Increased Age-Adjusted Cancer Mortality After the Third mRNA-Lipid Nanoparticle Vaccine Dose During the COVID-19 Pandemic in Japan.

During the COVID-19 pandemic, excess deaths including cancer have become a concern in Japan, which has a rapidly aging population. Thus, this study aimed to evaluate how age-adjusted mortality rates (AMRs) for different types of cancer in Japan changed during the COVID-19 pandemic (2020-2022). Official statistics from Japan were used to compare observed annual and monthly AMRs with predicted rates based on pre-pandemic (2010-2019) figures using logistic regression analysis. No significant excess mortality was observed during the first year of the pandemic (2020). However, some excess cancer mortalities were observed in 2021 after mass vaccination with the first and second vaccine doses, and significant excess mortalities were observed for all cancers and some specific types of cancer (including ovarian cancer, leukemia, prostate cancer, lip/oral/pharyngeal cancer, pancreatic cancer, and breast cancer) after mass vaccination with the third dose in 2022. AMRs for the four cancers with the most deaths (lung, colorectal, stomach, and liver) showed a decreasing trend until the first year of the pandemic in 2020, but the rate of decrease slowed in 2021 and 2022. This study discusses possible explanations for these increases in age-adjusted cancer mortality rates.

Estrogen receptors alpha and beta expression in different canine cancer types with an emphasis on hematopoietic malignancies.

Estrogen receptors (ERs) are located in both healthy and neoplastic tissues. The type of estrogen receptor expressed varies depending on its location, tumor type, and species. Estrogen action is mediated by binding to ER and activating the transcriptional and signaling processes that result in the control of gene expression. There are two main types of estrogen receptors: ER alpha (ERα) and ER beta (ERß). Both receptors are functionally different, they may act antagonistically and are distributed in different tissues but their structure is similar - as they are composed of 5 different domains: A/B, C, D, E, and F. The signaling pathway and hence regulation of the gene expression by ERs is a complex and multifactorial process that involves both genomic and nongenomic actions. In the human reproductive tract, both ERα and ß are present, with predominant expression of ERß, while there are no satisfactory data distinguishing the type of ERs expressed in the canine reproductive tract. In mammary gland neoplasia, a decreased or lacking ERα expression in humans is associated with a poorer prognosis. This is similar to dogs, where higher ERα expression intensity was noted in benign tumors than in carcinomas. In human hematopoietic malignancies, ERß is a predominant receptor. Selective and non-selective ERß agonists have an antiproliferative and pro-apoptotic effect on human lymphoma cell lines and may be effective in the therapy of ERß positive lymphomas and leukemias. In canine lymphoma tissues, none or only marginal expression of ERs was detected over the decades. Considering available data, we conducted preliminary studies proving that, in contrast to humans, the dominant ER expressed in canine hematopoietic tumors is ERα.

Evaluation of the safety and efficacy of high-dose rate brachytherapy for radiorecurrent prostate cancer: a systematic review and meta-analysis.

