bluuebunny/crossref_metadata_2025_split huggingface dataset:
DAB389 EGF for the treatment of superficial urothelial cancer.
Authors: Flaig T. W. , Su L. , Thorburn A. , Frankel A. E. , Li Y. , Woo J. H. , Varella-Garcia M. , La Rosa F. G. , Li C. , Yang X. 
Published: February 2017

255 Background: Intravesical BCG has remained the standard treatment for superficial bladder cancer for decades, despite frequent recurrences after its use. Toxic fusion proteins are a novel class of agents containing both a targeting and a treatment component; correspondingly, DAB389EGF contains an EGF and a diphtheria element, thereby targeting any cell expressing EGFR. Notably, the normal urothelium has little or no luminal EGFR expression in contrast to urothelial cancers, which frequently overexpress EGFR. Methods: DAB389EGF was tested in vitro to determine the effect of DAB389EGF on cell viability in culture. Tests of clonogenicity were performed by treating plated cells for 2 hours and following colony counts over 14 days. DAB389EGF was tested in an orthotopic murine model of bladder cancer with implanted HTB9 cells modified to express luciferase. DAB389EGF was administered intravesically via catheterization of the murine bladder and held in place for 2 hours with a temporary suture to close the urethra. Treatments were continued twice weekly for 2 weeks, with DT-GMCSF used as a control. Results: Treatment with DAB389EGF yielded IC50's ranging from 0.5 to 15.7 ng/ml in 8 tested bladder cancer cell lines, but the IC50 was > 500ng/ml in the EGFR- negative H520 control cell line. A single 2-hour exposure to DAB389EGF (50ng/ml) decreased colony formation in all of the bladder cancer cell lines, with complete suppression in HT1376 and T24 cells. In the animal model, luciferase activity was lost in 5 of 6 mice treated with DAB389EGF, versus 1 of 6 mice treated with control. After the 2 week treatment period, histological assessment of the treated mice was undertaken and was consistent with the luciferase findings. FISH was used to detect human or murine-originated cells in order to confirm the presence or absence of xenograft tissue histologically. Conclusions: Targeted-toxin fusion proteins represent a novel treatment approach for superficial bladder cancer. By capitalizing on the differential expression of EGFR between cancerous and normal urothelium, DAB389EGF selectively targets bladder cancer cells. Preliminary animal studies support the efficacy and tolerability of this approach with additionally animal work currently underway. No significant financial relationships to disclose.
Urinary Met level as a novel biomarker for urothelial carcinoma of the bladder.
Authors: Sorbellini M. , McNeil B. , Cohen B. , Athauda G. , Giubellino A. , Coleman J. , Netto G. J. , Getzenberg R. H. , Linehan W. , Bottaro D. P. 
Published: February 2017

257 Background: To determine whether urinary soluble Met (sMet) can differentiate between benign conditions and bladder cancer (CaB), and in cases of bladder cancer, between different stages of transitional cell carcinoma (TCC). Methods: Urinary samples from patients with (Total: 63, pTa: 12, pTis: 22, pT1: 13, ≥ pT2: 16) and without (Total: 27) CaB from three different institutions were prospectively collected prior to cystosopy, TURBT or cystectomy. sMet levels were determined by electrochemiluminescence immunoassay and normalized to urinary creatinine values. Normalized sMet values were compared to final pathologic stage. AUC values were obtained comparing patients with and without TCC. Results: Urinary sMet levels accurately differentiated between patients with and without CaB (AUC: 78%, sensitivity, specificity and negative predictive value were: 68%, 78% and 95%, respectively), patients with no CaB and those with lamina propria invasion (AUC: 79%, sensitivity, specificity and negative predictive value were: 65%, 81% and 95%, respectively) and patients with no CaB and those with muscle invasive CaB (AUC: 85%, sensitivity, specificity and negative predictive value were: 75%, 83% and 97%, respectively). Conclusions: Urinary sMet levels accurately distinguish patients with CaB from those without, and between patients with different CaB stages. These results suggest that urinary sMet may have utility as a bladder cancer marker for screening, treatment follow-up and clinical trial design. No significant financial relationships to disclose.
Use of a MET-specific photoprobe to identify bladder tumors in an orthotopic xenograft model of bladder cancer.
Authors: Sorbellini M. , Giubellino A. , Srivastava G. , Sourbier C. , Jagoda E. , Williams M. , Choyke P. L. , Pinto P. A. , Linehan W. , Bottaro D. P. 
Published: February 2017

