bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cancer-specific nanotheranostics to improve the diagnosis and treatment of bladder cancer.
Authors: Pan Chong-Xian , Lin Tzu-yin , Zhang Hongyong , Li Yuanpei , Airhart Susan D. , deVere White Ralph , Lam Kit S. 
Published: February 2017

323 Background: We recently developed a bladder cancer-specific targeting ligand named PLZ4, nanometer-scale micelles and nanoporphyrin. Here we report the diagnostic and therapeutic applications of these nanotheranostics coated with PLZ4. Methods: PLZ4 was synthesized through solid phase synthesis. Bladder cancer-specific PLZ4-coated nanomicelles (PNM) and nanoporphyrin (PNP) were developed through conjugating the nanotheranostics with PLZ4 on the surface, and loaded with therapeutic and/or imaging agents in the core. Bladder cancer cell lines and patient-derived xenografts (PDXs) were used to determine the diagnostic and therapeutic applications. Results: In vitro studies with cell lines revealed that both PNM and PNP could specifically deliver the drug load to bladder cancer cells, but not to adjacent confounding cells. After intravenous injection, PNM loaded with paclitaxel could specifically deliver the drug load to xenografts developed from a human and a dog bladder cancer cell line, and a PDX, but not to lung cancer xenografts in the same mice. These paclitaxel-loaded PNM could overcome cisplatin resistance, and prolong the overall survival of mice carrying PDXs from 27 days with free paclitaxel to 76 days (p<0.0001). PNP can be used for photodynamic diagnosis and therapy while being able to chelate gadolinium for cancer-specific magnetic resonance imaging (MRI), and load chemotherapeutic drugs for cancer-specific targeted chemotherapy. It is over 50 times more potent that 5-aminolevulinic acid in photodynamic therapy (p<0.0001). After intravesical instillation into the bladder cavity of an orthotopic PDX model, PNP could specifically target bladder cancer cells, but not adjacent normal urothelial cells in the same bladder. Conclusions: PNM and PNP can potentially be used for diagnosis, imaging detection and cancer-specific targeted delivery of therapeutic agents of both non-myoinvasive and advanced bladder cancer. A phase I clinical trial of PNM for intravesical instillation in human patients with non-myoinvasive bladder cancer, and another phase I trial with PNP for photodynamic diagnosis and therapy in dog bladder cancer patients have been funded.
Assessing the impact on morbidity and mortality of neoadjuvant chemotherapy in patients with high-risk and muscle invasive bladder cancer eligible for radical cystectomy.
Authors: Di Trapani Ettore , Sanchez-Salas Rafael , Rocchini Lorenzo , Gandaglia Giorgio , Moschini Marco , Lizee Daphne , Barret Eric , Rozet Francois , Galiano Marc , Colombo Renzo , Briganti Alberto , Montorsi Francesco , Cathelineau Xavier 
Published: February 2017

331 Background: Despite the increasing number of studies confirming the importance of neoadjuvant chemotherapy in patients addressed to radical cystectomy (RC) for bladder cancer (BC), its association remains controversial. We aimed to test the safety and the efficacy of neoadjuvant chemotherapy in pts underwent RC for BC in a multistitutional retrospective study Methods: We analyzed 768 pts who underwent RC and PLND with / without neoadjuvant chemotherapy in two European high volume centers between 2007 and 2013. Complete demographic, pre and postoperative functional data and oncologic outcomes were collected. T-tests and Chi-square analyses were used to evaluate the differences between the groups. Kaplan-Meier curves were used to assess time to cancer specific mortality (CSM) free and overall mortality (OM) free survival. Univariable (UVA) and multivariable (MVA) logistic and Cox regression analyses were developed to address predictors of perioperative complications and CSM- and OM-free survival. Results: The mean follow up was 20 months (range 1-24). Mean age at surgery was 67 yrs (median 67 yrs). Patients had mainly pT2 disease (79,6%). Overall, 14% of pts had preoperative cisplatinum based neoadjuvant chemotherapy. We did not find any difference in pre-operative and post-operative blood tests assessment (all p>0.1). Intraoperative blood loss was higher in patients who went directly to surgery (mean 1.200 vs 740 cc; p<0.001) but the number of transfusions was similar (p=0.77) as well as the hospital stay (p=0.8). The complication rate was not significant at the MVA logistic regression analysis (p=0.74) even after evaluating per Clavien-Dindo groups (p=0.11). Neoadjuvant chemotherapy showed a better CSM-free survival at UVA (p=0.035) and at MVA (p= 0.043; OR 0.44). Then a nomogram was developed to predict the 60 months CSM-free rate showing an accuracy of 72.6%. Conclusions: Neoadjuvant chemotherapy is associated with a better CSM-free survival in patients with high-risk bladder cancer eligible for RC and it’s not linked with perioperative morbidity. We finally developed the first nomogram predicting the CSM-free rate in these patients.
Trends in utilization, perioperative outcomes, and costs among open, laparoscopic, and robotic nephroureterectomies: A 10-year population-based analysis.
Authors: Gelpi-Hammerschdmidt Francisco Jose , Allard Christopher B. , Chung Benjamin I. , Chang Steven L. 
Published: February 2017

