Cem Akbal

Erectile dysfunction following radiotherapy and brachytherapy for prostate cancer: pathophysiology, prevention and treatment

ObjectivesAlthough detrimental impact on sexual function following radiotherapy (RT) and brachytherapy decreases the quality of life of prostate cancer survivors, the etiology, pathophysiology, prophylaxis and treatment of this condition has not yet been fully clarified. We reviewed the published literature in terms of etiology, treatment and possible prevention of erectile dysfunction (ED) following RT and/or brachytherapy.MethodWe have reviewed the literature through a MEDLINE search. Prostate cancer, erectile dysfunction, radiotherapy, brachytherapy, treatment and quality of life were used as keywords.ConclusionBoth RT and brachytherapy result in high rates of ED. Although arterial damage seems to be the main cause of ED after RT, exposure of neurovascular bundle to high levels of radiation dose has been also implicated in some studies with brachytherapy. The radiation dose received by the corpora cavernosa at the crurae of the penis may also be important in the etiology of ED. The most important predictive factor of ED following RT is the treatment modality. Intensity-modulated radiotherapy and vessel-sparing prostate radiotherapy are new techniques but those treatments may not guarantee complete preservation of the erectile function. Patients need to be correctly informed on the possible sequela of radiation-based treatments on their sexual well-being while planning their treatment. Patients should also be informed about the possible treatment modalities for ED, which may develop in due course.

Apocynin attenuates testicular ischemia–reperfusion injury in rats

OBJECTIVE This study was designed to examine the possible protective effect of apocynin, a NADPH oxidase inhibitor, against torsion/detorsion (T/D) induced ischemia/reperfusion (I/R) injury in testis. METHODS Male Wistar albino rats were divided into sham-operated control, and either vehicle, apocynin 20mg/kg- or apocynin 50mg/kg-treated T/D groups. In order to induce I/R injury, left testis was rotated 720° clockwise for 4 hours (torsion) and then allowed reperfusion (detorsion) for 4 hours. Left orchiectomy was done for the measurement of tissue malondialdehyde (MDA), glutathione (GSH) levels, myeloperoxidase (MPO) activity, and luminol, lucigenin, nitric oxide (NO) and peroxynitrite chemiluminescences (CL). Testicular morphology was examined by light microscopy. RESULTS I/R caused significant increases in tissue luminol, lucigenin, nitric oxide and peroxynitrite CL demonstrating increased reactive oxygen and nitrogen metabolites. As a result of increased oxidative stress tissue MPO activity, MDA levels were increased and antioxidant GSH was decreased. On the other hand, apocynin treatment reversed all these biochemical indices, as well as histopathological alterations that were induced by I/R. According to data, although lower dose of apocynin tended to reverse the biochemical parameters, high dose of apocynin provides better protection since values were closer to the control levels. CONCLUSION Findings of the present study suggest that NADPH oxidase inhibitor apocynin by inhibiting free radical generation and increasing antioxidant defense exerts protective effects on testicular tissues against I/R. The protection with apocynin was more pronounced with high dose.

Urinary NGF, TGF-β1, TIMP-2 and bladder wall thickness predict neurourological findings in children with myelodysplasia.

PURPOSE Dimercapto-succinic acid scintigraphy and urodynamic studies are gold standards to evaluate renal scarring and neurogenic bladder dysfunction, respectively. We sought to establish the value of bladder wall thickness together with urine NGF, TGF-β1 and TIMP-2 to predict the urodynamic profile and upper urinary tract damage in children with myelodysplasia. MATERIALS AND METHODS A total of 80 children with myelodysplasia underwent urodynamic investigation, bladder wall thickness measurement and dimercapto-succinic acid scintigraphy with basic neurourological evaluation. Two study and 2 control groups were created according to presence or absence of renal scarring on dimercapto-succinic acid scan (study and control groups 1) and according to detrusor leak point pressure greater or less than 40 cm H2O (study and control groups 2). Urine samples were analyzed with ELISA. RESULTS The study population consisted of 44 girls and 36 boys with a median ± SD age of 7.2 ± 3.6 years (range 2 to 17). Study and control groups 1 consisted of 35 and 45 children with abnormal and normal dimercapto-succinic acid scan findings, respectively. Study and control groups 2 included 30 and 50 children with detrusor leak point pressure greater and less than 40 cm H2O, respectively. Bladder wall thickness and urinary levels of TGF-β1, NGF and TIMP-2 were significantly increased in both study groups compared to controls. CONCLUSIONS Urine markers and bladder wall thickness measurement may predict urinary tract impairment in children with myelodysplasia. Such markers may differentiate at risk patients with either renal scarring or high detrusor leak point pressure, and decrease the need for urodynamics and renal scintigraphy.

