Supplementary Figure 1 from Intravesical Immunotherapy of Superficial Bladder Cancer with Chitosan/Interleukin-12

Supplementary Figure Legends 1-2 from Intravesical Immunotherapy of Superficial Bladder Cancer with Chitosan/Interleukin-12

Low temperature sensitive liposome (LTSL) encapsulated docetaxel were combined with mild hyperthermia (40–42°C) to investigate in vivo biodistribution and efficacy against a castrate resistant prostate cancer.

OBJECTIVE:To characterise the feasibility and safety of a novel transurethral ultrasound (US)-therapy device combined with real-time multi-plane magnetic resonance imaging (MRI)-based temperature monitoring and temperature feedback control, to enable spatiotemporally precise regional ablation of simulated prostate gland lesions in a preclinical canine model. To correlate ablation volumes measured with intra-procedural cumulative thermal damage estimates, post-procedural MRI, and histopathology. MATERIALS AND METHODS:Three dogs were treated with three targeted ablations each, using a prototype MRI-guided transurethral US-therapy system (Philips Healthcare, Vantaa, Finland). MRI provided images for treatment planning, guidance, real-time multi-planar thermometry, as well as post-treatment evaluation of efficacy. After treatment, specimens underwent histopathological analysis to determine the extent of necrosis and cell viability. Statistical analyses (Pearson's correlation, Student's t-test) were used to evaluate the correlation between ablation volumes measured with intra-procedural cumulative thermal damage estimates, post-procedural MRI, and histopathology. RESULTS:MRI combined with a transurethral US-therapy device enabled multi-planar temperature monitoring at the target as well as in surrounding tissues, allowing for safe, targeted, and controlled ablations of prescribed lesions. Ablated volumes measured by cumulative thermal dose positively correlated with volumes determined by histopathological analysis (r(2) 0.83, P < 0.001). Post-procedural contrast-enhanced and diffusion-weighted MRI showed a positive correlation with non-viable areas on histopathological analysis (r(2) 0.89, P < 0.001, and r(2) 0.91, P = 0.003, respectively). Additionally, there was a positive correlation between ablated volumes according to cumulative thermal dose and volumes identified on post-procedural contrast-enhanced MRI (r(2) 0.77, P < 0.01). There was no difference in mean ablation volumes assessed with the various analysis methods (P > 0.05, Student's t-test). CONCLUSIONS:MRI-guided transurethral US therapy enabled safe and targeted ablations of prescribed lesions in a preclinical canine prostate model. Ablation volumes were reliably predicted by intra- and post-procedural imaging. Clinical studies are needed to confirm the feasibility, safety, oncological control, and functional outcomes of this therapy in patients in whom focal therapy is indicated.

BACKGROUND AND PURPOSE Complications after robot-assisted prostatectomy are widely reported and varied. Our goal was to determine the incidence of surgical complications resulting from robot-assisted laparoscopic radical prostatectomy (RALP) during the initial phase of a new robotics program that was developed by two surgeons without laparoscopic or robotic fellowship training. A secondary goal was to see if experience changed the incidence of complications with this technology. PATIENTS AND METHODS A prospectively maintained database was used to evaluate the first 1000 consecutive patients who were treated with RALP from January 2004 to June 2009. The database was reviewed for evidence of complications in the perioperative period. All patients underwent robot-assisted laparoscopic radical prostatectomy by two surgeons. Complications were confirmed and supplemented by retrospectively reviewing the departmental morbidity and mortality reports, as well as the hospital records. The Clavien classification system, a standardized and validated scale for complication reporting, was applied to all events. The complication rate was determined per 100 patients treated and tested with logistic regression for a relationship with surgeon experience. RESULTS Ninety-seven (9.7%) patients experienced a total of 116 complications; 81 patients experienced a single complication and 16 patients experienced ≥2 complications. The majority of complications (71%) were either grade I or II. The complication rate decreased with experience when the first 500 cases were compared with the latter 500 cases (P=0.007). All the data were reviewed retrospectively. Involvement of residents/fellows increased as primary surgeon experience improved. CONCLUSIONS Complications after RALP are most commonly minor, requiring expectant or medical management only, even during the initiation of a RALP program. The complication rate improved significantly during the study period.