260 Background: Met over-expression has been found in bladder cancer (CaB). Stage and grade increases in urothelial carcinoma have been found to correlate with increases in Met expression. To assess whether molecular optical imaging could enhance the detection of bladder tumors, we used a Met-specific soluble photoprobe in an orthotopic xenograft model of bladder transitional cell carcinoma (TCC). Methods: An orthotopic xenograft murine model of CaB was developed with T24-Luciferase-positive bladder cancer cells. Presence of tumor was confirmed by luciferase optical imaging (Xenogen IVIS) of mice, 4 weeks after TCC cell implantation. Mice were euthanized and their bladders removed and bivalved. Bladders were incubated for 30 minutes with unbound fluorophore (Cy5**, Peak emission at 675 nM) and subsequently for another 30 minutes with Cy5** bound to a Met-specific peptide. Fluorescence imaging (Maestro) was performed before and after each incubation period. Following imaging, presence of tumor was confirmed histologically. Results: Cy5**-Met- peptide bound in sufficient density to tumor tissue in bladders for visualization by optical imaging. The tumor to normal bladder imaging ratio ranged from 2:1 to 8:1. Bladder regions with high uptake of Cy5**-Met-peptide corresponded to tumor areas confirmed by histological analysis. Conclusions: Cy5**-Met-peptide successfully targets Met in an orthotopic xenograft model of bladder cancer. Our results suggest that this agent maybe useful for the enhanced visualization of bladder cancer tumors during cystoscopy. No significant financial relationships to disclose.
Synergistic potentiation of anti-tumor immunity with light-activated drug therapy and anti-CTLA4 antibody treatment.
Authors: Bromley E. , Waitz R. , Wang S. , Allison J. P. 
Published: February 2017

27 Background: Talaporfin sodium (TS) is a light-activated, locally cytoreductive drug in phase III clinical trials for several different cancers. It is activated intratumorally with a thin, flexible LED array. TS treatment has been shown in preclinical studies to activate CD8+-dependent anti-tumor immunity in a model of metastatic breast cancer. Anti-CTLA4 antibody is an immunotherapy that acts by suppressing negative regulation of immune effectors. It has recently completed a successful phase III clinical trial in melanoma patients in which it was shown to prolong survival. TS and anti-CTLA4 antibody have great potential to synergistically reduce primary tumor burden and generate systemic anti-tumor immunity. Methods: This study examined combination treatment with these two therapies in a murine prostate cancer tumor model (C57BL/6 + TRAMP C2). A large, established tumor on the left side of each mouse was treated with light-activated TS (or light- only control). One day after treatment, mice were injected intradermally with 0.5 × 106 TRAMP C2 cells on the opposite flank. Anti-CTLA4 (or vehicle control) was given on days 1, 4, 7 and 10. Progression of the untreated tumor was measured. Results: Growth of untreated tumors was prevented or significantly delayed in 55% and 33% of combination-treated animals, respectively (n = 9). In addition, contralateral tumor growth was prevented in 1 of 9 animals given talaporfin sodium alone while another animal's tumor showed growth delay. None of the untreated controls or anti-CTLA4 only animals showed a similar response. Individual combination-treated mice with delayed tumor growth often showed an atypical tumor growth curve in which progression either tapered off or began to reverse between 30 and 40 days post treatment. Conclusions: Reduction of tumor using local treatment with a light-activated drug could potentiate the anti-tumor immune response resulting from anti-CTLA4 treatment and prevent growth of secondary tumors in a preclinical prostate cancer model. [Table: see text]
Multimodality therapy including surgical resection (SR) and intraoperative electron radiotherapy (IOERT) for locoregionally recurrent (LRR) or advanced primary malignancies of the urinary bladder (UB) or ureter.
Authors: Hallemeier C. L. , Karnes R. J. , Pisansky T. M. , Davis B. , Gunderson L. L. , Leibovich B. C. , Haddock M. G. , Choo R. 
Published: February 2017

