Environmental Exposure to Metals, Parameters of Oxidative Stress in Blood and Prostate Cancer: Results from Two Cohorts

We studied the potential role of exposure to various metal(oid)s (As, Cd, Cr, Hg, Ni, and Pb) in prostate cancer. Two cohorts were established: the Croatian cohort, consisting of 62 cases and 30 controls, and the Serbian cohort, consisting of 41 cases and 61 controls. Blood/serum samples were collected. Levels of investigated metal(oid)s, various parameters of oxidative stress, and prostate-specific antigen (PSA) were determined in collected samples. A comparison of the measured parameters between 103 prostate cancer patients and 91 control men from both Croatian and Serbian cohorts showed significantly higher blood Hg, SOD, and GPx levels and significantly lower serum SH levels in prostate cancer patients than in controls. Correlation analyses revealed the significant relationship between certain parameters of oxidative stress and the concentrations of the measured metal(loid)s, pointing to the possible role of metal(oid)-induced oxidative stress imbalance. Furthermore, a significant inverse relationship was found between the blood Pb and the serum PSA in prostate cancer patients, but when the model was adjusted for the impacts of remaining parameters, no significant association between the serum PSA and the measured parameters was found. The results of the overall study indicate a substantial contribution of the measured metal(loid)s to the imbalance of the oxidant/antioxidant system. Although somewhat conflicting, the results of the present study point to the possible role of investigated metal(oid)s in prostate cancer, especially for Hg, since the obtained relationship was observed for both cohorts, followed by the disturbances in oxidative stress status, which were found to be correlated with Hg levels. Nevertheless, further studies in larger cohorts are warranted to explain and confirm the obtained results

Comprehensive Evaluation of Quality of Life in Penile Cancer Patients following Surgical Treatment

Background: Penile cancer (PC) is a highly aggressive disease, with a significant tendency for lymphatic spreading and subsequent development of distant metastases. The mutilating nature of PC surgical treatment has profound implications on the patient’s body integrity and self-image, sexual life and intimacy, voiding and mental health. The aim of our study was to comprehensively evaluate PC patients’ post-treatment quality of life (QoL), sexual activity, self-esteem, fatigue and fear of disease recurrence. (2) Methods: A cross-sectional study was conducted at the Clinic of Urology, University Clinical Centre of Serbia, and included 31 PC patients. Data were collected by means of a questionnaire. (3) Results: The average score on the Global health status scale was 67.2 out of 100 (ranging from 16.7 to 100), and the SD was 22.5. Hierarchical linear regression analysis showed that demographic characteristics, Hospital Anxiety and Depression scale (HADS) anxiety and depression scores, total Multidimensional Fatigue Inventory, Fear of cancer recurrence and Rosenberg scores and erectile function score explained a total of 78.2% of the variance in the global health status/QoL scale of PC patients. (4) Conclusions: Efforts should be made not only to increase the survival of PC patients after surgical treatment but also to enable the best possible level of QoL in the post-operative period

Narušena homeostaza polnih hormona kod pacijenata sa karcinom dojke, prostate i testisa: koja je uloga kadmijuma i olova