PURPOSE:The biology of prostate cancer may be influenced by the index lesion. The definition of index lesion volume is important for appropriate decision making, especially for image guided focal treatment. We determined the accuracy of magnetic resonance imaging for determining index tumor volume compared with volumes derived from histopathology.MATERIALS AND METHODS:We evaluated 135 patients (mean age 59.3 years) with a mean prostate specific antigen of 6.74 ng/dl who underwent multiparametric 3T endorectal coil magnetic resonance imaging of the prostate and subsequent radical prostatectomy. Index tumor volume was determined prospectively and independently by magnetic resonance imaging and histopathology. The ellipsoid formula was applied to determine histopathology tumor volume, whereas manual tumor segmentation was used to determine magnetic resonance tumor volume. Histopathology tumor volume was correlated with age and prostate specific antigen whereas magnetic resonance tumor volume involved Pearson correlation and linear regression methods. In addition, the predictive power of magnetic resonance tumor volume, prostate specific antigen and age for estimating histopathology tumor volume (greater than 0.5 cm(3)) was assessed by ROC analysis. The same analysis was also conducted for the 1.15 shrinkage factor corrected histopathology data set.RESULTS:There was a positive correlation between histopathology tumor volume and magnetic resonance tumor volume (Pearson coefficient 0.633, p <0.0001), but a weak correlation between prostate specific antigen and histopathology tumor volume (Pearson coefficient 0.237, p = 0.003). On linear regression analysis histopathology tumor volume and magnetic resonance tumor volume were correlated (r(2) = 0.401, p <0.00001). On ROC analysis AUC values for magnetic resonance tumor volume, prostate specific antigen and age in estimating tumors larger than 0.5 cm(3) at histopathology were 0.949 (p <0.0000001), 0.685 (p = 0.001) and 0.627 (p = 0.02), respectively. Similar results were found in the analysis with shrinkage factor corrected tumor volumes at histopathology.CONCLUSIONS:Magnetic resonance imaging can accurately estimate index tumor volume as determined by histology. Magnetic resonance imaging has better accuracy in predicting histopathology tumor volume in tumors larger than 0.5 cm(3) than prostate specific antigen and age. Index tumor volume as determined by magnetic resonance imaging may be helpful in planning treatment, specifically in identifying tumor margins for image guided focal therapy and possibly selecting better active surveillance candidates.

Study Type – Diagnosis (case series)Level of Evidence 4What's known on the subject? and What does the study add?Benign prostatic hyperplasia is the most common symptomatic disorder of the prostate and its severity varies greatly in the population. Various methods have been used to estimate prostate volumes in the past including the digital rectal examination and ultrasound measurements.High‐resolution T2 weighted MRI can provide accurate measurements of zonal volumes and total volumes, which can be used to better understand the etiology of lower urinary tract symptoms of men.OBJECTIVE To use ability of magnetic resonance imaging (MRI) to investigate age‐related changes in zonal prostate volumes. PATIENTS AND METHODS This Institutional Review Board approved, Health Insurance Portability and Accountability Act‐compliant study consisted of 503 patients who underwent 3 T prostate MRI before any treatment for prostate cancer. Whole prostate (WP) and central gland (CG) volumes were manually contoured on T2‐weighted MRI using a semi‐automated segmentation tool. WP, CG, peripheral zone (PZ) volumes were measured for each patient. WP, CG, PZ volumes were correlated with age, serum prostate‐specific antigen (PSA) level, International Prostate Symptom Score (IPSS), Sexual Health Inventory for Men (SHIM) scores. RESULTS Linear regression analysis showed positive correlations between WP, CG volumes and patient age (P < 0.001); there was no correlation between age and PZ volume (P= 0.173). There was a positive correlation between WP, CG volumes and serum PSA level (P < 0.001), as well as between PZ volume and serum PSA level (P= 0.002). At logistic regression analysis, IPSS positively correlated with WP, CG volumes (P < 0.001). SHIM positively correlated with WP (P= 0.015) and CG (P= 0.023) volumes. As expected, the IPSS of patients with prostate volumes (WP, CG) in first decile for age were significantly lower than those in tenth decile. CONCLUSIONS Prostate MRI is able to document age‐related changes in prostate zonal volumes. Changes in WP and CG volumes correlated inversely with changes in lower urinary tract symptoms. These findings suggest a role for MRI in measuring accurate prostate zonal volumes; have interesting implications for study of age‐related changes in the prostate.

