Detection Of Positive Surgical Margins Research Articles

Intra-operative fluorescence-based detection of positive surgical margins during radical prostatectomy: Lessons learned from a pilot ex vivo translational study.

Nerve-sparing techniques during radical prostatectomy have been associated with an increased risk of positive surgical margins. The intra-operative detection of residual prostatic tissue could help mitigate this risk. The objectives of the present study were to assess the feasibility of using an anti-prostate-specific membrane antigen (anti-PSMA) antibody conjugated with a fluorophore to characterize fresh prostate tissue as prostatic or non-prostatic for intra-operative surgical margin detection. Fresh prostatic tissue samples were collected from transurethral resections of the prostate (TURP) or prostate biopsies, and either immunolabelled with anti-PSMA antibody conjugated with Alexa Fluor 488or used as controls. A dedicated, laparoscopy-compliant fluorescence device was developed for real-time fluorescence detection. Confocal microscopy was used as the gold standard for comparison. Spectral unmixing was used to distinguish specific, Alexa Fluor 488 fluorescence from nonspecific autofluorescence. The average peak wavelength of the immuno-labeled TURP samples (n = 4) was 541.7 ± 0.9 nm and of the control samples (n = 4) was 540.8 ± 2.2 nm. Spectral unmixing revealed that these similar measures were explained by significant autofluorescence, linked to electrocautery. Three biopsy samples were then obtained from seven patients and also displayed significant nonspecific fluorescence, raising questions regarding the reproducibility of the fixation of the anti-PSMA antibodies on the samples. Comparing the fluorescence results with final pathology proved challenging due to the small sample size and tissue alterations. This study showed similar fluorescence of immuno-labeled prostate tissue samples and controls, failing to demonstrate the feasibility of intra-operative margin detection using PSMA immuno-labeling, due to marked tissue autofluorescence. We successfully developed a fluorescence device that could be used intraoperatively in a laparoscopic setting. Use of the infrared rangeas well as newly available antibodies could prove interesting options for future research.

Bladder neck-sparing retropubic radical prostatectomy: assessing risk factors for detection of positive surgical margins

Background. Bladder neck preservation during retropubic radical prostatectomy (rRP) promotes a protective effect on urinary continence compared to standard rRP.Aim. To assessment of possible predictors for positive surgical margin (PSM) recognition is an important step.Materials and methods. 136 patients with localized prostate cancer (PCa) were studied in the study. Group 1, 90 patients (retrospective assessment), underwent standard rRP, group 2, 46 patients (prospective assessment), underwent rRP modified by bladder neck preservation with a part of the proximal prostatic urethra. The clinical and pathological stages of PCa were assessed; the groups were compared to the parameter PSM. Statistical analysis was performed using nonparametric statistical methods.Results. Both groups were comparable in age and baseline total prostate specific antigen (PSA) but differed in prostate volume and Gleason score. Also, there were differences in clinical and pathological stages of PCa. PSM-patients had more aggressive PCa according to the International Society of Urological Pathology (ISUP) and TNM classifications and had higher progression risk prognosis stages. In PSM-patients, correlations were determined between prostate volume and baseline Gleason index (r = 0.338; p >0.05); baseline total PSA and Gleason score before (r = 0.529; p >0.05) and after (r = 0.310; p >0.05) rRP, respectively. Nevertheless, the incidence of PSM among all subjects was 6.6 % of cases, while in groups 1 and 2 was 7.8 and 4.3 % of cases, respectively. In this way, surgical techniques that maximize bladder neck preservation with a part of proximal prostatic urethra have no significant effect on PSM. Ranges of total PSA, clinical stage of PCa, Gleason score and progression risk stages (prognostic group for PCa) were determined as predictors of PSM. Their use will make it possible to establish patient selection criteria for bladder neck preservation with proximal prostatic urethra during rRP.Conclusion. The identified predictors will allow determining during clinical staging minimal risks of detecting PSM. The rRP modified by bladder neck preservation with part of the proximal prostatic urethra does not increase the incidence of PSM compared to the standard rRP. The feasibility of this technique should be related to total PSA, clinical stage of PCa, Gleason score, and the progression risk stage.

