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Hailong Hao,1 Huiqing Chen,1 Liwu Xie,2 Hongyu Liu,1 Dongwen Wang3 1Department of Urology, Shanxi Cancer Hospital, Affiliated Cancer Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 2Department of Pathology, Shanxi Cancer Hospital, Affiliated Cancer Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 3National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, People’s Republic of ChinaCorrespondence: Dongwen Wang Email urology2007@126.comBackground: Bone metastasis after failure of castration therapy is the main reason of death in patients with prostate cancer (PCa). Therefore, full awareness of the metastasis mechanism of PCa and discovery of new therapeutic targets are necessary. Studies showed that lncRNA was involved in the development of cancer. However, its potential role and molecular mechanism in PCa metastasis are still unclear. YKL-40 is an 18 glycosyl hydrolase family protein encoded by CHI3L1, which is involved in the invasion and metastasis of various tumors. A previous study of the authors found that YKL-40 was related to the invasion and metastasis of PCa cells. However, the cause of its abnormal expression in PCa remains unclear. The present study explored the role of lncRNA KCNQ1OT1/miR-211-5p/CHI3L1 regulatory axis in the proliferation, invasion, and metastasis of PCa.Methods: RT-PCR and Western blot were used to measure the expression profiles of KCNQ1OT1 and YKL. CCK-8 and Transwell assays were used to examine their effects on cell proliferation and migration. Double luciferase reporter assay was used to verify the interactions between miR-211-5p and CHI3L1 3′-UTR.Results: KCNQ1OT1 expression was upregulated in PCa tissues and cells. Downregulating this expression inhibited PCa cell invasion, proliferation, and metastasis. KCNQ1OT1 bound miR-211-5p competitively, and miR-211-5p targeted CHI3L1 3′-UTR. miR-211-5p expression was downregulated, whereas CHI3L1 (YKL-40) expression was upregulated. miR-211-5p levels were negatively correlated with KCNQ1OT1 expression and CHI3L1 mRNA. The decrease in YKL-40 expression in PCa cells induced by the downregulation of KCNQ1OT1 expression could be offset by miR-211-5p inhibitor transfection.Conclusion: This study showed that lncRNA KCNQ1OT1, as a ceRNA, upregulated CHI3L1 and promoted PCa progression through competitive binding to miR-211-5p.Keywords: prostatic cancer, PCa, lncRNA KCNQ1OT1, miR-211-5p, CHI3L1, competing endogenous RNA

Metastasis of malignant tumors to the temporal bone is relatively rare. We report a case of facial nerve palsy due to the metastatic prostatic cancer to the temporal bone with favorable and functional results. A 76-year-old man with no history of malignant tumor was referred to our hospital with a complaint of right facial nerve palsy. Based on radiological findings and a biopsy from the prostate, the patient was finally diagnosed as having metastatic prostatic cancer to the right temporal bone. More than 18 months had passed after start of the hormonal therapy, the metastatic lesion of the temporal bone had diminished, and the facial nerve palsy gradually improved. The present case suggests that favorable and functional results even in advanced metastatic prostatic cancers to temporal bone, if hormonal therapy is effective. We must keep in mind the possibility of metastatic tumor in the treatment of facial nerve palsy.

Background:Magnetic Resonance Imaging (MRI) plays a vital role in diagnosing prostatic cancer routinely done before biopsy for the lesion's extent and defining the correct path for ultrasound-guided prostate biopsy. Diffusion-Weighted Imaging (DWI) is a non-invasive MRI sequence that shows improved sensitivity and specificity in the same setting with no additional cost. The study aims to evaluate the diagnostic accuracy of DWI in the detection of prostatic cancer. Methodology:A cross-sectional study was conducted at the radiology department of Dr. Ziauddin University Hospital between 15/ 04 /2016 to 15/ 4 /2017. A total of 201 patients who were clinically suspected of having prostatic tumors were in this study's inclusion criteria. MRI, including DWI, was done. The final diagnosis was based on an analysis of the histopathology report. Results:Out of 201 males with clinical suspicious of prostatic cancer, 160 were diagnosed with prostatic cancer on histopathology. Of these, 150 were positive on DWI. The sensitivity of diffusion-weighted MRI was found to be 93.7%, 75.60% specificity, and 90.0% diagnostic accuracy (DA) for the diagnosis of prostatic cancer. Conclusion:Diffusion-weighted sequence in MRI examination has a vital role in diagnosing prostatic cancer and should be considered a routine pre-biopsy investigation along with MRI in clinically suspected cases of prostate cancer. Link:http://aeirc-edu.com/ojs14/index.php/IJEHSR/article/view/463/615

Background The aim of this study is to investigate whether quantitative DW metrics can provide additive value to the reliable categorization of lesions within existing PI-RADSv2 guidelines. Fifty-eight patients with clinically suspicious prostate cancer who underwent PR examination, PSA serum levels, sextant TRUS-guided biopsies, and bi-parametric MR imaging were included in the study. Results Sixty-six lesions were detected by histopathological analysis of surgical specimens. The mean ADC values were significantly lower in tumor than non-tumor tissue. The mean ADC value inversely correlated with Gleason score of tumors with a significant p value < 0.001.Conversely, a positive relationship was found between the ADC ratio (ADC of benign prostatic tissue to prostate cancer) and the pathologic Gleason score with a significant elevation of the ADC ratio along with an increase of the pathologic Gleason score (p < 0.001). ROC curves constructed for the tumor ADC and ADC ratio helped to distinguish pathologically aggressive (Gleason score ≥ 7) from non-aggressive (Gleason score ≤ 6) tumors and to correlate it with PIRADSv2 scoring to predict the presence of clinically significant PCA (PIRADSv2 DW ≥ 4). The ability of the tumor ADC and ADC ratio to predict highly aggressive tumors (GS> 7) was high (AUC for ADC and ADC ratio, 0.946 and 0.897; p = 0.014 and 0.039, respectively). The ADC cut-off value for GS ≥ 7 was < 0.7725 and for GS ≤ 6 was > 0.8620 with sensitivity and specificity 97 and 94%. The cutoff ADC ratio for predicting (GS > 7) was 1.42 and for GS ≤ 6 was > 1.320 with sensitivity and specificity 97 and 92%. By applying this ADC ratio cut-off value the sensitivity and specificity of reader 1 for correct categorization of PIRADSv2 DW > 4 increased from 90 and 68% to 95 and 90% and that of reader 2 increased from 94 and 88% to 97 and 92%, respectively. Conclusion Estimation of DW metrics (ADC and ADC ratio between benign prostatic tissue and prostate cancer) allow the non-invasive assessment of biological aggressiveness of prostate cancer and allow reliable application of the PIRADSv2 scoring to determine clinically significant cancer (DW score > 4) which may contribute in planning initial treatment strategies.

Urinary incontinence is the most common adverse effects after radical prostatectomy, and it significantly impacts patients' quality of life after surgery. With the discovery of the fine anatomical structure of the prostate and the popularization of the concept of neurovascular bundle-sparing during surgery, the incidence of urinary incontinence after radical prostatectomy has been significantly reduced. Depending on the degree of urinary incontinence, the current treatment strategies include conservative treatment, behavioral therapy, pharmacotherapy, urethral bulking agents injection, male sling and artificial urethral sphincter. This article reviews the current status of treatment of urinary incontinence after radical prostatectomy, summarizes the scope of application, advantages and disadvantages of different treatment options and prospects for new treatment options in the future.

Radical prostatectomy was first performed more than 100 years ago and has since become the gold standard in treatment of localized prostate cancer. Open surgery has been almost entirely replaced by robotic operations referred to as robot-assisted radical prostatectomy (RARP). Th e article introduces the basics of this innovative standard of operative access and tackles medical and historical aspects, oncological, medical and economic management pros and contras of robotic aid over open radical prostatectomy. Surgical trauma in RARP is clearly less pronounced compared to open surgery due to a much earlier postoperative mobilisation and a faster rehabilitation of patients leading to a statistically significant reduction in the length of hospital stay after RARP. Along with advances in intracorporeal imaging with 16-fold optical magnification coupled with shorter urethral catheterisation, RARP facilitates an earlier start of pelvic floor exercises, which reduces postoperative incontinence and need for pain relievers. Th e already mentioned technical advantages of the robotic method hold value to both patient and surgeon by securing instant access for an experienced colleague without interrupting the surgery. Noteworthy, the increasing advancement of robotic systems across the globe is leading urologist surgeons to abandon open operations. A drawback of the robotic method is much higher economic costs. However, greater expenditures may pay off in the long run by shorter hospital stays, faster rehabilitation and fewer complications demanding extra management and care.

Background The aim of this study is to investigate the role of PET/CT imaging with the 68Ga-labeled PSMA-ligand in the follow up assessment of post-operative and post-therapeutic cases of prostate cancer. All data were collected and analyzed retrospectively, enrolling 30 patients (their age range from 53 to 80 years with a mean age 67.8). The patients had been referred to a private imaging center for their assessment by 68Ga-labeled PSMA-ligand PET/CT. Results By 68Ga-labeled PSMA-ligand PET/CT, prostatic recurrent/residual neoplastic lesion was depicted in 23 (76.6%) patients, nodal metastases was present in 7 (23.3%) patients, and distant metastasis was present in 11 (36.6%) patients. The clinical and/or PSA level and/or radiological follow-up and/or the histopathological assessment for the patients served as a reference in the present study.The 68Ga-labeled PSMA-ligand PET/CT had sensitivity, specificity, positive predictive value, negative predictive value, and an overall accuracy (96.5%, 100%, 100%, 50%, and 96.6%) respectively. Conclusion 68Ga-labeled PSMA-ligand PET/CT is a very helpful tool for detection of prostatic cancer residual/recurrent lesions and restaging which can help in performing treatment plans and improve the clinical outcome and survival of the patients.