BACKGROUND: High-dose-rate brachytherapy (HDR-BT) plays an important role in the treatment of locally recurrent prostate cancer after definitive treatment. The objective of this study is to summarize the efficacy and toxicity of HDR-BT in these patients. METHODS: We performed a systematic review of PubMed and EMBASE from inception to July 2023. The primary endpoint was relapse-free survival (RFS) in different subgroups, and the secondary endpoint was gastrointestinal (GI) and genitourinary (GU) toxicity. A semi-automated tool (WebPlotDigitizer) and a new Shiny application combined with R software (R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria; https://www.R-project.org/ ) helped to reconstruct survival curves. RESULTS: Twenty-six studies met the inclusion criteria for quantitative analysis, including 1447 patients. A total of 761 patients from 13 studies were included in survival reconstruction, and the median RFS time was 61.2 months (57.6-72.0 months). The estimated 2­, 3­, and 5­year rates were 75.9% (95% confidence interval [CI] 72.8 ~ 79.2%), 66.7% (95% CI 63.0 ~ 70.5%), and 52.3% (95% CI 47.5 ~ 57.4%), respectively. Whole-gland irradiation with multiple fractions (≥ 2 F) resulted in better RFS compared with focal gland irradiation with fewer fractions (1 F mostly; hazard ratio [HR]: 0.60, 95% CI 0.47-0.77, p < 0.0001). According to the different median time from primary treatment to salvage therapy (TRS) and median age at recurrence, short median TRS (56-67.2 months vs. 70-120 months; HR 0.52, 95% CI 0.68-0.40; p < 0.0001) and younger median age (60-70 years vs. 71-75 years; HR 0.58, 95% CI 0.46-0.74; p < 0.0001) were positive factors for RFS. The cumulative incidences estimated for grade ≥ 3 acute and late GU toxicities were 1% (95% CI 0 ~ 1%) and 5% (95% CI 4 ~ 7%), respectively. Three patients (3/992) experienced grade ≥ 3 late GI toxicity, and no cases of grade ≥ 3 acute GI toxicity were reported. CONCLUSION: HDR-BT has a high safety profile and good RFS benefit for salvage treatment of radiorecurrent prostate cancer. In terms of RFS, whole-gland irradiation with multiple fractions seems to be better than focal gland irradiation with fewer fractions, while short TRS and younger age are good prognostic factors. In view of the low level of evidence in the included studies and the large heterogeneity of each study, these conclusions still need to be confirmed by randomized controlled trials.

Tissue S100/calgranulin expression and blood neutrophil-to-lymphocyte ratio (NLR) in prostatic disorders in dogs.

BACKGROUND: Prostatic carcinoma (PCA) is a rare but severe condition in dogs that is similar to the androgen-independent form of PCA in men. In contrast to humans, PCA is difficult to diagnose in dogs as reliable biomarkers, available for PCA screening in human medicine, are currently lacking in small animal oncology. Calprotectin (S100A8/A9) and S100A12 are Ca2+-binding proteins of the innate immune system with promising potential to distinguish malignant from benign urogenital tract conditions, similar to the blood neutrophil-to-lymphocyte-ratio (NLR). However, both have not yet been extensively investigated in dogs with PCA. Thus, this study aimed to evaluate the expression of the S100/calgranulins (calprotectin, S100A12, and their ratio [Cal-ratio]) in prostatic biopsies from nine dogs with PCA and compare them to those in dogs with benign prostatic lesions (eight dogs with prostatitis and ten dogs with benign prostatic hyperplasia [BPH]) as well as five healthy controls. In addition, blood NLRs were investigated in twelve dogs with PCA and 22 dogs with benign prostatic conditions. RESULTS: Tissue S100A8/A9+ cell counts did not differ significantly between tissue from PCA and prostatitis cases (P = 0.0659) but were significantly higher in dogs with prostatitis than BPH (P = 0.0013) or controls (P = 0.0033). S100A12+ cell counts were significantly lower in PCA tissues than in prostatitis tissue (P = 0.0458) but did not differ compared to BPH tissue (P = 0.6499) or tissue from controls (P = 0.0622). Cal-ratios did not differ significantly among the groups but were highest in prostatitis tissues and significantly higher in those dogs with poor prostatitis outcomes than in patients that were still alive at the end of the study (P = 0.0455). Blood NLR strongly correlated with prostatic tissue S100A8/A9+ cell counts in dogs with PCA (ρ = 0.81, P = 0.0499) but did not differ among the disease groups of dogs. CONCLUSIONS: This study suggests that the S100/calgranulins play a role in malignant (PCA) and benign (prostatic inflammation) prostatic conditions and supports previous results in lower urinary tract conditions in dogs. These molecules might be linked to the inflammatory environment with potential effects on the inflammasome. The blood NLR does not appear to aid in distinguishing prostatic conditions in dogs. Further investigation of the S100/calgranulin pathways and their role in modulation of tumor development, progression, and metastasis in PCA is warranted.

A Case of Prostatic Signet-Ring Cell-like Carcinoma with Pagetoid Spread and Intraductal Carcinoma and Long-Term Survival: PD-L1 and Mismatch Repair System Proteins (MMR) Immunohistochemical Evaluation with Systematic Literature Review.