337 Background: Nephroureterectomy (NU) is the standard treatment for upper tract urothelial carcinoma (UTUC). Minimally invasive (MI) laparoscopic or robotic-assisted approaches have been introduced in an effort to reduce morbidity. We performed a population-based study to evaluate contemporary utilization trends, morbidity, and costs associated with NUs in the United States. Methods: Using the Premier Hospital Database (Premier, Inc., Charlotte, NC), a nationally representative discharge database with data from over 600 non-federal hospitals in the United States, we captured patients who underwent a NU (ICD-9 55.51) with diagnoses of renal pelvis (189.1) or ureteral (189.2) neoplasms from 2004 to 2013. We fitted regression models, adjusting for clustering by hospitals and survey weighting to evaluate 90-day postoperative complications, length of stay (LOS), OR time, and direct hospital costs among open, laparoscopic, and robotic NU. Results: The weighted cohort included 17,245 open, 13,298 laparoscopic, and 3,745 robotic NUs. MI surgeries increased from 36% to 54% from 2004 to 2013, while the number of NUs decreased by nearly 20% during the same period (Figure 1). The overall 90-day mortality, major (Clavien 3-5), and minor (Clavien 1-2) complication rates were 1.89%, 9.4%, and 27.7%, respectively, with no statistically significant differences between the three approaches based on adjusted logistic regression analyses. The LOS was decreased for laparoscopic (Incidence Risk Ratio [IRR]: 0.87, 95% CI: 0.82-0.92, p<0.001) and robotic (IRR: 0.76, 95% CI: 0.7-0.83, p<0.001) NU compared to open NU. OR time was 10.35 (p<0.05) and 56.35 (p<0.001) minutes longer for laparoscopic and robotic NU. Adjusted 90-day median direct hospital costs were $1,354 and $3,533 higher for laparoscopic and robotic NU (p<0.001). Conclusions: During this contemporary 10-year study, the use of MI NUs increased to over half of procedures with a recent surge in robotic NUs, along with a concurrent reduction in total NUs performed in the United States. Comparable perioperative outcomes suggest that the morbidity profile may be driven primarily by patient-specific characteristics as opposed to surgical approach.
Determining the optimal timing for radical cystectomy after neoadjuvant chemotherapy.
Authors: Mmeje Chinedu O. , Benson Cooper , Nogueras-Gonzalez Graciela M. , Jayaratna Isuru Sampath , Navai Neema , Gao Jianjun , Siefker-Radtke Arlene O. , Kamat Ashish M. , Dinney Colin P. N. , Shah Jay Bakul 
Published: February 2017

339 Background: We present the largest series reviewing complications and pathologic outcomes following neoadjuvant chemotherapy (NAC) and radical cystectomy (RC), to determine whether the interval between chemotherapy and surgery (ICS) affects 90-day post-operative morbidity and lymph node metastasis. Methods: We analyzed 338 patients treated with NAC followed by RC from January 1995 through December 2013. The association of ICS with 90-day surgical morbidity, incidence of major complication, 90-day readmission, and lymph node metastasis was determined. Generalized linear models were used to determine potential predictors of each endpoint. Patients were stratified into four groups by ICS days (18 – 42; 43 – 64; 64 – 85; > 85). Complications were classified using the Clavien system. Results: The overall morbidity of the cohort was 59%, with 66% being minor, and 34% being major complications. The median ICS was 46 days (18 – 199 days). There was no difference in the overall morbidity, readmission, or major complication rates among the four groups. Patients with an ICT > 85 days had the highest incidence of lymph node metastasis (40%), though this was not found to be significant (p = 0.1). On multivariate analysis including predictors of perioperative morbidity, extravesical (pT3 – 4) disease (OR = 1.97; p = 0.01) was an independent predictor of overall morbidity, while age at cystectomy (OR = 1.05; p = 0.004), and surgical time ≥ 7 hrs (OR = 2.87; p = 0.001) were independent predictors of major complications. Only surgical time ≥ 7 hrs (OR = 2.24; p = 0.006) was found to be a predictor of readmission. In a separate multivariate analysis that included risk factors for pathological node positivity, the predictors for lymph node metastasis included variant histology (OR = 2.06; p = 0.026) and extravesical disease (OR = 2.76; p = 0.002). Patients with an ICT > 85 days had a higher risk of node metastasis though this was not significant. Conclusions: Patients can undergo RC anytime between 2.5 – 12 weeks after NAC with no difference in risk of surgical complications or nodal metastasis.
Incidence and predictors of prostate cancer death in men with other prior malignancies: An analysis from SEER Database.
Authors: Dinh Kathryn Tindell , Mahal Brandon Arvin Virgil , Ziehr David R. , Muralidhar Vinayak , Chen Yu-Wei , Viswanathan Vidya Bhavani , Nezolosky Michelle Daniel , Beard Clair , Choueiri Toni K. , Orio Peter F. , Martin Neil E. , Sweeney Christopher , Trinh Quoc-Dien , Nguyen Paul Linh 
Published: February 2017