Automated gigapixel circumferential surface microscopy of the prostate

Positive surgical margins, or cancer cells found at the boundary of an excised tumor mass, are a significant problem in the management of many cancers resulting in worsened patient outcomes. The problem is exacerbated in organ sites such as the prostate, where unnecessarily wide local excisions can result in significant deterioration of post-operative quality of life due to collateral damage to neighboring structures. Yet, at the same time, incomplete tumor removal results in worsened prognosis and need for additional interventions. Here, we report the design and development of a rapid and completely automated system for intraoperative gigapixel ex vivo microscopy of the circumferential surgical prostate margin within intra-operative timeframes, called the Automated Prostate Positioning System (APPS). The APPS leverages the rotational geometry of the prostate and high speed structured illumination microscopy (SIM) to generate continuous gigapixel panoramas of the fresh intact prostate circumference, including areas of the prostate adjacent to the neurovascular bundles, the rectum, and the bladder wall. Our previous work using SIM and a manual prostate handling method demonstrated the promise of the imaging technique for accurate detection of positive surgical margins. Our work here advances the technology toward clinical adoption, by demonstrating 10% greater tissue surface coverage fraction, 1.6× faster imaging throughput, and reduced number of required operator steps, compared to our prior approach. The APPS may be operated by a single person in the operating room suite within intraoperative time limits, while simultaneously delivering nearly two orders of magnitude higher tissue surface coverage than destructive and labor-intensive frozen section analysis techniques.

Gigapixel surface imaging of radical prostatectomy specimens for comprehensive detection of cancer-positive surgical margins using structured illumination microscopy.

Achieving cancer-free surgical margins in oncologic surgery is critical to reduce the need for additional adjuvant treatments and minimize tumor recurrence; however, there is a delicate balance between completeness of tumor removal and preservation of adjacent tissues critical for normal post-operative function. We sought to establish the feasibility of video-rate structured illumination microscopy (VR-SIM) of the intact removed tumor surface as a practical and non-destructive alternative to intra-operative frozen section pathology, using prostate cancer as an initial target. We present the first images of the intact human prostate surface obtained with pathologically-relevant contrast and subcellular detail, obtained in 24 radical prostatectomy specimens immediately after excision. We demonstrate that it is feasible to routinely image the full prostate circumference, generating gigapixel panorama images of the surface that are readily interpreted by pathologists. VR-SIM confirmed detection of positive surgical margins in 3 out of 4 prostates with pathology-confirmed adenocarcinoma at the circumferential surgical margin, and furthermore detected extensive residual cancer at the circumferential margin in a case post-operatively classified by histopathology as having negative surgical margins. Our results suggest that the increased surface coverage of VR-SIM could also provide added value for detection and characterization of positive surgical margins over traditional histopathology.

Detecting Positive Surgical Margins Using Single Optical Fiber Probe During Radical Prostatectomy: A Pilot Study

To investigate for the potential of detection of positive surgical margins by the elastic light single-scattering spectroscopy (ELSSS) system with a single optical fiber probe during radical prostatectomy. ELSSS spectra in the 450- to 750-nm wavelength regions were obtained from a total of 31 benign tissue samples and 14 malignant tissue samples from 18 patients. The ELSSS spectral data were assessed by comparing these against the "gold standard" histopathology results. Data were analyzed using principal component analysis , followed by linear discriminant analysis. Receiver operating characteristic curve analysis was used for differentiating performance. Classification based on the discriminant score provided a sensitivity of 86% and a specificity of 97%, in differentiating benign from malignant surgical margins of prostate tissues, with a positive predictive value of 0.92, a negative predictive value of 0.94, and the area under the receiver operating characteristic curve of 0.87. The ELSSS system can accurately distinguish between benign and malignant surgical margins of prostate tissues with a high positive predictive value and negative predictive value. It is a promising technique, and it may be a valuable new tool for determining positive surgical margins during radical prostatectomy.

889 Preliminary clinical experience of photodynamic diagnosis for the detection of positive surgical margins during radical prostatectomy

889 Preliminary clinical experience of photodynamic diagnosis for the detection of positive surgical margins during radical prostatectomy

Vaccinia Virus GLV1h-153: Effective Novel Treatment Agent and Imaging Tool for the Detection of Positive Surgical Margins of Triple-Negative Breast Cancer

Vaccinia Virus GLV1h-153: Effective Novel Treatment Agent and Imaging Tool for the Detection of Positive Surgical Margins of Triple-Negative Breast Cancer

Evaluation of photodynamic diagnosis using 5-aminolevulinic acid during radical prostatectomy for the detection of positive surgical margins

Evaluation of photodynamic diagnosis using 5-aminolevulinic acid during radical prostatectomy for the detection of positive surgical margins

