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To quantitatively assess 12-month prostate volume (PV) reduction based on T2-weighted MRI and immediate post-treatment contrast-enhanced MRI non-perfused volume (NPV), and to compare measurements with predictions of acute and delayed ablation volumes based on MR-thermometry (MR-t), in a central radiology review of the Phase I clinical trial of MRI-guided transurethral ultrasound ablation (TULSA) in patients with localized prostate cancer. Treatment day MRI and 12-month follow-up MRI and biopsy were available for central radiology review in 29 of 30 patients from the published institutional review board-approved, prospective, multi-centre, single-arm Phase I clinical trial of TULSA. Viable PV at 12 months was measured as the remaining PV on T2-weighted MRI, less 12-month NPV, scaled by the fraction of fibrosis in 12-month biopsy cores. Reduction of viable PV was compared to predictions based on the fraction of the prostate covered by the MR-t derived acute thermal ablation volume (ATAV, 55°C isotherm), delayed thermal ablation volume (DTAV, 240 cumulative equivalent minutes at 43°C thermal dose isocontour) and treatment-day NPV. We also report linear and volumetric comparisons between metrics. After TULSA, the median 12-month reduction in viable PV was 88%. DTAV predicted a reduction of 90%. Treatment day NPV predicted only 53% volume reduction, and underestimated ATAV and DTAV by 36% and 51%. Quantitative volumetry of the TULSA phase I MR and biopsy data identifies DTAV (240 CEM43 thermal dose boundary) as a useful predictor of viable prostate tissue reduction at 12 months. Immediate post-treatment NPV underestimates tissue ablation. • MRI-guided transurethral ultrasound ablation (TULSA) achieved an 88% reduction of viable prostate tissue volume at 12 months, in excellent agreement with expectation from thermal dose calculations. • Non-perfused volume on immediate post-treatment contrast-enhanced MRI represents only 64% of the acute thermal ablation volume (ATAV), and reports only 60% (53% instead of 88% achieved) of the reduction in viable prostate tissue volume at 12 months. • MR-thermometry-based predictions of 12-month prostate volume reduction based on 240 cumulative equivalent minute thermal dose volume are in excellent agreement with reduction in viable prostate tissue volume measured on pre- and 12-month post-treatment T2w-MRI.

Purpose Management of localized radio-recurrent prostate cancer is not standardized, partly due to the absence of long-term data on oncologic control and the toxicity of various treatment modalities. We analyzed the long-term oncologic outcomes and morbidity of salvage cryoablation for radio-recurrent prostate cancer. Materials and Methods Patients undergoing salvage cryoablation for biopsy proven, localized radio-recurrent prostate cancer from 1995 to 2004 were prospectively accrued. Preoperative characteristics, perioperative morbidity and postoperative data were reviewed from a prospectively maintained database or via telephonic contact with the patient. The primary outcome was overall survival. Secondary outcomes were metastasis-free and biochemical disease-free survival. The Kaplan-Meier method was used for survival analysis and multivariable Cox regression analysis was performed. Results Of 187 patients 157 (84%) had records available for followup. Mean ± SD age was 69.4 ± 5.8 years and mean presalvage prostate specific antigen was 6.6 ± 5.7 ng/ml. Median followup was 117 months (IQR 55–154). Five and 10-year overall survival was 93% and 76%, respectively. Biochemical disease-free survival at 10 and 15 years was 35% and 22.6% whereas metastasis-free survival at 10 and 15 years was 86% and 71%, respectively. On multivariable analysis precryoablation and nadir prostate specific antigen values were significant predictors of metastasis-free and biochemical disease-free survival. Age at salvage cryoablation (p = 0.008) and nadir prostate specific antigen (p = 0.015) were significant predictors of overall survival. There were 157 Clavien-Dindo grade 1-2 and 22 grade 3 complications. Conclusions A single center, long-term experience documented by a prospectively maintained database shows that cryoablation is a viable salvage option for radio-recurrent prostate cancer as it provides durable biochemical disease-free survival with acceptable morbidity.

