Computerized metric assessment of glandular tissue volume within the peripheral zone of the prostate using combined magnetic resonance imaging and histopathology: Possible pathophysiological implications on prostate cancer development.

PURPOSE: Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are prevalent urological ailments in elderly males. Numerous clinical studies have revealed an invert association between BPH/prostate size and PCa growth. This study investigates the association between prostate size and total glandular tissue volume of the peripheral zone (GVPZ) using a unique blend of magnetic resonance imaging (MRI) and histo-anatomical imaging technique. MATERIALS AND METHODS: Patients were selected who underwent both radical prostatectomy and preoperative MRI scans. MRI scans provided quantitative measurements of prostatic zone dimensions, while histo-anatomical slides yielded quantitative data on glandular density of the peripheral zone (PZ) using imaging software. Integration of MRI and histopathology enabled the assessment of the GVPZ. Statistical analysis identified relationships between total prostate volume (TPV) and GVPZ. RESULTS: Seventy-two patients were selected and 40 cc was determined to be the optimal cutoff for small-to-moderate versus large prostates. Once the two subgroups in TPV were formed, the relationship between TPV and GVPZ was found to be highly significant (p<0.001). CONCLUSIONS: The combination of MRI and histopathology offers a novel approach for precise quantification of glandular tissue within the prostatic PZ. This study corroborates the hypothesis of PZ compression via an enlarging transition zone in larger BPH prostates, resulting in PZ glandular atrophy. Given that most PCa originates in the PZ, these results shed light on the potential protective role of larger BPH prostates against PCa growth.

Novel clinical risk calculator for improving cancer predictability of mpMRI fusion biopsy in prostates.

PURPOSE: Prostate Imaging-Reporting and Data System (PI-RADS) assists in evaluating lesions on multiparametric magnetic resonance imaging (mpMRI), but there are still ongoing efforts in improving the predictive value for the presence of clinically significant PCa (csPCa) with a Gleason grade group ≥ 2 on Fusion-Biopsy. This pilot study intends to propose an easily implementable method for augmenting predictability of csPCa for PI-RADS. METHODS: A cohort of 151 consecutive patients underwent mpMRI Fusion and random US Biopsy as a result of having at least one PI-RADS lesion grade 3-5 between January 1, 2019 and December 31, 2022. A single radiologist reads all films in this study applying PI-RADS V2. RESULTS: Of the 151 consecutive patients, 49 had a highest lesion of PI-RADS 3, 82 had a highest lesion of PI-RADS 4, and 20 had a highest lesion of PI-RADS 5. For each respective group, 12, 42, and 18 patients had proven csPCa. Two predictive models for csPCa were created by employing a logistical regression with parameters readily available to providers. The models had an AUC of 0.8133 and 0.8206, indicating promising effective models. CONCLUSION: PI-RADS classification has relevant predictability problems for grades 3 and 4. By applying the presented risk calculators, patients with PI-RADS 3 and 4 are better stratified, and thus, a significant number of patients can be spared biopsies with potential complications, such as infection and bleeding. The presented predictive models may be a valuable diagnostic tool, adding additional information in the clinical decision-making process for biopsies.

Comparative assessment of radiation therapy-induced vasculitis using [18F]FDG-PET/CT in patients with non-small cell lung cancer treated with proton versus photon radiotherapy.

