Urothelial cancer (UCa) is the most predominant cancer of the urinary tract and noninvasive diagnosis using hypermethylation signatures in urinary cells is promising. Here, we assess gender differences in a newly identified set of methylation biomarkers. UCa‐associated hypermethylated sites were identified in urine of a male screening cohort ( n = 24) applying Infinium‐450K‐methylation arrays and verified in two separate mixed‐gender study groups ( n = 617 in total) using mass spectrometry as an independent technique. Additionally, tissue samples ( n = 56) of mixed‐gender UCa and urological controls (UCt) were analyzed. The hypermethylation signature of UCa in urine was specific and sensitive across all stages and grades of UCa and independent on hematuria. Individual CpG sensitivities reached up to 81.3% at 95% specificity. Albeit similar methylation differences in tissue of both genders, differences were less pronounced in urine from women, most likely due to the frequent presence of squamous epithelial cells and leukocytes. Increased repression of methylation levels was observed at leukocyte counts ≥500/μl urine which was apparent in 30% of female and 7% of male UCa cases, further confirming the significance of the relative amounts of cancerous and noncancerous cells in urine. Our study shows that gender difference is a most relevant issue when evaluating the performance of urinary biomarkers in cancer diagnostics. In case of UCa, the clinical benefits of methylation signatures to male patients may outweigh those in females due to the general composition of women's urine. Accordingly, these markers offer a diagnostic option specifically in males to decrease the number of invasive cystoscopies.

You have accessJournal of UrologyProstate Cancer: Localized VII1 Apr 2015PD47-09 WHOLE SURFACE FROZEN SECTION OF THE PROSTATE AS ONCOLOGIC PARAMETER TO INTRAOPERATIVELY TAILOR TREATMENT AND MINIMIZE POSITIVE MARGIN RATE Christian von Bodman, Max Schulmeyer, Marko Brock, Björn Löppenberg, Florian Roghmann, Katharina Braun, Florian Sommerer, Joachim Noldus, and Rein Jüri Palisaar Christian von BodmanChristian von Bodman More articles by this author , Max SchulmeyerMax Schulmeyer More articles by this author , Marko BrockMarko Brock More articles by this author , Björn LöppenbergBjörn Löppenberg More articles by this author , Florian RoghmannFlorian Roghmann More articles by this author , Katharina BraunKatharina Braun More articles by this author , Florian SommererFlorian Sommerer More articles by this author , Joachim NoldusJoachim Noldus More articles by this author , and Rein Jüri PalisaarRein Jüri Palisaar More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2753AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Preoperative variables to plan radical prostatectomy (RP) are associated with a significant risk of misclassification. To evaluate whether frozen section analysis of the relevant prostate surface might provide significant information to intraoperatively identify misclassified patients and minimizing positive surgical margin (PSM) rate. METHODS Between June 2011 and July 2014, 783 patients treated with open retropubic RP (n=566; 72.3%) or robot assisted laparoscopic RP (n = 217; 27.7%) received intraoperative whole surface frozen section analysis of the removed prostate. Median patient age was 65.2 years (IQR: 59.9-70.0) and median pre-operative PSA 7.2 ng/ml (IQR: 5.3-10.2). The apex and base were circumferencially dissected as well as the whole posterolateral tissue corresponding to the neurovascular bundles. The dissected specimens were perpendicularly cut for frozen section analysis resulting in 22-24 surface sections to navigate the procedure. Pre-, intra- and postoperative parameters were prospectively collected. RESULTS Intraoperative frozen section analysis identified 215 PSM in 183 (23.4%) patients (posterolateral: 59.1% (127/215), apex 30.2% (65/215), base: 5.6% (12/215)). Nerve-sparing in pT2, pT3a and pT3b patients was performed in 95.0% (530/558), 90.6% (135/149) and 69.7% (53/76), respectively. Of 183 men with a PSM detected at frozen section analysis, 87.4% (160/183) could be converted to a negative status, while 12.6% (23/183) remained positive. Final PSM rate of the total cohort was 4.6% (36/783) including a false negative frozen section rate of 2.2% (13/600). In 16.5% (129/783) the initial nerve-sparing plan was intraoperatively changed due to positive frozen section results. In secondary resected specimen cancer was histopathologically detected in 22.8% (49/215). Final pathology showed Gleason upgrading (≤6 to 7 or 7 to ≥ 8) or upstaging (cT1c/cT2 to T3) in 47.1% (369/783) compared to preoperative variables. 8.5% (36/422) of patients who had exclusively unilateral positive transrectal biopsies at diagnosis showed an intraoperative PSM on the opposite, biopsy negative, site. CONCLUSIONS Whole surface frozen section provides additional oncologic information to intraoperatively tailor surgical procedure aiming to keep the PSM rate as low as possible. This strategy might identify preoperatively misclassified patients and allow safer nerve sparing in patients with higher preoperative risk. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e964 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Christian von Bodman More articles by this author Max Schulmeyer More articles by this author Marko Brock More articles by this author Björn Löppenberg More articles by this author Florian Roghmann More articles by this author Katharina Braun More articles by this author Florian Sommerer More articles by this author Joachim Noldus More articles by this author Rein Jüri Palisaar More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