Quercetin treatment against ischemia/reperfusion injury in rat corpus cavernosum tissue: a role on apoptosis and oxidative stress

Abstract Reactive oxygen metabolites play an important role in the ischemia/reperfusion (I/R)-induced tissue injury. This study was designed to investigate the possible protective effects of quercetin against I/R injury of the rat corpus cavernosum tissue. To induce I/R injury, abdominal aorta was clamped for 30 min and reperfused for 60 min. Quercetin (20 mg/kg) or vehicle was given before ischemia and just after reperfusion in the I/R group and in the sham-operated control group in which clamping was not performed. After decapitation, corpus cavernosum tissues were removed and either placed in organ baths or stored for evaluating biochemical parameters. Oxidative injury was examined by measuring lucigenin chemiluminescence (CL), nitric oxide (NO), malondialdehyde (MDA) and glutathione (GSH) levels, superoxide dismutase (SOD) and myeloperoxidase (MPO) activities and caspase-3 protein levels. In the I/R group, contractile responses to phenylephrine and relaxation responses to carbachol were impaired significantly compared with those in the control groups, while quercetin treatment in I/R group reversed both of the responses. On the other hand, increase in lucigenin CL, NO, MDA levels and MPO and caspase-3 activities and decrease in GSH levels and SOD activity in the cavernosal tissues of the I/R group were also significantly reversed by quercetin treatment. Furthermore, observed distorted morphology with ruptured endothelial cells and vacuolization in the cytoplasm of cavernosal tissues of I/R no longer persisted in the quercetin-treated I/R group. Thus, our results suggested that treatment with quercetin may have some benefits in controlling I/R-induced tissue injury through its anti-inflammatory, anti-apoptotic, and antioxidant effects.

Effect of Testicular Sperm Extraction Outcome on Sexual Function in Patients With Male Factor Infertility

OBJECTIVES To document the effects of the outcome of testicular sperm extraction (TESE) procedures on erectile function in patients with male factor infertility. METHODS A total of 66 nonobstructive azoospermic patients were divided into 2 groups: group I, with sperm-positive results and group II, with sperm-negative results. The patients were evaluated with the International Index of Erectile Function-5 (IIEF-5) and Hospital Anxiety-Depression Scale. Hormones were analyzed before and 6 months after the procedure. Each group was compared with the use of the paired t test, where P <.05 was accepted as statistically significant. RESULTS The mean patient age was 34.8 years (range 24-53). Of 66 cases, 26 (40%) experienced positive results for the TESE. The median IIEF-5 score before TESE for group I and group II was 22 (minimum: 11, maximum: 25) and 23 (minimum: 10, maximum: 25), respectively. The median IIEF-5 score after TESE for group I and group II was 23.5 (minimum: 10, maximum: 25) and 18 (minimum: 15, maximum: 25), respectively. In patients who reported new onset erectile dysfunction (ED) 6 months after surgery, the mean follicle-stimulating hormone and luteinizing hormone levels increased from 21 +/- 2 to 38 +/- 3 IU/L (P <.001), and from 11 +/- 2 to 14 +/- 2 IU/L (P >.05), respectively. The mean total testosterone level decreased from 7.83 +/- 2 to 2.8 +/- 2 ng/mL (P <.001). The Hospital Anxiety and Depression Scale revealed that patients who reported new onset ED also reported both depression and anxiety. CONCLUSIONS Unsuccessful TESE procedures might have a negative effect on erectile function because of hormonal and psychological reasons. The andrologist should treat the ED of the patients and refer them to the psychiatrist for anxiety and depression assessment.

Melatonin and tadalafil treatment improves erectile dysfunction after spinal cord injury in rats

Oxidative stress plays an important role both in spinal cord injury (SCI) and erectile dysfunction (ED). The present study investigated the effects of melatonin and tadalafil treatment alone or in combination on SCI‐induced ED. Male Wistar albino rats (n = 40) were divided into five groups: sham‐operated control and SCI‐injured rats given either vehicle, melatonin (10 mg/kg, i.p.), tadalafil (10 mg/kg, p.o.) or a combination of melatonin and tadalafil. Spinal cord injury was induced using a standard weight‐drop method. On Day 7 after SCI, intracavernosal pressure (ICP) was measured and all rats were decapitated. Cavernosal tissues were obtained to examine caspase 3, nitric oxide synthase (NOS), myeloperoxidase (MPO) and superoxide dismutase (SOD) activities, as well as cGMP, nerve growth factor (NGF), malondialdehyde (MDA) and glutathione (GSH) levels. Spinal cord injury caused oxidative damage, as evidenced by increases in MDA and cGMP levels. In addition, MPO and caspase 3 activites were increased after SCI, whereas GSH and NGF levels and SOD activity were reduced. Melatonin effectively reversed these oxidative changes. Furthermore, in rats treated with both melatonin and tadalafil, the recoveries were more pronounced than in rats given either melatonin or tadalafil alone. The ICP/mean arterial pressure value in vehicle‐treated SCI rats was significantly higher than in the control group, whereas in the tadalafil‐ and tadalafil + melatonin‐treated groups have returned this value had returned to control levels. As an individual treatment, and especially when combined with tadalafil, a well‐known agent in the treatment of ED, melatonin prevented SCI‐induced oxidative damage to cavernosal tissues and restored ED, most likely due to its anti‐oxidant effects.