277 Background: For patients (pts) with LRR or advanced primary tumors of the UB or ureter, limited therapeutic options exist. Outcomes of combined SR and IOERT are reported here. Methods: From 1983 to 2009, a total of 17 pts with urothelial (16 pts) or squamous cell carcinoma (1 pt) of the UB (n=13) or ureter (n=4) were treated with SR and IOERT. Pts had LRR after radical cystoprostatectomy or nephroureterectomy (n=15) or advanced primary tumor (n=2). Extent of SR was R0 (microscopic negative margins), R1 (microscopic positive margins), and R2 (gross residual tumor) in 7, 1, and 9 pts, respectively. After maximal SR, IOERT was delivered to the tumor bed. Median IOERT dose and energy delivered were 12.5 Gy (range; 10-20) and 9 MeV (range; 6-18), respectively, with 1 (n=15), 2 (n=1), or 3 (n=1) IOERT fields. Sixteen pts also received perioperative external beam radiotherapy (EBRT) with a median dose of 50.4 Gy (range; 21.6- 60). Five pts received concurrent chemotherapy (CT) with perioperative EBRT. Overall (OS), disease-free survival (DFS) and relapse patterns were estimated from the date of SR and IOERT using the Kaplan-Meier method. Results: The median pt age was 63 years (yrs) (range; 51-76). The median follow-up of surviving pts was 3.6 yrs (range; 1.1-10.0). OS and DFS at 1, 2, and 5 yrs were 53%, 31%, and 16%, and 24%, 18%, and 18%, respectively. Central (within the IOERT field), locoregional (tumor bed or first echelon draining lymphatics), and distant relapse at 2 yrs were 15%, 49%, and 67%, respectively. Seven pts received systemic CT after relapse. Mortality within 30 days of SR and IOERT was 0%. Two pts (12%) experienced grade 4-5 (NCI-CTCAE v. 4) toxicity potentially related to the multimodality therapy. Conclusions: For pts with LRR or advanced primary tumor of the UB or ureter, this multimodality therapy including SR and IOERT resulted in durable OS and DFS in a small but significant number of pts. Both LRR and distant relapse were common, indicating a need for more effective systemic therapy along with more refined locoregional therapy. No significant financial relationships to disclose.
A phase II trial of gemcitabine (G), carboplatin (C), and sorafenib (S) in patients (pts) with transitional cell carcinoma (TCC): Preliminary safety and outcome.
Authors: Mehnert J. M. , Mortazavi A. , Stein M. N. , Donadio A. C. , Zelterman D. , McDonough J. A. , Rowen E. , Hoimes C. J. , Gibney G. , Kelly W. K. 
Published: February 2017

278 Background: Sorafenib is an oral tyrosine kinase inhibitor with anti-angiogenic properties that may enhance the antitumor activity of GC and when administered as maintenance therapy after GC may delay disease recurrence. This study investigated the safety and clinical outcome of adding S to GC for pts with advanced TCC and the role of S maintenance after GC. Methods: Metastatic/unresectable chemotherapy naive TCC pts ECOG PS 0-1 received G 1,000 mg/m2 d1, 8 and C AUC = 5 d1 with S 400 mg bid d2-19 q21 d for 6 cycles. Pts with stable disease or PR/CR continued on 400 mg bid of S. The primary endpoint was proportion of pts free of progression at 5 months with secondary endpoint of proportion of pts with PR/CR. A Simon two-stage design would enroll 30 pts; if 8 of the initial 17 followed for 5 months or more post treatment showed disease progression, the trial would terminate. Results: 17 pts enrolled, 14 male, 3 female; median age 64 (47-86); ECOG 0 (7)/1 (10). The median number of cycles of GC + S given was 4.4 with multiple dose reductions in 71%. 7 pts (47%) experienced grade (gr) 3/4 neutropenia and 4 (24%) gr 3/4 anemia during GC + S; no neutropenic fever was seen. Gr 3/4 thrombocytopenia occurred in 59% with 2 events of hematuria, 1 epistaxis, and 1 bleeding colitis. Gr 3 nonhematologic toxicities: hypophosphotemia (29%), diarrhea (6%), fatigue (24%), anorexia (6%), dehydration (6%), hand foot syndrome (6%), rash (12%), hypertension (6%). Responses: 1 CR (6%), 4 PR (24 %), 8 SD (47%); 3 pts with evaluable disease showed tumor shrinkage, including 1 with resolution of bone metastases. 9 (53 %) were progression free at 5 months; 7 (41%) came off trial due to > 3 dose reductions (1 prior to first restaging) and 1 withdrew consent. 7 (41%) that achieved CR, PR or SD after a minimum of 4 cycles GC + S received maintenance S for a median of 8 cycles. Conclusions: GC + S showed clinical activity in advanced TCC similar to GC alone but prolonged progression-free intervals were observed in patients treated with S maintenance. GC + S was associated with increased hematologic toxicity although S maintenance was well tolerated. Further studies exploring the role of S maintenance after chemotherapy are warranted. [Table: see text]
Oncologic outcomes for node-positive patients undergoing robotic radical cystectomy.
Authors: Mmeje C. , Nunez-Nateras R. , Pruthi R. , Nielsen M. E. , Wallen E. , Humphreys M. , Castle E. P. 
Published: February 2017