Objective: To study the sedative effect of dexmedetomidine in elderly patients with prostate cancer undergoing three hole LRP, and its effect on nerve function and brain oxygen metabolism. Methods：From August 2016 to December 2019, 78 patients with LRP under general anesthesia in our hospital were randomly selected and divided into control group and observation group according to the random number table method, 39 cases in each group. During the operation, the observation group was given dextromethoridine, while the control group was given the same amount of normal saline. The changes of cognitive function index (MoCA score, POCD incidence rate), neurological function index (TGF - β 1, NSE, IGF-1), brain oxygen metabolism index (PaO2, map, PaCO2, rSO2) before and after operation were compared between the two groups. The visual analogue score (VAS), the amount of analgesic drugs and the times of pressing the analgesic pump were compared between the two groups. The incidence of adverse reactions was compared between the two groups. Results：Before operation, there was no significant difference in cognitive function index, neurological function index and brain oxygen metabolism index between the two groups (P > 0.05). On the first and third days after operation, MOCA score of the two groups was significantly lower, MOCA score of the observation group was significantly higher than that of the control group, POCD incidence of the observation group was significantly lower than that of the control group; on the third day after operation, TGF - β 1 and IGF-1 of the two groups were significantly lower, TGF - β 1 and IGF-1 of the observation group were significantly lower -The NSE in the observation group was significantly lower than that in the control group (P < 0.05). In this study, 1 hour after the establishment of pneumoperitoneum, PaCO2 and rSO2 in the two groups were significantly increased, 6 hours and 12 hours after the operation, the VAS score of the observation group was lower than that of the control group, and the dosage of analgesic pump and the number of times of compression of the analgesic pump were significantly lower than that of the control group (P < 0.05). There was no difference in the incidence of adverse reactions between the two groups (P> 0.05). Conclusion：DEX has a good sedative effect on the elderly prostate cancer patients undergoing LRP with three hole method. It has little effect on nerve function and brain oxygen metabolism, and has a good safety.

Purpose The goal of this study was to retrospectively compare systematic ultrasound-guided prostate biopsy (US-PB) and multiparametric magnetic resonance imaging-ultrasound fusion prostate biopsy (MRI-PB) in men undergoing primary or repeated biopsies. Methods A population of 2,200 patients with a prostate-specific antigen (PSA) level >4.0 ng/ dL and/or an abnormal rectal examination was divided into two groups. All patients underwent US-PB (n=1,021) or MRI-PB (n=1,179) between April 2015 and April 2019. Population demographics, including age, PSA level, digital rectal examination results, prostate volume, number of previous negative biopsies, Prostate Imaging Reporting and Data System (PI-RADS) version 2 (V2) score, and biopsy results, were acquired and compared with respect to these variables. Univariate regression analysis of the risk factors for a higher Gleason score (GS) was performed. Results The cancer detection rate (CDR) was 23.8% (243 of 1,021) in the US-PB group and 31.3% (399 of 1,179) in the MRI-PB group. Of those, 225 patients (22.0%) in the US-PB group and 374 patients (31.7%) in the MRI-PB group had clinically significant prostate cancer (csPCa). The patients with csPCa in the MRI-PB group included 10 (40%), 50 (62.5%), 184 (94.8%), and 32 (94.1%) patients with PI-RADS V2 scores of 2, 3, 4, and 5, respectively. Of the patients with csPCa, 155 (91.7%) in the US-PB group were diagnosed on the basis of the primary biopsy, compared to 308 (94.4%) in the MRI-PB group. We found the PI-RADS V2 score to be the best predictor of a higher GS. Conclusion MRI-PB showed a high CDR for csPCa. MRI-PB could be a reasonable approach in patients with high PI-RADS V2 scores at primary biopsy.

The aim of this study was to construct a nomogram for predicting prostate cancer (PCa) in patients with PSA ≤ 20 ng/mL at initial biopsy. The patients with PSA ≤ 20 ng/mL who underwent prostate biopsy were retrospectively included in this study. The nomogram was developed based on predictors for PCa, which were assessed by multivariable logistic regression analysis. The receiver operating characteristic curve, calibration plots and decision curve analysis (DCA) were used to evaluate the performance of the nomogram. This retrospective study included 691 patients, who were divided into training set (505 patients) and validation set (186 patients). The nomogram was developed based on the multivariable logistic regression model, including age, total PSA, free PSA, and prostate volume. It had a high area under the curve of 0.857, and was well verified in validation set. Calibration plots and DCA further validated its discrimination and potential clinical benefits. Applying the cut-off value of 15%, our nomogram would avoid 42.5% of unnecessary biopsies while miss only 4.4% of PCa patients. The nomogram provided high predictive accuracy for PCa in patients with PSA ≤ 20 ng/mL at initial biopsy, which could be used to avoid the unnecessary biopsies in clinical practice.

Aim:The aim of this study was to investigate whether serum ischemia-modified albumin (IMA) levels have a diagnostic value in prostate cancer (Pca).Methods:Thirty primary Pca patients and 30 age-matched healthy male subjects were included in this prospective case-control study. The patients were selected from the urology clinic of a tertiary university hospital. Healthy men included in the control group were selected from hospital staff and patient relatives. Patients with severe chronic diseases and other malignancies were excluded. Serum IMA level was measured using the colorimetric method. The results were reported in absorbance unit (ABSU).Results:Serum IMA levels were significantly higher in the study group when compared to the control group (0.843±0.76 and 0.443±0.49 ABSU, respectively; p=0.002). The mean IMA value in patients with a Gleason score ≥7 (1.08±0.053 ABSU) was significantly higher than in patients with Gleason score ≤6 (IMA 0.418±0.64 ABSU). According to the receiving operating characteristic (ROC) analysis, when the cut-off value was ABSU=0.57, the sensitivity and specificity were 80% and 56.7%, respectively.Conclusion:Serum concentrations of IMA are significantly elevated especially in clinically significant Pca patients. Its high sensitivity (80%) in ROC analysis suggests that IMA can be used an ancillary biomarker in diagnosis.

Yongliang Ma, Bo Fan, Zongtao Ren, Bin Liu, Yanchao WangDepartment of Urology Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of ChinaBackground: Chemotherapy is one of the available options for prostate cancer (PC). However, the acquisition of chemoresistance has become a major cause of chemotherapy failure. The long noncoding RNA DANCR is demonstrated to serve as an oncogene in various human cancers, including PC. However, the potential role of DANCR in docetaxel (DTX) resistance of PC and its underlying mechanism remains unclear.Methods: The abundance of DANCR, miR-34a-5p, and JAG1 mRNA was examined by quantitative reverse transcription PCR. The Cell Counting Kit-8 (CCK8) was used to determine the 50% inhibitory concentration value. Cell viability was evaluated by CCK8 and colony-formation assays. Transwells were utilized to analyze cell migration and invasion ability. The protein levels of LRP, P-gp, MRP1, and JAG1 were measured by Western blot assay. The target relationship between DANCR and miR-34a-5p, as well as miR-34a-5p and JAG1, was demonstrated by dual-luciferase, RNA immunoprecipitation, and RNA pull-down analysis. Tumor xenograft was undertaken to confirm the effect of DANCR on DTX resistance in PC.Results: DANCR and JAG1 were significantly upregulated, but miR-34a-5p was downregulated in DTX-resistant PC. Silencing of DANCR improved the DTX efficacy in DTX-resistant PC cells. DANCR served as a competing endogenous RNA of miR-34a-5p, leading to the derepression of miR-34a-5p target JAG1, which eventually triggered the resistance to DTX in DTX-tolerated PC.Conclusion: The DANCR/miR-34a-5p axis enhanced DTX resistance of PC via targeting JAG1, providing a novel insight to improve chemotherapy for PC.Keywords: DANCR, miR-34a-5p, JAG1, docetaxel resistance, prostate cancer

Objective: To evaluate the efficacy of multiparametric magnetic resonance imaging (mp-MRI) using Prostate Imaging Reporting and Data System version 2.0 (PI-RADSv2) definitions in detecting organ-confined prostate cancer. Methods: All patients who underwent radical prostatectomy between January 1, 2014 and December 30, 2014 were identified. All underwent mp-MRI within 180 days before surgery. Those with prior pelvic irradiation or androgen deprivation therapy were excluded. Fully embedded, whole-mount histopathology was centrally reviewed and correlated with imaging for tumour location, Gleason score (GS) and stage. Results: There were 39 patients included, of which 35 (90%) had mp-MRI done post-biopsy. A total of 93 cancer foci were identified on whole-mount pathology, of which mp-MRI detected 63 (68%). Of those detected by mp-MRI, 14 were PI-RADS 3 (n = 6 for GS 6, n = 8 for GS 7, no GS ≥ 8) and 49 were PI-RADS 4–5 (n = 7 for GS 6, n = 33 for GS 7, and n = 9 for GS ≥ 8). There were 30 (32%) cancer foci missed by mp-MRI (n = 15 for GS 6, n = 13 for GS 7 and n = 2 for GS ≥ 8). A lesion classified as PI-RADS 4–5 predicted a higher grade cancer on pathology as compared to PI-RADS 3 (for GS 7 lesions, odds ratio [OR] = 3.53, 95% CI: 0.93–13.45, p = 0.064). The mp-MRI size detection limit was 20 mm2 and 100 mm2 for 50% and 75% probability of cancer, respectively. In associating with radiological and pathologic stage, the weighted Kappa value was 0.69 (p

Objective: To evaluate the diagnostic performance of apparent diffusion coefficient (ADC) for local staging of prostate cancer. Methods: Databases of Web of Science, MEDLINE (Ovid and PubMed), Cochrane Library, EMBASE, and Google Scholar were searched up to May 31, 2018, with language restricted to English. All studies concerning multiparametric magnet resonance imaging (mpMRI) with ADC for detection of extracapsular extension (ECE, T3a) and/or extraprostatic extension (EPE, overall stage of T3) were identified by two reviewers independently, and quality of included studies was evaluated using Quality Assessment of Diagnostic Accuracy Studies-2 tool. True positive, false positive, false negative and true negative of each study were extracted to reconstruct the 2×2 tables for evaluating diagnostic accuracy. Summary estimates of sensitivity, specificity, and corresponding 95% CIs were calculated with bivariate model and hierarchical summary receiver operating characteristic model, then presented in forest plots. Multiple subgroup analyses and meta-regression were performed, and publication bias was evaluated with Deeks funnel. Results: A total of 18 studies were included, with 6 involved ECE and 12 for EPE. Pooled sensitivity was 80.5% (95% CI 76.5–83.9%) with specificity of 69.1% (95% CI 62.3–75.2%). Multiple subgroup analyses showed that if ADC and length of capsular contact are regarded as independent predictors, pooled sensitivity was 85% (95% CI 77–90%) and 81.1% (95% CI 76.0–85.3%), with specificity of 70.8% (95% CI 56.3–82.0%) and 66.6% (95% CI 57.6–74.5%), respectively. Meta-regression demonstrated that there was no substantially significant difference in types of coil, magnet field strength (1.5T versus 3.0T), and analysis method (per-lesion versus per-patient). Conclusion: By introducing ADC to MRI, we could obtain favorable sensitivity for diagnostic performance of EPE, but with a little decreased specificity.