Prostatic adenocarcinoma (PA) is the second most common malignancy in men globally. Signet-ring cell-like adenocarcinoma (SRCC) is a very rare PA subtype, with around 200 cases reported in the English literature. Histologically, the tumor cells show a vacuole compressing the nucleus to the periphery. Pagetoid spread in acini and ducts is usually related to metastases from urothelial or colorectal carcinomas, less commonly associated with intraductal carcinoma (IC); histologically, the tumor cells grow between the acinar secretory and basal cell layers. To our knowledge, we report the first prostatic SRCC (Gleason score 10, stage pT3b) associated with IC and pagetoid spread to prostatic acini and seminal vesicles. To our systematic literature review (PRISMA guidelines), it is the first tested case for both PD-L1 (<1% of positive tumor cells, clone 22C3) and mismatch repair system proteins (MMR) (MLH1+/MSH2+/PMS2+/MSH6+). We found no SRCC previously tested for MMR, while only four previous cases showed high expression of another PD-L1 clone (28-8). Finally, we discussed the differential diagnoses of prostatic SRCC.

A necroptosis gene signature predicts prostate cancer recurrence, and is linked to somatic mutation, therapeutic landscape, and immune infiltration.

OBJECTIVE: Necroptosis, a type of programmed necrotic cell death, has been implicated in cancer biology and therapeutics. Improved risk stratification is required for prostate carcinoma in individuals. In view of the importance of necroptosis, this work proposed a necroptosis-based genetic model for recurrence prediction, and clarified its characteristics. METHODS: A least absolute shrinkage and selection operator (LASSO) regression analysis was conducted based upon transcriptome data of necroptosis genes with clinical information in the Cancer Genome Atlas (TCGA) prostate carcinoma samples, which were externally verified in the GSE116918 cohort. Somatic mutation was characterized by Maftools method. The drug sensitivity was estimated via OncoPredict algorithm. T-cell inflammation score and tumor mutational burden (TMB) score were computed for inferring immunotherapy response. CIBERSORT was adopted for scoring the infiltration of immune cell compositions. RESULTS: The necroptosis gene model was defined, composed of BCL2, BCL2L11, BNIP3, CASP8, CYLD, HDAC9, IDH2, IPMK, MYC, PLK1, TNF, TNFRSF1A, and TSC1. Considering external verification, this model effectively predicted recurrence-free survival, notably within one year (area under the curve (AUC) = 0.841, 0.706, 0.776, and 0.893 in the discovery, verification, total and external independent sets, respectively). Patients who had a risk score > median value were defined as high risk, while those who had risk score ≤ median value were defined as low risk. Older age, more advanced T, N, M stage, shorter disease-free survival, and more recurred/progressed statuses were found in high-risk patients (all P<0.05). Moreover, the signature independently predicted patient recurrence (P<0.05). High-risk specimens had more frequent somatic mutation, especially of TP53, BSN, APC, TRANK1, DNAH9, and SALL1 (all P<0.05). The heterogeneity in sensitivity to small-molecule compounds was investigated in low- and high-risk patients. Also, high-risk individuals responded better to immunotherapy (P<0.05). CONCLUSION: Altogether, the necroptosis gene signature may effectively predict prostatic carcinoma recurrence and therapeutic responses, but its clinical feasibility must be verified.

Assessment of Prostate Carcinoma Aggressiveness: Relation to 68Ga-PSMA-11-PET/MRI and Gleason Score.

