Malignant Prostate Research Articles

DNA hypomethylation silences anti-tumor immune genes in early prostate cancer and CTCs

Cancer is characterized by hypomethylation-associated silencing of large chromatin domains, whose contribution to tumorigenesis is uncertain. Through high-resolution genome-wide single-cell DNA methylation sequencing, we identify 40 core domains that are uniformly hypomethylated from the earliest detectable stages of prostate malignancy through metastatic circulating tumor cells (CTCs). Nested among these repressive domains are smaller loci with preserved methylation that escape silencing and are enriched for cell proliferation genes. Transcriptionally silenced genes within the core hypomethylated domains are enriched for immune-related genes; prominent among these is a single gene cluster harboring all five CD1 genes that present lipid antigens to NKT cells and four IFI16-related interferon-inducible genes implicated in innate immunity. The re-expression of CD1 or IFI16 murine orthologs in immuno-competent mice abrogates tumorigenesis, accompanied by the activation of anti-tumor immunity. Thus, early epigenetic changes may shape tumorigenesis, targeting co-located genes within defined chromosomal loci. Hypomethylation domains are detectable in blood specimens enriched for CTCs.

Quercetin can be a more reliable treatment for metastatic prostate cancer than the localized disease: An in vitro study.

Quercetin is a plant flavonoid that has been recognized to have anti-inflammatory, antioxidant and anti-proliferative activities. This study aims to evaluate the inhibitory effects of quercetin against prostate malignancy in vitro and the underlying resistance mechanism. IC50 values of quercetin were determined by MTT assay. Annexin-V/PI staining was used to measure the rate of apoptosis. DNA cell cycle was analysed by PI staining method. Real-time PCR was performed to assess mRNA levels of OPN isoforms, VEGF isoforms, P53 and KLK2. Migration potential, proliferative capability and nucleus morphology of cells were evaluated by the scratch-wound assay, colony-forming assay and Hoechst staining, respectively. Quercetin significantly increased the apoptosis rate of PC-3 and LNCaP cell lines, arrested the cell cycle at the sub-G1/G1 phase, and reduced the migration potential and colony-forming capability. Moreover, upregulation of apoptosis-related genes and downregulation of genes involved in proliferation and angiogenesis was also observed. Although our results elucidated that quercetin has antitumor effects on PC-3 and LNCaP, for the first time, we showed that quercetin treatment causes alterations in the expression of OPN and VEGF isoforms, which are cancer-promoting modulators through various processes such as angiogenesis and drug-resistance. Prostate malignant cells can dodge the anti-carcinogenic properties of quercetin via modulation of OPN and VEGF isoforms in vitro. Therefore, quercetin acts as a double-edged sword in prostate cancer treatment.

The value of DISCO and MUSE-DWI combined with prostate specific antigen density in the diagnosis and risk stratification of prostate cancer

Objective: To explore the value of differential subsampling with cartesian ordering (DISCO) and multiplexed sensitivity-encoding diffusion weighted-imaging (MUSE-DWI) combined with prostate specific antigen density (PSAD) in the diagnosis and risk stratification of prostate cancer (PCa). Methods: The data of 183 patients [aged from 48 to 86 (68±8) years] with prostate diseases in the General Hospital of Ningxia Medical University from July 2020 to August 2021 were retrospectively collected. Those patients were divided into non-PCa group (n=115) and PCa group (n=68) based on the disease condition. According to the risk degree, PCa group was subdivided into low risk PCa group (n=14) and medium-to-high risk PCa group (n=54). The differences of volume transfer constant (Ktrans), rate constant (Kep), extracellular volume fraction (Ve), apparent diffusion coefficient (ADC) and PSAD between groups were analyzed. Receiver operating characteristic (ROC) curves analysis were conducted for evaluating the diagnostic efficacy of quantitative parameters and PSAD in distinguishing non-PCa and PCa, low-risk PCa and medium-high risk PCa. Multivariate logistic regression model was used for screening out the predictors, which was statistically significant differences between non-PCa group and PCa group, for PCa prediction. Results: Ktrans, Kep, Ve and PSAD of PCa group all were higher than those of non-PCa group, and ADC value was lower than that of non-PCa group, and the differences all were statistically significant (all P<0.001). Ktrans, Kep and PSAD of medium-to-high risk PCa group all were higher than those of low risk PCa group, and ADC value was lower than that of low risk PCa group, and the differences were all statistically significant (all P<0.001). When distinguishing non-PCa from PCa, the area under ROC curve (AUC) of the combined model (Ktrans+Kep+Ve+ADC+PSAD) was higher than that of any single index [0.958 (95%CI: 0.918-0.982) vs 0.881 (95%CI: 0.825-0.924), 0.836 (95%CI: 0.775-0.887), 0.672 (95%CI: 0.599-0.740), 0.940(95%CI: 0.895-0.969), 0.816(95%CI:0.752-0.869), all P<0.05]. When distinguishing low-risk PCa and medium-to-high risk PCa, the AUC of the combined model (Ktrans+Kep+ADC+PSAD) were higher than those of Ktrans, Kep and PSAD[0.933 (95%CI: 0.845-0.979) vs 0.846 (95%CI:0.738-0.922), 0.782 (95%CI:0.665-0.873), 0.84 8(95%CI: 0.740-0.923), all P<0.05]. The multivariate logistic regression analysis showed that Ktrans (OR=1.005, 95%CI:1.001-1.010) and ADC values (OR=0.992, 95%CI:0.989-0.995) were predictors of PCa (P<0.05). Conclusions: DISCO and MUSE-DWI combined with PSAD can distinguish benign and malignant prostate lesions. Ktrans and ADC values were predictors of PCa; Ktrans, Kep, ADC values and PSAD are helpful in predicting the biological behavior of PCa.

