Recent Research Advances in Double-Strand Break and Mismatch Repair Defects in Prostate Cancer and Potential Clinical Applications.

Prostate cancer remains a leading cause of cancer-related death in men worldwide. Recent research advances have emphasized the critical roles of mismatch repair (MMR) and double-strand break (DSB) in prostate cancer development and progression. Here, we provide a comprehensive review of the molecular mechanisms underlying DSB and MMR defects in prostate cancer, as well as their clinical implications. Furthermore, we discuss the promising therapeutic potential of immune checkpoint inhibitors and PARP inhibitors in targeting these defects, particularly in the context of personalized medicine and further perspectives. Recent clinical trials have demonstrated the efficacy of these novel treatments, including Food and Drugs Association (FDA) drug approvals, offering hope for improved patient outcomes. Overall, this review emphasizes the importance of understanding the interplay between MMR and DSB defects in prostate cancer to develop innovative and effective therapeutic strategies for patients.

Unprecedentedly High Level of Intracellular Vitamin C and DNA Epigenetic Marks in Prostate: Relevant for Male Fertility?

BACKGROUND/AIMS: Seminal plasma composition is affected by the physiological state of the prostate, the major male reproductive gland. Semen components, like vitamin C, can modulate sperm function. Vitamin C is an effective scavenger of free radicals and is an essential component of enzymes such as TET proteins involved in the DNA demethylation process. In the present study, a broad range of parameters which may influence the metabolic state of the prostate gland were analysed including blood and prostate tissue vitamin C, epigenetic DNA modifications and 8-oxo-7,8-dihydro-2'-deoxyguanosine in DNA of leukocytes and prostate tissues. METHODS: The experimental material were tissue samples from patients with benign prostatic hyperplasia (BPH), normal/marginal prostate tissues from prostate cancer patients, leukocytes from healthy donors, and blood plasma from BPH patients and healthy donors. We applied ultra-performance liquid chromatography methods with mass spectrometry and/or UV detection. RESULTS: We found an unprecedentedly high level of intracellular vitamin C in all analysed prostatic tissues (benign prostatic hyperplasia and normal, marginal ones), a value much higher than in leukocytes and most human tissues. DNA epigenetic patterns in prostate cells are similar to other soft tissues like the colon, however, its uniqueness is the unprecedentedly high level of 5-(hydroxymethyl)-2'-deoxyuridine and a significant increase in 5-formyl-2'-deoxycytidine value compared to aforementioned tissues. Moreover, the level of 8-oxo-7,8-dihydro-2'-deoxyguanosine, an established marker of oxidative stress, is significantly higher in prostate tissues than in leukocytes and many previously studied soft tissues. CONCLUSION: Our results pointed out that prostatic vitamin C (regarded as the main supplier of the vitamin C to seminal plasma) and the DNA modifications (which may be linked to the regeneration of prostate epithelium) may play important role to maintain the prostate health.

Not as black as it is painted? The impact of the first wave of COVID-19 pandemic on surgical treatment of urological cancer patients in Poland - a cross-country experience.

Introduction: In the majority of Western European countries, the coronavirus disease (COVID-19) pandemic has led to a dramatic reduction in urooncological surgeries. Our objective was to evaluate the impact of the pandemic on volume and patterns of urooncological surgery in Poland. Material and methods: This is a retrospective analysis of 10 urologic centres in Poland. Data regarding major oncological procedures performed after the COVID-19 pandemic outbreak (March 15, 2020 - May 31, 2020) were evaluated and compared with data from the respective period in 2019. Results: Between March 15, 2020 and May 31, 2020, a total of 968 oncological procedures were performed in participating centres. When compared to the respective period in 2019 (1063 procedures) the overall number of surgeries declined by 8.9%. The reduction was observed for transurethral resection of bladder tumour (TURBT) (20.1%) and partial nephrectomies (PN) (16.5%). Surgical activity considering radical nephrectomy (RN), nephroureterectomy (NU), and radical prostatectomy (RP) remained relatively unchanged, whereas radical cystectomy (RC) burden showed a significant increase (90.9%). Characteristics of patients treated with TURBT, RC, NU, PN, and RN did not differ significantly between the compared periods, whereas RP in the COVID-19 period was performed more frequently in patients with a higher grade group (p = 0.028) and positive digital rectal examination (p = 0.007). Conclusions: Surgical activity for urological cancers in Poland has been maintained during the first wave of the COVID-19 pandemic. The Polish strategy in the initial period of the COVID-19 crisis mirrors the scenario of hard initial lockdown followed by adaptive lockdown, during which oncological care remained undisrupted and did not require particular priority triage.

Quality of Life of Prostate Cancer Patients Undergoing Prostatectomy and Affective Temperament.