OBJECTIVE To demonstrate the use of a patient-specific magnetic resonance imaging (MRI)-based prostate mold to generate histologic sections that directly correlate to axial MRI slices in a patient with anteriorly located prostate cancer. Anteriorly located prostate cancer has traditionally been difficult to detect on digital rectal examination and transrectal ultrasound-guided biopsy. Multiparametric MRI has potential as a valuable tool for the diagnosis and focal treatment of prostate cancer. A significant difficulty to date has been accurate correlation between the magnetic resonance images and histopathologic specimens.METHODS A patient-specific mold from a preoperative T-2-weighted MRI scan was created to hold and shape the prostate specimen. Slots for slicing were positioned at 6-mm increments coplanar to the axial MRI slices. After surgical excision, the specimen was inked to maintain the orientation and fixed in formalin. The seminal vesicles were excised, and the prostate was oriented in the mold such that the color-coding matched the anatomic labels on the mold. The specimen was sliced with a single blade and the resultant 6-mm tissue blocks were used for histologic analysis.RESULTS Preoperative multiparametric MRI revealed a lesion in the right anterior transition zone that was positive on T-2-weighed MRI, apparent diffusion coefficient maps of diffusion-weighted MRI, magnetic resonance spectroscopy, and dynamic contrast-enhanced MRI. The histologic sections obtained using the mold demonstrated a similar Gleason score 6 (3 + 3) lesion in the right anterior transition zone, correlating with the MRI findings.CONCLUSION The use of patient-specific prostate molds to register the MRI findings with the histopathologic specimen in prostate cancer could offer several benefits compared with current specimen processing techniques. This technique might further validate MRI as an accurate tool for prostate cancer localization and staging. UROLOGY 79: 233-239, 2012. (C) 2012 Published by Elsevier Inc.

From the Urologic Oncology Branch (PAP, PHC, ARR, AAB, CJB, CC, GB, WML) and Molecular Imaging Program (BT, PLC), Center for Cancer Research, and Center for Interventional Oncology, Department of Radiology and Imaging Sciences (JKL, SPG, CB, BJW), Clinical Center & National Cancer Institute, National Institutes of Health, Bethesda, and Biometric Research Branch, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Rockville, Maryland, Philips Healthcare, Toronto, Canada (NDG), and Philips Research North America, Briarcliff Manor, New York (JK, SX, PY, SK, JHS)

During transrectal ultrasound (TRUS)-guided prostate biopsies, the actual location of the biopsy site is rarely documented. Here, we demonstrate the capability of TRUS-magnetic resonance imaging (MRI) image fusion to document the biopsy site and correlate biopsy results with multi-parametric MRI findings. Fifty consecutive patients (median age 61 years) with a median prostate-specific antigen (PSA) level of 5.8 ng/ml underwent 12-core TRUS-guided biopsy of the prostate. Pre-procedural T2-weighted magnetic resonance images were fused to TRUS. A disposable needle guide with miniature tracking sensors was attached to the TRUS probe to enable fusion with MRI. Real-time TRUS images during biopsy and the corresponding tracking information were recorded. Each biopsy site was superimposed onto the MRI. Each biopsy site was classified as positive or negative for cancer based on the results of each MRI sequence. Sensitivity, specificity, and receiver operating curve (ROC) area under the curve (AUC) values were calculated for multi-parametric MRI. Gleason scores for each multi-parametric MRI pattern were also evaluated. Six hundred and 5 systemic biopsy cores were analyzed in 50 patients, of whom 20 patients had 56 positive cores. MRI identified 34 of 56 positive cores. Overall, sensitivity, specificity, and ROC area values for multi-parametric MRI were 0.607, 0.727, 0.667, respectively. TRUS-MRI fusion after biopsy can be used to document the location of each biopsy site, which can then be correlated with MRI findings. Based on correlation with tracked biopsies, T2-weighted MRI and apparent diffusion coefficient maps derived from diffusion-weighted MRI are the most sensitive sequences, whereas the addition of delayed contrast enhancement MRI and three-dimensional magnetic resonance spectroscopy demonstrated higher specificity consistent with results obtained using radical prostatectomy specimens.