290 Background: Previous studies have shown robot assisted radical cystectomy (RARC) to have equivalent perioperative outcomes to open radical cystectomy. There are few reports that have examined the oncologic results of RARC specifically with respect to node-positive patients. We report the outcomes of node-positive patients who have undergone RARC with medium-term (at least 1 year) follow-up. Methods: A total of 275 patients underwent RARC at two institutions for invasive bladder cancer between 2005-present. We examined the 50 patients with node-positive disease that had a minimum of one year follow-up. Oncologic outcomes, recurrence free survival (RFS), and disease specific survival (DSS) were analyzed and compared to the open literature. Results: Mean clinical follow up in this case series was 29 months (range 12–64 months). The mean number of lymph nodes removed was 18 (range 5–35), and mean number of positive LNs was 3.1 (range 1–12). Overall rate of LN positivity was 26%. Mean LN density was 18%. Seventeen (34%) patients had ≤ pT2 disease and 33 (66%) pT3/T4 disease. At this follow-up, 29 patients have recurred, 21 patients died of disease, giving a RFS and DSS of 42% and 58%, respectively. Mean (median) time to recurrence was 10.2 months (9 months). A total of 60% of patients received peri-operative chemotherapy in this cohort. These findings are consistent with prior reports of such oncologic outcomes in node-positive patients in open series. Conclusions: The oncologic follow-up of patients undergoing RARC with LN positive disease appears to have acceptable outcomes during medium term (mean 29 months) follow-up. As our follow-up increases, we expect to continue to accurately define the long-term clinical suitability and oncologic success of this procedure in this high-risk population. No significant financial relationships to disclose.
The role of PET-CT in the follow-up of patients with urothelial cancer diagnosis.
Authors: Jankilevich G. , Ogresta F. , Gennari L. , Ominetti A. , Bermudez M. , Peña F. , Eleta M. 
Published: February 2017

291 Background: Positron emission tomography (PET) is an imaging technique whose principle is the detection of metabolic activity of tumor cells but in urology its use had been restricted due to urinary excretion of the radiotracer and overlap with urological structures, the use of hybrid PET (PET-CT) would allow its use for monitoring patients with urothelial tumors. Methods: Between 2007 and 2010 we performed PET-TC images in consecutive patients with suspected recurrences in CT scan or MRI. All patients had renal, bladder and uretral cancer and were treated with urothelial cancer diagnosis. We evaluate the usefulness of FDG PET-CT and its impact on behavior therapy in suspected recurrence in patients with urothelial carcinoma, compared with conventional studies. Results: 17 patients were studied for suspected recurrence. All patients had positive images previously on CT scan and MRI; positive PET-TC was observed in 14 and 3 studies were negative. The positive PET-CT showed more number of lesions and change the medical and surgical strategy. Of the three studies negative on PET- CT none had recurrence and remain disease free. PET/CT is in a great benefit to the detection recurrence in the follow up of patients with urothelial cancer diagnosis. These results showed an increased sensitivity and specificity over previous work with conventional PET technology. In the series studied, the implementation of PET-CT (FDG) in the follow up of patients with urothelial tumors were an useful tool. Conclusions: PET/CT is in a great benefit to the detection recurrence in the follow up of patients with urothelial cancer diagnosis. These results showed an increased sensitivity and specificity over previous work with conventional PET technology. In the series studied, the implementation of PET-CT (FDG) in the follow up of patients with urothelial tumors were an useful tool. However, multicenter studies and more patients are required to define its role. No significant financial relationships to disclose.
Does bladder urothelial cancer behave differently in young patients?
Authors: Wang Z. , Li Y. , Lu H. , Zeng X. , Zhuang Q. , Zhu H. , Hu Z. 
Published: February 2017