•We introduce a new method for automated FISH spot analysis in the urinary sediment.•Our method reduces operating time by enabling automated batch-scanning.•The assay automatically detects and counts quadruple FISH signals in urinary cells.•Automated and objective quantification of cells harboring any FISH pattern is enabled.•Several FISH patterns were indicative for bladder cancer in a pilot study.

PURPOSE:The fusion of multiparametric resonance imaging and ultrasound has been proven capable of detecting prostate cancer in different biopsy settings. The addition of real-time elastography promises to increase the precision of the outcome of targeted biopsies. We investigated whether real-time elastography improves magnetic resonance imaging/transrectal ultrasound fusion targeted biopsy in patients after previous negative biopsies.MATERIALS AND METHODS:Prospectively 121 men underwent 3T magnetic resonance imaging. Using magnetic resonance imaging/real-time elastography fusion every suspicious lesion was characterized according to its tissue density and sampled by 2 fusion guided targeted biopsies. Additionally, all patients underwent 12-core systematic biopsy. The detection rate of clinically significant and insignificant cancers was compared between targeted und systematic biopsies. The accuracy to predict high grade prostate cancer was evaluated for with the PI-RADS scoring system and compared to the magnetic resonance imaging/real-time elastography fusion score.RESULTS:Overall prostate cancer was detected in 52 patients (43%). Targeted fusion guided biopsy revealed prostate cancer in 32 men (26.4%) and systematic biopsy in 46 (38%). The proportion of clinically significant cancers was higher for targeted biopsy (90.6%) compared to systematic biopsy (73.9%). The detection rate per core was higher for targeted biopsies (14.7%) compared to systematic biopsies (6.5%, p <0.001). The prediction of biopsy result according to magnetic resonance imaging/real-time elastography fusion was better (AUC 0.86) than magnetic resonance imaging alone (AUC 0.79). Sensitivity and specificity for magnetic resonance imaging/real-time elastography fusion was 77.8% and 77.3% vs 74.1% and 62.9% for magnetic resonance imaging.CONCLUSIONS:Magnetic resonance imaging/transrectal ultrasound fusion enhances the likelihood of detecting clinically significant cancers in a repeat biopsy setting. Adding real-time elastography to magnetic resonance imaging supports the characterization of cancer suspicious lesions.