Koudi Bai,1 Yuan Sun,2 Wei Li,3 Lanlan Zhang41Department of Radiology, Yancheng First Peoples’ Hospital, Yancheng City, People’s Republic of China; 2Department of Orthopedics, No.97 Hospital of People’s Liberation Army of China, Xuzhou City, People’s Republic of China; 3Department of Medical Imaging, Jiangsu Vocational College of Medicine, Yancheng City, People’s Republic of China; 4Department of Pediatrics, Yancheng Maternal and Child Health Hospital, Yancheng City, People’s Republic of ChinaObjective: To evaluate the diagnostic performance of apparent diffusion coefficient (ADC) for local staging of prostate cancer.Methods: Databases of Web of Science, MEDLINE (Ovid and PubMed), Cochrane Library, EMBASE, and Google Scholar were searched up to May 31, 2018, with language restricted to English. All studies concerning multiparametric magnet resonance imaging (mpMRI) with ADC for detection of extracapsular extension (ECE, T3a) and/or extraprostatic extension (EPE, overall stage of T3) were identified by two reviewers independently, and quality of included studies was evaluated using Quality Assessment of Diagnostic Accuracy Studies-2 tool. True positive, false positive, false negative and true negative of each study were extracted to reconstruct the 2×2 tables for evaluating diagnostic accuracy. Summary estimates of sensitivity, specificity, and corresponding 95% CIs were calculated with bivariate model and hierarchical summary receiver operating characteristic model, then presented in forest plots. Multiple subgroup analyses and meta-regression were performed, and publication bias was evaluated with Deeks funnel.Results: A total of 18 studies were included, with 6 involved ECE and 12 for EPE. Pooled sensitivity was 80.5% (95% CI 76.5–83.9%) with specificity of 69.1% (95% CI 62.3–75.2%). Multiple subgroup analyses showed that if ADC and length of capsular contact are regarded as independent predictors, pooled sensitivity was 85% (95% CI 77–90%) and 81.1% (95% CI 76.0–85.3%), with specificity of 70.8% (95% CI 56.3–82.0%) and 66.6% (95% CI 57.6–74.5%), respectively. Meta-regression demonstrated that there was no substantially significant difference in types of coil, magnet field strength (1.5T versus 3.0T), and analysis method (per-lesion versus per-patient).Conclusion: By introducing ADC to MRI, we could obtain favorable sensitivity for diagnostic performance of EPE, but with a little decreased specificity.Keywords: apparent diffusion coefficient, prostatic cancer, magnetic resonance imaging, extraprostatic extension, length of capsular contact

Background Tumor cells exhibit enhanced metabolism of nutrients to satisfy the demand of sustained proliferation in vivo. Seminal reports have presented evidence that tryptophan (Trp) metabolic reprogramming induced by aberrant indoleamine 2,3-dioxygenases could promote tumor development in several cancer types. However, the underlying mechanism of Trp metabolism associated tumor progression is not fully understood. Materials and methods Prostatic cell lines LNCaP and VCaP were purchased from the Cell Bank of the Chinese Academy of Sciences (China). Human prostatic tumor tissue samples were obtained from the Tongji Hospital. Female NOD-SCID mice (6 ~ 8 weeks) were purchased from Huafukang Co. (China) and raised in SPF room. Commercial kits and instruments were used for cell apoptosis analysis, real-time PCR, western blotting, ELISA analysis and other experiments. Result Comparing the tumor tissues from prostatic cancer patients, we found elevated expression of tryptophan 2, 3-dioxygenase 2 (TDO2), and elevated Trp metabolism in chemo-resistant tumor tissues. In vitro, overexpression of TDO2 significantly promoted the Trp metabolism in prostatic cancer cell lines LNCaP and VCap, resulting in the multidrug resistance development. Mechanistically, we demonstrated that Trp metabolite kynurenine (Kyn) promoted the upregulation and nuclear translocation of transcription factor aryl hydrocarbon receptor (AhR). Subsequently, AhR collaborated with NF-κB to facilitate the activation of c-Myc. In turn, c-Myc promoted the up-regulation of ATP-binding cassette (ABC) transporters and Trp transporters, thereby contributing to chemoresistance and strengthened Trp metabolism in prostatic cancer. Interrupt of Trp/TDO2/Kyn/AhR/c-Myc loop with c-Myc inhibitor Mycro-3 efficiently suppressed the chemoresistance and improved the outcome of chemotherapy, which described a new strategy in clinical prostatic cancer treatment. Conclusion Our study demonstrates that elevated TOD2 expression promoted Trp metabolism and metabolite Kyn production, thus resulting in the activation of AhR/c-Myc/ABC-SLC transporters signaling pathway. Interrupt of Trp metabolism/c-Myc loop efficiently suppressed the drugs resistance induced by TDO2, which represented potential target to improve the outcome in drug-resistant prostatic cancer treatment.

U ovom istraživanju proučavala se povezanost trijodtironina (T3), slobodne frakcije tiroksina (fT4) te tireotropina (TSH) s diferenciranošću karcinoma prostate. Postavljena je hipoteza da su koncentracije T3 i fT4 veće, dok je koncentracija TSH manja u bolesnika sa slabije diferenciranim karcinomom. Ciljevi istraživanja bili su ustanoviti povezanost funkcije štitnjače i karcinoma prostate te otkrivanje mogućeg biomarkera slabije diferenciranosti, odnosno agresivnijeg oblika karcinoma. Dodatni ciljevi bili su utvrditi razliku u postotku tumora u tkivu prostate i patološkom T stadiju bolesti po radikalnoj prostatektomiji između skupina ispitanika s bolje i slabije diferenciranim karcinomom prostate. Ukupan broj ispitanika bio je 140, od kojih je 10 isključeno iz istraživanja zbog novootkrivene bolesti štitnjače, a pet zbog odustanka urologa i/ili ispitanika od zahvata. Ispitanici su podijeljeni u dvije skupine prema postoperativnom patohistološkom nalazu. Prvu skupinu (N=62) su činili bolesnici s karcinomom prostate Grade grupa 1 i 2 (bolje diferencirani karcinomi) a drugu skupinu (N=63) bolesnici s karcinomom prostate Grade grupa 3, 4 i 5 (slabije diferencirani karcinomi). Ustanovljeno je da je serumska koncentracija T3 statistički značajno veća u skupini ispitanika sa slabije diferenciranim karcinomom prostate (P=0,047). Ne postoji statistički značajna razlika u serumskim koncentracijama fT4 i TSH među dvjema skupinama ispitanika (P=0,68, P=0,801). Postotak tumora u tkivu prostate statistički je značajno veći u skupini ispitanika sa slabije diferenciranim karcinomom prostate (P, In this research, we studied the correlation of total triiodothyronine (T3), free fraction of the thyroxine (fT4), and thyrotropin (TSH) with prostate cancer (PCa) differentiation. We set the hypothesis that concentrations of T3 and fT4 are higher, while the TSH concentration is lower in patients with poorly differentiated PCa. Our goals were to determine the relationship between thyroid function and PCa, to detect the possible biomarkers of poorly differentiated PCa, and to determine the difference in the tumor percentage involvement (TPI) and pathological T (pT) stage of disease between the subjects with well-differentiated and poorly differentiated PCa. The total number of subjects was 140. Ten subjects were excluded from the study due to newly detected thyroid disease and 5 because of the withdrawal from the surgery. Subjects were divided into two groups according to postoperative histopathology. In the first group (N=62) there were patients with PCa Grade Groups 1 and 2 (well-differentiated cancer), while the second (N=63) group included patients with PCa Grade Groups 3, 4 and 5 (poorly differentiated cancer). Serum T3 concentration was significantly higher in poorly differentiated cancer group (P=0,047). There was no significant difference in concentrations of fT4 and TSH between the two groups (P=0,680, P=0,801, respectively). The TPI was significantly higher in poorly differentiated cancer group (P

We assessd the long-term outcomes from a large prospective cohort of men diagnosed with prostate cancer managed with active surveillance and determined the clinical prognostic factors that may predict the risk of metastases.We retrospectively reviewed data of men enrolled on active surveillance at our institution between 1990 and 2018 with low or intermediate risk disease (stage cT1-2, prostate specific antigen less than 20 ng/ml, and biopsy Grade Group [GG]1-2). Patients were classified into 3 groups by diagnostic GG and prostate specific antigen density. Primary outcome was metastatic prostate cancer detected on imaging or at prostatectomy. In addition, upgrade at surveillance biopsy, active treatment, and overall and prostate cancer specific survival outcomes were assessed. Cox proportional hazards regression models were used.A total of 1,450 men met the inclusion criteria. Median followup was 77 months (IQR 49-114). The 7-year metastasis-free survival rate was 99%. Metastases developed in 15 men at a median of 62 months (IQR 29-104), of which 69% were confined to lymph nodes. Men with GG2 had a lower metastasis-free survival rate compared to those with GG1 disease. GG2, prostate specific antigen velocity and PI-RADS® 4-5 lesions on multiparametric magnetic resonance imaging were associated with a higher risk of metastases. The 7-year prostate cancer specific survival was greater than 99%.Active surveillance seems to preserve favorable long-term prognosis, as metastases and prostate cancer specific death are rare. However, the higher risk of metastases associated with higher Gleason grade, prostate specific antigen velocity, and characteristics on multiparametric magnetic resonance imaging should be considered when selecting and counseling patients for active surveillance.

Background: 68Ga-PSMA-PET/CT (positron emission tomography/computed tomography) is a promising method for prostate cancer (PC) detection. However, the ability of 68Ga-PSMA-PET/CT to detect malignant bone lesions, and whether this method is superior to the existing bone imaging methods are still lack of systematic analysis. Purpose: To evaluate the value of 68Ga-PSMA-PET/CT and bone scan in clinical diagnosis of prostatic cancer from the perspective of evidence-based medicine. Methods: PubMed, The Cochrane Library, EMBASE, Springer Link, Sinomed, CNKI, Wanfang database, and CQVIP database were searched to find the satisfactory studies that needed systematic review of trials and compared the value of 68Ga-PSMA-PET/CT and bone scan. All studies published from inception to March 31, 2020. According to the inclusion and exclusion criteria, 2 reviewers independently evaluated and extracted the literature. Review Manager 5.3 was applied to evaluate the included literature quality. The heterogeneity of the included literature was tested by Meta Disc 1.4, and the effect model was selected according to the heterogeneity test results, and the sensitivity (SEN), specificity (SPE), PLR, NLR and diagnostic odds ratio (DOR) were analyzed. After testing the heterogeneity results of literature by using the 95% confidence interval and the forest map. Results: A total of 4 studies were eligible for inclusion in the meta-analysis, which included 318 patients, 120 cases with bone metastasis and 198 cases without bone metastasis. The results of summary evaluation for 68Ga-PSMA-PET/CT and bone scan in diagnosis of prostatic cancer as follow respectively: The SEN were 0.97 and 0.86; the SPE were 1.00 and 0.87; the DOR were 1468.33 and 36.23; PLR were 88.45 and 6.67; NLR were 0.05 and 0.19; and the area under curve (AUC) and 95% CI were 0.9973 (1.0000–0.9927) and 0.8838 (0.9584–0.8092). Conclusion: By comparing the diagnostic results of 68Ga-PSMA-PET/CT and bone scan imaging diagnosis methods, the 68Ga-PSMA-PET/CT has a higher SEN and SPE than bone scan, and it has a higher diagnostic efficiency for prostate cancer bone metastasis, which is worthy of clinical application.