The endocrine potential of Cd and Pb, an important mechanism of their toxicity, has been established in certain hormone-dependent cancers (1,2). This study aimed to determine Cd and Pb levels in blood, tumor and healthy surrounding tissue of patients with breast, prostate and testis cancer and investigate the correlation of Cd and Pb with sex hormone levels in the patient's blood. The study involved 55 breast, 41 prostate and 52 testis cancer patients, while healthy women (41) and men (61) represented control groups. Electrothermal atomic absorption spectrophotometry was used for Cd and Pb levels determination. Significantly higher Cd levels, i.e. lower Pb in tumor tissue compared to the healthy surrounding tissue were found in patients with breast cancer. A positive correlation was confirmed between Cd levels in the changed tissue and both human gonadotropins, and a negative correlation with estradiol, as well between Pb in tumor tissue and testosterone levels. Patients with prostate and testis cancer were characterized by significantly higher blood Cd levels compared to healthy subjects. Furthermore, significant Cd and Pb tumor tissue accumulation was shown in prostate and testis cancer patients. A significant positive correlation was found between blood Cd and estradiol levels in patients with prostate cancer. The study highlighted higher Cd level as a significant predictor of cancer, and confirmed impaired sex hormone homeostasis as pivotal mechanism of toxicity underlying the toxic effects of Cd and Pb in patients with breast, prostate and testis cancer.Endokrini potencijal kadmijuma (Cd) i olova (Pb), kao važan mehanizam toksičnosti oba metala, potvrđen je kod određenih hormon-zavisnih karcinoma (1,2). Ova studija je imala za cilj da utvrdi koncentracije Cd i Pb u krvi, tumorskom i okolnom zdravom tkivu pacijenata sa karcinomom dojke, prostate i testisa i ispita korelaciju Cd i Pb sa nivoom polnih hormona u krvi pacijenata. Obuhvatila je 55 pacijentkinja sa karcinomom dojke, 41 pacijenta sa karcinomom prostate i 52 pacijenta sa karcinomom testisa, dok su u kontrolnu grupu bile uključene zdrave žene (41) i zdravi muškarci (61). Koncentracije Cd i Pb su analizirane elektrotermalnom atomskom apsorpcionom spektrofotometrijom. Značajno više koncentracije Cd, odnosno niže Pb u tumorskom u odnosu na okolno zdravo tkivo utvrđene su kod pacijentkinja sa karcinomom dojke. Pozitivna korelacija je potvrđena između koncentracija Cd u tkivu izmenjene strukture i oba humana gonadotropina, a negativna sa estradiolom, te između Pb u tumorskom tkivu i testosterona. Pacijente sa karcinomom prostate i testisa karakterisale su značajno više koncentracije Cd u krvi u odnosu na zdrave ispitanike, a pokazana je i značajna akumulacija Cd i Pb u tumorskom tkivu prostate i testisa. Značajna pozitivna korelacija utvrđena je između koncentracije Cd i estradiola u krvi kod pacijenata sa karcinom prostate. Studija je pokazala da su više koncentracije Cd značajan prediktor za nastanak karcinoma i potvrdilanarušenu homeostazu polnih hormona kao važan mehanizam toksičnosti koji se nalazi u osnovi toksičnih efekata Cd i Pb kod obolelih od karcinoma dojke, prostate i testisa.VIII Kongres farmaceuta Srbije sa međunarodnim učešćem, 12-15.10.2022. Beogra

Modelovanje odnosa doza‐odgovor između nivoa Pb i Cd u tkivima karcinoma testisa i prostate i nivoa testosterona

Exposure to lead (Pb) and cadmium (Cd) poses risk to human health. It is known that these metals have toxic impact on male reproductive system, leading to physiological disorders and infertility. Limited data indicates the carcinogenic potential of Pb, while Cd has been recognized as carcinogen. Benchmark dose-effect modeling can be applied to data from human, animal and ecotoxicological studies with the aim to obtain Benchmark dose (BMD), starting point in human health risk assessment. The aim of this study was to use Benchmark modeling to determine the dose-effect relationship between Pb and Cd levels in tissues of testicular and prostate cancer patients and serum testosterone levels. The study was conducted at the Clinical Center of Serbia, and included 104 patients with prostate and testicular cancer. Cd and Pb levels (ng/g) were measured by atomic absorption spectrophotometry in isolated healthy surrounding and carcinoma-affected tissues. Testosterone levels (ng/mL) were measured using the chemiluminescence immunoassay (CLIA) method. Dose-effect modeling was performed using PROAST70.1 software with continuous data. The dose dependence was obtained between Cd levels in tumor tissue and testosterone levels (BMD: 0.0024 ng Cd/g, prostate cancer and 0.0038 ng Cd/g, testicular cancer). Dose dependence was obtained between Cd levels in healthy surrounding tissue and testosterone levels (BMD: 0.0092 ng Cd/g). No dose dependence was obtained when modeling Pb levels as a dose. The data from this study indicate a potential link between Cd and testosterone levels, i.e. potential association of Cd exposure with male reproductive health.Izloženost olovu (Pb) i kadmijumu (Cd) predstavlja rizik po zdravlje ljudi. Poznato je da ovi metali deluju toksično na muški reproduktivni sistem dovodeći do poremećaja fizioloških funkcija i neplodnosti. Ograničen broj studija ukazuje na kancerogeni potencijal Pb, dok je Cd poznatihumani karcinogen. Benchmark modelovanje odnosa doza-efekat se teoretski može primeniti na podacima iz humanih, animalnih i ekotoksikoloških studija, sa ciljem dobijanja Benchmark doze (BMD) kao polazne tačke u proceni rizika po zdravlje ljudi. Cilj ovog rada bio je da se Benchmark modelovanjem utvrdi odnos doza-efekat između nivoa Pb i Cd u tkivima karcinoma testisa i prostate pacijenata i nivoa testosterona u serumu. Studija je sprovedena na Kliničkom centru Srbije i uključila je 104 pacijenta sa karcinomom prostate i testisa. Nivoi Cd i Pb (ng/g) su izmereni metodom atomske apsorpcione spektrofotometrije u izolovanim zdravim okolonim i karcinomom zahvaćenim tkivima. Nivoi testosterona (ng/mL) su mereni pomoću metode direktnog kompetitivnog hemiluminiscentnog imunoeseja (CLIA). Modelovanje odnosa doza-efekat je vršeno pomoću PROAST 70.1 softvera (RIVM, Holandija) uz upotrebu kontinuiranih podataka. Dozna zavisnost je dobijena između nivoa Cd u tumorskom tkivu i nivoa testosterona gde je BMD vrednost iznosila 0,0024 ng Cd/g (karcinom prostate) i 0,0038 ng Cd/g (karcinom testisa). Dozna zavisnost je dobijena i za modelovanje odnosa nivoa Cd u zdravom tkivu i testosterona, sa BMD vrednošću 0,0092 ng Cd/g. Pri modelovanju nivoa Pb nije dobijena dozna zavisnost. Podaci ove studije ukazuju na potencijalnu vezu između nivoa Cd u tkivu i nivoa testosterona, ukazujući na efekte izloženosti ovom metalu na muško reproduktivno zdravlje.VIII Kongres farmaceuta Srbije sa međunarodnim učešćem, 12-15.10.2022. Beogra