294 Background: From 2000 to 2008, the incidence of bladder urothelial cancer in the young adults was diagnosed at an increasing trend at the Tongji Hospital, China. To investigate whether bladder urothelial cancer in patients under the age of 40 years behaves significantly differently from the bladder urothelial cancer in elder patients. Methods: From 1994 to 2008, the records of 4,568 patients with pathological diagnosis of bladder urothelial cancer presented to the Tongji Hospital were retrospectively reviewed. 82 patients were younger than 40 at the time of diagnosis. The clinicopathologic parameters were compared between this group and a serial of 164 older patients during the same time period. The Kaplan-Meier and Cox regression analyses were performed for the survival analysis. Results: 2.05% of patients with pathological diagnosis of bladder urothelial cancer presented to the Tongji Hospital were younger than 40 years (median age 32.93). Compared to the older group, young adults group had a lower sex ratio (male-to-female ratio, 3.4:1vs.6.5:1, p<0.05); much less likely with advanced stages (the percentage of invasive tumor, i.e., T1 or above, 28.1% vs. 52.4%, p<0.01); less with a high grade (the percentage of high grade tumor, 14.6% vs. 22.6%, p<0.05); lower recurrence rate (23.2% vs. 39.6%, p<0.05); less with big tumor size (the percent of tumor size greater than 3 cm, 18.3% vs. 22.0%, p<0.05); and less with multifocal (12.2% vs. 50.6%, p<0.01). Kaplan-Meier method and the log-rank test showed a significantly better cancer specific and overall survival for the group of young patients (p<0.01). The multivariate Cox regression analyses showed the following criteria were independent prognostic factors of overall survival: bladder tumor multiplicity, size greater than 3 cm, T2 or above stage, and high grade. Conclusions: Despite an increasing trend of diagnosis, both the pathologic features and clinical outcomes were significantly better in the young patients with bladder urothelial cancer when compared to their elderly counterparts. These findings suggested that more consevertive management approaches may be warranted for this group of patients even under the circumstances of extensive bladder involvement. No significant financial relationships to disclose.
Evaluation of the role of second TUR for transurethral resection of bladder tumor in one piece (TURBO).
Authors: Ikeda H. , Nomura M. , Shou T. , Ishikawa K. , Kashiwagi E. , Dejima T. , Sanefuji H. , Okumura K. 
Published: February 2017

298 Background: Since transurethral resection of bladder tumor in one piece (TURBO) was reported in the Journal of Urology in 2000 by Ukai, some urologists carried out TURBO. We analyzed treatment results of TURBO in our hospital and examined the value of this procedure, especially for the pathological findings, recurrence and necessity of second TUR for TURBO. Methods: A total of 14 patients with bladder tumors carried out TURBO under spinal anesthesia, in some cases blocking the obtulater nerve, from April 2006 to June 2009 in our hospital. All cases were followed for over 1 year. The procedure is 1. point marking; 2. circular incision; 3. level incision; and 4. specimen retrieval using a needle electrode in accordance with the Ukai's method. We investigated pathological findings (margin situation), operation time, complications and recurrence. Results: It is possible to diagnose the precise pathlogical findings by TURBO. We judged the width and depth ew in sequential section. There were no complications during and after the operation. Operation time of TURBO (35–170 min) was longer than TUR-BT. Urethral catheter holding period and hospitalization period after TURBO was the same as TUR-BT. TURBO is a relatively safe procedure even for beginners. 5 cases had a recurrence in 13 cases. 2 cases had a recurrence in under 1 year, but the locations were other places. One case had a same place recurrence after 13 months. There were no cases of same place recurrence in under 1 year among margin-negative cases. Therfore we judged that ew-negative cases had no residual cancers. Conclusions: TURBO is a safe and useful procedure that provides precise pathological findings with minimal complications. Second TUR is not necessary for TURBO. TURBO has a possibility to be gold standard of the treatment for non-muscle invasive bladder cancer. No significant financial relationships to disclose.