Bladder cancer (BC) is the third and fifth cancer in men in terms of incidence and mortality in the US. Overexpression and mutations of fibroblast growth factor receptor 3 (FGFR3) are frequently found in BC and can represent a very interesting therapeutic target. Different FGFR3-targeted strategies have been investigated through in vitro and in vivo settings, including FGFR3 tyrosine kinase inhibitors such as dovitinib .The authors review the data that provide a scientific rationale for FGFR3-targeted therapy in BC. They also provide an evaluation of the currently available in vitro and in vivo data on the use of dovitinib in BC patients.The development and progression of BC rely on a very complex signaling network that involves many different receptors aside from FGFR3 and VEGFR2. The involved signaling network can also be very different from one BC to the other, and can also evolve through time in the same patient. Inhibiting only one single target may thus not be sufficient to achieve a complete downstream oncogenic signaling blockage. Additionally, in vitro data on the use of neutralizing monoclonal antibodies targeting FGFR3 show that it can be a more efficient strategy to reach the same goal, with the potential advantage of less toxicity.

In this prospective registry we prospectively assessed the oncologic, functional and safety outcomes of salvage high intensity focused ultrasound for radiorecurrent prostate cancer.A total of 81 men were prospectively recruited and evaluated at regular scheduled study visits to 6 months after high intensity focused ultrasound and thereafter as per standard of care. Transrectal ultrasound guided biopsy was performed at 6 months. The primary end point was absence or histological persistence of disease at 6-month biopsy. Secondary end points included quality of life, biochemical recurrence-free survival, overall survival, cancer specific survival and progression to androgen deprivation therapy. Survival analysis was performed according to the Kaplan-Meier method and multivariate analysis was performed using the log rank (Mantel-Cox) test.Mean ± SD prostate specific antigen before high intensity focused ultrasound was 4.06 ± 2.88 ng/ml. At 6 months 63 men underwent biopsy, of whom 22 (35%) had residual disease. At a mean followup of 53.5 ± 31.6 months median biochemical recurrence-free survival was 63 months. The 5-year overall and cancer specific survival rates were 88% and 94.4%, respectively. Nadir prostate specific antigen less than 0.5 ng/ml was a significant predictor of biochemical recurrence-free survival (p=0.014, 95% CI 1.22-5.87). I-PSS significantly increased (p0.001) while IIEF-5 scores decreased and the SF-36 score did not change significantly. The rate of rectal fistulization and severe incontinence was 3.7% each. A total of 223 complications were recorded in the 180 days after high intensity focused ultrasound (Clavien-Dindo grade 1-195, grade II-20, grade III-7, grade IVa-1).Salvage high intensity focused ultrasound appears to be a viable treatment option for radiorecurrent prostate cancer, with acceptable morbidity.