Congenital arteriovenous fistula of the horseshoe kidney with multiple hemangiomas

Introduction. Congenital renal arteriovenous fistulas (AVF) are rare, especially if they are associated with other developmental renal anomalies. Case Outline. A 34-year-old female was hospitalized due to total painless hematuria and bladder tamponade. Excretory urography revealed a horseshoe kidney with normal morphology of pyelocaliceal system and ureters. Aortography and selective renovasography detected a cluster-like vascular formation with multiple arteriovenous fistulas (AVF). Due to a large AVF gauge and poor flow of the efferent vein to the inferior vena cava, a surgical procedure of two renal artery segmentary branches ligation and division was performed. During the operative procedure, the presence of multiple superficial renal hemangiomas was detected. Conclusion. Although selective arterial embolization represents the preferable treatment option, conventional surgery remains favorable alternative in selected cases with large and complex AVF

Benign prostatic hyperplasia and prostate-specific antigen

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A quantitative analysis of two-dimensional manually segmented transrectal ultrasound axial images in planning high dose rate brachytherapy for prostate cancer

Background/Aim. Prostate delineation, pre-planning and catheter implantation procedures, in high-dose rate brachytherapy (HDR-BT), are commonly based on the prostate manually segmented transrectal ultrasound (TRUS) images. The aim of this study was to quantitatively analyze the consistency of prostate capsule delineation, done by a single therapist, prior to each HDR-BT fraction and the changes in the shape of the prostate capsule during HDR-BT, using two dimensional (2D) TRUS axial image. Methods. A group of 16 patients were treated at the Medical System Belgrade Brachytherapy Department with definitive HDRBT. The total applied median dose of 52 Gy was divided into four individual fractions, each fraction being delivered 2– 3 weeks apart. Real time prostate axial visualization and the manual segmentation prior to each fraction were performed using B-K Medical ultrasound. Quantitative analyses, analysis of an area and shape were applied on 2D-TRUS axial images of the prostate. Area analyses were used to calculate the average value of the cross-sectional area of the prostate image. The parameters of the prostate shape, the fractal dimension and the circularity ratio of the prostate capsule contour were estimated at the maximum axial cross section of the prostate image. Results. The sample group consisted of four phases, each phase being performed prior to the first, second, third and fourth HDR-BT fraction, respectively. Statistical analysis showed that during HDR-BT fractions there were no significant differences in the average value of area, as well as in the maximum shape of prostate capsule. Conclusions. Quantitative analysis of TRUS axial prostate segmented images shows a successful capsule delineation in the series of manually segmented TRUS images, and the prostate maximum shape remaining unchanged during HDR-BT fractions