Visualization of Intermetastatic Heterogeneity in Mixed Neuroendocrine Carcinoma-Acinar Adenocarcinoma of the Prostate by 68Ga-PSMA, 68Ga-FAPI, and 18F-FDG PET/CT.

Mixed neuroendocrine carcinoma-acinar carcinoma is an uncommon histological type of neuroendocrine prostate cancer. It has been rarely reported in de novo prostate malignancies. In this case, we present 68Ga-PSMA (prostate-specific membrane antigen), 68Ga-FAPI, and 18F-FDG PET/CT findings in the de novo form of mixed large-cell neuroendocrine carcinoma-acinar adenocarcinoma of the prostate. Different levels of radiotracer uptake were observed in different metastatic sites on 68Ga-PSMA, 68Ga-FAPI, and 18F-FDG PET/CT. This case demonstrates that the multitracer PET/CT strategy may be used for the noninvasive detection of the intermetastatic heterogeneity in metastatic neuroendocrine prostate cancer.

Antiproliferative polycyclic polyprenylated acylphloroglucinols from Garcinia paucinervis

Bioassay-guided isolation of the stems of Garcinia paucinervis led to one new adamantane-type polycyclic polyprenylated acylphloroglucinols (PPAPs), (-)-garpauvinin A (1), and four known analogues (2–5). The structure and absolute configuration of 1 was established via spectroscopic techniques and ECD method. All the isolates displayed moderate antiproliferative activity against HL-60, PC-3 and Caco-2 human cancer cell lines with IC50 values ranging from 0.81 to 19.92 μM, and exhibited low toxicity on WPMY-1 normal human cells, showing selectivity between normal and malignant prostate cells. The biosynthetic pathways of the isolated PPAPs were proposed.

Detection of high-risk Human Papillomavirus in prostate cancer from a UK based population

Human papillomavirus (HPV) infection is one of the sexually transmitted diseases which have been implicated in the etiology of multiple cancers. To date, several studies have been conducted to evaluate the incidence of high-risk (HR) HPV in prostate cancer (PCa) which have generated widely conflicting data. Hence, this leaves a lack of awareness on the causal role of persistent HPV infection in the development of PCa. Although this has been investigated in a handful of countries, to the best of our knowledge, no prior studies have been conducted in the UK. In this study, polymerase chain reaction (PCR) and Sanger sequencing were implemented to analyze a total of 49 fresh prostate specimens (35 benign and 14 malignant specimens) for the presence of viral DNA of 12 HR-HPV types. Data obtained confirmed the presence of HR-HPV in 32.7% of analyzed benign and malignant prostate tissues with HPV 35 being identified as the most frequent type. Moreover, HR-HPV positivity rate was found to be higher in abnormal prostate tissues (adenocarcinoma and benign with prostatitis) compared those with normal prostate condition. Using immunohistochemistry, we have confirmed the expression of HPV E7 protein in prostate tissues positive for HPV DNA. This observation, the first reported from a UK population, suggests that the presence of HPV in prostate tissue is likely to be a related factor in the progression of certain cases of prostate cancer.