You have accessJournal of UrologyProstate Cancer: Localized (I)1 Apr 2013355 INTRAOPERATIVE SURFACE FROZEN SECTION OF THE PROSTATE TO MINIMIZE POSITIVE MARGIN RATE AND ENSURE PRESERVATION OF NEUROVASCULAR BUNDLES Christian von Bodman, Marko Brock, Björn Löppenberg, Florian Roghmann, Anne Byers, Katharina Braun, Jobst Pastor, Florian Sommerer, Joachim Noldus, and Jüri Palisaar Christian von BodmanChristian von Bodman Herne, Germany More articles by this author , Marko BrockMarko Brock Herne, Germany More articles by this author , Björn LöppenbergBjörn Löppenberg Herne, Germany More articles by this author , Florian RoghmannFlorian Roghmann Herne, Germany More articles by this author , Anne ByersAnne Byers Washington, DC More articles by this author , Katharina BraunKatharina Braun Herne, Germany More articles by this author , Jobst PastorJobst Pastor Herne, Germany More articles by this author , Florian SommererFlorian Sommerer Bochum, Germany More articles by this author , Joachim NoldusJoachim Noldus Herne, Germany More articles by this author , and Jüri PalisaarJüri Palisaar Herne, Germany More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.1742AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Preoperative variables used to plan radical prostatectomy are associated with a significant risk of misclassification. To evaluate whether intraoperative frozen section analysis of the relevant prostate surface might provide significant information ensuring nerve-sparing and minimizing positive margin rates. METHODS Between June 2011 and September 2012, 236 patients treated with radical prostatectomy (RP) (n=176 open retropubic RP; n=60 robot assisted laparoscopic RP) received intraoperative whole surface frozen section analysis of the removed prostate. Median patient age was 64 years (IQR: 60 - 70) and median pre-operative PSA 6.75 ng/ml (IQR: 5.1 - 10.0). The apex and base were circumferencially dissected as well as the whole posterolateral tissue corresponding to the neurovascular bundles (NVB). The dissected specimens were perpendicularly cut for frozen section analysis resulting in 22-24 surface sections to navigate the procedure. Pre-, intra- and postoperative parameters were prospectively collected. RESULTS Intraoperative frozen section analysis identified positive surgical margins in 22% (NVB: 56.9%, apex 34.5%, base: 8.6%). Nerve-sparing in pT2, pT3a and pT3b patients was performed in 96.5%, 84.1% and 81.8%, respectively. Of men with a positive surgical margin detected at frozen section analysis, 92.3% could be converted to a negative status, while 7.7% remained positive. Final positive margin status of the total cohort was 3% including a false negative frozen section rate of 1.6%. In 14.8% the initial nerve sparing plan was intraoperatively changed due to positive frozen section results. In secondary resected specimen cancer was histopathologically detected in 25%. Final pathology showed Gleason upgrading (≤6 to 7 or 7 to ≥ 8) or upstaging (cT1c + cT2 to T3) in 40.7% compared to preoperative variables. Comparing the group of patients with positive versus negative margins on frozen section, preoperative variables were not significantly different while postoperatively pathologic stage, tumor volume, length of surgery and final margin status were. 13% of patients who had exclusively unilateral positive biopsies showed an intraoperative positive surgical margin on the opposite, biopsy negative, site. CONCLUSIONS Frozen section analysis might help to keep the positive surgical margin rate as low as possible but allow safer preservation of functional anatomic structures in misclassified patients or even patients at higher preoperative risk. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e144 Peer Review Report Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Christian von Bodman Herne, Germany More articles by this author Marko Brock Herne, Germany More articles by this author Björn Löppenberg Herne, Germany More articles by this author Florian Roghmann Herne, Germany More articles by this author Anne Byers Washington, DC More articles by this author Katharina Braun Herne, Germany More articles by this author Jobst Pastor Herne, Germany More articles by this author Florian Sommerer Bochum, Germany More articles by this author Joachim Noldus Herne, Germany More articles by this author Jüri Palisaar Herne, Germany More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