PURPOSE: To assess radiation therapy (RT)-induced vasculitis in patients with non-small cell lung cancer (NSCLC) by examining changes in the uptake of 18F-fluoro-D-deoxyglucose ([18F]FDG) by positron emission tomography/computed tomography (PET/CT) images of the ascending aorta (AA), descending aorta (DA), and aortic arch (AoA) before and after proton and photon RT. METHOD: Thirty-five consecutive locally advanced NSCLC patients were definitively treated with proton (n = 27) or photon (n = 8) RT and concurrent chemotherapy. The patients were prospectively enrolled to undergo [18F]FDG-PET/CT imaging before and 3 months after RT. An adaptive contrast-oriented thresholding algorithm was applied to generate mean standardized uptake values (SUVmean) for regions of interest (ROIs) 3 mm outside and 3 mm inside the outer perimeter of the AA, DA, and AoA. These ROIs were employed to exclusively select the aortic wall and remove the influence of blood pool activity. SUVmeans before and after RT were compared using two-tailed paired t-tests. RESULTS: RT treatments were associated with increased SUVmeans in the AA, DA, and AoA-1.9%, 0.3%, and 1.3% for proton and 15.8%, 9.5%, and 15.5% for photon, respectively. There was a statistically significant difference in the ∆SUVmean (post-RT SUVmean - pre-RT SUVmean) in patients treated with photon RT when compared to ∆SUVmean in patients treated with proton RT in the AA (p = 0.043) and AoA (p = 0.015). There was an average increase in SUVmean that was related to dose for photon patients (across structures), but that was not seen for proton patients, although the increase was not statistically significant. CONCLUSION: Our results suggest that patients treated with photon RT for NSCLC may exhibit significantly more RT-induced inflammation (measured as ∆SUVmean) in the AA and AoA when compared to patients who received proton RT. Knowledge gained from further analyses in larger cohorts could aid in treatment planning and help prevent the significant morbidity and mortality associated with RT-induced vascular complications. TRIAL REGISTRATION: NCT02135679.

Comparison of Intermittent and Continuous Androgen Deprivation Therapy in Prostate Cancer Patients: An Up-to-Date Meta-analysis for Urologists and Medical Providers.

INTRODUCTION: Androgen deprivation therapy first became the treatment of choice for advanced prostate cancer in the 1940s with Charles Huggins' discoveries. Eight decades later, androgen deprivation therapy has significantly evolved, and yet is still utilized in various ways to treat certain forms of prostate cancer. For local recurrence after failed primary treatment and for locally advanced and metastatic disease, continuous androgen deprivation therapy has been standard of treatment. However, intermittent androgen deprivation therapy has emerged as a therapeutic alternative to continuous androgen deprivation therapy. The purpose of this meta-analysis is to provide an update on mortality, specifically prostate cancer-specific and nonprostate cancer causes, in order to offer some guidance when selecting the appropriate form of systemic androgen deprivation therapy. METHODS: The PubMed database was searched for prospective randomized clinical trials. Inclusion and exclusion criteria were defined. Using statistical software, we analyzed random-effects models with the assumption that the data were randomly sampled, estimated the pooled log risk ratio, assessed heterogeneity, and created funnel plots to evaluate publication bias. RESULTS: A total of 12 randomized clinical trials met all inclusion criteria for final analysis. There was no statistically significant difference in prostate cancer-specific mortality between intermittent androgen deprivation therapy and continuous androgen deprivation therapy (RR=1.10 [0.85-1.42]). The analysis of nonprostate cancer mortality favored intermittent androgen deprivation therapy over continuous androgen deprivation therapy, but the difference was statistically insignificant (RR=0.94 [0.76-1.17]). CONCLUSIONS: These 2 treatment modalities can be considered as equivalent in long-term treatment outcomes. As intermittent androgen deprivation therapy is more cost-efficient and less likely to yield adverse side effects, future treatment guidelines should consider these advantages over continuous androgen deprivation therapy.

Association between prostate size and glandular tissue volume of the peripheral zone via novel combined MRI and histopathology: possible pathophysiological implications on prostate cancer development.