Canonical and truncated transglutaminase-2 regulate mucin-1 expression and androgen independency in prostate cancer cell lines

Androgen independency is associated with poor prostate cancer (PCa) survival. Here we report that silencing of transglutaminase-2 (TG2) expression by CRISPR-Cas9 is associated with upregulation of androgen receptor (AR) transcription in PCa cell lines. Knockout of TG2 reversed the migratory potential and anchorage independency of PC3 and DU145 cells and revealed a reduced level of mucin-1 (MUC1) RNA transcript through unbiased multi-omics profiling, which was restored by selective add-back of the truncated TG2 isoform (TGM2_v2). Silencing of AR resulted into increased MUC1 in TG2KO PC3 cells showing that TG2 affects transcriptional regulation of MUC1 via repressing AR expression. Treatment of PC3 WT cell line with TG2 inhibitor ZDON led to a significant increase in AR expression and decrease in MUC1. ZDON also blocked the formation of MUC1-multimers labelled with TG amine-donor substrates in reducing conditions, revealing for the first time a role for TG2, which we show to be externalised via extracellular vesicles, in MUC1 stabilisation via calcium-dependent transamidation. A specific antibody towards TGM2_v2 revealed its restricted nuclear location compared to the canonical long form of TG2 (TGM2_v1), which is predominantly cytosolic, suggesting that this form contributes to the previously suggested TG2-mediated NF-κB activation and AR transcriptional repression. As TGM2_v2 transcription was increased in biopsies of early-stage prostate adenocarcinoma (PRAD) patients compared to subjects presenting inflammatory prostatitis, and total TG2 protein expression significantly increased in PRAD versus normal tissue, the role of TG2 and its truncated form as a prostate malignancy marker is suggested. In conclusion, this investigation has provided the first unbiased discovery of a novel pathway mediated by TG2 via MUC1, which is shown to contribute to androgen insensitivity and malignancy of PCa cells and be upregulated in PCa biopsies, with potential relevance to cancer immune evasion.

Value of synthetic MRI quantitative parameters in preprocedural evaluation for TRUS/MRI fusion-guided biopsy of the prostate.

Transrectal ultrasonography (TRUS)/magnetic resonance imaging (MRI) fusion-guided biopsy has a high clinical application value. However, this technique has some limitations, which limit its use in routine clinical practice. Therefore, the selection of suitable proatate lesions for this technique is worthy of our attention. Synthetic MRI (SyMRI) is capable of quantifying multiple relaxation parameters, which might have potential value in preprocedural evaluation for TRUS/MRI fusion-guided biopsy of the prostate. The aim of our study is to examine the value of SyMRI quantitative parameters in preprocedural evaluation for TRUS/MRI fusion-guided biopsy of the prostate. We prospectively selected 148 lesions in 137 patients who underwent prostate biopsy in our hospital. Next, 2-4 needles of TRUS/MRI fusion-guided biopsy combined with 10 needles of system biopsy(SB) were used as the protocol for prostate biopsy. Before biopsy, the MAGiC sequences of the MRI images of the enrolled patients underwent post-processing, and the longitudinal relaxation time (T1), transverse relaxation time (T2), and proton density (PD) were extracted. The biopsy pathology results were used as a gold standard to compare the differences in SyMRI quantitative parameters between benign and malignant prostate lesions in the peripheral and transitional zones. The receiver operating characteristic (ROC) curves were plotted to confirm the optimal SyMRI quantitative parameter for prostate lesion benignancy/malignancy performance, and the cutoff values of these parameters were used for grouping the lesions. The single-needle biopsy prostate cancer (PCa)-positivity rates (number of positive biopsy needles/total biopsy needles) and PCa overall detection rates by TRUS/MRI fusion-guided biopsy and SB were compared in different subgroups. The T1 and T2 values can determine the benignancy/malignancy of prostate transition lesions(p < 0.01), and the T2 value has a greater diagnostic performance (p = 0.0376). The T2 value can determine the benignancy/malignancy of prostate peripheral lesions. The optimal diagnostic cutoff values for T2 were 77 and 81 ms, respectively. The single-needle PCa positivity rate of TRUS/MRI fusion-guided biopsy was higher than SB for any prostate lesions in different subgroups (p < 0.01). However, only in the subgroup of transition zone lesions with T2 ≤ 77 ms, the PCa overall detection rate of TRUS/MRI fusion-guided biopsy was significantly higher than that of SB (p = 0.031). SyMRI-T2 value can provide a theoretical basis for the selection of suitable lesions for TRUS/MRI fusion-guided biopsy.