Purpose: We determined the prostate cancer detection rate of multiparametric magnetic resonance imaging at 3T. Precise one-to-one histopathological correlation with magnetic resonance imaging was possible using prostate magnetic resonance imaging based custom printed specimen molds after radical prostatectomy.Materials and Methods: This institutional review board approved prospective study included 45 patients (mean age 60.2 years, range 49 to 75) with a mean prostate specific antigen of 6.37 ng/ml (range 2.3 to 23.7) who had biopsy proven prostate cancer (mean Gleason score of 6.7, range 6 to 9). Before prostatectomy all patients underwent prostate magnetic resonance imaging using endorectal and surface coils on a 3T scanner, which included triplane T2-weighted magnetic resonance imaging, apparent diffusion coefficient maps of diffusion weighted magnetic resonance imaging, dynamic contrast enhanced magnetic resonance imaging and spectroscopy. The prostate specimen was whole mount sectioned in a customized mold, allowing geometric alignment to magnetic resonance imaging. Tumors were mapped on magnetic resonance imaging and histopathology. Sensitivity, specificity, positive predictive value and negative predictive value of magnetic resonance imaging for cancer detection were calculated. In addition, the effects of tumor size and Gleason score on the sensitivity of multiparametric magnetic resonance imaging were evaluated.Results: The positive predictive value of multiparametric magnetic resonance imaging to detect prostate cancer was 98%, 98% and 100% in the overall prostate, peripheral zone and central gland, respectively. The sensitivity of magnetic resonance imaging sequences was higher for tumors larger than 5 mm in diameter as well as for those with higher Gleason scores (greater than 7, p < 0.05).Conclusions: Prostate magnetic resonance imaging at 3T allows for the detection of prostate cancer. A multiparametric approach increases the predictive power of magnetic resonance imaging for diagnosis. In this study accurate correlation between multiparametric magnetic resonance imaging and histopathology was obtained by the patient specific, magnetic resonance imaging based mold technique.

You have accessJournal of UrologyKidney Cancer: Localized1 Apr 20111262 ROBOT-ASSISTED LAPAROSCOPIC PARTIAL NEPHRECTOMY FOR HEREDITARY OR MULTIFOCAL KIDNEY CANCER: FEASIBILITY AND PERIOPERATIVE OUTCOMES Kevin Asher, Gopal Gupta, Compton Benjamin, Peter Pinto, W. Marston Linehan, and Gennady Bratslavsky Kevin AsherKevin Asher Bethesda, MD More articles by this author , Gopal GuptaGopal Gupta Bethesda, MD More articles by this author , Compton BenjaminCompton Benjamin Bethesda, MD More articles by this author , Peter PintoPeter Pinto Bethesda, MD More articles by this author , W. Marston LinehanW. Marston Linehan Bethesda, MD More articles by this author , and Gennady BratslavskyGennady Bratslavsky Bethesda, MD More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.947AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Partial nephrectomy has emerged as the preferred treatment strategy for hereditary or multifocal renal cell carcinoma (RCC). We describe perioperative, functional, and oncologic outcomes of patients with hereditary or multifocal RCC using robot-assisted laparoscopic partial nephrectomy (RALPN). METHODS We queried our prospectively maintained urologic oncology database to identify all hereditary RCC patients or those with multifocal RCC who underwent RALPN. Demographic and perioperative data were reviewed. Preoperative radiographic characteristics, pathology, renal functional (preoperative and at 3 months postop) as well as oncologic outcomes were recorded. Comparisons of preoperative and postoperative renal function were performed using the student T-test. RESULTS Fifty-five RALPN (including 8 staged bilateral) were performed in 47 patients that included 23 (49%) VHL, 12 (25%) BHD, 5 (11%) BMF papillary RCC, and 7 others with various familial RCC syndromes. Six cases (11%) required conversion to open procedure, two of which were performed in patients with previous ipsilateral renal intervention. Two intraoperative complications occurred (4.1%) including a pneumothorax and a renal vein injury necessitating conversion to open surgery and nephrectomy. Operative and pathologic outcomes are listed in the Table.. There was no difference in mean preoperative and postoperative estimated GFR which was 87.8 ml/min/1.73m2 (30.8–186.9) and 83.5 (29.9–176.0), respectively (p=0.25), while mean ipsilateral renal scan function was significantly lower postoperatively (52.4% (42–70) preop vs 48.4% (29–73) postop, p<0.01). At a median follow up of 12.9 months (range 0.1–36.2) overall survival was 98% with one patient dying from metastatic disease that was present prior to surgery. No other patient has required reintervention or developed metastasis. Operative Outcomes and Tumor Histology Number of Procedures 55 Number Completed Robotically, (%) 49(89) Mean age, yrs (range) 45.9(19–76) No. of Cases Performed on Kidney with prior ipsilateral intervention, (%) 11(20) Median Largest Radiographic Tumor Size, cm (range) 3.2(1.3–8) Median Nephrometry Score, (range) 8(4–11) Mean Operative time, min (range) 330(152–535) Mean Estimated Blood Loss, mL (range) 580(100–1600) Cases performed without renal ischemia (%) 16(33) Median warm ischemia time in cases with hilar clamping, min, (range) 27 (14–61) Reasons for the 6 conversions Bleeding (n=3), positive surgical margin (n=1), additional tumor identified (n=1), failure to progress (n=1) Histology of Resected Lesions, no, (%) Clear Cell 40(73) Hybrid Oncocytic 8(15) Papillary 5(9) Chromophobe 1(2) Lymphangiomyoma 1(2) CONCLUSIONS RALPN is feasible and safe for select patients with hereditary renal cancer syndromes or those who present with multifocal RCC. A significant proportion of RPNs in hereditary RCC may be completed without hilar occlusion allowing for excellent renal functional outcomes. Oncologic outcomes are encouraging but will require longer follow up. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e504 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kevin Asher Bethesda, MD More articles by this author Gopal Gupta Bethesda, MD More articles by this author Compton Benjamin Bethesda, MD More articles by this author Peter Pinto Bethesda, MD More articles by this author W. Marston Linehan Bethesda, MD More articles by this author Gennady Bratslavsky Bethesda, MD More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