Objectives To determine the chemical composition of pure and mixed urinary calculi by multislice helical computed tomography (CT) in an in-vitro setting. CT is becoming the preferred radiologic examination in diagnosis and management of calculus disease. The management of calculus disease can be facilitated by ascertaining stone composition. Recent in-vitro studies have suggested that CT can be used to predict the composition of urinary stones on the basis of differences in radiodensity (measured in Hounsfield units, HU) supporting the clinician in selecting the more opportune therapeutic strategy. Aim of our study is to compare the radiodensity and chemical composition of urinary stones with the purpose of identifying the cut-off value of HU with high specificity. Materials e Methods A total of 76 patients with urinary stones, candidate to treatment, were assessed in a multislice helical scanner within an air-filled environment (Ge Healthcare light Speed, 120 KV; 150–250 mA 1.5 pitch thick speed 2.5; interval 2.5) differentiating dimensions and radiodensity. The chemical compositions of urinary stones were assessed on the basis of the differences in densities measured in Hounsfield units. Chemical analysis of stone has been done, using colorimetrical kit Ecoline (DiaSys Diagnostic System GmbH, Germany) validated versus IR Spectrometry. HU density values are expressed as median and interquantile range (IQR). Statistic analysis has been done using SPSS 15.0 (SPSS Inc., Chicago, IL, USA). Results The stones were assigned to seven different groups according to the chemical composition: calcium oxalate in 57%, calcium oxalate and phosphate in 16%, calcium urate-oxalate 12%, uric acid in 5%, struvite and calcium phosphate in 4%, struvite and calcium oxalate in 5%, cystine in 1%. Uric acid stone density (Ur+Ur/Ox-Ca, n=13; HU 487, IQR 352 - 594) was significantly lower than both Ox-Ca pure (n=44; HU 639, IQR 460 -942) (Bonferroni correction p=0012) and phosphate (Ox / P-Ca+struvite, n=19; HU 801, IQR 502 -1205) (Bonferroni correction p=0006), while no difference was evident between oxalate and phosphate stones. Areas under ROC curve for uric acid stone identification (toward phosphate and oxalate) or for phosphate stone identification (toward uric acid and oxalate) were respectively 0.73 (95%IC 0.59–0.87) and 0.62 (95%IC 0.46–0.79). Cut-off values of 352 HU (first quartile uric distribution) and 1205 HU (third quartile phosphates distribution) allow to identify a specificity of 91% and 96%, respectively, for uric acid or phosphates stones. Conclusions Although our data underline an association between radiodensity and chemical composition, confirming literature, the big overlap of distributions of HU values limits clinical application. It is possible to identify specific HU cut-off values for uric acid and phosphates stone, however it is necessary to verify these results in a larger sample. The spiral TC is useful to study the chemical composition of the urinary stone, but a larger sample is necessary to calculate more accurate radiodensity cut-off values.

Prostate core saturation biopsy (SB) is today considered in patients where clinical or biochemical hypothesis of prostate cancer (PCa) is still present after previous normal core biopsies. The technique rationale is to increase the detection rate (DT) both by increasing the number of cores for the pathologist, in order to obtain more tissue to be analyzed, and both by mapping regions that are not usually investigated with a standard or extended prostate biopsy. Moreover, the technique is not free from complications and today, one of the main controversies about SB is how many cores have to be taken in order to maintain high detection rate with low complication rate. Aim of the present retrospective study is to compare safety and DT of 3 different schemes of SB, performed with different number of cores. Materials and Methods We retrospectively reviewed the data of 106 patients who underwent SB from January 2003 to December 2008 at 2 urological divisions. SB was performed in all cases as a further biopsy because of biochemical and/or clinical hypothesis of PCa, in patients previously undergoing one or more baseline core biopsies. SB was performed under general anesthesia by 3 urologists in each division. Core biopsies were obtained using a Boston Scientific TruPath 18G 15cm needle, in transrectal ultrasound-guided approach. All patients were submitted to a 32.core SB scheme. We compared the 32-core scheme with a 28 and a 24-core scheme, each one including peripheral, transitional and anterior prostatic portion biopsies. End-points of the study were: DT and safety. Statistical analysis was carried out using chi-square test (pResults Mean age was 65.4 (50–79) years, mean PSA at biopsy was 11.2 ng/ml (3.23–30) and mean number of previous biopsies was 1.5 (1–5). Median value of cores positive for PCa in the 32, 28 and 24-core scheme was 2 (1–10), 2 (2–12) and 1.5 (0–11), respectively. Homogeneous distribution of positive cores was registered in all records, but in 3 areas (right base external, left base external, left transitional basal) the detection rate was very low (0–0.1%). PCa was found more frequently in base in median portion of left and right prostatic lobes. In the 32-core SB scheme, DT was 30.1 %, whereas in the 28 and 24-core SB scheme DT proved to be 28.7% and 29.1%, respectively. No statistical difference was found among the schemes in terms of detection rate (p>0.05). A Gleason score >7 was registered in 62.5% of cases. As far as safety is concerned, 20 patients (19%) developed complications. In all cases neither hospitalization nor surgery were required and all patients were treated by medical therapy (e.g. indwelling catheterization, antibiotics). Conclusions SB after a previous standard core biopsy is a safe technique and increases DT of PCa. Although there is a propensity in increasing the number of core biopsies to obtain higher DT, our data suggests that DT does not increase when more than 24 cores are taken. Therefore, SB should be considered as second biopsy in patients with previous negative first standard core biopsy.