Detection efficacy of [89Zr]Zr-PSMA-617 PET/CT in [68Ga]Ga-PSMA-11 PET/CT-negative biochemical recurrence of prostate cancer

RationaleIn patients with biochemical recurrence of prostate cancer (BCR), preliminary data suggest that prostate-specific membrane antigen (PSMA) ligand radiotracers labeled with zirconium-89 (89Zr; half-life ~ 78.41 h), which allow imaging ≥ 24 h post-injection, detect suspicious lesions that are missed when using tracers incorporating short-lived radionuclides.Materials and methodsTo confirm [89Zr]Zr-PSMA-617 positron emission tomography/computed tomography (PET/CT) detection efficacy regarding such lesions, and compare quality of 1-h, 24-h, and 48-h [89Zr]Zr-PSMA-617 scans, we retrospectively analyzed visual findings and PET variables reflecting lesional [89Zr]Zr-PSMA-617 uptake and lesion-to-background ratio. The cohort comprised 23 men with BCR post-prostatectomy, median (minimum–maximum) prostate-specific antigen (PSA) 0.54 (0.11–2.50) ng/mL, and negative [68Ga]Ga-PSMA-11 scans 40 ± 28 d earlier. Primary endpoints were percentages of patients with, and classifications of, suspicious lesions.ResultsAltogether, 18/23 patients (78%) had 36 suspicious lesions (minimum–maximum per patient: 1–4) on both 24-h and 48-h scans (n = 33 lesions) or only 48-h scans (n = 3 lesions). Only one lesion appeared on a 1-h scan. Lesions putatively represented local recurrence in 11 cases, and nodal or bone metastasis in 21 or 4 cases, respectively; 1/1 lesion was histologically confirmed as a nodal metastasis. In all 15 patients given radiotherapy based on [89Zr]Zr-PSMA-617 PET/CT, PSA values decreased after this treatment. Comparison of PET variables in 24-h vs 48-h scans suggested no clear superiority of either regarding radiotracer uptake, but improved lesion-to-background ratio at 48 h.ConclusionsIn men with BCR and low PSA, [89Zr]Zr-PSMA-617 PET/CT seems effective in finding prostate malignancy not seen on [68Ga]Ga-PSMA-11 PET/CT. The higher detection rates and lesion-to-background ratios of 48-h scans versus 24-h scans suggest that imaging at the later time may be preferable. Prospective study of [89Zr]Zr-PSMA-617 PET/CT is warranted.

Cell-by-cell quantification of the androgen receptor in benign and malignant prostate leads to a better understanding of changes linked to cancer initiation and progression.

The androgen receptor (AR) plays a crucial role in the development and homeostasis of the prostate and is a key therapeutic target in prostate cancer (PCa). The gold standard therapy for advanced PCa is androgen deprivation therapy (ADT), which targets androgen production and AR signaling. However, resistance to ADT develops via AR-dependent and AR-independent mechanisms. As reports on AR expression patterns in PCa have been conflicting, we performed cell-by-cell AR quantification by immunohistochemistry in the benign and malignant prostate to monitor changes with disease development, progression, and hormonal treatment. Prostates from radical prostatectomy (RP) cases, both hormone-naïve and hormone-treated, prostate tissues from patients on palliative ADT, and bone metastases were included. In the normal prostate, AR is expressed in >99% of luminal cells, 51% of basal cells, and 61% of fibroblasts. An increase in the percentage of AR negative (%AR-) cancer cells along with a gradual loss of fibroblastic AR were observed with increasing Gleason grade and hormonal treatment. This was accompanied by a parallel increase in staining intensity of AR positive (AR+) cells under ADT. Staining AR with N- and C-terminal antibodies yielded similar results. The combination of %AR- cancer cells, %AR- fibroblasts, and AR intensity score led to the definition of an AR index, which was predictive of biochemical recurrence in the RP cohort and further stratified patients of intermediate risk. Lastly, androgen receptor variant 7 (ARV7)+ cells and AR- cells expressing neuroendocrine and stem markers were interspersed among a majority of AR+ cells in ADT cases. Altogether, the comprehensive quantification of AR expression in the prostate reveals concomitant changes in tumor cell subtypes and fibroblasts, emphasizing the significance of AR- cells with disease progression and palliative ADT.