PURPOSE:A novel platform was developed that fuses pre-biopsy magnetic resonance imaging with real-time transrectal ultrasound imaging to identify and biopsy lesions suspicious for prostate cancer. The cancer detection rates for the first 101 patients are reported.MATERIALS AND METHODS:This prospective, single institution study was approved by the institutional review board. Patients underwent 3.0 T multiparametric magnetic resonance imaging with endorectal coil, which included T2-weighted, spectroscopic, dynamic contrast enhanced and diffusion weighted magnetic resonance imaging sequences. Lesions suspicious for cancer were graded according to the number of sequences suspicious for cancer as low (2 or less), moderate (3) and high (4) suspicion. Patients underwent standard 12-core transrectal ultrasound biopsy and magnetic resonance imaging/ultrasound fusion guided biopsy with electromagnetic tracking of magnetic resonance imaging lesions. Chi-square and within cluster resampling analyses were used to correlate suspicion on magnetic resonance imaging and the incidence of cancer detected on biopsy.RESULTS:Mean patient age was 63 years old. Median prostate specific antigen at biopsy was 5.8 ng/ml and 90.1% of patients had a negative digital rectal examination. Of patients with low, moderate and high suspicion on magnetic resonance imaging 27.9%, 66.7% and 89.5% were diagnosed with cancer, respectively (p <0.0001). Magnetic resonance imaging/ultrasound fusion guided biopsy detected more cancer per core than standard 12-core transrectal ultrasound biopsy for all levels of suspicion on magnetic resonance imaging.CONCLUSIONS:Prostate cancer localized on magnetic resonance imaging may be targeted using this novel magnetic resonance imaging/ultrasound fusion guided biopsy platform. Further research is needed to determine the role of this platform in cancer detection, active surveillance and focal therapy, and to determine which patients may benefit.