Introduction: The aim of this study was to correlate cribriform pattern (CP) with other parameters in a large prospective series of Gleason score ≥7/ISUP grade ≥2 prostate cancer (PC) cases undergoing radical prostatectomy (RP). Methods: This is a prospective single-center study on 210 consecutive patients. Gleason pattern 4 and individual tumor growth patterns determination were performed either in biopsy or in surgical specimens for all patients. Results: At multiparametric magnetic resonance, a higher percentage of PI-RADS 5 was associated to CP (53.3% vs 17.7%, P = .038). CP was significantly and inversely (r = −0.261; P = .001) correlated with perineural invasion (PNI) but not with other pathological parameters. Kaplan-Meier analysis showed that mean biochemical (Bp) and radiological (Rp) progression-free survival were similar (Bp = χ2 0.906; P = .341; Rp = χ2 1.880; P = .170) independently to CP. In PNI positive cases, Bp-free survival was higher (χ2 = 3.617; P = .057) in cases without CP. Conclusions: In a homogeneous population excluding ISUP 1 cases, CP showed limited prognostic value. We first described an association with PNI and a prognostic value influenced by PNI status.

Background Studies have shown diverse results regarding the association between H. pylori (HP) infection and the risk of malignancy. There is accumulating evidence relating HP infection to urological diseases. We investigated whether there was an association between HP-infected peptic ulcers and the subsequent risk of prostate cancer. Methods We collected HP-infected male patients from 1998 to 2008 from the Longitudinal Health Insurance Database (LHID). HP-infected patients were identified as those who had a diagnosis of peptic ulcers upon admission and received HP eradication therapy within 1 year after diagnosis. The date of HP infection diagnosis upon admission was defined as the index date. Patients aged Results A total of 2620 HP infection treatment patients and 10,480 matched comparisons were selected. There were 36 patients in the HP-infected treatment cohort and 117 patients in the comparison cohort with documented prostate cancer development (1.52 and 1.21 per 1000 person-years, respectively). Compared to the comparison cohort, the HP infection cohort had a 1.26-fold increased prostate cancer risk in the Cox models after adjusting for matched-pairs (95% CI = 0.87–1.34). There were no significant differences in subsequent prostate cancer development between HP-infected treatment patients and the comparison cohort. Conclusion Our findings showed no significant association between HP-infected peptic ulcers and the subsequent risk of prostate cancer. Further studies are warranted to investigate whether this observation is attributable to an HP eradication policy.

Trabalho Final do Mestrado Integrado em Medicina apresentado à Faculdade de Medicina Introdução: Os exames imagiológicos apresentam uma baixa sensibilidade para deteção da localização de recidivas bioquímicas do carcinoma da próstata, quando os doentes apresentam antigénio específico da próstata (PSA) inferior a 1 ng/mL. Por outro lado, sabemos que quanto mais cedo for tratado o doente com recidiva bioquímica, melhor é seu o prognóstico.Objetivo: Pretende-se compreender os avanços dos últimos dois anos acerca da taxa de deteção de doença dos exames de imagem no contexto de recidiva bioquímica do carcinoma da próstata com PSA inferior a 1 ng/mL.Métodos: Realizada pesquisa na base de dados PUBMED, com seleção dos artigos que abordavam a temática em estudo. Foram avaliadas as taxas de deteção de doença para diferentes valores de PSA e diferentes exames constantes dessas publicações, assim como variáveis de caraterização demográfica e terapêutica.Resultados: Foram identificadas 19 publicações, que envolveram maioritariamente técnicas de tomografia por emissão de positrões associada a tomografia computorizada (PET/CT) ou ressonância magnética (PET/MRI). A PET/CT com 18F-PSMA e 68Ga-PSMA, assim como a PET/MRI com 68Ga-PSMA foram as técnicas com melhores taxas de deteção de doença nos doentes com recidiva bioquímica com PSA inferior a 1 ng/mL, demonstrando capacidade para guiar a terapêutica de resgate nestes doentes. Também o radiotraçador 64CuCl2 mostrou potencial papel na deteção de recidiva local. A utilização de tomografia computorizada isoladamente e de cintigrafia óssea apresentaram piores resultados para deteção de lesões. Na análise dos estudos incluídos foi ainda possível verificar que é possível a existência de metastização à distância com PSA inferior a 1 ng/mL.Discussão/Conclusão: A PET/CT com 18F-PSMA, a PET/CT com 68Ga-PSMA e a PET/MRI com 68Ga-PSMA apresentam-se como a que melhores taxas de deteção obtiveram para doentes com recidiva bioquímica e PSA inferior a 1 ng/mL, apesar de carecerem de maior validação em estudos prospetivos e comparativos. A validação destas técnicas poderá permitir a sua utilização futura em contexto clínico. Introduction: In patients with biochemical recurrence (BCR) of prostatic cancer and prostate-specific-antigen (PSA) values lower than 1ng/mL imaging has a low sensibility for detection of suspicious lesions. On the other hand, its known that the prognosis of these patients is better when the treatment starts earlier.Aim: Assess the breakthroughs of the last two years on imaging that allow better detection rates in patients with BCR and PSA values lower than 1ng/mL.Methods: Through a search on PUBMED database, several articles were selected by its relevance for the topic. We evaluated the detection rates of disease for different PSA values and different techniques, as well as variables for demographic characterization and treatment.Results: 19 studies were identified. The majority of imaging techniques were based on positron emission tomography associated with computed tomography (PET/CT) or magnetic resonance (PET/MRI). 18F-PSMA and 68Ga-PSMA PET/CT, as well as 68Ga-PSMA PET/MRI, were the techniques with better detection rates for disease in BCR patients with PSA levels lower than 1ng/mL, showing their ability to guide salvage therapy in these patients. Also, the radiotracer 64CuCl2 showed great potential in detecting local recurrence. The use of CT and bone scan alone presented the worse results for lesion detection. In this analysis we verified that the presence of distant metastasis was possible for patients with BCR and PSA values lower than 1ng/mL.Discussion/Conclusions: 18F-PSMA and 68Ga-PSMA PET/CT, as well as 68Ga-PSMA PET/MRI, were the procedures with better detection rate in BCR patients with PSA levels lower than 1ng/mL, although there is a lack of validation in prospective and comparative studies. Validation of this techniques is therefore needed and may allow their future inclusion in clinical practice.

Background: Physical exercises play a supportive role in the treatment of prostate cancer by modulating angiogenesis in tumor tissue. The hypoxia-inducible factor-1 (HIF-1) modulates angiogenesis and tumor growth. Prostate specific antigen (PSA) is the most widely available tumor marker for the rapid diagnosis of prostate cancer. The purpose of this study was to investigate the effect of physical exercises in the expression of HIF-1 gene levels in plasma, and the PSA level in the sera of men with prostate cancer. Methods: In this clinical trial study, 20 men with prostate cancer were randomly selected from the pathology department of Baqiyatallah al-Azam subspecialty hospital in Tehran, Iran, during the middle 6 months of 2016. Patients were divided into two groups of experimental [age: 63 ± 10 years, weight: 78 ± 11 kg, body mass index (BMI): 28.5 ± 2.4 kg/m2] and control [age = 62 ± 4 years, weight: 79 ± 11 kg, BMI: 27.9 ± 2.9 kg/m2). The experimental group performed 8 weeks of 60 minutes per session training including 3 sessions per week. The workouts were the combination of exercises with resistance and endurance training per session as 60-75 percent of one repetition maximum, and 60-75 percent of maximum heart rate. The control group did not receive any intervention. Blood samples were tested for PSA and HIF-1 using enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (PCR) methods, respectively, and the data were analyzed using dependent and independent t test. Findings: Combined exercise significantly decreased the plasma level (P = 0.007) and gene expression (P = 0.005) of HIF-1, as well as serum PSA level (P = 0.005) in the experimental group compared with control group. Conclusion: Considering the importance of PSA in the diagnosis of prostate cancer, and the role of HIF-1 in tumor angiogenesis, the combined exercise can be effective in reducing the progression of prostate cancer by modifying HIF-1 and PSA.

Song Gao,1 Zhiying Zhao,2 Rong Wu,1 Lina Wu,1 Xin Tian,1 Zhenyong Zhang1 1The Second Department of Clinical Oncology, Shengjing Hospital, China Medical University, Shenyang 110022, China; 2Department of computer science and engineering, Northeastern University, Shenyang 110004, China Introduction: Prostate cancer (PCa) is one of the most common malignancies in men. However, a lack of understanding of the mechanism underlying PCa metastasis has strongly limited the effectiveness of therapy for this disease. Thus, investigating the mechanism of PCa may help improve the prognosis of PCa patients. The goal of this study was to investigate the role of microRNA-194 (miR-194) in PCa. Materials and methods: The expression of miR-194 and cadherin 2 (CDH2) at the transcriptional level was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The MTT assay cell apoptosis assay and Western blotting were used to determine the role of miR-194 and CDH2 in the PC3 human PCa cell line. The dual luciferase reporter assay system was performed to clarify the relationship between miR-194 and CDH2. qRT-PCR results showed that miR-194 was downregulated and CDH2 was upregulated in PC3 cells. Results: Transfection with miR-194 mimics decreased cell viability and increased the rate of apoptosis compared with the control group of PC3 cells. Bioinformatics and the luciferase reporter assay indicated that CDH2 was a target of miR-194, and Western blot analysis suggested that CDH2 was negatively regulated by miR-194. Further studies revealed that the downregulation of CDH2 suppressed cell viability and promoted the apoptosis of PC3 cells and that miR-194 directly targeted CDH2 in PC3 cells. Finally, the in vivo experiments showed that miR-194 mimics suppressed tumor growth and induced apoptosis in a greater proportion of cells by decreasing the expression of CDH2 compared with the control group. Conclusion: The results of this study showed that miR-194 targeted CDH2 to regulate PCa cell survival invitro and suppress tumor growth invivo. These findings suggest that miR-194 may be a useful therapeutic target in PCa. Keywords: prostatic cancer, microRNA-194, CDH2, cell viability, apoptosis