Purpose: Prostate cancer (PC) is one of the most common malignancies in men. The population of PC survivors is growing, and understanding the roles of different factors that affect quality of life (QoL) is important. We investigated the effects of affective temperament on the QoL of PC patients. Patients and Methods: All subjects (n=100) underwent medical evaluation [including demographic data, medical history, physical examination, biochemical tests, and assessment of urinary incontinence (ICIQ-UI SF scale) and erectile dysfunction (ED) (IIEF-5 and subjective ED scale)] and psychological evaluation [including assessment of affective temperament using the TEMPS-A scale, depression and anxiety (using HADS), and QoL (EORTC-QLQ-C30 and EORTC-PR25)]. The relationships between individual variables were examined. Results: Erection quality after treatment was associated with better QoL in most parameters. Similar strong relationships were observed between the urinary incontinence scale and QoL. Depressive, cyclothymic, irritable, and anxious temperaments were associated with decreased QoL. On the EORTC-PR25 scale, associations were observed between a depressive temperament and worse sexual function and urinary symptoms, between a cyclothymic temperament and worse urinary symptoms, and between an irritable temperament and worse sexual functioning. Multivariate analysis identified the severity of anxiety and depression symptoms measured by HADS as the most important psychological factors affecting QoL. Conclusion: QoL in PC survivors depends on many factors, including age, interval since diagnosis, tumor stage, treatment, complications, and affective temperament profile. Depressive, cyclothymic, irritable, and anxious temperaments were associated with poorer QoL in selected domains, which was not observed for a hyperthymic temperament. The temperament profile of patients was associated with mood and anxiety level, which were important determinants of a poorer QoL.

Prostate-Specific Antigen and Testosterone Levels as Biochemical Indicators of Cognitive Function in Prostate Cancer Survivors and the Role of Diabetes.

Prostate cancer (PC) is one of the most common malignancies in men. The increase in the number of PC survivors is associated with many problems including cognitive impairment. Early detection of such problems facilitates timely protective intervention. This study examined the association between prostate-specific antigen (PSA) or testosterone (T) levels and cognitive function in patients undergoing radical prostatectomy. Such a correlation could help identify patient groups at risk of cognitive impairment. Participants underwent clinical (demographic data, medical history, physical examination, and blood analyses) and neuropsychological assessment (cognitive test battery). Preoperative PSA or T levels were not associated with cognitive function. However, long-term follow-up after prostatectomy showed a strong correlation between PSA levels and the results of verbal memory and executive function tests. A trend toward significance was also observed for visuospatial memory. The levels of free T and total T were not correlated with cognitive function. Only the levels of free T after hormonal treatment were significantly correlated with executive functions. Comorbid diabetes affected these correlations. In conclusion, PSA levels at a distant postoperative time and free T level after hormonal treatment may be biomarkers of cognitive function.

Randomized-Controlled Trial Examining the Effect of Pelvic Floor Muscle Training in the Treatment of Stress Urinary Incontinence in Men after a Laparoscopic Radical Prostatectomy Pilot Study.

AIM: The aim of this study was to assess the impact of pelvic floor muscle training (PMFT) in the treatment of stress urinary incontinence (SUI) in men after they received radical prostatectomy (RP). METHODS: From November 2018 to September 2019, patients who underwent radical prostatectomy were assessed for eligibility. A total of 37 men were then randomly assigned to the experimental group (EG) and the control group (CG). The EG group received supervised exercise twice a week for 12 weeks, and the CG did not receive any intervention. To objectify the results obtained in both groups before and after the intervention, the authors assessed myostatin concentration. Moreover, the Expanded Prostate Cancer Index Composite (EPIC-26) was applied to assess the quality of life, and Beck's Depression Inventory (BDI-II) was used to measure depression severity. RESULTS: Study results demonstrated a statistically significant reduction of myostatin concentration in the EG following the treatment and no statistically significant differences in this parameter in the CG. In addition, a comparison of the EPIC-26 scores in the EG at the initial and final assessments revealed a statistically significant improvement in the quality of life in each domain. A comparison of the EPIC-26 scores in the CG at the initial and final assessments showed there is a statistically significant decline in quality of life in the "overall urinary problem" and "sexual" domain. A comparison of the BDI-II scores at the initial and final assessments showed a statistically significant decline in depressive symptoms in the EG and no statistically significant differences in the CG. CONCLUSIONS: PFMT is an effective treatment for urinary incontinence (UI) in men who received radical prostatectomy.

Simultaneous bilateral native nephrectomy by retroperitoneal approach.