You have accessJournal of UrologyProstate Cancer: Detection and Screening1 Apr 2011846 MRI/US FUSION PROSTATE BIOPSIES: CANCER DETECTION RATES Ardeshir Rastinehad, Jochen Kruecker, Compton Benjamin, Paul Chung, Baris Turkbey, Sheng Xu, Julia Locklin, Stacey Gates, Carey Buckner, Marston Linehan, Gennady Bratslavsky, Neil Glossop, Peter Choyke, Bradford Wood, and Peter Pinto Ardeshir RastinehadArdeshir Rastinehad Bethesda, MD More articles by this author , Jochen KrueckerJochen Kruecker Bethesda, MD More articles by this author , Compton BenjaminCompton Benjamin Bethesda, MD More articles by this author , Paul ChungPaul Chung Bethesda, MD More articles by this author , Baris TurkbeyBaris Turkbey Bethesda, MD More articles by this author , Sheng XuSheng Xu Bethesda, MD More articles by this author , Julia LocklinJulia Locklin Bethesda, MD More articles by this author , Stacey GatesStacey Gates Bethesda, MD More articles by this author , Carey BucknerCarey Buckner Bethesda, MD More articles by this author , Marston LinehanMarston Linehan Bethesda, MD More articles by this author , Gennady BratslavskyGennady Bratslavsky Bethesda, MD More articles by this author , Neil GlossopNeil Glossop Bethesda, MD More articles by this author , Peter ChoykePeter Choyke Bethesda, MD More articles by this author , Bradford WoodBradford Wood Bethesda, MD More articles by this author , and Peter PintoPeter Pinto Bethesda, MD More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.667AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The fusion platform combines the benefits of MRI and real time TRUS imaging to perform image guided biopsies. We report the cancer detection rates for the system. METHODS Two radiologists reviewed multiparametric MRI in patients with suspicion or diagnosis of prostate cancer (CaP), 193 patient encounters were evaluated. The MRI of the prostate included T2, DCE, DWI, and spectroscopy images. All lesions were identified and graded by number of sequences positive: low (<2), moderate (3) and high (4) suspicion. An EM generator was placed above the pelvis which allows for real-time tracking of a biopsy guide with an embedded EM tracking sensor (Philips Healthcare, Canada). A manual 2D prostate sweep was reconstructed in 3D, registered and fused to the prostate MR images and assigned targets for biopsy. The ‘protocol' biopsy included a standard 12 core biopsy followed by a MRI/US fusion biopsy of the suspicious MR targeted lesions. RESULTS The mean age was 61.5 + 8.1 years with a median PSA 5.8 ng/ml, and 15/193 (7.7%) patients had a positive DRE. A chi-squared analysis revealed a direct correlation with the degree of MR suspicion and incidence of CaP detected per patient and per MR target lesion (p<0.01) (Table 1). A comparison between the 22 patients only positive on the 12 core biopsy and the 20 patients only positive on the MR/US biopsy revealed that the 12 core biopsy failed to diagnose 9 patients with Gleason 6, 7 patients with Gleason 7, and 4 patients with Gleason >8. The fusion biopsy system missed no patients with Gleason > 8 (p=0.005). (Chart 1) MRI Suspicion NO CANCER DETECTED CANCER DETECTED LOW Patient 63.9% 46/72 36.1% 26/72 Lesion 85% 255/300 15.0% 45/300 MODERATE Patient 41.6% 32/77 58.4% 45/77 Lesion 65.1% 114/175 34.5% 60/174 HIGH Patient 15.9% 7/44 84.1% 37/44 Lesion 33.8% 23/68 67.6% 46/68 CONCLUSIONS The fusion platform can stratify patients in to 3 groups which have a statistically different incidence of CaP. 84.1% of patients with a high suspicion lesion(s) were found to have CaP on the ‘protocol' biopsy. Secondly, when the platform fails to detect cancer compared to the 12 core biopsy, the cancer missed was statistically lower risk. This platform will help improve the quantification of a patient's CaP and possibly improve the selection of patients for focal therapy, active surveillance and/or whole gland therapy. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e340 Peer Review Report Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ardeshir Rastinehad Bethesda, MD More articles by this author Jochen Kruecker Bethesda, MD More articles by this author Compton Benjamin Bethesda, MD More articles by this author Paul Chung Bethesda, MD More articles by this author Baris Turkbey Bethesda, MD More articles by this author Sheng Xu Bethesda, MD More articles by this author Julia Locklin Bethesda, MD More articles by this author Stacey Gates Bethesda, MD More articles by this author Carey Buckner Bethesda, MD More articles by this author Marston Linehan Bethesda, MD More articles by this author Gennady Bratslavsky Bethesda, MD More articles by this author Neil Glossop Bethesda, MD More articles by this author Peter Choyke Bethesda, MD More articles by this author Bradford Wood Bethesda, MD More articles by this author Peter Pinto Bethesda, MD More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