PET radiotracers for whole-body in vivo molecular imaging of prostatic neuroendocrine malignancies.

Prostatic neuroendocrine malignancies represent a spectrum of diseases. Treatment-induced neuroendocrine differentiation (tiNED) in hormonally treated adenocarcinoma has been the subject of a large amount of recent research. However, the identification of neuroendocrine features in treatment-naïve prostatic tumor raises a differential diagnosis between prostatic adenocarcinoma with de novo neuroendocrine differentiation (dNED) versus one of the primary prostatic neuroendocrine tumors (P-NETs) and carcinomas (P-NECs). While [18F]FDG is being used as the main PET radiotracer in oncologic imaging and reflects cellular glucose metabolism, other molecules labeled with positron-emitting isotopes, mainly somatostatin-analogues labeled with 68Ga and prostate-specific membrane antigen (PSMA)-ligands labeled with either 18F or 68Ga, are now routinely used in departments of nuclear medicine and molecular imaging, and may be advantageous in imaging prostatic neuroendocrine malignancies. Still, the selection of the preferred PET radiotracer in such cases might be challenging. In the current review, we summarize and discuss published data on these different entities from clinical, biological, and molecular imaging standpoints. Specifically, we review the roles that [18F]FDG, radiolabeled somatostatin-analogues, and radiolabeled PSMA-ligands play in these entities in order to provide the reader with practical recommendations regarding the preferred PET radiotracers for imaging each entity. In cases of tiNED, we conclude that PSMA expression may be low and that [18F]FDG or radiolabeled somatostatin-analogues should be preferred for imaging. In cases of prostatic adenocarcinoma with dNED, we present data that support the superiority of radiolabeled PSMA-ligands. In cases of primary neuroendocrine malignancies, the use of [18F]FDG for imaging high-grade P-NECs and radiolabeled somatostatin-analogues for imaging well-differentiated P-NETs is recommended. KEY POINTS: • The preferred PET radiotracer for imaging prostatic neuroendocrine malignancies depends on the specific clinical scenario and pathologic data. • When neuroendocrine features result from hormonal therapy for prostate cancer, PET-CT should be performed with [18F]FDG or radiolabeled somatostatin-analogue rather than with radiolabeled PSMA-ligand. • When neuroendocrine features are evident in newly diagnosed prostate cancer, differentiating adenocarcinoma from primary neuroendocrine malignancy is challenging but crucial for selection of PET radiotracer and for clinical management.

Quantification of Multi-Parametric Magnetic Resonance Imaging Based on Radiomics Analysis for Differentiation of Benign and Malignant Lesions of Prostate.

The most common cancer (non-cutaneous) malignancy among men is prostate cancer. Management of prostate cancer, including staging and treatment, playing an important role in decreasing mortality rates. Among all current diagnostic tools, multiparametric MRI (mp-MRI) has shown high potential in localizing and staging prostate cancer. Quantification of mp-MRI helps to decrease the dependency of diagnosis on readers' opinions. The aim of this research is to set a method based on quantification of mp-MRI images for discrimination between benign and malignant prostatic lesions with fusion-guided MR imaging/transrectal ultrasonography biopsy as a pathology validation reference. It is an analytical research that 27 patients underwent the mp-MRI examination, including T1- and T2- weighted and diffusion weighted imaging (DWI). Quantification was done by calculating radiomic features from mp-MRI images. Receiver-operating-characteristic curve was done for each feature to evaluate the discriminatory capacity and linear discriminant analysis (LDA) and leave-one-out cross-validation for feature filtering to estimate the sensitivity, specificity and accuracy of the benign and malignant lesion differentiation process is used. An accuracy, sensitivity and specificity of 92.6%, 95.2% and 83.3%, respectively, were achieved from a subset of radiomics features obtained from T2-weighted images and apparent diffusion coefficient (ADC) maps for distinguishing benign and malignant prostate lesions. Quantification of mp-MRI (T2-weighted images and ADC-maps) based on radiomics feature has potential to distinguish benign with appropriate accuracy from malignant prostate lesions. This technique is helpful in preventing needless biopsies in patients and provides an assisted diagnosis for classifications of prostate lesions.