The indication for simultaneous bilateral native nephrectomy and the choice of surgical technique is of key importance, as these patients are burdened with a large comorbidity. The paper reports our experience of seven successful and completed simultaneous bilateral native nephrectomy procedures with retroperitoneal approach in the patient's flank position. Seven patients (mean age 34), were indicated for the removal of both kidneys before the planned transplant. Six patients underwent haemodialysis from 48 to 84 months, and one underwent peritoneal dialysis for 60 months. Two patients had undergone graftectomy. The indications were chronic infection or hypertension. The length of the kidneys ranged from 5.8 to 10cm. All procedures were performed by the laparoscopic technique with retroperitoneal approach, with the patient in the flank position. Three trocars were used on each side. The retroperitoneal space created did not require balloon dilatation. The kidneys were removed through the 10mm trocar hole after splitting. The duration of the procedure ranged from 150 to 240 minutes, average 139 minutes and blood loss ranged from100 to 250mL, average 142mL. There were no complications. In 6 patients, the postoperative dialysis was performed at zero-day. One patient continued peritoneal dialysis. Patients were discharged on the 2nd day, except one with peritoneal dialysis, who was discharged on the 3rd day. Retroperitoneal laparoscopic bilateral native nephrectomy is a safe and effective technique, and it can be considered as an ideal approach for native nephrectomy. It allows for the preservation of peritoneal integrity and vessels for future vascular access.

Laparoscopic radical prostatectomy and extended pelvic lymph node dissection: a combined technique.

INTRODUCTION: The important part of radical prostatectomy (RP) for high risk (HR) is extended pelvic lymph node dissection (ePLND). This method consists of two stages of surgery usually performed at the compartment (pre- or transperineally). AIM: We present our new combined technique of RP using two different approaches: a pre-peritoneal approach for laparoscopic radical prostatectomy (LRP) and a transperitoneal approach for ePLND. MATERIAL AND METHODS: This study included 30 patients aged 53 to 75 years (mean age: 64 years) with prostate cancer who underwent LRP and ePLND using a combined technique. After the pre-peritoneal LRP, transposition of the trocars into the peritoneal cavity was performed without changing their location, except the extreme left trocar, which was inserted through a new approach. RESULTS: The total duration of surgery was 155 to 290 min (mean: 215 min); ePLND lasted from 35 to 85 min (mean: 56 min). The movement of trocars into the peritoneal cavity was a very simple maneuver, taking up to 1 min without any complications. The number of removed lymph nodes (LNs) ranged from 13 to 28 (mean: 16.8). A positive margin was found in 5 (16%) patients. We recognized positive nodes in 9 (30%) patients. CONCLUSIONS: The combined technique is both feasible and safe. Performing the most difficult maneuver, removal of the prostate, in the first stage appears to be more comfortable for the operator. The timing of the PLND stage in the combined technique and the number of removed LNs do not differ from the standard lenticular access.

Simultaneous bilateral native nephrectomy by retroperitoneal approach

ABSTRACT The indication for simultaneous bilateral native nephrectomy and the choice of surgical technique is of key importance, as these patients are burdened with a large comorbidity. The paper reports our experience of seven successful and completed simultaneous bilateral native nephrectomy procedures with retroperitoneal approach in the patient's flank position. Seven patients (mean age 34), were indicated for the removal of both kidneys before the planned transplant. Six patients underwent haemodialysis from 48 to 84 months, and one underwent peritoneal dialysis for 60 months. Two patients had undergone graftectomy. The indications were chronic infection or hypertension. The length of the kidneys ranged from 5.8 to 10cm. All procedures were performed by the laparoscopic technique with retroperitoneal approach, with the patient in the flank position. Three trocars were used on each side. The retroperitoneal space created did not require balloon dilatation. The kidneys were removed through the 10mm trocar hole after splitting. The duration of the procedure ranged from 150 to 240 minutes, average 139 minutes and blood loss ranged from100 to 250mL, average 142mL. There were no complications. In 6 patients, the postoperative dialysis was performed at zero-day. One patient continued peritoneal dialysis. Patients were discharged on the 2nd day, except one with peritoneal dialysis, who was discharged on the 3rd day. Retroperitoneal laparoscopic bilateral native nephrectomy is a safe and effective technique, and it can be considered as an ideal approach for native nephrectomy. It allows for the preservation of peritoneal integrity and vessels for future vascular access.

Urology resident training in laparoscopic surgery - results of the first national survey in Poland.