You have accessJournal of UrologyProstate Cancer: Basic Research1 Apr 20111624 LOW TEMPERATURE-SENSITIVE LIPOSOME ENCAPSULATED DOCETAXEL AND DOXORUBICIN IN A XENOGRAFT MURINE MODEL OF PROSTATE CANCER Saurin Chokshi, Compton Benjamin, Ashish Ranjan, Paul Chung, Ayele Negussie, Ardeshir Rastinehad, Katherine Klos, Matthew Dreher, W. Marston Linehan, Bradford Wood, and Peter Pinto Saurin ChokshiSaurin Chokshi Bethesda, MD More articles by this author , Compton BenjaminCompton Benjamin Bethesda, MD More articles by this author , Ashish RanjanAshish Ranjan Bethesda, MD More articles by this author , Paul ChungPaul Chung Bethesda, MD More articles by this author , Ayele NegussieAyele Negussie Bethesda, MD More articles by this author , Ardeshir RastinehadArdeshir Rastinehad Bethesda, MD More articles by this author , Katherine KlosKatherine Klos Bethesda, MD More articles by this author , Matthew DreherMatthew Dreher Bethesda, MD More articles by this author , W. Marston LinehanW. Marston Linehan Bethesda, MD More articles by this author , Bradford WoodBradford Wood Bethesda, MD More articles by this author , and Peter PintoPeter Pinto Bethesda, MD More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1732AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Low-temperature sensitive liposomes (LTSLs) release their encapsulated drug into targeted tissue when activated by a source of hyperthermia. The efficacy of an LTSL formulation of docetaxel (DOC) or doxorubicin (DOX) was compared against prostate cancer in a xenograft mouse model. METHODS Under an approved IACUC protocol, Luciferase transfected human prostate PC-3M-luciferase cells were inoculated (3×106 cells) subcutaneously in the right hind leg of 8 wk old female athymic nude mice. When tumors reached a volume of 200–300 mm3, mice were randomized to receive one intravenous injection of saline, Stealth liposomal DOX (5 mg/kg), LTSL DOX (5 mg/kg), or LTSL DOC (15 mg/kg), with or without hyperthermia treatment (LTSL DOX and LTSL DOC were supplied by Celsion Corp., Columbia, MD). Mice undergoing hyperthermia treatment were anesthetized and stabilized in a holder that allowed for only the leg with tumor to be heated to 41–42C that triggered LTSL drug release. Mice were monitored daily for tumor volume and body weight. Study end-points included growth of tumor to 5x the initial treatment volume or monitoring of survival for 60 days. RESULTS The LTSL DOC delayed tumor growth longer (20 days) than DOX (7 days) or LTSL DOX (9 days) with hyperthermia (P<0.05). Mice treated with LTSL DOC and hyperthermia survived longest (60 days) compared to all other mice (range 6–8 days, P<0.05). LTSL in the setting of hyperthermia demonstrated complete regression of tumor in 57% of mice. CONCLUSIONS LTSL DOC with hyperthermia delayed tumor growth more than all other treatments. Survival studies suggest LTSL DOC is a more effective temperature sensitive delivery system against PC-3M prostate tumors. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e651 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Saurin Chokshi Bethesda, MD More articles by this author Compton Benjamin Bethesda, MD More articles by this author Ashish Ranjan Bethesda, MD More articles by this author Paul Chung Bethesda, MD More articles by this author Ayele Negussie Bethesda, MD More articles by this author Ardeshir Rastinehad Bethesda, MD More articles by this author Katherine Klos Bethesda, MD More articles by this author Matthew Dreher Bethesda, MD More articles by this author W. Marston Linehan Bethesda, MD More articles by this author Bradford Wood Bethesda, MD More articles by this author Peter Pinto Bethesda, MD More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Purpose: To determine the feasibility of bladder cryoablation (BC) applied laparoscopically, percutaneously, and transurethrally in a porcine survival study. The expected and observed area of cell death after BC was also examined. Materials and Methods: Nine pigs were divided equally into the three treatment groups. Cryoablation was performed with two freeze-thaw cycles after the bladder had been insufflated with CO2. Each animal was observed for 7 days after the procedure for treatment-related complications. After cystectomy, each specimen was examined pathologically to determine the degree and dimension of cell death achieved. Results: BC applied via the laparoscopic and percutaneous approach is feasible and safe. No BC-related complications occurred in these two groups. A complication resulting from BC developed in all three animals that were treated cystoscopically, including two intraperitoneal bladder perforations at the time of BC necessitating immediate sacrifice, and one enterovesical fistula discovered at cystectomy. Transmural necrosis was demonstrated in seven of seven animal specimens that survived to the end of the protocol. The observed diameter of tissue necrosis was highly predictable based on the reported cryoprobe isotherms given by the manufacturer. Conclusion: All locations within the bladder can be successfully and predictably treated with cryoablation. Of the three approaches, laparoscopically administered BC appears to be the most safe and consistent method. Transurethral BC was not safe with the equipment available without laparoscopic assistance to prevent bowel complications.

