Differences in PI-RADS Classification of Prostate Cancer Based on mpMRI Scans Taken 6 Weeks Apart

Objectives: This study aimed to investigate the consistency of lesion identification by Prostate Imaging Reporting and Data System (PI-RADS) and the related clinical and histological characteristics in a high-volume tertiary care center. Materials and methods: The analysis used real-world data from 111 patients between 2018 and 2022. Each patient underwent two multiparametric magnetic resonance imaging (MRI) scans of the prostate at different institutions with a median interval of 42 days between the scans, followed by an MRI-fused biopsy conducted 7 days after the second MRI. Results: The PI-RADS classifications assigned to the index lesions in the in-house prostate MRI were as follows: PI-RADS V, 33.3% (n = 37); PI-RADS IV, 49.5% (n = 55); PI-RADS III, 12.6% (n = 14); and PI-RADS II, 4.5% (n = 5). Cancer detection rates for randomized and/or targeted biopsies were 91.9% (n = 34) for PI-RADS V, 65.5% (n = 36) for PI-RADS IV, 21.4% (n = 3) for PI-RADS III, and 20% (n = 1) for PI-RADS II. Overall, malignant histology was observed in 64.9% (n = 72) of the targeted lesions and 57.7% (n = 64) of the randomized biopsies. In the first performed, external MRI, 18% (n = 20) and 10.8% (n = 12) of the patients were classified in the higher and lower PI-RADS categories, respectively. The biopsy plan was adjusted for 57 patients (51.4%); nevertheless, any cancer could have possibly been identified regardless of the adjustments. Conclusion: The 6-week interval between the MRI scans did not affect the quality of the biopsy results significantly

Oral doxycycline prevents skin-associated adverse effects induced by injectable collagenase in a rodent model of capsular contracture around silicone implants

Background The collagenase of the bacterium Clostridium histolyticum (CCH) is already an established treatment for fibroproliferative diseases like M. Dupuytren and M. Peyronie Although results are comparable to surgical intervention, skin laceration is a severe and relevant side effect. Doxycycline (DOX) recently rose interest as an inhibitor of matrix-metalloproteinases alongside its capabilities of skin accumulation. It therefore might be a potential skin protective agent in the use of CCH. Methods For simulation of a fibroproliferative disease adjacent to the skin, we utilized a rodent model of capsular fibrosis involving silicone implants and subsequent fibrotic capsule formation. For in-vitro studies, fibrotic capsules were excised and incubated with 0.9 mg/ml CCH and four different doses of DOX. For in-vivo experiments, animals received 0.0, 0.3 or 0.9 mg/ml CCH injections into the fibrotic capsules with or without prior oral DOX administration. Outcome analysis included histology, immunohistochemistry, gene expression analysis, chemical collagen and DOX concentration measurements as well as μCT imaging. Results In-vitro, DOX showed a dose-dependent inhibition of CCH activity associated with increasing capsule thickness and collagen density and content. In-vivo, oral DOX administration did neither interfere with capsule formation nor in effectiveness of CCH dissolving fibrotic capsule tissue. However, skin thickness and especially collagen density was significantly higher compared to control groups. This led to a reduced rate of clinical skin lacerations after DOX administration. Conclusion DOX inhibits CCH and accumulates in the skin. Thereby, DOX can effectively reduce skin laceration after CCH treatment. </jats:sec

Oral doxycycline prevents skin-associated adverse effects induced by injectable collagenase in a rodent model of capsular contracture around silicone implants.

BackgroundThe collagenase of the bacterium Clostridium histolyticum (CCH) is already an established treatment for fibroproliferative diseases like M. Dupuytren and M. Peyronie Although results are comparable to surgical intervention, skin laceration is a severe and relevant side effect. Doxycycline (DOX) recently rose interest as an inhibitor of matrix-metalloproteinases alongside its capabilities of skin accumulation. It therefore might be a potential skin protective agent in the use of CCH.MethodsFor simulation of a fibroproliferative disease adjacent to the skin, we utilized a rodent model of capsular fibrosis involving silicone implants and subsequent fibrotic capsule formation. For in-vitro studies, fibrotic capsules were excised and incubated with 0.9 mg/ml CCH and four different doses of DOX. For in-vivo experiments, animals received 0.0, 0.3 or 0.9 mg/ml CCH injections into the fibrotic capsules with or without prior oral DOX administration. Outcome analysis included histology, immunohistochemistry, gene expression analysis, chemical collagen and DOX concentration measurements as well as μCT imaging.ResultsIn-vitro, DOX showed a dose-dependent inhibition of CCH activity associated with increasing capsule thickness and collagen density and content. In-vivo, oral DOX administration did neither interfere with capsule formation nor in effectiveness of CCH dissolving fibrotic capsule tissue. However, skin thickness and especially collagen density was significantly higher compared to control groups. This led to a reduced rate of clinical skin lacerations after DOX administration.ConclusionDOX inhibits CCH and accumulates in the skin. Thereby, DOX can effectively reduce skin laceration after CCH treatment

Results of in-vivo collagen quantification.

Mean values (X) are graphed on a box plot and individual data points are shown. Brackets indicate statistically significant differences (p < 0.0083). Group size: n = 12.</p

Example pictures of H&E staining of in-vivo study groups.

Slides at 40x magnification with arrows indicating skin thickness and red lines indicating capsule thickness. Group size: n = 12.</p

In-vivo results of capsule measurements.

left) capsule thickness and right) capsule collagen density measurements. Mean values (X) are graphed on a box plot and individual data points are shown. Density is measured as percentage of stained pixels in relation to the whole image pixel count. Brackets indicate statistically significant differences (p < 0.0083). Group size: n = 12.</p

Postulated mechanism of action.

Schematic description of the potential mechanism of action for skin protection after CCH-injection through doxycycline. CCH (collagenase of the bacterium C. histolyticum) needs to bind metal cations (Cat+) for active degradation of collagen, which is the main component of the fibrotic capsule around silicone implants. Doxycycline (DOX) accumulates in the skin and acts as a metal cation chelator. CCH-molecules diffusing into the skin from the capsule are inactivated, due to the competitive binding of Cat+ to DOX-molecules. This leads to reduction of CCH-induced collagen degradation in the skin and thus protection from CCH-related skin affection.</p

Minimal dataset.

(XLSX)</p

Summary of results of all outcome parameters for all groups.

Units are given in the first column. Results are given as mean ± standard deviation. For qRT-PCR, Col = Collagen.</p

In-vivo results of skin measurements.

left) skin thickness and right) skin collagen density measurements. Mean values (X) are graphed on a box plot and individual data points are shown. Density is measured as percentage of stained pixels in relation to the whole image pixel count. Brackets indicate statistically significant differences (p < 0.0083). Group size: n = 12.</p