PURPOSE:We evaluated whether intraoperative frozen section analysis of the prostate surface might provide significant information to ensure nerve sparing and minimize the positive margin rate.MATERIALS AND METHODS:In 236 patients treated with radical prostatectomy between June 2011 and September 2012 whole surface frozen section analysis of the removed prostate was done intraoperatively. The apex and base were circumferentially dissected as well as the whole posterolateral tissue corresponding to the neurovascular bundles. Multiple perpendicular sections were cut systematically for frozen section analysis. Pathology results were reported to navigate the procedure.RESULTS:Frozen section analysis identified positive surgical margins in 22% of cases, including the neurovascular bundles in 56.9%, apex in 34.5% and base in 8.6%. Of positive frozen section cases 92.3% could be converted to negative status, while 7.7% remained positive. The final positive margin rate in the total cohort was 3%, including a false-negative frozen section rate of 1.6%. In 14.8% of cases the initial nerve sparing plan was changed intraoperatively due to the positive frozen section and the secondary resected specimen detected cancer in 25%. Final pathology results showed Gleason upgrading or up-staging in 40.7% of cases compared to preoperative variables. When comparing patients with positive vs negative frozen sections, preoperative variables did not significantly differ, while postoperatively pathological stage, tumor volume, operative time and final margin status differed significantly. Of patients with exclusively unilateral positive biopsies 13% had a positive surgical margin intraoperatively on the opposite, biopsy negative side.CONCLUSIONS:The surface frozen section technique is associated with a low false-negative surgical margin rate. It might allow for safer preservation of functional anatomical structures in misclassified patients or even patients at higher preoperative risk.

PURPOSE:We prospectively assessed whether a combined approach of real-time elastography and contrast enhanced ultrasound would improve prostate cancer visualization.MATERIAL AND METHODS:Between June 2011 and January 2012, 100 patients with biopsy proven prostate cancer underwent preoperative transrectal multiparametric ultrasound combining real-time elastography and contrast enhanced ultrasound. After initial elastographic screening for suspicious lesions, defined as blue areas with decreased tissue strain, each lesion was allocated to the corresponding prostate sector. The target lesion was defined as the largest cancer suspicious area. Perfusion was monitored after intravenous injection of contrast agent. Target lesions were examined for hypoperfusion, normoperfusion or hyperperfusion. Imaging results were correlated with final pathological evaluation on whole mount slides after radical prostatectomy.RESULTS:Of 100 patients 86 were eligible for final analysis. Real-time elastography detected prostate cancer with 49% sensitivity and 73.6% specificity. Histopathology confirmed malignancy in 56 of the 86 target lesions (65.1%). Of these 56 lesions 52 (92.9%) showed suspicious perfusion, including hypoperfusion in 48.2% and hyperperfusion in 48.2%, while only 4 (7.1%) showed normal perfusion patterns (p = 0.001). The multiparametric approach decreased the false-positive value of real-time elastography alone from 34.9% to 10.3% and improved the positive predictive value of cancer detection from 65.1% to 89.7%.CONCLUSIONS:Perfusion patterns of prostate cancer suspicious elastographic lesions are heterogeneous. However, the combined approach of real-time elastography and contrast enhanced ultrasound in this pilot study significantly decreased false-positive results and improved the positive predictive value of correctly identifying histopathological cancer.

Purpose: We evaluated whether real-time elastography guided biopsy improves prostate cancer detection compared to conventional systematic gray scale ultrasound guidance.Materials and Methods: A total of 353 consecutive patients suspicious for prostate cancer were prospectively randomized for real-time elastography (178) or gray scale ultrasound (175). Each patient enrolled in the study underwent a 10-core prostate biopsy. Six lateral prostate sectors (base, mid, apex) were scanned for cancer suspicious areas, defined as stiffer blue lesions using real-time elastography and hypoechoic lesions using gray scale ultrasound. Suspicious areas were sampled by a single targeted biopsy and considered representative of a defined prostate sector. If real-time elastography or gray scale ultrasound did not visualize a suspicious area in a sector, the biopsy core was taken systematically. Imaging findings were correlated with histopathological reports. Real-time elastography and gray scale ultrasound cases were compared in terms of cancer detection rate and imaging guidance accuracy.Results: Characteristics of patients undergoing real-time elastography and gray scale ultrasound, including age, prostate specific antigen, prostate volume and digital rectal examination, were not significantly different (p > 0.05). Prostate cancer was detected in 160 of 353 patients (45.3%). The prostate cancer detection rate was significantly higher in patients who underwent biopsy with the real-time elastography guided approach compared to the gray scale ultrasound guided biopsy at 51.1% (91 of 178) vs 39.4% (69 of 175) (p = 0.027). Overall sensitivity and specificity to detect prostate cancer was 60.8% and 68.4% for real-time elastography vs 15% and 92.3% for gray scale ultrasound, respectively.Conclusions: Sensitivity to visualize and detect prostate cancer improved using real-time elastography in addition to gray scale ultrasound during prostate biopsy. Overall sensitivity did not reach levels to omit a systematic biopsy approach.