Background Magnetic resonance imaging–guided transurethral ultrasound ablation (MRI-TULSA) is a novel minimally invasive technology for ablating prostate tissue, potentially offering good disease control of localized cancer and low morbidity. Objective To determine the clinical safety and feasibility of MRI-TULSA for whole-gland prostate ablation in a primary treatment setting of localized prostate cancer (PCa). Design, setting, and participants A single-arm prospective phase 1 study was performed at three tertiary referral centers in Canada, Germany, and the United States. Thirty patients (median age: 69 yr; interquartile range [IQR]: 67–71 yr) with biopsy-proven low-risk (80%) and intermediate-risk (20%) PCa were treated and followed for 12 mo. Intervention MRI-TULSA treatment was delivered with the therapeutic intent of conservative whole-gland ablation including 3-mm safety margins and 10% residual viable prostate expected around the capsule. Outcome measurements and statistical analysis Primary end points were safety (adverse events) and feasibility (technical accuracy and precision of conformal thermal ablation). Exploratory outcomes included quality of life, prostate-specific antigen (PSA), and biopsy at 12 mo. Results and limitations Median treatment time was 36min (IQR: 26–44) and prostate volume was 44ml (IQR: 38–48). Spatial control of thermal ablation was ±1.3mm on MRI thermometry. Common Terminology Criteria for Adverse Events included hematuria (43% grade [G] 1; 6.7% G2), urinary tract infections (33% G2), acute urinary retention (10% G1; 17% G2), and epididymitis (3.3% G3). There were no rectal injuries. Median pretreatment International Prostate Symptom Score 8 (IQR: 5–13) returned to 6 (IQR: 4–10) at 3 mo (mean change: −2; 95% confidence interval [CI], −4 to 1). Median pretreatment International Index of Erectile Function 13 (IQR: 6–28) recovered to 13 (IQR: 5–25) at 12 mo (mean change: −1; 95% CI, −5 to 3). Median PSA decreased 87% at 1 mo and was stable at 0.8 ng/ml (IQR: 0.6–1.1) to 12 mo. Positive biopsies showed 61% reduction in total cancer length, clinically significant disease in 9 of 29 patients (31%; 95% CI, 15–51), and any disease in 16 of 29 patients (55%; 95% CI, 36–74). Conclusions MRI-TULSA was feasible, safe, and technically precise for whole-gland prostate ablation in patients with localized PCa. Phase 1 data are sufficiently compelling to study MRI-TULSA further in a larger prospective trial with reduced safety margins. Patient summary We used magnetic resonance imaging–guided transurethral ultrasound to heat and ablate the prostate in men with prostate cancer. We showed that the treatment can be targeted within a narrow range (1mm) and has a well-tolerated side effect profile. A larger study is under way. Trial registration NCT01686958, DRKS00005311.

Objective of the study is to review the current 7th edition of the TNM classification of renal tumors and to perform a critical analysis of the recent evidence in order to identify the limitations of this new staging system. A search of the english literature was performed through the Medline and Pubmed database using the following keywords: renal cell carcinoma, staging system and TNM. Overall, 2600 references were initially scrutinized. Forty papers were selected based on their pertinence with the topic of the review, level of evidence provided and overall contribution to the field. Few changes have been made in the current version of the TNM staging system of renal tumors. pT2 tumors have been divided in 2 subgroups based on tumor size with a cut-off at 10 cm; the invasion of the renal vein was classified as pT3a; finally, the invasion of the ispsilateral adrenal gland was classified as pT4. However, other changes were suggested by the analysis of the recent literature and have not been introduced in this new version. Further improvements of the TNM classification for renal tumors are needed especially with regard to locally advanced tumors and node-positive disease, in order to improve the accuracy of this important prognostic tool in renal oncology.