MP29-08 RISK OF NEUROCOGNITIVE DISORDERS IN PROSTATE CANCER ON ANDROGEN DEPRIVATION THERAPY: A META-ANALYSIS

You have accessJournal of UrologyCME1 Apr 2023MP29-08 RISK OF NEUROCOGNITIVE DISORDERS IN PROSTATE CANCER ON ANDROGEN DEPRIVATION THERAPY: A META-ANALYSIS David E. Hinojosa-Gonzalez, Affan Zafar, and Dimitar V. Zlatev David E. Hinojosa-GonzalezDavid E. Hinojosa-Gonzalez More articles by this author , Affan ZafarAffan Zafar More articles by this author , and Dimitar V. ZlatevDimitar V. Zlatev More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003257.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Androgen Deprivation Therapy (ADT) is used to treat select localized prostate cancer, biochemical recurrence and overt metastatic cancer. Androgens play a role in maintaining synaptic density, neuronal plasticity and beta-amyloid degradation. Cognitive decline and dementia due to ADT have been proposed as possible long-term consequences. This study aims to analyze the currently available evidence for the risk of dementia and other neurocognitive disorders in patients receiving ADT. METHODS: In February 2022, a systematic search was performed according to PRISMA guidelines, querying databases for “Androgen Deprivation Therapy”, “Prostate Cancer”, AND “Dementia”, “Alzheimer’s disease”(AD), and “vascular dementia”(VD). Data was analyzed in Review Manager V 5.4.2(Cochrane). Heterogeneity was assessed using Higgins I2%. RESULTS: A total of 22 studies were included, which provided 2,413,131 patients, of which 846,394 had prostate cancer and received ADT. Our analysis found an increased risk of dementia (all-cause) (HR 1.21[1.11,1.31] p<0.00001), AD (HR 1.26[1.10,1.43], p=0.0007, depression (HR 1.87 [1.74,2.00], p<0.00001), and Parkinson’s disease (HR 1.57[1.31,1.88], p<0.00001). Risk for vascular dementia was increased but not statistically significant (HR 1.30 [0.97,1.73], p=0.08). Subgroup performed by type of ADT demonstrated an increased risk of dementia for orchiectomy (HR1.36 [1.17,1.59] p < 0.0001), antiandrogens (HR 1.15 [1.07,1.23] p<0.0001) and GnRH Agonists (HR 1.11 [ 1.05,1.17] p = 0.0002). Subgroup analysis by treatment duration demonstrated an increased risk of dementia regardless of duration. CONCLUSIONS: Meta-analysis of the currently available clinical literature demonstrates that ADT for prostate cancer is associated with a significantly increased risk of dementia, AD, PD, and depression. Further studies are needed to better characterize the interaction of ADT, aging and the underlying prostatic malignancy. Source of Funding: No funding was received. © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e383 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information David E. Hinojosa-Gonzalez More articles by this author Affan Zafar More articles by this author Dimitar V. Zlatev More articles by this author Expand All Advertisement PDF downloadLoading ...

Experience of King Abdullah Medical City in Bone Metastases Detection by Different Radiological Modalities and Tumor Marker Sensitivity

RSSA conference&#x0D; Abstract&#x0D; Objective&#x0D; The study aims to evaluate the detectability of bone metastases (BM) by CT scan vs. bone&#x0D; Scintigraphy (BS) and the sensitivity of tumor markers in different oncological settings for predicting the presence of skeletal metastases.&#x0D; Methods&#x0D; Medical information was collected for 299 patients who fit the inclusion criteria from patient files and medical image reports using (AGFA PACS® and Trakcare® systems) between January 2013 and December 2021 at KAMC-HC in Makkah.&#x0D; Results&#x0D; BS detected BM in breast cancer patients in 135 cases, while CT scan detected BM in 122 cases. In prostate cancer patients, the BS detected BM in all 38 cases, while the CT scan detected BM in 32 cases. Regarding Gastro-Intestinal (GI) malignancies, the BS detected BM in 27 cases, while the CT scan detected BM in 23 cases only.&#x0D; PSA was conducted on 40 patients and 28 (70%) of them were elevated. Breast cancer patients showed tumor marker elevation in 46 (38.9%) of 118 patients. GI malignancy revealed the highest rate of tumor markers elevation in 24 (80%) of 30 patients.&#x0D; Conclusion&#x0D; Our study showed that BS has higher sensitivity than CT scan in detecting BM for breast, prostate and GI malignancies. Further collaboration is needed to determine the sensitivity of each modality, compare them with other monitoring methods like MRI or PET/CT, optimize the hospital resources utilization for each type of malignancy and reduce the patient’s exposure to unnecessary radiation.&#x0D; &#x0D; &#x0D;