The use of a mesh with good biocompatibility properties is of decisive importance for the avoidance of recurrences and chronic pain in endoscopic hernia repair surgery. As we know from numerous experiments and clinical experience, large-pore, lightweight polypropylene meshes possess the best biocompatibility. However, large-pore meshes of different polymers may be used as well and might be an alternative solution.

OBJECTIVE:•To evaluate whether transrectal real-time elastography (RTE) improves the detection of intraprostatic prostate cancer (PCa) lesions and extracapsular extension (ECE) compared with conventional grey-scale ultrasonography (GSU).PATIENTS AND METHODS:•In total, 229 patients with biopsy-proven PCa were prospectively screened for cancer-suspicious areas and ECE using GSU and RTE. •The largest tumour focus detected by RTE was defined as the index lesion. •The prostate gland was stratified into six sectors on GSU and RTE, which were compared with histopathological whole mount sections after radical prostatectomy.RESULTS:•Histopathologically, PCa was confirmed in 894 out of 1374 (61.8%) evaluated sectors and ECE was identified in 47 (21%) patients. •Of these 894 sectors, RTE correctly detected 594 (66.4%) and GSU 215 (24.0%) cancer suspicious lesions. •Sensitivity was 51% and specificity 72% using RTE compared to 18% and 90% for GSU. •RTE identified the largest side specific tumour focus in 68% of patients. •ECE was identified with a sensitivity of 38% and specificity of 96% using RTE compared to 15% and 97% using GSU.CONCLUSIONS:•Compared with GSU, RTE provides a statistically significant improvement in detection of PCa lesions and ECE. •RTE enhances GSU, although improvement is still needed to achieve a clinically meaningful sensitivity.

We report on a 33-year-old female patient with invasive ductal breast cancer. Despite breast augmentation with injected hydrophilic polyacrylamide gel in her history, she was successfully treated with breast-conserving therapy. The widespread migration of the gel conglomerates first complicated diagnostic imaging, surgical treatment and tumour aftercare. Removing the gel proved a difficult task. Nevertheless, the gel was macroscopically totally removed allowing a breast-conserving therapy. Wound healing took place without complications. After adjuvant chemotherapy, radiotherapy and hormonal therapy, the patient stays tumour free with a satisfactory cosmetic result.

OBJECTIVES:To assess the peri- and postoperative outcome of patients treated with open radical retropubic prostatectomy (RRP) for prostate cancer and who had previously undergone transurethral resection of the prostate (TURP).PATIENTS AND METHODS:Prospectively collected data from a consecutive series of 1760 patients who had RRP between July 2003 and June 2007 at our institution were used to retrospectively match 62 cases (with previous TURP) with the same number of controls (without previous TURP). Matching variables were patient age, body mass index, prostate volume, preoperative total prostate-specific antigen (PSA) level, Gleason score, pathological stage, and intraoperative nerve-sparing procedure. Complete 1-year follow-up data were available for all patients. All collected data on surgery and perioperative complications were analysed. Functional outcome data at the 1-year follow-up were evaluated by applying an institutional questionnaire. Sexual function was assessed using the abbreviated International Index of Erectile Function-5 questionnaire, and urinary control was evaluated by defining complete urinary control as no pad usage.RESULTS:The rate of complete urinary control rate in cases and controls was similar (81% vs 82%). When nerves were spared, 60% (15/25) of patients in either group were capable of sexual intercourse. The overall positive surgical margin rate was insignificantly higher in cases (19% vs 13, P>0.05). After 1 year of follow-up the biochemical recurrence rate (PSA>0.04 ng/mL) did not differ significantly in patients who had RRP after TURP vs RRP alone (six of 62, 10%, vs five of 62, 8%; P=0.77).CONCLUSIONS:RRP for prostate cancer in patients who have had previous TURP does not result in a higher perioperative complication rate, or a worse functional outcome.