INTRODUCTION: For many urological procedures the open approach is being replaced by the laparoscopic approach. Laparoscopy technique requires special training conditions. A well-designed, step-by step training program is significantly important for shortening the learning curve. AIM: The purpose of the study was to evaluate urology residents' (UR) experience in laparoscopic procedures, training patterns and facilities available in departments of urology in Poland. MATERIAL AND METHODS: The survey developed by the authors included 18 questions concerning laparoscopy training and was distributed among UR who participated in 2 courses in laparoscopic surgery for UR in Poland in 2017. The survey consisted of questions regarding the number of laparoscopic procedures, acquired laparoscopic experience, laparoscopic simulation training and motivation for further learning. RESULTS: Of the 2017 invited UR in Poland, 108 (34%) completed the survey. Seventy-two (78%) UR from the study group have access to laparoscopic surgery in their department. Only 20 (25%) of urology departments are equipped with a laparoscopy box and a small number of UR perform regular training. As a primary operator basic (varicocele repair) and advanced (e.g. radical nephrectomy, radical prostatectomy, nephron-sparing surgery) laparoscopic procedures are performed respectively by 55 (71%) UR and 8 (10%) UR. Most residents evaluated their laparoscopic skills as poor (15, 19%), very poor (31, 40%) or absent (10, 13%), while only 22 (28%) evaluated them as at least satisfactory. CONCLUSIONS: Laparoscopic technique is available in most Polish training centers. However, the majority of UR consider their skills unsatisfactory. Additionally, a large number of Polish UR do not have access to intensive training. UR considered that their availability of training courses and fellowships is low. Surgical exposure among Polish UR comprises mainly minor laparoscopic procedures.

Cognitive function, depression, and anxiety in patients undergoing radical prostatectomy with and without adjuvant treatment.

BACKGROUND: Prostate cancer (PC) is one of the most common malignant tumors in developed countries. Both PC and treatment for PC have an adverse impact on physical and mental well-being, and are associated with decreased quality of life. The aim of the present study was to examine the relationship between neuropsychological symptoms and clinical course in PC patients undergoing radical prostatectomy with or without adjunct therapy. METHODS: The cohort comprised 100 patients aged 50-77 years who underwent radical, laparoscopic prostatectomy for PC. Twenty-three patients with a more advanced clinical stage also received adjuvant therapy (radiotherapy and hormonotherapy). Clinical evaluation included self-report assessment, physical examination, and biochemical tests (testosterone and prostate-specific antigen). In addition, the presence and intensity of sexual dysfunction, urinary dysfunction, anxiety-depressive symptoms, and cognitive dysfunction were assessed. RESULTS: The group of patients undergoing complex therapy was characterized by a significantly worse result of deferred memory (p=0.04). A significant correlation was found between post-surgery erectile function and scores for the visual working memory test (correct answers; VWMT-C; p=0.006) and Hospital Anxiety and Depression Scale depression (p=0.045) and anxiety scores (p=0.02). A trend toward significance was also observed for simple reaction time (correct answers; p=0.09). A significant correlation was found between results for the delayed verbal memory test and all physical symptoms (International Consultation on Incontinence Questionnaire-total, p=0.02; International Index of Erectile Function-5, p=0.006). Similarly, a significant correlation was found between the VWMT-C and score for sexual dysfunction (p=0.003). CONCLUSION: Patients undergoing both surgical and adjunct therapy for PC are at risk for psychological burden and cognitive disorders. In the present cohort, physical complications of therapy were associated with depression, anxiety, and delayed memory dysfunction. Furthermore, this study has proven that fewer complications after surgery are associated with better psychological and cognitive functioning. Appropriate neuropsychological and psychiatric care can improve compliance and quality of life among patients after prostatectomy.

Affective temperament in inflammatory bowel diseases: Another brick in the wall of differentiation.

Psychiatric disorders are significantly common complications among patients suffering from inflammatory bowel diseases (IBD). Affective temperament is a concept of core personality traits, which can decribe the vulnerability to mood disorders, therefore its evaluation might convey useful information about patients' mental status in autoimmune disorders. The aim of the study was to evaluate the affective temperament in patients with Crohn's disease (CD) and ulcerative colitis (UC) as characteristic features of these diseases, but also in the clinical course and the severity of anxiety and depression.Due to our knowledge this is the first study of this kind. The study enrolled 130 patients with IBD, including 68 with CD and 62 with UC. We used TEMPS-A to evaluate affective temperament and HADS scales to assess the intensity of depressive and anxiety symptoms. Harvey Bradshaw scale, Crohn's Disease Activity Index (CDAI) and Mayo Score were used to evaluate clinical severity of the diseases. We observed significantly higher prevalence of depressive, cyclothymic and anxiety temperaments in CD patients compared to the control group. Harvey Bradshaw scale, CDAI and Mayo Self Report showed statistically significant outcomes, including significant positive correlations with depressive, cyclothymic and anxiety subscales of TEMPS-A, and negative correlation with the hyperthymic temperament in CD subjects. Our findings indicate significant differences between CD and UC due to temperament traits, and suggest distinct pathogenesis of mood disorders in IBD.