Song Gao,1 Zhiying Zhao,2 Rong Wu,1 Lina Wu,1 Xin Tian,1 Zhenyong Zhang1 1The Second Department of Clinical Oncology, Shengjing Hospital, China Medical University, Shenyang 110022, China; 2Department of computer science and engineering, Northeastern University, Shenyang 110004, China Introduction: Prostate cancer (PCa) is one of the most common malignancies in men. However, a lack of understanding of the mechanism underlying PCa metastasis has strongly limited the effectiveness of therapy for this disease. Thus, investigating the mechanism of PCa may help improve the prognosis of PCa patients. The goal of this study was to investigate the role of microRNA-194 (miR-194) in PCa. Materials and methods: The expression of miR-194 and cadherin 2 (CDH2) at the transcriptional level was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The MTT assay cell apoptosis assay and Western blotting were used to determine the role of miR-194 and CDH2 in the PC3 human PCa cell line. The dual luciferase reporter assay system was performed to clarify the relationship between miR-194 and CDH2. qRT-PCR results showed that miR-194 was downregulated and CDH2 was upregulated in PC3 cells. Results: Transfection with miR-194 mimics decreased cell viability and increased the rate of apoptosis compared with the control group of PC3 cells. Bioinformatics and the luciferase reporter assay indicated that CDH2 was a target of miR-194, and Western blot analysis suggested that CDH2 was negatively regulated by miR-194. Further studies revealed that the downregulation of CDH2 suppressed cell viability and promoted the apoptosis of PC3 cells and that miR-194 directly targeted CDH2 in PC3 cells. Finally, the in vivo experiments showed that miR-194 mimics suppressed tumor growth and induced apoptosis in a greater proportion of cells by decreasing the expression of CDH2 compared with the control group. Conclusion: The results of this study showed that miR-194 targeted CDH2 to regulate PCa cell survival invitro and suppress tumor growth invivo. These findings suggest that miR-194 may be a useful therapeutic target in PCa. Keywords: prostatic cancer, microRNA-194, CDH2, cell viability, apoptosis

Highlights • ADCratio is a reliable and reproducible tool in quantification of diffusion restriction for clinically significant PCa foci. • Comparing an experienced and a new MRI reader, Inter-reader reliability in the calculation of ADCratio was excellent. • ADCratio has potential to replace the current practice of visual analysis of ADCtumour reduction, and provide an objective tool., Introduction The purpose was to investigate the usefulness of ADCratio on Diffusion MRI to discriminate between benign and malignant lesions of Prostate. Methods Images of patients who underwent in-gantry MRI guided prostate lesion biopsy were retrospectively analyzed. Prostate Cancers with 20% or more Gleason score (GS) pattern 3 + 3 = 6 in each core or any volume of higher Gleason score pattern were included. ADCratio was calculated by two reviewers for each lesion. The ADCratio was calculated for each lesion by dividing the lowest ADC value in a lesion and highest ADC value in normal prostate in peripheral zone (PZ). ADCratio values were compared with the biopsy result. Data was analysed using independent samples T-test, Spearman correlation, intra-class correlation coefficient (ICC) and Receiver operating characteristic (ROC) curve. Results 45 lesions in 33 patients were analyzed. 12 lesions were in transitional zone (TZ) and 33 in perpheral zone PZ. All lesions demonstrated an ADCratio of 0.45 or lower. GS demonstrated a negative correlation with both the ADC value and ADCratio. However, ADCratio (p

Seminal vesicles are paired secretory glands located posterior to the bladder in men that produce seminal fluid to maintain sperm. Seminal vesicle reflux into the prostatic ducts may be associated with prostatitis in older patients or may represent a very rare complication of transurethral prostate resection in patients with prostatic cancer. This condition is frequently accidentally diagnosed on excretory urography and/or retrograde urethrogram. Clinical presentation includes pain, fever, recurrent epididymitis-prostatitis, and post void dribbling.

Made available in DSpace on 2018-12-11T17:16:40Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-12-06 Background: c-KIT expression has been related to bone metastasis in human prostate cancer, but whether c-KIT expression can be similarly classified in canine prostatic tissue is unknown. This study assessed c-KIT and Ki67 expression in canine prostate cancer (PC). c-KIT gene and protein expression and Ki67 expression were evaluated in forty-four canine prostatic tissues by immunohistochemistry, RT-qPCR and western blot. Additionally, we have investigated c-KIT protein expression by immunoblotting in two primary canine prostate cancer cell lines. Results: Eleven normal prostates, 12 proliferative inflammatory atrophy (PIA) prostates, 18 PC, 3 metastatic lesions and two prostate cancer cell cultures (PC1 and PC2) were analysed. The prostatic tissue exhibited varying degrees of membranous, cytoplasmic or membranous/cytoplasmic c-KIT staining. Four normal prostates, 4 PIA and 5 prostatic carcinomas showed positive c-KIT expression. No c-KIT immunoexpression was observed in metastases. Canine prostate cancer and PIA samples contained a higher number of Ki67-positive cells compared to normal samples. The median relative quantification (RQ) for c-KIT expression in normal, PIA and prostate cancer and metastatic samples were 0.6 (0.1-2.5), 0.7 (0.09-2.1), 0.7 (0.09-5.1) and 0.1 (0.07-0.6), respectively. A positive correlation between the number of Ki67-positive cells and c-KIT transcript levels was observed in prostate cancer samples. In the cell line, PC1 was negative for c-KIT protein expression, while PC2 was weakly positive. Conclusion: The present study identified a strong correlation between c-KIT expression and proliferative index, suggesting that c-KIT may influence cell proliferation. Therefore, c-KIT heterogeneous protein expression among the samples (five positive and thirteen negative prostate cancer samples) indicates a personalized approach for canine prostate cancer. Univ. Estadual Paulista - UNESP Department of Veterinary Clinic School of Veterinary Medicine and Animal Science, Rua Prof. Dr Walter Correa, s/n, Unesp, Mail box- 560 The University of Queensland Gatton Campus School of Veterinary Science Univ. Estadual Paulista - UNESP Department of Veterinary Clinic School of Veterinary Medicine and Animal Science, Rua Prof. Dr Walter Correa, s/n, Unesp, Mail box- 560

Previous studies have suggested that changes in sex hormone receptor expression may be associated with the initiation and progression of prostate cancer (PCa). Therefore, the present study aimed to investigate the association and possible pathways between two sex hormone receptors and PCa by measuring the expression levels of the androgen receptor (AR) and the estrogen receptor subtypes alpha (ERα) and beta (ERβ) in prostatic cancer PC-3 cell lines. The pcDNA3.1-hERβ plasmid was transfected into PC-3 cell lines. The expression levels of AR, ERα and ERβ were detected at the mRNA level by reverse transcription-polymerase chain reaction (RT-PCR) and quantitative PCR (qPCR). The results demonstrated that the expression levels of AR, ERβ and ERα were downregulated to different degrees: ERβ test group vs. PC-3 cell group (P=0.000; 95% confidence interval: 0.9803-1.6331). ERβ and AR expression was detected continuously in the PC-3 cells, but the expression of ERα was not. AR expression levels exhibited an upward trend whilst the expression of ERβ demonstrated a marked downward trend. There is a correlation between the expression levels of ERβ and the incidence of PCa, and ERβ may inhibit the growth of PC-3 cell lines by regulating the expression levels of AR. ERβ may provide a novel target for PCa therapies.

Part 1: Physiology of the neonate and indicators for its well-being Veterinary neonatology is a rather young field of research. Important differences between the physiology of the neonate compared to the adult have to be taken into consideration in its clinical evaluation. The first topic of the present PhD thesis describes the current knowledge of neonatal physiology and different methods for evaluation of the newborns’ viability. Methods such as the Apgar scoring system and blood gas analysis are successfully used in veterinary medicine. Birth weight and neonatal growth have been evaluated as parameters to estimate a puppy’s risk for neonatal mortality. Although such a correlation has been proven, the populations used for this prove are composed of a high number of different breeds. To evaluate the usefulness of such an approach a comparison with a breed-specific evaluation has been made (Appendix 1). This comparison has shown important differences and the importance of breed-specific investigations of birth weight and growth of the neonate. Part 2: Current knowledge on beneficial and noxious effects of gonadectomy Elective gonadectomy is an important part of the daily veterinary practice. Although beneficial effects of gonadectomy on the dog have been proven, over the last two decades the number of studies reporting an increased risk for neoplastic and other disorders in the castrated animal increased. These reports, although predominantly retrospective, statistical investigations have caused concern and doubt within practitioners and owners. Easy access to information granted by the internet increased this doubt in the group of owners. Results of these investigations have been cited and described in scientific papers, as well as on non-scientific web-sites. In both, although most frequently in the latter, results of studies have been mentioned without describing or considering the study design, the population and the context in which the results have been presented. The lack of this information lead to premature conclusions which have an important impact on many stakeholders. It is therefore that the second part of the present PhD thesis presents a literature review of beneficial and noxious effects of gonadectomy. Prostatic neoplasia in the dog was used as an example of problematic differences in study design, population composition and interpretation of the results (Appendix 2). This part further presents the motivation for the experimental design of Part 3. 5 Part 3 and 4: Immunohistochemical evaluation of steroid hormone receptor expression in extra-genital tissue in the bitch motivated by reports on negative long-term health effects of gonadectomy Hormone receptor expression has proven to be of importance not only in the research of a pathological pathway, but gave also indications on possible treatment options (e.g. human breast cancer). In veterinary medicine the research on hormone receptor expression is not yet as commonly used as in human medicine. The presence of hormone receptors in a tissue may be considered the basis for a direct effect of a hormone on a tissue. Nevertheless, their absence does not exclude the possibility that a certain hormone may not have an impact following a secondary pathway. Reports on effects of gonadectomy on extra-genital tissue gave reason to investigate the expression of Estrogen and Progesterone receptors. Immunohistochemistry is a viable method to evaluate hormone receptor expression. Samples of 14 bitches between the age of 2.1 to 16.7 years were taken within a maximum of 4 hours postmortem. Ten bitches resulted gonadectomized at the moment of death. Collected tissues include the right cardiac ventricle, the splenic hilum and the popliteal and retromandibular lymph nodes. Samples were formalin- fixed, paraffin-embedded and stained with hematoxylin and eosin for histological evaluation. Expression of progesterone receptor (PR) and estrogen receptor alpha (ERa) was evaluated with anti-human antibodies: monoclonal rabbit PR (Clone 1E2) and monoclonal mouse ERa (Clone EP1) using an automatic immunostainer (Ventana BenchMark GX, Roche Diagnostic). Reactivity with canine tissue was confirmed using dog uterus and ovaries showing strong positive nuclear staining for both ERa and PR. Tissues of 11 dogs were considered physiologic or mildly compromised, whereas 3 dogs presented neoplasia in heart (n=2) and spleen (n=1). IHC showed negative immunostaining within investigated tissues for neither ERa not PR. Prior to drawing final conclusions, additional tests have to be performed to confirm the absence of ERa and PR expression. Despite the preliminary results in our study, we consider further research on hormone receptor expression necessary to understand the possible impact of gonadectomy on extra-genital tissue in the dog.