34 Background: Men with cancer are screened 22% more for prostate cancer (PCa) than men without cancer, yet very little has been published on their prostate cancer outcomes. We aim to describe PCa death and clinical factors associated with dying from PCa in this population. Methods: We studied 22,769 men in the Surveillance, Epidemiology, and End Results database diagnosed with PCa as a second cancer from 1973 to 2006. Proportions of PCa death versus primary-cancer death were calculated, stratified by the nine primary cancers with highest incidence among US men and then further stratified by PCa grade and interval between primary and PCa diagnoses. Results: Urinary-bladder (30.4%), colorectal (27.9%) and lung cancer (10.5%) were the most common primary cancers. Overall, 12.4% of men died from PCa. A greater proportion of patients died from PCa than their first cancer with primary melanoma (11.7 vs 6.97%) and oral cavity/pharynx cancer (15.3 vs 6.98%), a similar proportion for colorectal (14.8% vs 13.7%) and kidney/renal pelvis cancer (11.1 vs 12.7%), but a lower proportion for lung (11.3 vs 42.1%) and bladder cancer (10.8 vs 17.4%). When the interval between cancer diagnoses was more than 5 years, PCa was the leading cause of death for five of the nine cancers. Patients who died from PCa compared to those who died from their primary had higher baseline PSA (39.5 vs 16.9 ng/mL, p<0.001), more Gleason 8-10 (36.7 vs 18.2%, p<0.001), more N1/M1 PCa (2.35 vs 0.30%, p<0.001), were older at PCa diagnosis (74.7 vs 71.9 years, p=0.015), and had a longer interval between diagnoses (63.9 vs 28.8 months, p<0.001). Conclusions: PCa remains a significant cause of mortality when diagnosed as a second cancer, especially if the interval from prior cancer is greater than 5 years, suggesting that treatment of aggressive prostate cancer may be reasonable for many patients with prior cancers.
Preliminary study of combined use of PDD and NBI for detection for flat urothelial lesion.
Authors: Naya Yoshio , Oishi Masakatsu , Ueda Takashi , Naitoh Yasuyuki , Nakanishi Hiroyuki , Hongo Fumiya , Nakamura Terukazu , Kamoi Kazumi , Okihara Koji , Miki Tsuneharu 
Published: February 2017

340 Background: This prospective preliminary study is a first report to compare photodynamic diagnosis (PDD) with narrow band imaging (NBI) in the same patients with flat suspicious lesions of carcinoma in situ (CIS) of bladder. Methods: PDD was approved by the ethics committees of our institution for 10 patients with non muscle invasive bladder cancer. Between November 2012 and April 2013, 10 patients with abnormal cytology (class III or more) but undefined papillary mucosa underwent TURBT using PDD and NBI in same time. Each patient received 1.0g ALA hydrochloride (Cosmo Bio Co., Tokyo, Japan) dissolved in 50 mL water, and was given orally 3 hours before the TURBT. The bladder was mapped first under white light (WL), then under NBI, and subsequently under blue light (BL) in odd-numbered patients. The bladder was mapped first under WL, then under BL, and subsequently under NBI in even- numbered patients. Biopsies were carried out from all suspicious areas noting if NBI, PDD or both detected lesions. Random cold cup biopsies were performed from negative lesions of PDD and NBI. Results: The sensitivity and specificity of PDD for detection CIS were 1.00 and 0.714, and those of NBI were 0.75 and 0.814, respectively. There were no cancer and dysplasia in 43 lesions both PDD and NBI negative. Of 50 lesions with negative PDD, only 2 (4%) were dysplasia and there was no cancerous lesion. Of 60 lesions with negative NBI, 3 (5%) were cancer and 6 (10%) were dysplasia. The AUC for detection CIS in PDD, in NBI and in combined use of PDD and NBI were 0.869, 0.782 and 0.964, respectively. Conclusions: When both PDD and NBI were negative, the possibility of CIS might be very low. The usefulness of the combination of PDD with NBI was suggested in this study. [Table: see text]
Impact of socioeconomic factors on the incidence of urothelial cell carcinoma in Germany.
Authors: Brandt Maximilian Peter Johannes Karl , Gust Kilian , Vallo Stefan , Mani Jens , Bartsch Claudia , Schertzer Adrien , Tsaur Igor , Reiter Michael Andreas , Schilling David , Haferkamp Axel , Herrmann Eva , Bartsch Georg 
Published: February 2017

