectiveness of intensity modulated radiation therapy (IMRT), proton therapy (PT), and conformal radiation therapy (CRT) in the treatment of localized prostate cancer.
Authors: Sheets Nathan Christopher , Goldin Gregg , Meyer Anne-Marie , Wu Yang , Chang YunKyung , Sturmer Til , Holmes Jordan A , Reeve Bryce B. , Godley Paul Alphonso , Carpenter William Ruffin , Chen Ronald C. 
Published: February 2017

3 Background: Comparative effectiveness research is urgently needed in prostate cancer because of the rapid adoption of newer and costlier radiation treatments such as IMRT and PT despite limited demonstrated benefit compared to prior technologies. We compared the morbidity and disease control outcomes of IMRT, PT and the older CRT for primary prostate cancer treatment. Methods: Population-based study using Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data from 2000 through 2009 for patients with non-metastatic prostate cancer. Propensity score adjustment was used to balance demographic, disease and institutional characteristics. Rates of morbidity (gastrointestinal, urinary, erectile dysfunction, hip fractures) and additional cancer therapy (surrogate for recurrence) were calculated. Results: IMRT use increased from 0.15% in 2000 to 95.9% in 2008. In propensity score-adjusted analyses, men who received IMRT vs. CRT were less likely to be diagnosed with GI morbidity (13.4 vs. 14.7 per 100 person-years, p<0.001) and hip fractures (0.8 vs. 1.0, p=0.006), but more likely to be diagnosed with erectile dysfunction (5.9 vs. 5.3, p=0.006). IMRT patients were less likely to receive additional cancer therapy (2.5 vs. 3.1, p<0.001). In a propensity-score matched comparison between PT and IMRT, PT patients had a higher rate of GI morbidity (17.8 vs. 12.2 per 100 person-years, p<.001). No significant differences in rates of other morbidities or additional therapies between PT and IMRT. Conclusions: IMRT vs. CRT was associated with less GI morbidity and hip fractures, more erectile dysfunction, and less need for additional cancer therapy. This large-scale population-based study is the first to suggest a simultaneous reduction in disease recurrence and morbidity in patients treated with IMRT vs. CRT for localized prostate cancer. Proton therapy did not significantly improve outcomes compared to IMRT, but had increased GI morbidity. These results provide new and long-needed information to decision-makers regarding the currently available evidence on the comparative effectiveness of different RT techniques.
Pooled analysis of phase II trials evaluating weekly or conventional cisplatin as first-line therapy for advanced urothelial carcinoma (UC).
Authors: Agarwal Neeraj , Boucher Kenneth M. , Maughan Benjamin , Hussain Syed A. , Kaufman Donald S. , Lorusso Vito , Moore Malcolm J. , Galsky Matt D. , Sonpavde Guru ,   SWOG
Published: February 2017

308 Background: Weekly gemcitabine with day 1 cisplatin 70 mg/m2 every 3-4 weeks (GC) is considered a conventional first line chemotherapy for advanced UC. Weekly split-dose cisplatin (delivering a similar cumulative dose per cycle) with concurrent weekly gemcitabine (wGC) may be less toxic and have similar activity, but has not been compared with GC. We pooled published phase II trials of GC and wGC to compare efficacy and safety. Methods: Two trials of wGC (n=74) patients and 3 trials of GC (n=131) were identified. A Cr Cl ≥60 ml/minute was required, except one trial of wGC that enrolled 19 patients with Cr Cl 40-60 ml/minute. Since the data were not derived from randomized trials, GC and wGC were not formally compared, and exact 95% quasi-binomial confidence intervals (CI), which allows for heterogeneity between studies in the same grouping, for response rates and grade ≥3 toxicities were calculated. Long-term outcomes were not uniformly reported and hence inevaluable. Results: The 95% CI overlapped, suggesting agreement between wGC and GC (Table). After accounting for random variability, no clear difference in the CR, PR, SD and grade ≥3 toxicities between GC and wGC were observed. Limitations of a retrospective study apply. Conclusions: GC and wGC yielded similar responses and grade ≥3 toxicities in advanced UC. These results are hypothesis-generating and in the absence of randomized trials, wGC should not be routinely substituted for GC in cisplatin-eligible patients. [Table: see text]
Association between cancer stem-like cell gene expression and clinical outcome in localized prostate cancer: A nested case-control study.
Authors: Fairey Adrian Stuart , Yang Dongyun , Groshen Susan G. , Kim Philip , Virk Navneet , Wang Lina , Martin Sue Ellen , Stephens Craig , Cooc Janine , Goldkorn Amir 
Published: February 2017