Outcomes of Hem-o-Lok clip migration at vesico-urethral anastomotic site post-robotic-assisted laparoscopic radical prostatectomy: a single centre experience.

Robotic-assisted laparoscopic prostatectomy (RALP) is the most preferred intervention for the management of prostatic malignancy worldwide. Hem-o-Lok clips (HOLC) are widely used for haemostasis and lateral pedicle ligation. These clips are prone to migrate and lodge at the anastomotic junction as well as inside the bladder causing lower urinary tract symptoms (LUTS) secondary to bladder neck contracture (BNC) or bladder calculi. The objective of this study is to describe the incidence, clinical presentation, management, and outcome of HOLC migration. Retrospective analysis of the database of Post RALP patients who developed LUTS secondary to HOLC migration was done. Cystoscopy findings, number of procedures required, number of HOLC removed intra-operatively, and follow-up of the patients was reviewed. The incidence of HOLC migration requiring intervention was 1.78% (9/505). The mean age of the patient, BMI, Pre-operative Serum PSA were 62.8years, 27.8kg/m2, and 9.8ng/mL, respectively. The mean duration of appearance of symptoms due to HOLC migration was 9months. Two patients presented with Haematuria and 7 presented with LUTS. Seven patients required a single intervention while 2 required up to 6 procedures for recurrent symptoms secondary to recurrent HOLC migration. HOLC use in RALP may present with migration and associated complications. HOLC migration is associated with severe BNC and may require multiple endoscopic interventions. Severe dysuria and LUTS not responding to medical management should be treated using an algorithmic approach and there should be a low threshold for performing cystoscopy and intervention in these cases to improve outcomes.

Disparities in Prostate Cancer Screening for Transgender Women: An Analysis of the MarketScan Database

To describe the prevalence of PSA screening amongst transgender women. A transgender individual is someone whose gender identity differs from their birth sex or the societal norms of that assigned sex. There are no formal guidelines regarding PSA screening in transgender women, even though they retain prostatic tissue throughout the gender-affirming process, and there is a lack of existing data to adequately inform clinical practice. We identified a cohort of transgender women in the IBM MarketScan dataset using ICD codes. The patient...s eligibility for inclusion was determined on an annual basis for the years 2013-2019. For each year, we required continuous enrollment, 3 months of post-transgender diagnosis follow-up, and aged 40-80 without a prior diagnosis of prostate malignancy. This cohort was compared to cisgender men with similar eligibility criteria. The proportions of individuals undergoing PSA screening were compared using log-binomial regression. A group of 2957 transgender women met the inclusion criteria. We saw significantly lower PSA screening rates among transgender individuals for ages 40-54 and 55-69, but higher rates within the age group 70-80 (P.ß<.ß.001 for all). This is the first study evaluating PSA screening rates for insured transgender women. While the rates for screening in transgender women over the age of 70 are higher, the overall rate of screening for all other age groups lags below the general population in this dataset. Further investigation is necessary to provide equitable care for the transgender community.

Overview of imaging used to guide management for prostate and bladder malignancy

AbstractThis article aims to present updates and review current practise on the main imaging modalities used in diagnosis of bladder and prostate cancer and provide this to readers. Patients diagnosed with or having treatment for a urological cancer are a huge part of any urological nurses' rota or clinical responsibilities, particularly now in an era of ever changing and improving diagnosis and management options. In this manuscript a practical overview of imaging is given to influence a fuller understanding of therapeutic management in prostate and bladder malignancies. For the purpose of this article there is only a focus on imaging in terms of diagnosis and staging purposes. It is hoped that detailed use of imaging in radiotherapy and brachytherapy for planning and treatment verification will be the subject of a separate paper but, for now, it is briefly mentioned for readers that may be less familiar with radiation oncology. Discussion and overview of imaging modalities used in the diagnosis of prostate and bladder cancer will improve understanding for urology nurses, especially junior career nurses.