BACKGROUND/AIM: To test the correlation of 68Ga-PSMA-11 uptake and the expression of PSMA (prostatic specific membrane antigen) with the Gleason score, apparent diffusion coefficient (ADC) and pharmacokinetic parameters obtained from dynamic contrast agent-enhanced MRI/PET. PATIENTS AND METHODS: Forty newly diagnosed, therapy naïve patients with prostatic carcinoma (PC) (mean age of 56.7, range=34-79), who were referred for 68Ga-PSMA-11-PET/MRI for primary staging and had undergone radical prostatectomy (RAPE) were included in this prospective study. Their blood samples were tested for serum levels of prostate-specific antigen (PSA) and proPSA. The patients' prostates were evaluated using whole-mount sections, which helped determine the extent and grade of the tumor; tests were performed to determine immunohistochemical PSMA expression. RESULTS: A correlation between PSMA expression and the accumulation of 68Ga-PSMA-11 was found using the Spearman correlation coefficient (p=0.0011). A stronger correlation was found between Gleason patterns 3 or 4 and PSMA expression (p=0.06). Furthermore, the correlation of Gleason score with the overall 68Ga-PSMA-11 accumulation within the tumor or non-tumor tissue was found to be significant (p=0.0157). A significant relation was found only with the Kep elimination rate constant, which was stronger in Gleason pattern 4 than in Gleason pattern 3. A weaker correlation was found between the accumulation of 68Ga-PSMA-11 and Ktrans in Gleason pattern 4: the most significant relation being between ADCmin and Gleason pattern 3 and 4 (p=0.0074). The total size of the tumor correlated with levels of proPSA (p<0.0001), and its extra prostatic extension correlated with levels of proPSA (p<0.0001). CONCLUSION: 68Ga-PSMA-11 correlates well with the expression of PSMA. Gleason pattern 3 and 4 had a higher correlation with 68Ga-PSMA-11 levels than did Gleason pattern 5. Either no correlation, or a weak correlation, was established with pharmacokinetics.

MRI characteristics of canine prostatic neoplasia.

Magnetic resonance imaging (MRI) has been used to evaluate dogs with suspected prostatic neoplasia, however, published studies describing MRI characteristics of canine prostatic neoplasia are currently lacking. The aims of the current retrospective case series study were to describe MRI findings of the pelvic region in dogs with a histopathologic or cytologic diagnosis of prostatic neoplasia. Retrospective analysis of these images was then performed by a board-certified veterinary radiologist for shared imaging characteristics. The most consistent characteristics were heterogeneous hyperintensity of the tumor on T2-weighted images (10/10) and short tau inversion recovery images (10/10), prostatic capsular margin distortion by the tumor (10/10), cavitations (10/10), complete effacement of the prostatic architecture (9/10), neurovascular bundle (NVB) compression or invasion (9/10), heterogeneous isointensity of the tumor on T1-weighted images (9/10), and strong contrast enhancement of the tumor (8/10). Additional features included an overlying pattern of distorted radiating striations (7/10), regional lymphadenomegaly (5/10), mineralization within the mass (5/10), urinary bladder trigone involvement (6/10), and post-prostatic urethral involvement (7/10). These findings supported the use of MRI as an adjunct imaging modality for diagnosis and therapeutic planning of prostatic neoplasia and including prostatic neoplasia as a likely differential diagnosis for dogs with these MRI characteristics.

Prostatic Metastasis Mimicking a Ligamentum Flavum Cyst in Thoracic Spine: A Case Report

@#A rare finding of a prostatic carcinoma metastasized in a ligamentum flavum at thoracic spine causing posterior column spinal cord compression. We reported a man with prostatic carcinoma presented with ataxic gait. Magnetic resonance imaging revealed an extradural cystic mass adjacent to the T4 intralaminar region indenting on the spinal cord. T4 posterior decompression via en bloc excision of the ligamentum flavum cyst and laminectomy was performed. Histopathology confirmed glandular tissue within the cyst wall which corresponds to prostatic adenocarcinoma cells. Two months post-operative, patient showed improvement in his muscle strength on left L2 myotome. The preoperative diagnosis is a challenge because of the ligamentum flavum cysts rarity in the thoracic spine and non-specific clinical signs and symptoms. To our best knowledge, this is the first report of metastatic adenocarcinoma of the prostate found as ligamentum flavum cysts.

Prostate Artery Embolization in the Treatment of Massive Intractable Bleeding from Prostatic Neoplasms: A Case Report and Systematic Review.