348 Background: In the European Union (EU) differences in tumor incidence for urothelial cell carcinoma (UCC) have been reported. Besides occupational exposure, tobacco smoke and nitrite have been identified as risk factors for UCC. No study has evaluated the regional incidence of UCC in Germany in consideration of socioeconomic landscape. We investigated if a different allocation to agriculture (A), industrial use (I) and land settlement (S) are associated with the incidence of UCC. Methods: In collaboration with the German Centre for Cancer Registry Data, Robert Koch Institute, Berlin, all new cases of UCC between 2003 and 2010 were included, with partly dropped out information due to incomplete reporting. Kulldorff spatial cluster test was used to detect clusters with high incidence rates. Furthermore, information within the different administrative areas of Germany from 2010 for land use factors A, I and S were obtained from the Regional Database Germany, and calculated as both, a proportion of the total area of the respective administrative region and as a smoothed proportion including values from neighbouring regions. A negative binomial model was used to test the association of the area information in addition to the expected cases information for age and sex distribution. All tests were two-sided and a significance level of α=5% was used. Results: In a follow up of 437,847,835 person years, 171,086 incident cases of UCC were identified. Cluster analysis revealed areas with a significant higher incidence of UCC than others (p=0.0002). Multivariate analysis on land use (as smoothed proportion) in all available counties showed that each such factor is an independent risk factor for UCC (p< 0.00001, respectively). The interquartile range of the respective proportions and the relative risk (RR) for raising the respective proportion from first to third quantile of different land use were 35%-60% (RR 1.10), 0.5%-2.3% (RR 1.07) and 10%-29% (RR 1.21) for all three factors A, I, and S, respectively. Conclusions: This study displays regional differences in UCC incidence in Germany. Furthermore, results suggest that environmental exposure based on socioeconomic factors may present a relevant carcinogenic risk for UCC.
Patterns of lymphatic metastases in upper tract urothelial carcinoma: Experience from three comprehensive cancer centers.
Authors: Matin Surena F. , Espiritu Patrick , Coleman Jonathan A. , Sfakianos John P. , Spiess Philippe E. 
Published: February 2017

349 Background: Data on patterns of lymph node metastasis (LNM) for upper tract urothelial carcinoma (UTUC) is sparse despite its critical relevance for staging and therapeutic potential, with only 1 prior study detailing patterns of spread in 23 pathologically confirmed cases (Kondo T et al, Urol. 2007). Methods: We retrospectively identified and reviewed patients with pTany N+ M0 UTUC at 3 comprehensive cancer centers which routinely perform template-based dissections for UTUC. Anatomic locations of the primary tumor and positive lymph nodes based on the pathological specimens were analyzed, and maps of the location and incidence of LNM constructed. Results: A total of 92 patients with pN+ UTUC were identified, 63 of whom had renal pelvis (n=43) or proximal ureteral (n=20) tumors. LNM from left renal pelvis tumors occurred to the hilar (29.4%), pre- and para-aortic (50.0%) regions, with secondary spread to suprarenal (1.8%), interaortocaval (5.9%), and common iliac (2.9%) regions. LNM from right renal pelvic tumors occurred to the hilar (24.1%), pre- and para-caval (38.0%), retrocaval (13.8%), and inter-aortocaval (24.1%) areas. Left proximal ureteral tumors primarily had LNM to the hilar (46.1%), para-aortic (46.1%), and retro-aortic (7.7%) regions. Right proximal ureteral tumors had LNM to the hilar (36.4%), paracaval (54.5%), and retrocaval (9.1%) regions. A significant difference in survival was noted with patients who had organ confined tumor (p = 0.002) and a lymph node density of less than 25% (p = 0.005). The 1, 2, and 5-year cancer-specific survival rates of the overall cohort were 69%, 49%, and 27%, respectively. Conclusions: Our multi-institutional study provides data regarding the primary landing zones for LNM in renal pelvis and proximal ureter UTUC as well as guidance for developing anatomic dissection templates for prospective studies in UTUC incorporating surgical methodologies as a variable.
Radiosensitivity of orthotopic ileal neobladders.
Authors: Ballas Leslie K. , Bian Shelly X. , Miranda Gus , Daneshmand Siamak 
Published: February 2017