PURPOSE: Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are the two most prevalent urologic diseases affecting elderly men. An inverse relationship between BPH/prostate size and PCa incidence is well documented in the current literature, but the precise mechanism is poorly understood. This study aims to investigate the effect of total prostate volume on total glandular tissue volume of the peripheral zone via a novel combination of magnetic resonance imaging (MRI) and histo-anatomical imaging. METHODS: 42 male patients between ages 53-79 years underwent both radical prostatectomy and pre-operative MRI scans. Prostate sizes ranged from 14.8-133.3cc. Quantitative measurements of surgical capsule thickness and glandular epithelial cell density within the peripheral zone (PZ) were obtained on histo-anatomical slides using computer-based imaging software. Quantitative prostatic zonal measurements were obtained from MRI scans. Combining MRI- and histopathology-obtained parameters allowed measurement of the total glandular tissue volume of the PZ (GVPZ). Statistical analysis was performed to identify associations between total prostate volume (TPV) and GVPZ. RESULTS: The Mann-Whitney U-test showed significant decreases in GVPZ in larger prostates when compared to smaller prostates. CONCLUSIONS: Combined MRI and histopathology techniques provide a novel method for accurate measuring of glandular tissue content within the prostatic PZ. The findings of this pilot study support the hypothesis of PZ compression by an expanding transition zone in large BPH prostates, leading to atrophy of PZ glandular tissue. As the majority of PCa originates in the PZ, this dynamic process may explain the protective effect of large BPH prostates against PCa development.

MRI determined prostate volume and the incidence of prostate cancer on MRI-fusion biopsy: a systemic review of reported data for the last 20 years.

PURPOSE: Magnetic resonance imaging (MRI) is a precise, systemic and advantageous imaging technique when compared to transrectal ultrasound (TRUS) which is very operator dependent. The negative correlation between prostate volume and the incidence of prostate cancer (PCa) obtained by TRUS biopsy has been well documented in the literature. The purpose of this systemic review is analyzing the reported MRI-fusion study results on prostate biopsies regarding any correlation between prostate volume and the incidence of PCa. METHODS: After defining the inclusion and exclusion criteria an in-depth review were performed between 01.01.2000 and 02.08.2022 using the PubMed database and applying the "PRISMA" guidelines. RESULTS: Twelve studies qualified, and all showed an inverse/negative relationship between prostate volume and incidence of PCa. Sample sizes ranged from 33 to 2767 patients in single and multi-institutional studies. All studies showed a statistically significant inverse relationship with a p value < 0.05. The graph summarizing all of studies and using Fisher's method revealed a highly significant combined p level of 0.00001. Additionally, not one single study was found showing the contrary (a positive correlation between prostate size and the incidence of PCa). CONCLUSION: To our knowledge, this is the first systemic review of reported MRI-Fusion data on the incidence of PCa in correlation with prostate volume. This MRI review confirms previous TRUS-biopsy studies which demonstrated an inverse relationship between prostate volume and the incidence of PCa, and thus further supports the hypothesis that large prostates size may be protective against PCa when compared to smaller prostates.

Association Between Prostate Size and MRI Determined Quantitative Prostate Zonal Measurements.

Purpose: Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are the two most prevalent and common urologic diseases impacting elderly men. The current literature has well documented an inverse relationship between prostate/BPH-size and incidence of PCa, but the exact interaction between these two disease entities is not well understood. The purpose of this study is to analyze prostatic zonal measurements with magnetic resonance imaging (MRI) in order to investigate the dynamic changes of the transition zone (TZ) and peripheral zone (PZ) in response to prostate/BPH growth. Methods: Multiparametric magnetic resonance imaging (mpMRI) scans of 430 consecutive male patients aged 18-89 years were obtained to measure the different zonal areas of the prostate. The data were statistically analyzed to identify specific associations between the different measurement parameters and total prostate volume (TPV). Results: The Mann-Whitney U-test showed a significant decline of the average peripheral zone thickness (PZT) (z = -4.5665, p < 0.0001) in larger prostates when compared to smaller prostates. The Spearman correlation between TPV and PZT demonstrated a significant negative correlation (-0.20, p < 0.0001). Conclusion: The data revealed that PZT was significantly smaller in the subgroup of patients with higher TPV. This supports the hypothesis of PZ compression and thinning caused by the growing and expanding TZ in BPH prostates. This dynamic growth-related process in the different prostatic zones may explain the protective effect of BPH against PCa.

Discrepancies between tumor genomic profiling and germline genetic testing.