1623 A FLUORESCENT IMAGING AGENT SPECIFICALLY TARGET PROSTATE SPECIFIC MEMBRANE ANTIGEN-EXPRESSING CELLS

You have accessJournal of UrologyProstate Cancer: Basic Research1 Apr 20111623 A FLUORESCENT IMAGING AGENT SPECIFICALLY TARGET PROSTATE SPECIFIC MEMBRANE ANTIGEN-EXPRESSING CELLS John Eifler, Wasim Chowdhury, Catherine Foss, Mark Castanares, Ying Chen, Netto George, Martin Pomper, and Ronald Rodriguez John EiflerJohn Eifler Baltimore, MD More articles by this author , Wasim ChowdhuryWasim Chowdhury Baltimore, MD More articles by this author , Catherine FossCatherine Foss Baltimore, MD More articles by this author , Mark CastanaresMark Castanares Baltimore, MD More articles by this author , Ying ChenYing Chen Baltimore, MD More articles by this author , Netto GeorgeNetto George Baltimore, MD More articles by this author , Martin PomperMartin Pomper Baltimore, MD More articles by this author , and Ronald RodriguezRonald Rodriguez Baltimore, MD More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1731AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES A urea-based small molecule conjugated to a near-infrared fluorophore (YC-27)has been developed at our institution which targets the prostate specific membrane antigen (PSMA). Such an agent may be suitable for real-time fluorescence-based surgery for detection of positive surgical margins and micrometastatic disease intraoperatively. We sought to determine the sensitivity of this compound in vitro. METHODS A PSMA-expressing prostate cancer cell line and a non-PSMA-expressing prostate cancer cell line were incubated with 10nM YC-27 at 37° C for 30 minutes. The cells were then washed twice with phosphate buffered saline (PBS). 1 million cells were added to each well in a 96-well plate, with a different percentage of PSMA-positive cells in each well, to determine the minimum number of cells that may be differentiated from background. The cells were then imaged using an optical imaging instrument, the PEARL Imager (Li-Cor Biosciences). In a separate experiment, 75,000 PC3-PIP, PC3-Control, and PC3 transfected with PSMA were incubated with YC-27, washed, and placed in a 96-well plate. After 24 hours, increasing numbers of unstained PC3 cells were added to the plate. The plate was then centrifuged and the cells were imaged with the PEARL Imager. RESULTS In the first experiment, the PSMA-based compound was detected above background and were visible with the PEARL imager when 10,000 cells were present (Figure 1) and the level of signal displayed a linear relationship. In a separate experiment, it was seen that 75,000 PC3-PIP, PC3 Control, and PC3-PSMA cells formed a confluent layer at 24h. After plating 75,000 stained cells, signal was not diminished by the addition of unstained cells, even up to 10 layers of unstained cells (Figure 2). CONCLUSIONS A fluorescent-labeled urea-based small molecule can target PSMA with high sensitivity and specificity in an in vivo model and fluorescence signal is able to penetrate at least 10 cell layers. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e650-e651 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information John Eifler Baltimore, MD More articles by this author Wasim Chowdhury Baltimore, MD More articles by this author Catherine Foss Baltimore, MD More articles by this author Mark Castanares Baltimore, MD More articles by this author Ying Chen Baltimore, MD More articles by this author Netto George Baltimore, MD More articles by this author Martin Pomper Baltimore, MD More articles by this author Ronald Rodriguez Baltimore, MD More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Photodynamic Diagnosis Using 5-Aminolevulinic Acid for the Detection of Positive Surgical Margins during Radical Prostatectomy in Patients with Carcinoma of the Prostate: A Multicentre, Prospective, Phase 2 Trial of a Diagnostic Procedure

BackgroundSurgical margin status after radical prostatectomy (RP) is a significant risk factor for tumour recurrence. It is an intriguing concept to find a fluorescence marker for photodynamic diagnosis (PDD) to make tumour margins visible during surgery. ObjectiveTo investigate the feasibility of identification of positive surgical margins (PSM) during open retropubic or endoscopic extraperitoneal RP by 5-aminolevulinic acid (5-ALA)–induced protoporphyrin IX (PpIX) to enhance surgical radicality. Design, setting, and participantsThirty-nine patients (Gleason score 6–10, prostate-specific antigen [PSA] 2.3–120ng/ml) received 20mg/kg of body weight of 5-ALA orally and underwent RP (24 endoscopic extraperitoneal, 15 open retropubic). MeasurementsA PDD-suitable laparoscopy optic (Karl-Storz GmbH, Tuttlingen, Germany) with a yellow long-pass filter was coupled to a fibre-optic light cord with an excitation light source (380–420nm, D-Light, Karl-Storz GmbH, Tuttlingen, Germany) for fluorescence excitation of PpIX and to a PDD-suitable camera for video and photo documentation by the AIDA DVD system (Karl-Storz GmbH, Tuttlingen, Germany). Results and limitationsThere were more false-negative cases in the open group (four vs two) than in the endoscopic group but more false-positive cases in the endoscopic group (two vs none) than in the open group. The overall sensitivity and specificity were 56% and 91.6%, respectively. The sensitivity of the endoscopic cases was much higher (75% vs 38%) than for the open cases, while the specificity was higher for the open group (88.2% vs 100%). ConclusionsPDD with 5-ALA–induced PpIX during RP might be a feasible and effective method for reducing the rate of PSM. The technique seems to be more practicable during endoscopic RP rather than open RP. Further clinical studies with higher patient volumes and further development of the technique seem justified. Trial registrationEudraCT: 2005-004406-93.