Lower urinary tract symptoms (LUTS) and hematuria are common symptoms in men with neoplasms, mainly affecting the elderly population. Prostatic arterial embolization (PAE) is a minimally invasive procedure that has shown promising results in managing LUTS and massive intractable prostatic hematuria in patients with benign prostatic hyperplasia (BPH) and prostate cancer (PCa). A few studies, however, have provided valuable insights into the durability and efficacy of PAE focusing on the long-term effectiveness, quality of life, and cancer-specific control of hemostasis and urinary symptoms. As a result of concomitant cardiovascular conditions, these patients often take anticoagulants or antithrombotics, which can worsen their hematuria and clinical status. Transurethral resection of the prostate (TURP) is considered a very high-risk procedure, even without massive bleeding, and requires discontinuation of vitamin K antagonists and antiplatelet therapies. Such patients usually have their surgery postponed, and PAE should be considered a safe alternative treatment. We aimed to report a narrative review from 1976 to June 2023 of the current state of PAE for massive and intractable hematuria, highlighting recent developments in this technique, including prospective cohort studies, and focusing on long-term outcome, safety, and complication management of patients with prostatic neoplasms who develop significant hemorrhagic symptoms. Additionally, we present a case report and a simple algorithm for treating intractable bleeding in a 92-year-old man with PCa and massive hematuria.

Cytomorphology, immunoprofile, and clinicopathologic correlation of metastatic prostatic carcinoma.

It may be challenging to diagnose metastatic prostatic carcinoma (PC). This study focused on clinicopathologic correlation, and pitfalls of cytomorphology and immunostains of metastatic PCs. A total of 146 metastatic PCs including 134 (92%) PC without neuroendocrine differentiation-prostatic adenocarcinoma (PAC) and 12 (8%) with neuroendocrine differentiation (PC-NED) were retrieved. Triplicate tissue microarrays (TMA) of 54 surgically excised PCs were constructed for immunostains. Most cases showed Gleason 4 or 5 patterns. Nine percent of cases did not have a prior history of PC and 7% had 2 or more primary malignancies. PAC metastasized more commonly to lymph nodes (49%), and PC-NED metastasized more commonly to liver (58%). Cytologically, metastatic PCs show acini, cribriform, nest, and solid clusters. Most PACs showed conspicuous or prominent nucleoli. PC-NEDs showed typical cytologic features of low-grade or high-grade neuroendocrine neoplasm, or small cell carcinoma features. PACs could be immunoreactive to CDX2 (25%), CK20 (11%), NKX3.1 (99%), PSA (88%), PSAP (78%), and PSMA (92%). PC-NEDs were immunoreactive to neuroendocrine immunomarkers (CD56 [100%], chromogranin [67%], and synaptophysin [100%]) and p63 (25%), and lost expression of prostate-specific markers (NKX3.1, PSA, PSAP, and PSMA). Both PACs and PC-NEDs might be immunoreactive to CK7 (18% versus 33%), GATA3 (4% versus 0%), PAX8 (2% versus 50%, P < .05), and TTF1 (3% versus 57%, P < .05). It is critical to recognize these cytologic features and abbreviation of immunomarkers of metastatic PCs to avoid misinterpretation as metastatic carcinoma from nonprostate organs and inappropriate treatment. In addition, NED may be seen after hormone and chemoradiation treatment.

HIF1α lactylation enhances KIAA1199 transcription to promote angiogenesis and vasculogenic mimicry in prostate cancer.

Prostate cancer (PCa) is one of the most prevalent malignancies in adult males. However, PCa is resistant to multi-kinase inhibitors-based anti-angiogenic therapies, and the mechanism and effective targeting thereof remains unclear. In this study, single-cell and bulk-transcriptomic datasets analysis revealed that KIAA1199, a hyaluronic acid (HA) binding protein, was involved in glycolysis, hypoxia and angiogenesis pathways. Moreover, boosted KIAA1199 expression in PCa tissues was positively correlated with tumor stage, hypoxia-inducible factor (HIF)-1α overexpression, as well as angiogenesis markers. Tube formation, Western blot, enzyme-linked immunosorbent assay, and in vivo tumorigenesis results demonstrated that KIAA1199 silencing significantly inhibited angiogenesis and vasculogenic mimicry (VM), both in vitro and in vivo, by increasing semaphoring 3A (sema3A) expression while decreasing expressions of VEGFA, VE-cadherin, phosphorylated EphA2, and depolymerized HA levels. KIAA1199 overexpression was also found to promote angiogenesis and VM via increasing secretory VEGFA, however, this activity could be reversed by the HA biosynthesis inhibitor 4-methylumbelliferone (4MU). Furthermore, dual-luciferase and ChIP-PCR revealed that HIF1α is the transcriptional enhancer of KIAA1199, while lactate imported to PCa cells by monocarboxylate transporter 1 (MCT1) stabilizes HIF1α under normoxia via HIF1α lactylation. Our findings may provide a better understanding of angiogenesis and a promising therapeutic target of PCa.