BACKGROUND: Tumor genomic profiling (TGP) often incidentally identifies germline pathogenic variants (PVs) associated with cancer predisposition syndromes. Methods used by somatic testing laboratories, including germline analysis, differ from designated germline laboratories that have optimized the identification of germline PVs. This study evaluated discrepancies between somatic and germline testing results, and their impact on patients. PATIENTS AND METHODS: Chart reviews were carried out at a single institution for patients who had both somatic and designated germline genetic testing. Cases with discrepant results in which germline PVs were not detected by the somatic laboratory or in which variant classification differed are summarized. RESULTS: TGP was carried out on 2811 cancer patients, 600 of whom also underwent designated germline genetic testing. Germline PVs were identified for 109 individuals. Discrepancies between germline genetic testing and tumor profiling reports were identified in 20 cases, including 14 PVs identified by designated germline genetic testing laboratories that were not reported by somatic testing laboratories and six variants with discrepant classifications between the designated germline and somatic testing laboratories. Three PVs identified by designated germline laboratories are targets for poly adenosine diphosphate-ribose polymerase (PARP) inhibitors and resulted in different treatment options. Of the PVs identified by designated germline laboratories, 60% (n = 12) were in genes with established associations to the patients' cancer, and 40% of the PVs were incidental. The majority (90%) of all discrepant findings, both contributory and incidental, changed management recommendations for these patients, highlighting the importance of comprehensive germline assessment. CONCLUSIONS: Methods used by somatic laboratories, regardless of the inclusion of germline analysis, differ from those of designated germline laboratories for identifying germline PVs. Unrecognized germline PVs may harm patients by missing hereditary syndromes and targeted therapy opportunities (e.g. anti-programmed cell death protein 1 immunotherapy, PARP inhibitors). Clinicians should refer patients who meet the criteria for genetic evaluation regardless of somatic testing outcomes.

Evolution of Androgen Deprivation Therapy (ADT) and Its New Emerging Modalities in Prostate Cancer: An Update for Practicing Urologists, Clinicians and Medical Providers.

Androgen deprivation therapy (ADT) has been the main management strategy for prostate cancer for more than eight decades, nowadays achieved commonly by administration of luteinizing hormone-releasing hormone agonists. ADT markedly suppresses androgen hormones with the long-term risks of adverse events such as muscle weakness, impairment of glucose and lipid metabolism, impotence, osteoporosis, and secondary fractures. Extensive research has provided significantly better insight into the dynamics of ADT including identification of the benefits of sequential and combination therapies. This has led to the development of new pharmaceutical ADT modalities. This review provides a general overview of the evolution of ADT in the context of the new emerging pharmaceutical ADT modalities so that clinicians and medical providers have a better understanding of personalizing the available ADT options with their different risk-benefit profiles.

Any Correlation Between Prostate Volume and Incidence of Prostate Cancer: A Review of Reported Data for the Last Thirty Years.

PURPOSE: Prostate cancer (PCa) is the most common non-skin cancer in men worldwide and more than 80% of men with PCa also have histo-anatomical findings of benign prostate hyperplasia (BPH). It is well documented that BPH develops in the transition zone (TZ), whereas 80-85% of PCa originates in the peripheral zone (PZ) of the prostate. Possible causal links between both disease entities are controversially discussed in the current literature. Some studies have reported that larger prostates have a decreased incidence of PCa compared to smaller prostates. The purpose of this systematic review is to comprehensively summarize studies analyzing any association between prostate gland volume and incidence of PCa. METHODS: A thorough literature review was performed between 01.01.1990 through 02.28.2020 using PubMed and applying the "PRISMA" guidelines. Inclusion and exclusion criteria were defined. RESULTS: Our systematic review found 41 articles reporting an inverse (negative) relationship between prostate gland volume and incidence of prostate cancer. Sample sizes ranged from 114 to 6692 patients in these single institutional and multi-institutional studies. Thirty-nine (95%) of the 41 articles showed a statistically significant inverse relationship. In our search, no study was found showing a positive correlation between BPH size and the incidence of PCa. CONCLUSION: To our knowledge, this is the first systematic review on the important clinical question of interaction between prostate size and the incidence of PCa. The results are demonstrating an inverse relationship, and therefore reveal strong evidence that large prostates may be protective of PCa when compared to smaller prostates.