Background Men normally have shorter heart rate-corrected QT interval (QTc) than women, at least in part due to accelerating effects of testosterone on ventricular repolarization. Accumulating data suggest that androgen-deprivation therapy (ADT) used for the treatment of prostatic cancer, may increase Torsades de Pointes (TdP) risk by prolonging QTc. However, the evidence for such an association is currently limited to few case reports, in most cases deriving from the analysis of uncontrolled sources such as pharmacovigilance databases. Objective To better determine the clinical impact of ADT on TdP development, we examined the prevalence of this therapy in a consecutive cohort of 66 TdP patients, prospectively collected over a ~10 years period. Methods and results We found and described four patients who were under ADT for prostatic cancer when TdP occurred, and in two cases degenerated to cardiac arrest. Notably, in this unselected population, ADTs unexpectedly represented the second most frequently administered QT-prolonging medication in males (4/24, 17%), after amiodarone. Moreover, in the ADT patients, a blood withdrawal was performed within 24 h from TdP/marked QTc prolongation occurrence and circulating concentration of androgens and gonadothropins were measured. As expected, all cases showed markedly reduced testosterone levels (total, free, and available). Conclusion We provide evidence that a significant proportion of patients developing TdP were under treatment with ADT for prostatic cancer, thus confirming the clinical relevance of previous pharmacovigilance signals. An accurate assessment of the arrhythmic risk profile should be included in the standard of care of prostatic cancer patients before starting ADT.

African American men have the highest prostate cancer-related mortality nationally. In response to this disparity, targeted interventions are emerging to enhance African American men’s prostate cancer (PrCA) knowledge to ensure they are equipped to make informed decisions about PrCA screening with health-care providers. African American men’s PrCA knowledge has been measured inconsistently over time with limited psychometric evidence. The factor structure of this construct in African American men is relatively unknown. This study describes the development and psychometric evaluation of an 18-item Prostate Cancer Knowledge Scale among 352 African American men. Exploratory factor analysis (EFA) was conducted using weighted least square mean and variance estimation with Geomin rotation. EFA yielded three factors: PrCA Anatomy and Screening (6 items), Risk Factors (5 items), Warning Signs (7 items) with good internal consistency reliability at KR-20 = .80 for the total scale and .64, .66, and .75, respectively, for each subscale. Factor loadings ranged from .31 to .86. The standardized root mean square residual (0.08) indicated that the factor structure explained most of the correlations. The three-factor, 18-item Prostate Cancer Knowledge Scale demonstrates that PrCA knowledge is a multidimensional construct and has utility for reliably measuring PrCA knowledge among African American men. Future research is required to confirm this factor structure among socio-demographically diverse African Americans.

Background The goal of our study was to find out whether the immunohistochemical expression of nuclear factor-kappa beta (NF-κB) p65 in biopsy samples with Gleason score 3 + 3 = 6 (GS 6) can be a negative predictive factor for Prostate cancer (PCa) indolence. Patients and methods Study was conducted on a retrospective cohort of 123 PCa patients with initial total PSA ≤ 10 ng/ml, number of needle biopsy specimens ≥ 8, GS 6 on biopsy and T1/T2 estimated clinical stage who underwent laparoscopic radical prostatectomy and whose archived formalin-fixed and paraffin-embedded (FFPE) prostate needle biopsy specimens were used for additional immunohistochemistry staining for detection of NF-κB p65. Both cytoplasmic and nuclear NF-κB p65 expression in biopsy cores with PCa were correlated with postoperative pathological stage, positive surgical margins, GS and biochemical progression of disease. Results After follow-up of 66 months, biochemical progression (PSA ≥ 0.2 ng/ml) occurred in 6 (5.1%) patients, 3 (50%) with GS 6 and 3 (50%) with GS 7 after radical prostatectomy. Both cytoplasmic and nuclear NF-κB p65 expressions were not significantly associated with pathological stage, positive surgical margin and postoperative GS. Patients with positive cytoplasmic NF-kB reaction had significantly more frequent biochemical progression than those with negative cytoplasmic NF-kB reaction with PSA 0.2 ng/ml as cutoff point (p = 0.015) and a trend towards more biochemical progression with PSA ≥ 0.05 ng/ml as cutoff point (p = 0.068). Conclusions Cytoplasmic expression of NF-κB is associated with more biochemical progression and might be an independent prognostic factor for recurrence-free survival (RFS), but further studies including larger patient cohorts are needed to confirm these initial results.

Ovim su radom analizirani podaci pacijenata kojima su u razdoblju od siječnja do prosinca 2016. u KBC Zagreb učinjene transrektalne biopsije prostate. U analizu su uključeni osnovni klinički i laboratorijski podaci. U analiziranom razdoblju učinjeno je 356 biopsija prostate, od kojih 348 standardnih sa uzetih 12 uzoraka te 8 proširenih biopsija s 18 uzoraka. U 255 ispitanika radilo se prvoj, a u 101 o ponovljenoj biopsiji. Pacijenti su bili starosti od 48 do 88 godina (medijan 67 godina). Većina biopsija je učinjena u starosnoj skupini od 61-70 godina (186; 52,24%) uz PSA vrijednost 4-10 ng/ml (233; 65,44%). Ukupno gledajući, benigne promjene u bioptatima prostate (N=356) nađene su u 144 (40,45 %) pacijenata, nalaz suspektan na tumor je nađen u 37 (10,40 %) pacijenata, a jasni nalaz adenokarcinoma prostate je nađen u 175 (49,16 %) pacijenata. Pacijenti s dokazanim adenokarcinomom su u prosjeku bili 3 godine stariji od pacijenata s benignim ili suspektnim nalazom. Dok je većina pacijenata s benignim ili suspektnim nalazom imala vrijednosti PSA 4-10 ng/ml (75,69% i 75,68%), istu vrijednost je imalo samo polovina pacijenata (54%) s dokazanim adenokarcinomom, a značajan broj (41,7%) je imao vrijednosti PSA veće od 10 ng/ml. Pacijenti s klinički potvrđenom lokaliziranom bolešću imali su niže vrijednost PSA, manje od 4 pozitivnih cilindara prostate te histološki nalaz nižih gradusnih grupa, dok su pacijenti s uznapredovalim karcinomom imali vrijednosti PSA više od 10 ng/ml, često više od 8 pozitivnih cilindara i dokazan adenokarcinom viših gradusnih grupa (Gradus Grupa I vs Gradus Grupa IV). Kasniji podaci su bili dostupni za 305 pacijenata. U razdoblju praćenja do 36 mjeseci, 107 (35,08%) pacijenata nije pokazivalo znakove maligne bolesti, a u 27 (8,85%) je novo dijagnosticiran adenokarcinom prostate. U skupini pacijenata s ranije postavljenom dijagnozom adenokarcinoma (N=150), 21 (147%) je i dalje u statusu aktivnog nadzora, a kod 3 (2%) je započeto aktivno liječenje. Stabilno stanje bez znakova recidiva nađeno je u 112 (74,67%) ranije aktivno liječenih pacijenata, a progresija u metastatsku bolest u 14 (9,33%) pacijenata. This study included patients who underwent prostate core needle biopsy at University Hospital Centre Zagreb between January and December 2016. Main clinical and pathological features were analyzed. During analyzed period a total of 356 prostate core needle biopsies were performed, including 348 standard biopsies with 12 cores and 8 extended with 18 cores. In 255 cases prostate biopsy was performed for the first time, and 101 patient had previous prostate biopsy. Patients age ranged between 48 and 88 years (median 67 years). Most of biopsies were performed in group of patients aged 61-70 years (186; 52,24%) and with PSA levels 4-10 ng/ml (233; 65,44%). Overall, histological analysis in 144 (40,45 %) patients showed benign features, suspicious findings had 37 (10,40 %) patients and 175 (49,16 %) had definitive diagnosis of adenocarcinoma. Patients with proved adenocarcinoma on prostate biopsy were 3 years older than patients with benign or suspicious findings. While majority of patient with benign and suspicious findings had PSA levels 4-10 ng/ml (75,69% and 75,68% respectively), same levels had only half of patients (54%) with biopsy proven adenocarcinoma and significant amount (41,7%) of patients with adenocarcinoma had higher levels of PSA. Patients with clinically proven localized disease tend to have lower levels of PSA, less than 4 cores positive on biopsy and lower Grade Groups, while patients with advanced disease tend to have PSA levels higher than 10 ng/ml, more than 8 cores positive showing adenocarcinoma of higher grades (Grade Group I vs Grade Group IV). Follow-up data were available for 305 patients. In follow-up period (up to 36 months) 107 (35,08%) patients showed no signs of malignant disease, and 27 (8,85%) had newly diagnosed prostatic cancer. Of patients with previous diagnosis of prostate cancer (N=150), 21(14%) were still in active surveillance, 3 (2%) underwent active treatment. Stable state with no signs of progression were found in 112 (74,67%) previously treated patients, and progression to metastatic disease in 14 (9,33%) patients.