Hepatoid prostatic carcinoma with adrenal metastasis and novel genetic alterations.

Hepatoid carcinoma (HC) encompasses epithelial extrahepatic tumors exhibiting features of hepatocellular carcinoma (HCC) both by morphology and immunohistochemistry. Distinguishing metastatic HCC from HC may be challenging, particularly when limited material, such as a cytologic specimen, is available. HC from prostatic origin is unusual and has only rarely been characterized by cytology. Herein we present an 86-year-old male with history of castration-resistant prostate cancer developing a left adrenal gland nodule. Fine needle aspiration revealed a poorly differentiated malignant neoplasm diagnosed as metastatic hepatoid prostatic adenocarcinoma based on immunohistochemistry (positive for HepPar1, AFP, NKX3.1, PSMA, and Racemase; and negative for CK7, CK20, cytokeratin 34betaE12, p63, and Arg-1). Because prostatic carcinoma with hepatoid features is rare, and the patient had failed standard therapy, next generation sequencing was performed in an attempt to identify druggable molecular targets. Well-known prostate carcinoma-related alterations were found in three genes (CDK12, AR, and SPOP). In addition, three variants of uncertain significance (DDR2 R128C, SRC P428L, and HNRNPU K574Sfs*32) were identified, which to the best of our knowledge have not been previously reported. Our results support the power of an immunohistochemistry panel including Arg-1 and HepPar1 when HC is suspected, and highlight the value of cytology for comprehensive diagnostic evaluation.

Long-Term Survival of a Lynch Syndrome Patient With Eight Primary Tumors: A Case Report.

With the modern technological developments in the diagnosis and treatment of cancer, the survival rate of cancer patients has increased. On the other hand, the incidence of multiple primary tumors is increasing annually. Lynch syndrome (LS), an autosomal dominant disorder with germline mutations in DNA mismatch repair genes, increases the risk of cancer in patients carrying those mutations. In this report, we present an extremely rare case of an 81-year-old male patient with eight primary malignancies and LS. The patient is still alive having survived for more than 41 years since the initial discovery of the first tumor. The eighth and most recently diagnosed primary cancer was a malignant peripheral nerve sheath tumor. Although there have been numerous reports of malignancies in LS, malignant peripheral nerve sheath tumors have not been reported previously with LS. Here, we report, to the best of our knowledge, the first case of a malignant peripheral nerve sheath tumor with LS.

Incidental Prostate Cancer from Prostate with Benign Biopsies: A Predictive and Survival Analysis from Cohort Study.

Purpose: This cohort was to evaluate incidental prostate cancer (iPCa) from men with preoperative benign biopsies and demonstrate their outcomes under different managements. Patients and Methods: Between 2015 and 2017, we analyzed the risk factors having iPCa from surgical specimens from men provided with benign preoperative biopsies of their prostates. Furthermore, we compared the survival outcomes according to the different managements after iPCa was diagnosed. Receiver operating characteristic (ROC) curve was utilized to find the best thresholds. Univariable and multivariable nested logit regression were performed to estimate the effect size of different independent variables. Odds ratio (OR) was expressed with 95% confidence interval, and the alpha level was 5%. Results: In 295 men we enrolled, there were 57 (19%) men having iPCa from surgical specimens. In univariable logit regression, we found significant variables of age, PSA, prostatic volume, PSA velocity ≥ 0.75 ng/mL/year for 3 years, taking 5α reductase inhibitors, abnormal digital rectal examination, cores of biopsy and surgical methods. In multivariable model, PSA was the strongest variable predicting iPCa (OR 3.81 [2.04-7.07]; Wald: 17.75; p < 0.001). In ROC curve, the best threshold was 9.025 ng/mL (area under curve: 0.95; sensitivity: 0.947; specificity: 0.866). In Kaplan-Meier curve of 27.89-month follow-up, robot-assisted simple prostatectomy (RASP) can provide similar PSA progression-free period as robot-assisted radical prostatectomy (RARP) following transurethral surgeries in organ-confined cancer (Log rank test, p = 0.293), and both of them were better than external-beam radiation therapy (RT) following transurethral surgeries (Log rank test, p < 0.001). Conclusion: PSA was the strongest variable to predict iPCa out of prostate with preoperative benign biopsies. RASP was parallel to RARP following transurethral surgeries in organ-confined cancer in the short term.