Possible clinical implications of prostate capsule thickness and glandular epithelial cell density in benign prostate hyperplasia.

PURPOSE: The negative correlation between BPH-size and incidence of prostate cancer (PCa) is well-documented in the literature, however the exact mechanism is not well-understood. The present study uses histo-anatomical imaging to study prostate volume in correlation to prostate capsule thickness, and glandular epithelial cell density within the peripheral zone (PZ). MATERIALS AND METHODS: Specimens were selected from radical prostatectomies ranging from 20 to 160 mL based on ease of anatomical reconstruction by the slides. A total of 60 patients were selected and underwent quantitative measurements of prostate capsule thickness and glandular epithelial density within the PZ using computer-based imaging software. Pearson's correlation and a stepwise multiple linear regression analysis was conducted to determine the relationship between these measured parameters and the clinical characteristic of these patients. RESULTS: Pearson's correlation analysis revealed a strongly significant, negative correlation between prostate volume and glandular epithelial cell density (r(58)=-0.554, p<0.001), and a strongly significant, positive correlation between prostate volume and average capsule thickness (r(58)=0.462, p<0.001). Results of multiple regression analysis showed that average glandular epithelial cell density added statistically to this prediction (p<0.05). CONCLUSIONS: The results suggest that growth of the transition zone in BPH causes increased fibrosis of the PZ, leading to atrophy and fibrosis of glandular cells. As 80% of PCa originates from the glandular epithelium within the PZ, this observed phenomenon may explain the inverse correlation between BPH and PCa that is well-documented in the literature.

Association between prostate size and the incidence of prostate cancer: a meta-analysis and review for urologists and clinicians.

PURPOSE: To review the literature regarding any clinically significant association between prostate size and the incidence of prostate cancer (PCa). No previous review or meta-analysis has reported this clinical question. METHODS: A thorough literature review was performed using PubMed and applying the 'PRISMA' guidelines. Inclusion and exclusion criteria were defined. RESULTS: A total of 30 articles met the search criteria. Of these 30 articles, 27 reported an inverse correlation between prostate volume (PV) and incidence of biopsy-proven PCa. The remaining three articles provided no clear statistically significant results, and there was no study showing a direct or positive correlation between PV and the incidence of PCa. CONCLUSION: This review and meta-analysis is the first report summarizing the literature on the clinical question of whether prostate size affects the incidence of PCa. Ninety percent of studies (27/30) show significant evidence supporting the hypothesis that prostate size may be protective of PCa. This review and the outlined discussion should encourage other clinical investigators to explore the relationship between PV and the incidence and aggressiveness of PCa. If future studies should confirm the hypothesis of the dynamic interactions between the different prostatic zones in a growing prostate, it will have relevant clinical implications on the management of BPH and PCa.

Quantitative measurements of prostatic zones by MRI and their dependence on prostate size: possible clinical implications in prostate cancer.

AIM: Many studies support an inverse relationship between benign prostate hypertrophy (BPH) size and incidence of prostate cancer (PCa), but the causal link between these conditions is poorly understood. Recent studies suggest that a growing transition zone (TZ) in the prostate may induce pressure on the outer peripheral zone (PZ), leading to atrophy of the glandular tissue where PCa often originates, providing a possible explanation for this interaction. To further investigate this phenomenon, our pilot study uses magnetic resonance imaging (MRI) to examine quantitative zonal changes in a consecutive cohort of prostates. METHODS: MRI scans of male patients [n = 204, 61.57 ± 13.90 years, average body mass index (BMI) 29.05 kg/m2] with various prostate sizes were analyzed statistically to identify possible associations between prostate parameters, such as total prostate volume (TPV) and peripheral zone thickness (PZT). RESULTS: TPV and PZT demonstrated a weak, inverse correlation (r = -0.21, p = 0.002). However, when examining the plotted data, the relationship between TPV and PZT was significantly different when the cohort was divided into two groups; lower TPV: ⩽87.5 ml (n = 188, TPV x- = 36.01 ± 18.18 ml), and higher TPV: >87.5 ml (n = 17, TPV x- = 125.69 ± 41.13 ml). Average PZT differed significantly between these groups (z = -3.5554, p = 0.0004). CONCLUSIONS: PZT was significantly different for patients with lower versus higher TPVs, suggesting that, above a certain point of BPH growth, the PZ is unable to withstand pressure from an expanding TZ, supporting the notion that growing BPH causes compression of the PZ glandular tissue, and, therefore, BPH may be protective against PCa.