350 Background: A prior report from our institution documented that Kock ileal reservoirs can tolerate doses of 45-50.4Gy. This study provides retrospective information on the radiosensitivity of orthotopic neobladders by reviewing the acute and late toxicity in patients who underwent post-operative radiotherapy following radical cystoprostatectomy with orthotopic ileal neobladder reconstruction. Methods: The USC bladder cancer database was queried for all patients who underwent cystoprostatectomy and neobladder reconstruction followed by adjuvant radiation therapy related to their bladder cancer. The original patient charts and radiation therapy records were reviewed to determine the dose of radiation received by the neobladder. The patient charts were also reviewed to determine acute and late toxicity related to radiation. Results: From 1980 to 2013, 1,742 patients underwent radical cystoprostatectomy with orthotopic neobladder reconstruction. Of those 1,742 patients, 10 patients met the criteria of the study. The median age of the patients who received post-operative radiotherapy was 66.9 years. Forty percent of the study population received a dose of 50.4Gy, 50% received a dose of 45-46.8Gy and one patient, while prescribed a dose of 61.2Gy, only received 39.6Gy secondary to progression of disease on treatment that required termination of RT. All patients received 1.7-1.8Gy per fraction. The most common indications for radiotherapy were close or positive surgical margins. Two patients were treated with IMRT while the rest of the patients received 4 field or AP-PA beam arrangements. Of the patients that completed radiation, 3 had grade 2 or less CTCAE v4.0 acute GI toxicity; no patients reported acute GU toxicity. Two patients reported chronic grade 1 GU toxicity, likely related to their neobladders, with no reports of chronic GI toxicity. No patients experienced neobladder perforation, leak, or fistula. Conclusions: The use of moderate doses of pelvic radiotherapy (45-50.4Gy) was well tolerated among the 10 patients who had radiotherapy following cystoprostatectomy with orthotopic neobladder creation. This data supports the use of post-operative radiotherapy to moderate doses in this patient population when clinically indicated.
ERCC1 as a prognostic factor for survival in patients with advanced urothelial cancer treated with platinium-based chemotherapy: A systematic review and meta-analysis.
Authors: Urun Yuksel , Leow Jeffrey J. , Fay Andre Poisl , Albiges Laurence , Choueiri Toni K. , Bellmunt Joaquim 
Published: February 2017

351 Background: Platinium based chemotherapy (CT) is an essential part in the treatment of advanced urothelial cancer (AUC). However, not all patients derive benefit. A body of evidence suggests that excision repair cross-complementation group 1 (ERCC1) expression level may correlate with outcome in platinum treated patients. We thought to perform a systematic review and meta-analysis to better elucidate its role in AUC. Methods: A comprehensive literature review was performed to identify all studies comparing platinum-based regimens according to expression levels of ERCC1 for patients with AUC. The search included the PubMed, Embase, Cochrane Central Register of Controlled Trials databases, and abstracts from the American Society of Clinical Oncology meetings up to June 2014. Pooled analyses were conducted using fixed and random effects models. Results: A total of 554 patients included in eight studies were evaluated. ERCC1 expression was positive in 270 (49%) patients and negative in 284 (51%) patients. The median age of patients was 63 years. The overall survival (OS) was significantly better in patients with negative ERCC1 expression (pooled hazard ratio (HR) 1.90 (95% confidence interval [CI], 0.98–3.67; p=0.006). There was moderate amount of between-study heterogeneity present (I-square 70%). Conclusions: This study's findings support the hypothesis that low ERCC1 expression is associated with benefit from cisplatin-based treatment. The substantial amount of between-study heterogeneity may indicate the need for standardized methods to classify ERCC1 expression level. Prospective studies are necessary to determine the role of ERCC1 levels for treatment selection in patients with AUC.