Noncoding-RNA-Based Therapeutics with an Emphasis on Prostatic Carcinoma-Progress and Challenges.

Noncoding RNAs (ncRNAs) defy the central dogma by representing a family of RNA molecules that are not translated into protein but can convey information encoded in their DNA. Elucidating the exact function of ncRNA has been a focus of discovery in the last decade and remains challenging. Nevertheless, the importance of understanding ncRNA is apparent since these molecules regulate gene expression at the transcriptional and post-transcriptional level exerting pleiotropic effects critical in development, oncogenesis, and immunity. NcRNAs have been referred to as "the dark matter of the nucleus", and unraveling their role in physiologic and pathologic processes will provide vast opportunities for basic and translational research with the potential for significant therapeutic progress. Consequently, strong efforts are underway to exploit the therapeutic utility of ncRNA, some of which have been approved by the US Food and Drug Administration and the European Medicines Agency. The use of ncRNA therapeutics (or "vaccines" if defined as anti-disease agents) may result in improved curative strategies when used alone or in combination with existing treatments. This review will focus on the role of ncRNA therapeutics in prostatic carcinoma while exploring basic biological aspects of these molecules that represent about 97% of the transcriptome in humans.

Expression of Autophagy Markers Beclin1 and LC3B in Prostatic Carcinoma: An Immunohistochemical Case-Control Study.

BACKGROUND & OBJECTIVE: Prostatic carcinoma represents the second most common cancer diagnosed in men worldwide after lung cancer and the fourth common male malignancy in Egypt. Autophagy is a natural process that has both oncogenic and tumor-suppressive activities. This study aimed to evaluate the role of Beclin1 and LC3B in prostatic carcinoma. METHODS: This retrospective case-control study was conducted on 110 prostate biopsies divided into three groups (55 prostatic carcinomas, 45 pure benign prostatic hyperplasias (BPH), and 10 BPH with adjacent prostatic carcinoma) retrieved from the archive of the Pathology Department, Faculty of Medicine, Menoufia University, in the period between 2017 and 2020. All biopsies were stained for Beclin1 and LC3B antibodies. RESULTS: There was a highly significant association between higher Beclin1 and LC3B immunoreactivity score and Gleason score (score 8 and 9) (P=0.002 and 0.000, respectively). Moreover, there was a highly significant direct association between Beclin1 and LC3B expression (r=0.52, P=0.000). Also, there was a significant stepwise increase in Beclin1 positivity among the three studied groups starting from BPH to prostatic carcinoma passing through cases of BPH with neighboring tumor (P=0.000). CONCLUSION: From the results obtained in the present study, autophagy markers Beclin1 and LC3B showed upregulation in prostatic carcinoma. Moreover, both were associated with poor prognostic factors. So, it might be necessary to control autophagy flux in prostatic carcinoma. This might be one of the future therapeutic targets for the management of prostatic carcinoma.

A Review of High-Intensity Focused Ultrasound in Urology.