Trabalho Final do Mestrado Integrado em Medicina apresentado à Faculdade de Medicina Segundo os dados da European Association of Urology (EAU) o cancro da próstata (CaP) tem uma incidência na Europa de aproximadamente 417 000 casos/ano e uma mortalidade de 92 300/ano. Em Portugal, a incidência é de cerca de 12 415 casos/ano (2.98% dos casos Europeus) e a mortalidade de 3 643/ano segundo dados da DGS. A taxa de sobrevivência aos 5 anos depende, essencialmente, do estadio da doença, sendo extremamente elevada na doença localizada e 29% na disseminada. Torna-se assim crucial diagnosticar o mais prematuramente possível esta patologia investindo na prevenção e deteção precoce desta doença, tendo em conta que é das doenças oncológicas com melhor prognóstico. No entanto, o seu sobrediagnóstico e consequente sobretratamento tornaram-se num problema sério e que urge o aparecimento de novas ferramentas de combate a esta “epidemia”.Dependendo do estadio tumoral e da esperança média de vida do paciente, as diferentes guidelines internacionais recomendam como principais abordagens ao CaP localizado a vigilância ativa, a prostatectomia radical ou a radioterapia. Estas terapias são associadas a complicações e riscos significativos como debilidades físicas causadas pelo excesso de tratamento invasivo, quer fragilidades psicológicas devido à ausência de tratamento “efetivo”, que se encontram bem documentadas na literatura. Tendo isto em conta, a terapia focal revela-se como uma ponte de equilíbrio entre estas diferentes abordagens, oferecendo tratamento com baixa morbilidade associada.Este trabalho pretende então estudar e apresentar algumas das abordagens focais ao CaP tentando definir também quais as técnicas de diagnóstico, de seleção de candidatos e follow-up mais indicados. Para tal foi usada a base de pesquisa PubMed em que, através de vários filtros e das palavras MESH: Prostate; Prostatic Neoplasms; Biopsy; Therapeutics, foram selecionados um total de 42 artigos.Existe, contudo, uma grande escassez na literatura quer de dados quer de estudos, acerca das técnicas focais direcionadas ao CaP, bem como comparações entre as mesmas e entre estas e uma abordagem mais radical, o que tornou as conclusões deste trabalho um pouco subjetivas. According to data from the European Association of Urology (EAU), prostate cancer (PCa) has an incidence in Europe of approximately 417,000 cases / year and a mortality of 92,300 / year. In Portugal, the incidence is around 12 415 cases / year (2.98% of European cases) and mortality of 3 643 / year according to data from the DGS. The survival rate at 5 years, depends primarily on the stage of the disease, being extremely high in the localized disease and 29% in the disseminated one. It becomes crucial to diagnose this disease as early as possible by investing in prevention and early detection of this pathology, considering that it is one of the oncological diseases with the best prognosis. However, its overdiagnosis and consequent overtreatment have become a serious problem and it urges the emergence of new tools to combat this "epidemic."Depending on the tumor stage and the average life expectancy of the patient, the different international guidelines recommend active surveillance, radical prostatectomy or radiotherapy as the main approaches to localized PCa. These therapies are associated with significant complications and risks such as physical weaknesses, caused by excessive invasive treatment, or psychological weaknesses due to the absence of "effective" treatment, which are well documented in the literature. Focal therapy proves to bridge the gap between these different approaches, offering treatment with associated low morbidity.This work intends to study and present some focal approaches to the PCa and tries to define also the diagnostic techniques, the selection of candidates and the follow-up more indicated. To accomplish this, was used the PubMed search base in which, through several filters and the words MESH: Prostate; Prostatic Neoplasms; Biopsy; Therapeutics, a total of 42 articles were selected.There is, however, a great shortage in the literature of both, data and studies, about focal techniques directed to PCa, as well as comparisons between them and between the focal approach and a more radical one, which made the conclusions of this work somewhat subjective.

Background Type 5 phosphodiesterase (PDE5) expression in the normal and pathological prostate is controversial. Objectives This study aimed at identifying the cell type/s, if any, expressing PDE5 in human healthy or pathological prostate sections in order to further validate the rationale of PDE5 inhibitor (PDE5i) treatment of benign prostatic hyperplasia (BPH) and their safety in the treatment of erectile dysfunction following prostate cancer (PCa) surgery. Materials and methods By immunohistochemical analysis, we studied PDE5 expression in tissue microarrays containing sections obtained from healthy, BPH, and PCa samples. Results Our results showed that PDE5 is barely expressed in the epithelial or stromal compartment of normal human prostates, but it is highly expressed in the stromal compartment of BPH sections. We also found that a low but significant number of PCa samples (22%) expressed PDE5 in the epithelial cancer cells but not in stromal cells and that such expression was not correlated with the tumor aggressiveness, according to their Gleason score. Discussion and conclusion PDE5 overexpression in the stromal compartment of BPH samples supports the rationale of PDE5 as a target in lower urinary tract symptoms of BPH. PDE5 expression in a significant percentage of PCa samples but the lack of correlation with the Gleason score suggests that this enzyme is not correlated with tumor aggressiveness; however, a role of PDE5 in the minimal residual disease of PCa cannot be excluded.

Mixed cryoglobulinemia (MC) is well known for its association with chronic hepatitis C virus (HCV) infection. However, it has also been linked to autoimmune disorders and hematological malignancies, particularly of B-cell lymphoid origin. Association with solid malignancies is poorly described in the literature. Non-HCV-related MC, in the setting of prostate cancer, has been reported only twice. Here, we describe a case of MC in a prostate cancer patient complicated by membranoproliferative glomerulonephritis (MPGN) that responded well to plasma exchange therapy and treatment with both corticosteroids and rituximab.

Prostatic ductal adenocarcinoma, is an uncommon entity in the spectrum of prostatic carcinoma. Clinically it is different from common prostatic acinar adenocarcinoma. It is usually more aggressive than prostatic acinar adenocarcinoma. We are presenting a case report on prostatic ductal adenocarcinoma, a cystic variant of prostatic carcinoma in a 55-year-old man who complained of obstructive urinary symptoms with mildly raised prostate-specific antigen (PSA). On further evaluation in our radiology department a cystic lesion with enhancing polypoidal soft tissue component was noted in prostatic parenchyma. Histopathology confirmed the diagnosis of ductal adenocarcinoma.

The histopathologic diagnosis of prostate cancer (PCa) from biopsies is a current challenge if double or triple staining is needed. Therefore, there is an urgent need for development of a new reliable biomarker to diagnose PCa patients. We aimed to explore and compare the expression of TMTC4 in PCa cells and tissue specimens and evaluate its sensitivity and specificity. The expression of TMTC4 in PCa and normal prostate epithelial cells was determined by real-time PCR and Western blot analyses. Immunohistochemical (IHC) staining of TMTC4 was performed on tissues collected from PCa and benign prostatic hyperplasia (BPH). Our results show a high expression of TMTC4 on mRNA and protein levels in PCa versus BPH1 and normal cells (p &lt, 0.05). IHC results show strong cytoplasmic expressions in PCa cases (p &lt, 0.001) as compared to BPH cases. The overall accuracy as measured by the AUC was 1.0 (p &lt, 0.001). The sensitivity and specificity of the protein were 100% and 96.6%, respectively. Taken together, we report a high TMTC4 expression in PCa cells and tissues and its ability to differentiate between PCa and BPH with high sensitivity and specificity. This finding can be carried over to clinical practice after its confirmation by further studies.

Background: Diseases primarily inflicting prostate gland are inflammation, benign prostatic hyperplasia and cancer. Prostate specific antigen is a protein produced by the cells of prostate gland. It has been widely used in the diagnosis and management of patients with prostatic cancer. The aim this study was to determine the correlation between serum prostate specific antigen level and histological findings in biopsy specimens of men with prostatic disease.Materials and methods: This study was carried out at Kathmandu Medical College and Teaching Hospital, department of Pathology over a period of 2 years. One hundred and twenty eight cases with prostatic lesions were included in this study. Prostate specific antigen values of these cases were recorded before the surgical process. Histology of the tissue samples collected after transurethral resection of prostate was studied and relationship with prostate specific antigen level were analyzed.Results: Benign prostatic hyperplasia was the most common histological lesion encountered (n=95; 74.22%). Prostatic adenocarcinomas were seen a decade older than those with benign lesions. Maximum number of the benign cases had the Prostate specific antigen range of 0-7ng/ml. Most of the prostatic intraepithelial neoplasia lesions were seen within the PSA range of 0-7ng/ml and adenocarcinoma in the range of >20ng/ml.Conclusion: Prostate specific antigen is specific for the prostate but not for prostate cancer. Both benign and malignant lesions in prostate can cause increase in serum prostate specific antigen levels, but the chances of malignancy it rising level.

The authors analyzed the positioning error for branchytherapy needle inserted with original robotic system «Oncorobot» (Central Research Institute of Robotic And Technical Cybernetics, St. Petersburg) compared with traditional methods of insertion and other technical systems. The gelatin phantom of prostate gland was used for experiments. Needle insertion robotic program was written according to coordinates of dosimetric plan of microsourse localization. A coordinate of the needle tip location was measured after each injection of the needle into phantom and the mean-square error was calculated. It was shown that needle tip positioning error wasn’t more than 0,5 mm at insertion speeds from 3,0 to 30,00 mm/sec. Positioning error enlarged with increase of insertion speed. Needle positioning accuracy of insertion was significantly higher in case of developed robotic system, than in manual brachytherapy. The accuracy indices of the system were correlated with other described robotic systems.

Although cancer stem-like cells (CSC) are thought to be the most tumorigenic, metastatic, and therapy-resistant cell subpopulation within human tumors, current therapies target bulk tumor cells while tending to spare CSC. In seeking to understand mechanisms needed to acquire and maintain a CSC phenotype in prostate cancer, we investigated connections between the ETS transcription factor ESE3/EHF, the Lin28/let-7 microRNA axis, and the CSC subpopulation in this malignancy. In normal cells, we found that ESE3/EHF bound and repressed promoters for the Lin28A and Lin28B genes while activating transcription and maturation of the let-7 microRNAs. In cancer cells, reduced expression of ESE3/EHF upregulated Lin28A and Lin28B and downregulated the let-7 microRNAs. Notably, we found that deregulation of the Lin28/let-7 axis with reduced production of let-7 microRNAs was critical for cell transformation and expansion of prostate CSC. Moreover, targeting Lin28A/Lin28B in cell lines and tumor xenografts mimicked the effects of ESE3/EHF and restrained tumor-initiating and self-renewal properties of prostate CSC both in vitro and in vivo. These results establish that tight control by ESE3/EHF over the Lin28/let-7 axis is a critical barrier to malignant transformation, and they also suggest new strategies to antagonize CSC in human prostate cancer for therapeutic purposes. Cancer Res; 76(12); 3629–43. ©2016 AACR.