Fresh amniotic membrane has been used in medicine since 1910. The reconstruction of immunologic privileged ocular surfaces with cryopreserved amniotic membrane was introduced in the 1990s. The aim of this study was to analyze the use of cryopreserved human amniotic membrane (HAM) as a surgical patch in immunologic unprivileged anatomic sites. In part I of the investigation, the abdominal wall muscle of 36 rats was covered with mono- and multilayered HAM. After 3, 14, and 28 days, respectively, these grafts were evaluated macro- and microscopically. Multilayer samples displayed slower degradation and less inflammation compared with monolayer coverage. In part II of the study, abdominal wall closure with multilayer HAM and with polypropylene mesh was conducted in 20 rats. All rats showed sufficient closure after 21 days, but significantly lower intraabdominal adhesion formation was observed in the HAM rats. The results of this study might pave the way for the use of cryopreserved HAM as graft material in reconstructive surgery.

In recent years, laparoscopic repair of abdominal wall hernias has become increasingly established in routine clinical practice thanks to the myriad advantages it confers. Apart from the risk of intestinal damage following adhesiolysis, to date no information is available on the best way of preventing the formation of new adhesions in the vicinity of the implanted meshes. Numerous experimental investigations, mainly conducted on an open small-animal model, have demonstrated the advantages of coating meshes, inter alia with absorbable materials, compared with uncoated polypropylene meshes. In our established laparoscopic porcine model we set about investigating three of these meshes, which are already available on the market.

BACKGROUND:Intraperitoneal repair of incisional hernias using a mesh makes particular demands on the material used. In addition to good integration of the mesh on the parietal side, adhesions to the visceral peritoneum must be avoided. Large-pore, light-weight meshes induce fewer adhesions than heavy-weight polypropylene meshes. Although numerous adhesion-barrier substances for use in combination with a polypropylene mesh have been tested already, mostly in open small animal models, unequivocal benefits have been identified to date in only a few of the experiments.METHODS:Using the laparoscopic intraperitoneal onlay mesh technique, six pigs were implanted with either a lightweight polypropylene mesh (TiMesh light) or TiMesh plus an adhesion-barrier film made of polylactide (SurgiWrap). After 3 months, the animals underwent a postmortem laparoscopy, and specimens were obtained for planimetric and histologic investigations.RESULTS:No adhesions to intestinal structures were found in any of the animals. Adhesions between the greater omentum and the mesh did not differ significantly between the TiMesh (32%) and SurgiWrap (33.5%) groups. The shrinkage of the mesh's surface area was comparable between the two groups (18% vs. 21%). Histology showed pronounced inflammatory reaction and bridging of scar tissue between the filaments with the use of SurgiWrap versus TiMesh light without film. However, immunohistochemical investigations examining the partial volume of the inflammatory cells, the proliferation marker Ki67, and the apoptotic index at the interface of the filaments all failed to show any significant differences.CONCLUSION:To avoid adhesions, it is essential that the acute and chronic inflammatory reaction to the implanted material be as small as possible. This requirement is met specifically by the lightweight polypropylene mesh TiMesh light. The additional application of a slowly absorbable adhesion-barrier film made of polylactide (SurgiWrap) does not appear to confer any further benefit.