31 Background: New biomarkers are needed to better predict outcome after radical prostatectomy for clinically localized prostate cancer. Recent data suggest that subpopulations of cancer stem-like cells (CSC) are present in prostate cancer, and the CSC phenotype has been associated with high tumorigenicity, drug resistance, and disease progression. We sought to determine whether the expression of genes associated with the CSC phenotype are associated with disease recurrence. Methods: A nested case-control study was performed. Cases were men who underwent radical prostatectomy and had disease recurrence (n=147). Controls were men who underwent radical prostatectomy and did not have disease recurrence (n=59). Cases and controls were matched based on D’Amico risk stratification group. Laser capture microdissection with mRNA extraction and quantitative RT-PCR were used to measure the expression of 9 novel candidate CSC-associated genes (Axin2, Bmi1, CD133, CD44a, CTNNB1, ITGA2, Nkx3-1, Notch1, TACSTD2) in formalin-fixed, paraffin-embedded radical prostatectomy specimens. The Wilcoxon test was used to examine the association between CSC-associated gene expression and D’Amico risk stratification group. The optimal chi-square approach and recursive partitioning analysis were used to determine the association between CSC-associated gene expression and disease recurrence. Results: Complete gene expression data were evaluable for 206 out of 261 patients (79%). The median age was 64 years (range, 42-78 years). High expression of TACSTD2 (p=0.04) and CD44a (p=0.05) were associated with D’Amico low risk group. The optimal chi-square approach showed that Axin2 was associated with disease recurrence (recurrence rate: Axin2 ≤ 3.83 = 80% versus Axin2 > 3.83 = 43%, p=0.0015). Recursive partitioning analysis confirmed an association between Axin2 and disease recurrence. Conclusions: A novel finding of the current study was that a low gene expression level of Axin2 was associated with disease recurrence. High gene expression levels of TACSTD2 and CD44a were associated with D’Amico low risk group. Further analysis of the Wnt/beta-catenin pathway is ongoing in this cohort.
Trends in the adoption of robotic technology for radical cystectomy: A population-based analysis.
Authors: Chang Steven Lee , Jiang Wei , Chung Benjamin I. 
Published: February 2017

311 Background: The adoption of the da Vinci Surgical System (Intuitive Surgical, Inc.) for robotic surgery requires a substantial financial investment by hospitals, acquisition of new surgical skills by surgeons, and demand from patients. Although the benefits of this technology have been previously described, the prevalence and adoption rate for robotics in the management of bladder cancer is not currently known. We performed a population-based analysis to determine how the introduction of robotic technology has altered the surgical management of bladder cancer. Methods: We analyzed patient-level data from the Prospective Rx Comparative Database (Premier, Inc., Charlotte, NC), which collects data from over 600 non-federal hospitals throughout the United States. We captured all patients who underwent a radical cystectomy with a diagnosis of bladder cancer between January 1, 2003, and December 31, 2010, based on codes from the International Classification of Disease, 9th edition. Radical cystectomies utilizing the da Vinci Surgical System were identified by a detailed review of the hospital charge data. Results: There was an increase in an overall adoption of robotic radical cystectomy from <2% in 2003 to 23% in 2010. Since 2005, teaching hospitals had a relative increased utilization of robotic radical cystectomy by approximately 40% each year compared to non-teaching hospitals. Hospitals in the West had the highest odds (odds ratio [OR] 3.1, p<0.001 [vs Midwest]) of utilizing robotic surgery for radical cystectomy while larger hospitals (>200 beds) were more likely to adopt robotic technology for radical cystectomy (OR 1.78, p<0.0001). Conclusions: There has been a relatively rapid adoption of the da Vinci Surgical System in the performance of radical cystectomy. This increased utilization is potentially secondary to the acquisition of robotic surgical skills and familiarity with transperitoneal pelvic anatomy following the widespread use of robotic technology for radical prostatectomy during the same time period.
Small cell carcinoma of the genitourinary tract: A 10-year single institution experience.
Authors: El-Gehani Faraj , Dechaphunkul Arunee , Kamal Muna , Pertschy Danielle , Joseph Kurian , North Scott A. , Venner Peter , Pervez Nadeem 
Published: February 2017