Background: Prostate-specific antigen (PSA) is a widely used biochemical marker for the early detection and monitoring of patients with prostatic cancer. PSA level show ever may vary with patient age, race and may be elevated in conditions such as benign prostatic hyperplasia (BPH) and prostatitis. Any diagnostic or surgical maneuver that alters the normal prostate architecture can lead to diffusion of PSA into the stroma and thus into the vasculature. Objectives: The present study was done to study the efficacy of PSA to categorize men with prostate pathology into benign, premalignant, and malignant lesions. Materials and Methods: Two years prospective study from September 2012 to August 2014 in the Department of Pathology, MVJ Medical College and Research Hospital, rural Bengaluru on 62 cases of prostate biopsies in men with prostatism. Clinical digital rectal examination (DRE) findings and PSA levels of each patient were noted from the case records. The levels of PSA in the various pathological lesions encountered were analyzed. Results: 62 prostate biopsies were received over a 2-year period, 41 cases satisfied the inclusion criteria were analyzed. DRE findings showed majority of the benign lesions (82.7%) to be firm. PSA levels below 4 ng/mL efficiently could segregate the benign lesions but with values beyond 4 ng/mL the picture becomes murkier with contributions from inflammation and BPH raising PSA to levels where malignancy would be suspected. Conclusion: In our study, PSA levels appear to be elevated in both benign and malignant lesions, therefore, the usefulness of PSA alone as an early detector of prostatic cancer by itself is questionable. In elderly patients with PSA levels above 4 ng/mL and with abnormal DRE, a prostatic biopsy is advisable to rule out cancer.

Purpose The aim of this study was to define the pattern of relapse of postoperative prostate cancer in patients by using 68Ga-labeled prostate-specific membrane antigen positron-emission tomography/computed tomography ([68Ga]-PSMA PET/CT). Material and methods Forty patients received a (68Ga)-PSMA PET/CT for biochemical failure. Following the Radiation Therapy Oncology Group (RTOG) guidelines, the pelvic clinical target volume has been contoured. Bone metastases were considered as outside the clinical target volume. Two subgroups of patients were defined, patients having relapse: (1) inside, or (2) outside the clinical target volume. Results Globally, eight patients out of 32 presented with a positive lymph node failure inside the clinical target volume according to RTOG guidelines (25%), 22 patients had nodal relapses outside this clinical target volume (68.75%) and in two patients nodal relapses occurred both inside and outside of the clinical target volume (6.25%). Overall, 36 positive lymph node lesions were identified: of these, 23 nodal relapses were identified within the clinical target volume contoured according to RTOG and/or at the lomboaortic level (63%). To cover 95% of these 23 relapses, a hypothetical clinical target volume should encompass the nodal regions of the RTOG-defined clinical target volume as well as the paraaortic lymph node level up to T12-L1. Conclusion Most of the patients in the present study, presented with distant lymph node and/or bone metastases. Therefore, larger target volumes should be adopted to treat at least 95% of lymph node regions at risk for an occult relapse.

Introduction: Although the literature about prostate cancer is vast in tracking discussion about diagnosis and treatment of prostate cancer, there are few publications about the best form of surgical specimen processing of radical prostatectomy. After the surgery, the urologist limits his responsibility to forward surgical specimen for analysis. Aim: To evaluate if the urologist manipulation trying to locate and demarcate suspicious areas of a tumour can improve the microscopic examination. Materials and Methods: Twenty surgical specimens of radical prostatectomy performed in patients with localised prostate cancer were macroscopically analysed by a single urologist and suspicious areas for cancer were marked with surgical thread. Later these areas were correlated with the findings in the microscopic study. Results: It was observed that in 75.8% of cases, there was a positive correlation between the pit and the clinical pathology report on the cancer presence, and in 50% of cases, the demarcated areas corresponded to the area of most considerable extent of cancer throughout the prostate. Conclusion: The demarcation of cancer suspected areas by Urologist, in surgical specimens from radical prostatectomy may provide additional information to the pathologist, directing the histopathological analysis of the prostate to the areas with more significant tumour extension compared to the other sections.

Introduction: Histopathological diagnosis of benign prostatic hyperplasia and prostatic carcinoma may pose problems due to presence of mimickers. p63 is confined to basal cells/ myoepithelial cells of prostate and is absent in prostatic cancer. In prostate cancer there is presence of reactive stroma instead of normal fibro muscular stroma. Calponin is expressed in cytoplasm of smooth muscle cells of normal stroma and its decreased or loss of expression is believed to play a role in tumorigenesis. Aim: To assess the expression of p63, a nuclear marker and calponin, a cytoplasmic marker in prostatic lesions and the relationship between the immunostaining and histologic grade of prostatic carcinoma. Materials and Methods: Biopsy specimen from a total of 30 cases between ages 70-90 years which included 15 cases of Benign Prostatic Hyperplasia (BPH), 15 cases of prostatic carcinoma were obtained by Transurethral Resection of Prostate (TURP) and needle biopsies. For each case biochemical parameters were obtained. Immunohistochemical analysis was performed on routinely processed, formalin fixed, paraffin embedded tissue. Tissue sections were cut at 5 μm thickness and mounted on gelatin coated slides. Immunohistochemical staining was done for both p63 and calponin. Expression of each of markers was graded accordingly. Results: p63: Out of the 30 cases, 93% of BPH showed positive staining and 100% of prostatic carcinoma showed negative staining of which 8 cases showed cytoplasmic staining. Sensitivity was 93% and specificity was 100% respectively. Calponin: Out of the 30 cases, 100% BPH cases showed moderate to high staining index and 73% of prostatic carcinoma showed zero to low staining index. Sensitivity of calponin was 100% and specificity was 74%. Conclusion: p63 and calponin are highly expressed in benign and pre neoplastic lesions. p63 is a valuable tool with high specificity in differentiating BPH from prostatic carcinoma. The decreased or absent stromal staining of calponin which indicates a reactive stroma in malignancy can be used in conjunction with p63 for confirmation of diagnosis of prostatic carcinoma.

BACKGROUND: Prostatic cancer is one of the most common cancers of males in a Sudanese population. The early detection is very important, as it is only curable at an early stage. AIM: The objective of this study was to investigate the expression pattern of Ki-67 in benign and malignant prostatic lesions to improve the diagnosis that may help in better management and prevention of disease. MATERIAL AND METHODS: Fifty-eight formalin fixed paraffin blocks from diagnosed cases of prostatic tumours with different grade, and stages were included in this study. Ki-67 expression was examined immunohistochemically by using monoclonal mouse anti-human Ki67 IS626. The results were correlated with Gleason score and tumour differentiation and stage. RESULTS: The frequency of histological types was as follow: 11 cases of benign prostate,atic hyperplasia (19%) and 47 cases of prostatic cancer (81%). Our results stated that prostatic adenocarcinoma among Sudanese patients was of low grade which means tumours are less aggressive. Furthermore, the findings demonstrate that Ki-67 expression in prostatic carcinoma smears was correlated significantly with the degree of Gleason score (P < 0.05). CONCLUSIONS: We found that the prostatic adenocarcinoma among Sudanese patients was less aggressive. Furthermore, Ki-67 expression was proportional to the grade of a tumour and it was a useful prognostic and diagnostic biomarker.

Background The goal of this study is to evaluate the status and future perspectives of clinical trials on positron emission tomography in prostate cancer for diagnostic or therapeutic as well as for surveillance purposes. Methods The www.ClinicalTrials.gov database was searched on the 20th of January 2017 for all trials containing terms describing “prostate cancer” (prostate, prostatic, malignant, malignancy, cancer, tumor) and “positron emission tomography”. In total 167 trials were identified. Trials that included diseases other than PCa were excluded (n = 27; 16%). Furthermore, we excluded trials (n = 4, 2%) withdrawn prior to first patient enrollment. The remaining trials (n = 137, 82%) were selected for further manual classification analysis. Results One hundred thirty-seven trials were detected and analyzed. Majority of trials were in “active” recruitment status (n = 46, 34%) followed by trials that had been “completed” - (n = 34, 25%) and trials with “closed recruitment but active follow-up” (n = 23, 17%). Phase 1 and 2 comprised 46% of the complete trial portfolio. Locally confined disease was of major interest (n = 46, 34%), followed by metastatic disease – not otherwise specified (n = 43, 13%). Evaluation of PET was the primary goal of the trial in 114 (83%) cases. Most of the trials evaluated only one agent (n = 122, 89%). Choline and PSMA represented two major groups (total 50%) and they were equally distributed across trial portfolio with 25% (n = 34) each. PSMA trials showed the highest average annual growth rate of 56%. The trials were conducted in 17 countries. Conclusion The scientific community is showing a strong and ever-growing interest in the field and we expect that in the coming years, more phase III trials will be initiated ultimately delivering the required Level 1 evidence. Electronic supplementary material The online version of this article (10.1186/s13014-018-1057-3) contains supplementary material, which is available to authorized users.

Molecular pathology of benign prostatic hyperplasia is multifactorial and involves endocrine, biochemical, immunological interactions. The mechanisms involved in the onset and progression of benign prostatic hyperplasia are: infections, 50 years of age, hormones and neurotransmitters imbalances, inflammation, oxidative stress. The potential role of glycosylation in the pathogenesis of prostate disease has been neglected. In this study we documented the profile of gangliosides in normal and pathological prostatic tissues together with the pathologic changes seen in the level of extracellular gangliosides in patients with prostate pathology. Analysis of the data in the literature suggests that gangliosides may represent immunologic markers useful in the differential diagnosis between prostate cancer and benign prostatic hyperplasia.

Background: Prostatism is an ailment of the geriatric age group leads to a colossal morbidity worldwide. Benign prostatic hyperplasia followed by prostatic adenocarcinoma account for most of the cases of prostatic disease. The concept of geriatrics has not been well-established in India. With increase in life expectancy, better education and increased public awareness the specific diagnosis offered to men with prostatism would increase. Objectives: The present study was done to determine the spectrum of pathological lesions in transurethral resection prostate (TURP) and needle biopsies from men with prostatism and to analyze the clinical and microscopic anatomy of the lesions encountered. Materials and Methods: 2 years prospective study from September 2012 to August 2014 in the Department of Pathology, MVJMC and RH, rural Bengaluru on 62 cases of prostate biopsies in men with prostatism. The clinical and laboratory data of each patient were noted from the case records. The clinical and histomorphology findings of the pathological lesions encountered were analyzed. Results: A total of 62 prostate biopsies were studied over a 2-year period which included TURP (88.70%) and needle biopsy specimens (11.30%). The most common pathology encountered was benign lesions constituting 80.6% (50 cases). Premalignant and malignant lesions constituted 19.4% (12 cases). Both benign and malignant lesions were common in the age group of 51-80 years and had presented clinically with frequency, hesitancy, and dysuria. Gleason’s score of 7 was the most common, seen in 36.3% of cases. Gleason score of 8 and 9 was seen in 27.2% cases each. One case of adenocarcinoma showed neuroendocrine differentiation. Conclusion: More studies are needed in future to identify environmental and psychosocial factors contributing prostate disease. All prostate carcinomas encountered were of high-grade. Hence, screening of the rural population would have a definitely have a positive impact on the patient outcome.