Quantitative measurements of prostate capsule and gland density and their correlation to prostate size: possible clinical implications in prostate cancer.

PURPOSE: To study histo-anatomical imaging features and possible association between prostate volume, capsule thickness and glandular density within the peripheral zone (PZ) of prostates of different sizes. METHODS: Patients were selected who had undergone radical prostatectomy. Specimen selection was based on two factors: first, easy reconstruction of prostate anatomy by the histological slides; and second, based on prostate size. Specimens were chosen with small (< 35 cc) and also with large size (> 80 cc). A total of 20 patients were selected. None of these patients had undergone previous treatment. Computer-based imaging for quantitative measurements of capsule thickness and glandular density within the PZ were performed. Multiple regression analysis was performed to determine the relationship between these measured parameters and the clinical characteristics of these patients. RESULTS: Multiple regression analysis revealed a strong, positive association between prostate size and average capsule thickness; on the contrary, we found a negative correlation between prostate volume and average glandular density. Fibrotic thickness of the capsule was associated with gland atrophy and decreased gland density within the PZ. CONCLUSIONS: The results suggest that BPH may be associated with the development of fibrosis and gland atrophy within the peripheral zone. As 80% of prostate cancer originates from the glandular epithelium within the peripheral zone, this observed phenomenon may explain the inverse relationship between BPH and incidence of prostate cancer well documented in the literature.

Gas-loading furnace for deuterium-charged alloy-casting.

A furnace was developed and characterized to allow for safe and controlled gas-loading or degassing of alloys. This oven is able to process samples under varying atmospheres, such as high vacuum or nitrogen containing 10 vol. % deuterium, as well as for pressures up to 800 hPa. Thermal desorption spectroscopy and scanning electron microscopy demonstrate the enhancing effects of high loading-gas concentration, high pressures, high temperatures above liquidus (50-150 K above the liquidus temperature of the cast hypoeutectic aluminum-copper model-alloy), and long holding times (up to 60 min) on the amount of retained gas in the solidified sample. Lack of copper segregation in the casting is confirmed by energy dispersive x-ray diffraction and Rutherford backscattering spectroscopy. It is shown that the facility allows for the controlled generation of distinct amounts of gas pores, down to a nil amount (only shrinkage porosity appearing in the sample).

Possible clinical implications of peripheral zone changes depending on prostate size.

PURPOSE: Although numerous studies have observed an inverse relationship between the size of benign prostate hypertrophy (BPH) and the incidence of prostate cancer (PCa), few studies have explored specific mechanisms by which BPH and PCa may influence one another. In a recent study, one possibility has been brought up that growth in the transition zone due to BPH may cause pressure-induced fibrotic changes in the peripheral zone, an area where 80% of cancer occurs, leading to gland atrophy and the thickening of the prostatic capsule. To shed more light on this phenomenon, we conducted a pilot study examining the quantitative and qualitative histo-anatomical changes that occur in the peripheral zone associated with BPH. METHODS: Thirty-nine prostate specimens of various sizes were selected from patients who had undergone radical prostatectomies. Each prostate was evaluated in six different locations along the dorsal aspect of the peripheral zone by measuring the thickness of the peripheral fibrotic zone (prostate capsule) and its association with gland atrophy. Multiple regression analysis was performed to determine the relationship between prostate size and the average thickness of the prostate capsule. RESULTS: Multiple regression analysis revealed a strong, positive relationship between prostate size and average capsule thickness with a Pearson coefficient of 0.707 (p < 0.05). Fibrotic histo-anatomical changes were spatially associated with gland atrophy: glands found within the peripheral fibrotic zone appeared elongated and atrophic. CONCLUSION: The results suggest that BPH may be associated with the development of fibrotic material and atrophy of glands within the peripheral zone. Because this atrophy involves glands where 80% of prostate cancer originates, this potentially explains the inverse relationship between PCa and BPH.