312 Background: Small cell carcinoma (SCC) of the genitourinary (GU) tract is rare and there is no standard treatment strategy for managing these patients. The objective of this study is to report the clinical experience and management of patients with SCC of the GU tract, treated in the Cross Cancer Institute, Edmonton, AB, Canada from 1999 to 2009. Methods: A retrospective chart review of all patients diagnosed with SCC of the GU tract between 1999 to 2009 was undertaken. Data was collected on demographics, clinical and pathological characteristics, and patient outcomes. Results: Fifty-eight patients were identified with primary sites as follows: urinary bladder (UB) 35 (60%), prostate 17 (29%) and upper urinary tract (UUT) 6 (11%). Mean age for the entire group was 68 years; 12/58 were female and 46/58 were male. Sixty-six percent (37/58) had pure SCC; the rest had mixed histology. Seventy percent (41/58) were positive for at least one neuroendocrine marker. Overall, 27/58 had limited stage disease, 25/58 had extensive disease and six were unknown. Treatment of limited stage patients was 10/27 (37%) concurrent chemotherapy with radiation, 5/27 (19%) surgery +/- adjuvant chemotherapy, 5/27 (19%) chemotherapy alone, 2/27 (7%) radiation alone and 5/27 (19%) supportive care only. For extensive stage patients, 5/25 (20%) received chemotherapy alone, 3/25 (12%) received radiation alone, 4/25 (16%) received RT and chemotherapy, 4/25 (16%) surgery alone and 9/25 (36%) supportive care only. One patient with limited stage disease received prophylactic cranial irradiation. Despite this, only one patient in the entire cohort presented with brain metastases as the site of initial relapse. Median survival for the entire cohort was 24 months (28 months for limited stage disease and 7 months for extensive). Prostate patients tended to do worse, with a survival of only eight months. Conclusions: SCC of the GU tract is aggressive with an overall poor prognosis. As there is no standard of care for these patients, they are treated according to local protocols. Further efforts should be made to develop more effective treatments and the role of PCI should be investigated in the setting of a clinical trial, in conjunction with other extrapulmonary SCCs.
Could a salvage lymphadenectomy after chemotherapy have clinical impact on cancer survival in patients with metastatic urothelial carcinoma?
Authors: Saika Takashi , Bekku Kensuke , Kishimoto Ryo , Ebara Shin , Edamura Kohei , Kurose Kyohei , Nasu Yasutomo , Kumon Hiromi ,   Okayama Urological Research Group
Published: February 2017

321 Background: A clinical impact of salvage lymphadenectomy after chemotherapy in urothelial carcinoma patients with metastatic lymphnodes swelling is controversial. We verified a clinical role of salvage lymphadenectomy with analyzing long-term outcome after salvage surgery in the patients treated with cisplatin/gemcitabine-based chemotherapy. Methods: From 2003 to 2011, 20 of 28 (71%) urothelial carcinoma patients with metastatic lymphnodes showed objective responses (CR in 2, PR in 18) after multiple courses of the chemotherapy. Thirteen of the PR patients underwent salvage lymphadenectomy after the chemotherapy (9 male and 4 female, median 64.0 years old). Seven of the patients underwent radical surgeries for primary lesions as well. Remaining 5 patients denied salvage surgery. Progression free survival and overall survival of the patients were analyzed retrospectively in comparison with those of patients without salvage surgery. Results: All 13 patients could achieve surgical CR. Pathological findings showed pathological CR in 9 patients. In median follow-up 26.9 months (range: 4.5-74.6), progression free survival and cause specific survival in patients with salvage lymphadenectomy showed better trends in comparison with those in 5 PR patients without the surgery (63.5% vs 20.0%, and 85.7% vs 40.0% at 2 years, p=0.0907 and 0.0229; log-rank test). Conclusions: Although this study was retrospective and nonrandomized, salvage lymphadenectomy in patients with residual tumor after GCP chemotherapy could have an impact on cancer survival. Surgical CR should be achieved in an affordable patient who is responder of GCP therapy.