Idiopathic retroperitoneal fibrosis: A report on 15 patients

Background/Aim. Retroperitoneal fibrosis (RPF) represents a chronic pathological process characterized by fibrosis which entraps and compresses the ureters and the great blood vessels in the retroperitoneal space. A specific form of RPF is idiopathic RPF, an uncommon collagen vascular disease of unclear etiology. The series of 15 patients which underwent open surgical repair due to idiopathic RPF is presented herein. Methods. From 1989 to 2012, 11 male and 4 female patients underwent surgery due to primary RPF. The ureters were entrapped unilaterally (7 patients), or bilaterally (8 patients). Major symptoms included low back pain due to hydronephrosis (9 patients), uremia (4 patients), and urinary tract infection (2 patients). The diagnosis was based on intravenous urography (IVU), retrograde ureteropyelography and computed tomography (CT). Results. Surgical procedures included intraperitoneal ureteral displacement (8 patients) and ureteral wrapping with omental flap (6 patients). One patient underwent bilateral ureteral stenotic segments resection and oblique ureterography, followed by wrapping with omental flap. Pathological examination confirmed primary RPF in all patients. The mean operative time was 3.5 h (range 2.5-4.5 h). The average intrahospital stay was 21 days (range 16-26 days). The mean follow up was 32 months (6-46 months). During the follow up, 12 patients had improvement on IVU. Conclusion. Early recognition of signs and symptoms of RPF is of the utmost importance for the outcome. Surgical procedures, including ureteral wrapping with omental flap, or intraperitoneal ureteral displacement, usually represent definitive treatment

Impact of surgical treatment of benign prostate hyperplasia on lower urinary tract symptoms and quality of life

Background/Aim. Benign prostatic hyperplasia (BPH) is a pathological process, which is one of the most common causes of so-called lower urinary tract symptoms (LUTS). LUTS affect many aspects of daily activities and almost all domains of health-related quality of life (HRQoL). The objective of this study was to evaluate the effects of operative treatment of BPH using standard clinical diagnostic procedures and effects on LUTS using the symptom-score validated to Serbian language as well as implications on HRQoL. Methods. Seventy-four patients underwent surgical treatment for BPH. The study protocol included objective and subjective parameters of the following sets of variables measured before and after the surgery: voiding and incontinence symptoms were measured using the International Continence Society male Short Form (ICS male SF) questionnaire, HRQoL was measured using the SF-36 questionnaire along with standard clinical measurement of residual urine and urine flow. Results. After the surgery, all patients had decrease of voiding scores (13.5 ± 3.3 before and 1.5 ± 1.4 after surgery) and incontinence symptoms (5.7 ± 3.9 before and 0.6 ± 0.8 after surgery) in comparison to period before operative treatment. Significant improvements in all dimensions of HRQoL were noticed, particularly in emotional health. Although mental and physical total scores were significantly better than prior to the surgery, the level of improvement of voiding and incontinence scores were significantly correlated only with the level of improvement of mental score. Conclusion. After BPH surgery, patients are likely to have normal voiding symptoms, barely some involuntary control over urination and overll better HRQoL, particularly in emotional domain

Cadmium and lead implication in testis cancer; is there a connection?

Testis cancer (TC) is the most common malignancy of young men. Current evidence from studies, alongside genetics and hormonal status, suggests a significant role of toxic metals, cadmium (Cd) and lead (Pb), in the origin and development of TC. Besides oxidative stress and endocrine disruption, interaction with bioelements is one of the critical mechanisms of Cd and Pb toxicity and malign transformation. This study aimed to investigate metal levels in blood, healthy, and tumor testis tissue and to reveal hormone, oxidative status, and bioelements levels in patients with TC. The study enrolled 52 patients with TC and 61 healthy volunteers. Toxic metals and bioelements levels were analyzed by atomic absorption spectrophotometry (AAS) while electrochemiluminescence immunoassay (ECLIA) and spectrophotometry methods were used for hormone and oxidative parameters evaluation. Significantly higher blood Cd levels were depicted in TC cohort. Furthermore, blood Cd elevation was associated with a 1.98 higher probability of TC developing. However, a metal concentration between healthy and tumor testis tissue did not differ significantly. Lower levels of estradiol and testosterone, established in a cohort of TC patients, followed the significant role of hormones in TC development. At the same time, ischemia-modified albumin (IMA) has been recognized as a parameter with very good accuracy as a potential diagnostic marker for TC. The study revealed different distribution patterns of copper (Cu) and zinc (Zn) in the three compartments of the patients, as well significant correlation between essential metals Cu/Zn and toxic metals Cd/Pb indicating metal-metal interactions as pivotal mechanisms of metals toxicity