Histological changes of the peripheral zone in small and large prostates and possible clinical implications.

INTRODUCTION: It is well documented in literature that most prostate carcinomas (PCa) arise in the peripheral zone (PZ). Additionally, an inverse relationship between prostate size and the incidence of PCa has been demonstrated in recent studies. However, little is known about gland distribution in the peripheral zone of larger prostates compared to smaller prostates. In this study, we examined the histo-anatomical gland distribution within the peripheral zone in small and large prostates and discuss possible clinical implications. METHODS: A semi-quantitative analysis of gland density and capsule thickness was performed using light microscopy on 10 large (≥80 g) prostate specimens and 10 small (<30 g) prostate specimens from patients who underwent radical prostatectomy at Texas Tech University Health Sciences Center between the years 2010 and 2016. Samples from radical prostatectomies were used to ensure a whole, preserved prostate with an intact surgical capsule. Gland counts were performed on five random fields under 100 × magnification, while capsule thickness was measured on three random fields per case; thus, a total 50 fields and 30 fields were analyzed for each of the two groups for gland counts and capsule thickness measurements, respectively. Microscopy was standardized to the posterior aspect of the prostate, between 4 o'clock and 6 o'clock along the equatorial region between the apex and base. RESULTS: Large prostates possessed a significantly lower mean gland count per field compared to small prostates (10.34±4.15, n=50 vs 18.00±5.41, n=50; t=8.16, df=49, P<0.001). Additionally, large prostates showed a significantly higher average capsule thickness in millimeters compared to small prostates (1.80 mm, ±1.12 mm, n=30 vs 0.90 mm, ±0.56, n=30; t=8.16, df=49, P<0.001). CONCLUSION: The results demonstrate that prostate hypertrophy leads to both decreased gland density in the peripheral zone and increased capsule thickness, suggesting that growth-induced expansion of the prostate against its capsule leads to compression-induced atrophy and fibrosis of glandular tissue within the peripheral zone (PZ). A decrease in gland density within the PZ may have clinical implications shedding light, for instance, on the reduction in PCa incidence in patients with large prostates as compared to smaller prostates, a phenomenon well documented in the literature.

Pertuzumab, trastuzumab, and standard anthracycline- and taxane-based chemotherapy for the neoadjuvant treatment of patients with HER2-positive localized breast cancer (BERENICE): a phase II, open-label, multicenter, multinational cardiac safety study.

Background: Anti-HER2 therapies are associated with a risk of increased cardiac toxicity, particularly when part of anthracycline-containing regimens. We report cardiac safety of pertuzumab, trastuzumab, and chemotherapy in the neoadjuvant treatment of HER2-positive early breast cancer. Patients and methods: BERENICE (NCT02132949) is a nonrandomized, phase II, open-label, multicenter, multinational study in patients with normal cardiac function. In the neoadjuvant period, cohort A patients received four cycles of dose-dense doxorubicin and cyclophosphamide, then 12 doses of standard paclitaxel plus four standard trastuzumab and pertuzumab cycles. Cohort B patients received four standard fluorouracil/epirubicin/cyclophosphamide cycles, then four docetaxel cycles with four standard trastuzumab and pertuzumab cycles. The primary end point was cardiac safety during neoadjuvant treatment, assessed by the incidence of New York Heart Association class III/IV heart failure and of left ventricular ejection fraction declines (≥10 percentage-points from baseline and to a value of <50%). The main efficacy end point was pathologic complete response (pCR, ypT0/is ypN0). Results are descriptive. Results: Safety populations were 199 and 198 patients in cohorts A and B, respectively. Three patients [1.5%; 95% confidence interval (CI) 0.31% to 4.34%] in cohort A experienced four New York Heart Association class III/IV heart failure events. Thirteen patients (6.5%; 95% CI 3.5% to 10.9%) in cohort A and four (2.0%; 95% CI 0.6% to 5.1%) in cohort B experienced at least one left ventricular ejection fraction decline. No new safety signals were identified. pCR rates were 61.8% and 60.7% in cohorts A and B, respectively. The highest pCR rates were in the HER2-enriched PAM50 subtype (75.0% and 73.7%, respectively). Conclusion: Treatment with pertuzumab, trastuzumab, and common anthracycline-containing regimens for the neoadjuvant treatment of early breast cancer resulted in cardiac and general safety profiles, and pCR rates, consistent with prior studies with pertuzumab. Clinical Trial Information: NCT02132949.