This review provides an introduction to high-intensity focused ultrasound (HIFU) and reviews its historical and current use in urological surgery. Current and historical literature (1927-2020), including that describing trials and review articles in the medical and ultrasonic literature, has been reviewed, using Pub Med and Cochrane search engines. HIFU is currently one of a number of treatments for prostate cancer, both as a primary treatment that can be repeated, and as a salvage treatment post-radiotherapy. HIFU is not yet sufficiently mature to be a standard treatment for renal cancer or other urological diseases, although there has been some success in early clinical trials. As the technology improves, this situation is likely to change. HIFU has been understood as a concept for a century, and has been applied in experimental use for half that time. It is now an accepted treatment with low morbidity in many diseases outside the scope of this review. In urological surgery, prostate HIFU is accepted as a localised treatment in selected cases, with potentially fewer side effects than other localised therapies. Currently the treatment for renal cancer is hindered by the perinephric fat and the position of the kidneys behind the ribs; however, as the technology improves with image fusion, faster treatments, and the ability with phased array transducers and motion compensation to overcome the problems caused by the ribs and breathing, successful treatment of kidney tumours will become more of a reality. In due course, there will be a new generation of machines for treating prostate cancer. These devices will further minimise the side effects of radical treatment of prostate cancer.

Uncommon histopathological variant of prostate carcinoma: signet ring cells. / Variante histopatológica poco frecuente de carcinoma prostático: células en anillo de sello.

INTRODUCTION: Prostatic carcinoma withsignet ring cells is a very rare histopathological entity, withfew infected cases in the literature, for which there is nomanagement protocol.  DESCRIPTION OF CASES: Two patients are presented,one 46 years old and the other 76 years old, the firstdebuts with a decompensated picture of urinary and intestinalobstruction, and the second presents a torpid evolutionof his disease with progression from stage I to III in threemonths.  DISCUSSION: Mucosacretory prostate tumors have theirown morphohistological and immunohistochemical characteristics,which differentiate them from classic adenocarcinomas.  CONCLUSIONS: Prostatic carcinoma with signet ring cellsis an entity that must be borne in mind, especially in patientswith rapid progression of their disease.

INTRODUCCIÓN: El carcinoma prostáticocon células en anillo de sello es una entidad histopatológicamuy rara, con pocos casos descritos en la literatura, porlo cual no hay un protocolo de manejo. DESCRIPCIÓN DE CASOS: Se presentan dos pacientes,uno de 46 años y otro de 76 años, el primero debuta conun cuadro descompensado de obstrucción urinaria e intestinal,y el segundo presenta una evolución tórpida de suenfermedad con avance de un estadio I a III en tres meses. DISCUSIÓN: Los tumores de próstata mucosecretores tienencaracterísticas morfohistológicas e inmunohistoquímicaspropias, que los diferencian de los adenocarcinomasclásicos. CONCLUSIONES: El carcinoma prostático con células enanillo de sello es una entidad que hay que tener presente,sobre todo en pacientes con rápida progresión de su enfermedad.

Variante histopatológica poco frecuente de carcinoma prostático: células en anillo de sello / Rare histopathological variant of prostatic carcinoma: signet ring cells

Introducción: El carcinoma prostáticocon células en anillo de sello es una entidad histopatológica muy rara, con pocos casos descritos en la literatura, porlo cual no hay un protocolo de manejo. Descripción de casos: Se presentan dos pacientes,uno de 46 años y otro de 76 años, el primero debuta conun cuadro descompensado de obstrucción urinaria e intestinal, y el segundo presenta una evolución tórpida de suenfermedad con avance de un estadio I a III en tres meses. Discusion: Los tumores de próstata mucosecretores tienen características morfohistológicas e inmunohistoquímicas propias, que los diferencian de los adenocarcinomasclásicos. Conclusiones: El carcinoma prostático con células enanillo de sello es una entidad que hay que tener presente,sobre todo en pacientes con rápida progresión de su enfermedad.(AU)

Introduction: Prostatic carcinoma withsignet ring cells is a very rare histopathological entity, withfew infected cases in the literature, for which there is nomanagement protocol. Description of cases: Two patients are presented,one 46 years old and the other 76 years old, the firstdebuts with a decompensated picture of urinary and intestinal obstruction, and the second presents a torpid evolutionof his disease with progression from stage I to III in threemonths. Discussion: Mucosacretory prostate tumors have theirown morphohistological and immunohistochemical characteristics, which differentiate them from classic adenocarcinomas. Conclusions: Prostatic carcinoma with signet ring cellsis an entity that must be borne in mind, especially in patients with rapid progression of their disease.(AU)