AbstractIntravesical BCG has been used successfully to treat superficial bladder cancer for three decades. However, 20% to 30% of patients will fail initial BCG therapy and 30% to 50% of patients will develop recurrent tumors within 5 years. Alternative or complementary strategies for the management of superficial bladder cancer are needed. Interleukin-12 (IL-12) is a potent TH1 cytokine with robust antitumor activity and the ability to potentiate immunologic memory. Unfortunately, intravesical IL-12 did not show antitumor efficacy in a recent clinical study of patients with recurrent superficial bladder cancer. We hypothesized that coformulation of IL-12 with chitosan, a biocompatible, mucoadhesive polysaccharide, could improve intravesical IL-12 delivery and provide an effective and durable alternative for the treatment of superficial bladder cancer. In antitumor studies, 88% to 100% of mice bearing orthotopic bladder tumors were cured after four intravesical treatments with chitosan/IL-12. In contrast, only 38% to 60% of mice treated with IL-12 alone and 0% treated with BCG were cured. Antitumor responses following chitosan/IL-12 treatments were durable and provided complete protection from intravesical tumor rechallenge. Urinary cytokine analysis showed that chitosan/IL-12 induced multiple TH1 cytokines at levels significantly higher than either IL-12 alone or BCG. Immunohistochemistry revealed moderate to intense tumor infiltration by T cells and macrophages following chitosan/IL-12 treatments. Bladder submucosa from cured mice contained residual populations of immune cells that returned to baseline levels after several months. Intravesical chitosan/IL-12 is a well-tolerated, effective immunotherapy that deserves further consideration for testing in humans for the management of superficial bladder cancer. [Cancer Res 2009;69(15):6192–9]

You have accessJournal of Urology1 Apr 2008RETROCAVAL PHEOCHROMOCYTOMAS: TIPS FOR SUCCESSFUL LAPAROSCOPIC ADRENAL-SPARING SURGERY Kiranpreet Khurana, Nick Liu, Compton Benjamin, Adam Metwalli, Peter A Pinto, and Gennady Bratslavsky Kiranpreet KhuranaKiranpreet Khurana More articles by this author , Nick LiuNick Liu More articles by this author , Compton BenjaminCompton Benjamin More articles by this author , Adam MetwalliAdam Metwalli More articles by this author , Peter A PintoPeter A Pinto More articles by this author , and Gennady BratslavskyGennady Bratslavsky More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(08)62072-8AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "RETROCAVAL PHEOCHROMOCYTOMAS: TIPS FOR SUCCESSFUL LAPAROSCOPIC ADRENAL-SPARING SURGERY." The Journal of Urology, 179(4S), p. 711 © 2008 by American Urological AssociationFiguresReferencesRelatedDetails Volume 179Issue 4SApril 2008Page: 711 Advertisement Copyright & Permissions© 2008 by American Urological AssociationMetricsAuthor Information Kiranpreet Khurana More articles by this author Nick Liu More articles by this author Compton Benjamin More articles by this author Adam Metwalli More articles by this author Peter A Pinto More articles by this author Gennady Bratslavsky More articles by this author Expand All Advertisement PDF downloadLoading ...