Towards clinical application: prompt gamma imaging of passively scattered proton fields with a knife-edge slit camera.

Prompt γ-ray imaging with a knife-edge shaped slit camera provides the possibility of verifying proton beam range in tumor therapy. Dedicated experiments regarding the characterization of the camera system have been performed previously. Now, we aim at implementing the prototype into clinical application of monitoring patient treatments. Focused on this goal of translation into clinical operation, we systematically addressed remaining challenges and questions. We developed a robust energy calibration routine and corresponding quality assurance protocols. Furthermore, with dedicated experiments, we determined the positioning precision of the system to 1.1 mm (2σ). For the first time, we demonstrated the application of the slit camera, which was intentionally developed for pencil beam scanning, to double scattered proton beams. Systematic experiments with increasing complexity were performed. It was possible to visualize proton range shifts of 2-5 mm with the camera system in phantom experiments in passive scattered fields. Moreover, prompt γ-ray profiles for single iso-energy layers were acquired by synchronizing time resolved measurements to the rotation of the range modulator wheel of the treatment system. Thus, a mapping of the acquired profiles to different anatomical regions along the beam path is feasible and additional information on the source of potential range shifts can be obtained. With the work presented here, we show that an application of the slit camera in clinical treatments is possible and of potential benefit.

[Effects of Vibrax (Mechanical Vibrations) on the Arterial Blood Gases of Patients in the Intensive Care Unit after Cardiac Surgery]. / Effekte der Vibraxanwendung (mechanische Vibration) auf die Blutgaswerte von Patienten auf der Intensivstation nach einem kardiochirurgischen Eingriff.

OBJECTIVE: Respiratory physiotherapy is an integral part of the care of patients in intensive care units (ICU) after cardiac surgery. One of the most commonly used techniques in ICU to prevent pulmonary complications are mechanical vibrations, which can be applied with a tool called Vibrax.The aim of this study was to investigate the effects of Vibrax (mechanical vibrations) on the arterial blood gases of patients in ICU during the 1. or 2. day after cardiac surgery. METHODS: A randomized controlled pilot study was conducted with 23 patients. The participants of the control group (CG) received a cardiovascular training with mobilization to the edge of the bed and active breathing exercises. On the patients of the intervention group (IG) additionally Vibrax was applied for 5 minutes. As primary outcome parameter the PaO2/FiO2 ratio was measured. RESULTS: In the CG no significant changes over time were observed (p ≥ 0.06). The IG showed a significant (p = 0.009) increase in the PaO2/FiO2 ratio from before the physiotherapy intervention (M = 296.52, SE = 34.94 mmHg) to 60 minutes after completion of the physiotherapy intervention (M = 331.39, SE = 48.14 mmHg). There was no significant difference between the CG and IG at any measuring time (p ≥ 0.09). CONCLUSION: The results of this pilot study indicate that the application of Vibrax has positive effects on the arterial blood gases of patients in ICU on the 1. or 2. day after cardiac surgery. But whether the effects are clinically relevant could not be clarified.