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

ABSTRACT: 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.

SUBMITTER: Wang M

PROVIDER: S-EPMC4891779 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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

Wang Mei M Tulman David B DB Sholl Andrew B AB Kimbrell Hillary Z HZ Mandava Sree H SH Elfer Katherine N KN Luethy Samuel S Maddox Michael M MM Lai Weil W Lee Benjamin R BR Brown J Quincy JQ

Scientific reports 20160603

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 int ...[more]

PMID: 27257084

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Project description:BACKGROUND:A positive surgical margin (PSM) following radical prostatectomy (RP) for prostate cancer is associated with increased risk of biochemical recurrence. We sought to examine whether the pathologist is an independent predictor of PSMs. METHODS:We performed a retrospective review of 3,557 men who underwent RP for localized prostate cancer at our institution from 2003 to 2015. We evaluated 29 separate pathologists. Univariate and multivariable logistic regression were used to test variables previously shown to influence PSM rates. RESULTS:Overall rate of PSM was 18.9%. Compared with patients without PSM, patients with PSM had higher body mass index (mean: 28.8 vs. 28.3), Gleason score?7 (84% vs. 66%), extracapsular extension (51% vs. 20%), and median prostate-specific antigen (5.9 vs. 5.1ng/ml) (all P<0.05). Univariate logistic regression showed that surgeon experience, pathologist experience, and pathologist genitourinary fellowship training were all predictors of PSMs (all P<0.05). Multivariable regression analysis confirmed that decreased surgeon experience, increased pathologist experience, higher pathologic Gleason score, higher pathologic stage, and higher prostate-specific antigen were significant predictors of PSMs. Increasing surgeon experience was associated with decreased odds of PSM (odds ratio = 0.79 per 1 standard deviation increase, 95% CI [0.70-0.89]). In contrast, increasing pathologist experience was associated with increased odds of PSM (odds ratio = 1.11 per 1 standard deviation increase, 95% CI [1.03-1.19]). The relationship between pathologist experience and PSM appeared to be nonlinear (Fig. 2). CONCLUSIONS:Greater pathologist experience appears to be associated with greater odds of PSMs following radical prostatectomy, even after controlling for case mix, pathologist fellowship training, and surgeon experience. Based on these findings, pathologists with less experience reviewing RP specimens may consider requesting rereview by a dedicated genitourinary pathologist.

Project description:Importance:Prostate cancer is the most common malignant neoplasm among men and is the one with the highest positive surgical margin (PSM) rate. This high rate is due to the difficulty in balancing the risk of extraprostatic disease and excising periprostatic structures, which ultimately affects patients' quality of life. In the case of a PSM, the appropriateness of adjuvant radiation therapy (aRT) should be discussed. The financial burden of PSMs on health systems has not been investigated. Objective:To estimate the financial costs associated with a PSM during radical prostatectomy on the basis of the odds of undergoing aRT. Design, Setting, and Participants:This cohort study used data on men with prostate cancer from the US National Cancer Database (January 1, 2010, through December 31, 2015). Data were requested in March 2019, accessed in April 2019, and analyzed in August 2019. Exposure:Treatment with radical prostatectomy followed by aRT, if indicated. Main Outcomes and Measures:The attributable risk fraction of PSMs on undergoing aRT was estimated from a logistic regression with aRT administration as the outcome. The analysis was adjusted for patients' socioeconomic and demographic characteristics and tumor characteristics. The aRT cost for the year 2019 was calculated using the Medicare Physician Fee Schedule and the Hospital Outpatient Prospective Payment System. The fraction of this cost attributable to a PSM was estimated according to its attributable risk fraction. Results:In total, 230?175 men were identified (median [interquartile range] age at diagnosis, 62.0 [56.0-67.0] years). Overall, 22.8% of the patients had a PSM. Patients with PSMs were more likely than those without PSMs to be older (median [interquartile range] age, 62.0 [56.0-66.0] years vs 62.0 [57.0-67.0] years) and nonwhite (9320 patients [17.8%] vs 29?872 patients [16.8%]), to have higher comorbidity scores (1604 patients [3.1%] vs 4884 patients [2.7%] with a Charlson-Deyo Comorbidity Index score ?2) and worse tumor characteristics (category T3 and T4 disease, 26?394 patients [50.3%] vs 36?040 patients [20.3%]), and to have lower socioeconomic indicators (median annual income <$30?000, 5708 patients [10.9%] vs 17?874 patients [10.1%]; proportion of individuals without a high school degree in the area ?29%, 6925 patients [13.2%] vs 22?648 patients [12.7%]). In addition, PSMs were documented more frequently at nonacademic institutions than academic ones (31?702 patients [60.5%] vs 20?714 patients [39.5%]). A total of 11?585 patients (5.0%) underwent aRT, and 7698 of them (3.3%) had a PSM at the final pathology examination. When controlling for patients' socioeconomic and demographic characteristics and tumor characteristics, men with PSMs were more likely than those with negative margins to undergo aRT, with an odds ratio of 3.79 (95% CI, 3.63-3.96; P?<?.001). The attributable risk fraction of the presence of a PSM on aRT was 44% (95% CI, 42%-45%). The attributable cost of a PSM was calculated as $17?356 (95% CI, $16?567-$17?751). Assuming 60?000 prostatectomies in 2019 and similar trends of PSM and aRT, the overall health burden attributable to PSMs was calculated to be $52?068?000 (95% CI, $49?701?000-$53?253?000). Conclusions and Relevance:The estimated aRT cost attributable to the presence of a PSM was $17?356, resulting in $52?068?000 in spending on aRT in 2019. Strategies to reduce PSMs could be associated with a reduction in the overall health costs of surgically treated PCa.

Dataset Information

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

Publications

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

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