Inceptor correlates with markers of prostate cancer progression and modulates insulin/IGF1 signaling and cancer cell migration

ObjectiveThe insulin/insulin-like growth factor 1 (IGF1) pathway is emerging as a crucial component of prostate cancer progression. Therefore, we investigated the role of the novel insulin/IGF1 signaling modulator inceptor in prostate cancer. MethodsWe analyzed the expression of inceptor in human samples of benign prostate epithelium and prostate cancer. Further, we performed signaling and functional assays using prostate cancer cell lines. ResultsWe found that inceptor was expressed in human benign and malignant prostate tissue and its expression positively correlated with various genes of interest, including genes involved in androgen signaling. In vitro, total levels of inceptor were increased upon androgen deprivation and correlated with high levels of androgen receptor in the nucleus. Inceptor overexpression was associated with increased cell migration, altered IGF1R trafficking and higher IGF1R activation. ConclusionsOur in vitro results showed that inceptor expression was associated with androgen status, increased migration, and IGF1R signaling. In human samples, inceptor expression was significantly correlated with markers of prostate cancer progression. Taken together, these data provide a basis for investigation of inceptor in the context of prostate cancer.

Urinary endogenous peptides as biomarkers for prostate cancer.

Prostate cancer (PCa) is one of the most prevalent types of cancer in men worldwide; however, the main diagnostic tests available for PCa have limitations and a biopsy is required for histopathological confirmation of the disease. Prostate-specific antigen (PSA) is the main biomarker used for the early detection of PCa, but an elevated serum concentration is not cancer-specific. Therefore, there is a need for the discovery of new non-invasive biomarkers that can accurately diagnose PCa. The present study used trichloroacetic acid-induced protein precipitation and liquid chromatography-mass spectrometry to profile endogenous peptides in urine samples from patients with PCa (n=33), benign prostatic hyperplasia (n=25) and healthy individuals (n=28). Receiver operating characteristic curve analysis was performed to evaluate the diagnostic performance of urinary peptides. In addition, Proteasix tool was used for in silico prediction of protease cleavage sites. Five urinary peptides derived from uromodulin were revealed to be significantly altered between the study groups, all of which were less abundant in the PCa group. This peptide panel showed a high potential to discriminate between the study groups, resulting in area under the curve (AUC) values between 0.788 and 0.951. In addition, urinary peptides outperformed PSA in discriminating between malignant and benign prostate conditions (AUC=0.847), showing high sensitivity (81.82%) and specificity (88%). From in silico analyses, the proteases HTRA2, KLK3, KLK4, KLK14 and MMP25 were identified as potentially involved in the degradation of uromodulin peptides in the urine of patients with PCa. In conclusion, the present study allowed the identification of urinary peptides with potential for use as non-invasive biomarkers in PCa diagnosis.

Tropical Pyomyositis of Atypical Etiology: A Case Report

Introduction: Tropical pyomyositis is a bacterial infection of the skeletal muscle caused by Staphylococcus aureus in 90% of cases. The most predisposed patients are those who are immunocompromised. Case Report: A 58-year-old male patient with a history of malignant prostate cancer undergoing treatment with hormonal therapy and radiotherapy, went to the emergency room for presenting, 1 week prior to admission, fever of 39°C associated with pain of progressive appearance located in the supracondylar region of the right lower limb, radiating to the inguinal region, of moderate to strong intensity, of an oppressive nature, which limited the movement of the entire right lower limb. After multiple negative tests, an MRI of the abdomen, pelvis, and lower limbs reported myositis of infectious etiology. From there, the relevant antibiotic treatment was indicated, and an ultrasound-guided biopsy of the iliopsoas muscle was performed, which reported Streptococcus agalactiae resistant to ampicillin and penicillin as the responsible pathogen. The evolution of the patient was favorable. Conclusions: Tropical pyomyositis is a disease little known by the medical community, which makes early diagnosis difficult. Immunosuppression plays an important role in its pathogenesis, so a thorough investigation must be carried out to exclude multiple predisposing conditions.