Introduction: We compared the morbidity of whole gland salvage ablation using cryotherapy (CRYO) and high-intensity focused ultrasound (HIFU) for radio recurrent prostate cancer at a single centre over a 17-year period. Methods: Patients were divided in 3 cohorts. Group 1 included the first 65 patients treated with CRYO (1995–1998); Group 2 included the last 65 patients treated with CRYO (2002–2004), and Group 3 included 65 patients treated with HIFU (2006–2011). We analyzed the complications reported within at least 90 days of treatment or up to the last follow-up. Results: We tallied Clavien grade complications. For Groups 1, 2 and 3, we recorded the following Clavien I-II complications: 78, 49 and 13, respectively. For Clavien grade IIIa, 2, 5 and 4 for Groups 1, 2 and 3, respectively. For Clavien grade IIIb, 8, 2 and 3 for Groups 1, 2 and 3, respectively. Clavien grade II complications were statistically higher in Group 1 versus Group 2 (p = 0.005) and in Group 2 versus Group 3 (p = 0.0001). The rate of mild-moderate incontinence was significantly higher in the CRYO group compared to the HIFU cohort (p ≤ 0.05). The rate of urinary retention was significantly higher in Group 2 compared to Group 3 (p = 0.0005). The rates of severe incontinence (range: 1.5%–5%), need for surgical intervention (uniform at 1.5%), and recto-urethral fistulae (range: 1.5%–3%) were not statistically different. Conclusions: CRYO was associated with higher overall morbidity. The morbidity during the early experience with HIFU was lower than both subgroups of CRYO. This may reflect the advancement of technology or cumulative learning experience.

Textile structures are widely used as medical implants to replace and support soft and load bearing tissues and they serve as scaffolds in tissue engineering applications. In this study the potential of embroidery technology is investigated for the development of textile scaffold structures for tissue engineering and for medical applications. In a comparative experimental study the influence of ingrowing tissue on the mechanics of the thereby formed vital-avital composite has been investigated. An interlock knitted fabric has been compared to a specially designed embroidered fabric and a gelatine matrix has been used to simulate the ingrown tissue. It could be shown that due to the specific structure of the embroidery, stiffening effects known from other textiles i.e. woven and knitted fabrics could be inhibited. This observation together with the potential structural variety of embroidered fabrics, makes them interesting candidates for medical textiles applied to mechanically stressed tissues.

Flow cytometry, light and fluorescence microscopy, and designated biochemical techniques were used to examine the type of death which occurs in cerebral cortex cells when grown under crowded vs. sparse conditions or after brief anoxia/hypoglycemia. A 4 hr episode of anoxia combined with glucose deprivation enhanced apoptotic cell death as assessed by 4',6-diamidino-2-phenylindole (DAPI) staining and reduced neutral red eye uptake. An additional form of cell death involving exclusion of the nucleus was recorded by time lapse cinematography and DAPI stain. The presence of the endonuclease inhibitor aurintricarboxylic acid (0.1 mM) reduced cell death by 56.6%, while the protein and RNA synthesis inhibitors actinomycin D and cycloheximide (each at 5 micrograms/ml) effectively decreased cell death by 83.3% and 90.6%, respectively. In contrast, 5 mM glutamate had no effect on cell death in accord with the immature state of the cells. Growth of cells under crowded conditions improved cell survival; after 2 h or 4 days in culture, cells seeded at high density (34 microgram cellular DNA/cm2) showed a nearly 3-fold decline in the amount of cell death in comparison to cells seeded at low density (5 micrograms cellular DNA/cm2). At high cell density, anoxic episodes enhanced cell death most likely by preventing a cell density-mediated rescue. Neutral red dye uptake, an index for cell viability, was enhanced with increasing cell density and in vitro maturation, but was reduced in dense cultures exposed to anoxic/hypoglycemic conditions. The data suggest that cell density may play a critical role in brain organogenesis and that anoxic stress is more deleterious in dense than sparse cell assemblies.

Purpose Purpose of this prospective, multi-institutional Phase I clinical study was to investigate whether MRI-guided transurethral ultrasound ablation (MR-TULSA), a novel minimally-invasive technology to treat organ-confined prostate cancer (PCa), is safe, feasible and effective. It employs directional plane-wave high-intensity ultrasound, which ablates prostate tissue using real-time thermometry with active temperature feedback control.