Is 40 cm H2O detrusor leak point pressure cut-off reliable for upper urinary tract protection in children with myelodysplasia?

The purpose of this study, is to find out the most accurate cut‐off level for the detrusor leak point pressure (DLPP) in terms of upper urinary tract (UUT) protection in a cohort of children with myelodysplasia.

Intradetrusor Injections of Onabotulinum Toxin-A in Children With Urinary Incontinence due to Neurogenic Detrusor Overactivity Refractory to Antimuscarinic Treatment

Purpose This was a prospective single-arm study to assess the efficacy and safety of intradetrusor injections of onabotulinum toxin-A in children with urinary incontinence associated with neurogenic detrusor overactivity due to myelomeningocele. All patients had failed the first-line treatment of a combination of oral antimuscarinics and intermittent catheterization. Materials and Methods The study group consisted of 31 children with myelomeningocele with a mean age of 7.95 years (range, 5-3 years) who were followed up for a mean of 29 weeks. The amount of onabotulinum toxin A injected was 10 U/kg with a maximal dose of 300 U. There were 20 to 30 injection sites with rigid cystoscopic guidance under general anesthesia. Results Thirty of 31 patients reported dryness between intermittent catheterization intervals. The mean reduction in maximum detrusor pressure and the mean increase in maximum cystometric capacity from baseline were 53% and 51.5%, respectively, 6 weeks after injection. We found a 324% increase in mean bladder compliance and a 57% increase in mean intermittent catheterization volumes. The mean duration of efficacy was 28 weeks with a single injection and 36 weeks for repeated injections (minimum, 16 weeks; maximum, 52 weeks). The mean time interval between repeated onabotulinum toxin-A injections was 7 months (maximum, 13 months). Intradetrusor injections of onabotulinum toxin-A were well tolerated. Conclusions Onabotulinum toxin-A injections into the bladder wall provide a significant symptomatic and urodynamic improvement in children with neurogenic detrusor overactivity due to myelomeningocele who are on intermittent catheterization. The treatment seems to be safe and very well tolerated.

Nonalcoholic Fatty Liver Disease is Associated With Erectile Dysfunction: A Prospective Pilot Study

INTRODUCTION Nonalcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome (MetS). Although the link between MetS and erectile dysfunction (ED) is well known, clinical studies investigating the association between NAFLD and ED are scant. AIM To evaluate the relationship between NAFLD and ED. METHODS Male patients with biopsy-proven NAFLD were prospectively asked to fill the five-item International Index of Erectile Function (IIEF-5) questionnaire. Their clinical and histologic variables were compared with the IEFF scores. MAIN OUTCOME MEASURES IIEF scores; proportions of NAFLD patients who demonstrated ED and/or MetS; association between the severity of histological hepatic damage and ED. RESULTS Forty male patients having an age range of 33 (24-57) and a mean age of 40.13 ± 10.22 years with biopsy-proven NAFLD had a median IIEF-5 score of 16 (9-25) and MetS was present in 23 (57.5%). ED severity distributions as moderate, mild, and no ED were 11 (27.5%), 16 (40%), and 13 (32.5 %), respectively. Histological NAFLD score was significantly higher in patients having ED compared with patients with no ED (5.63 ± 1.39 vs. 4.15 ± 1.46; P = .006). MetS diagnosis was significantly more common in patients having ED, compared with those without ED [19 (70.4%) vs. 4 (30.8%), respectively, P = .018)]. When patients with and without ED were compared, gamma glutamyl transferase was significantly lower in ED, whereas components of MetS did not correlate with ED. After multivariate analysis, NAFLD score has remained the only significant outcome associated with ED [P = .03; OR (95% CI): 2.38 (1.079-5.238)]. CONCLUSION The current clinical study demonstrates a significant association between nonalcoholic steatohepatitis and ED for the first time. Our findings suggest liver damage may play role in the pathogenesis of ED in patients with NAFLD. Future studies are needed to expand the underlying common mechanisms responsible for this novel hypothesis.

Clinical and Urodynamic Results of Repeated Intradetrusor Onabotulinum Toxin A Injections in Refractory Neurogenic Detrusor Overactivity: Up to 5 Injections in a Cohort of Children With Myelodysplasia

OBJECTIVE To determine the efficacy and safety of repeated intradetrusor onabotulinum toxin A (onaBoNT-A) injections in children with neurogenic detrusor overactivity due to myelodysplasia. MATERIALS AND METHODS The study group consisted of 19 children (4 boys and 15 girls) with a mean age of 10.3 ± 3.1 years old, who had received at least 2 injections of 10 U/kg onaBoNT-A for the treatment of urinary incontinence resistant to anticholinergic treatment and clean intermittent catheterization in our clinic, between 2010 and 2015. Controlled urodynamic studies were performed at the baseline and 3 months after each injection. RESULTS Eight of the children received 3 injections, 5 children had 4 injections, and 2 children had 5 injections. From the baseline to the fifth injection, the detrusor compliance (1.3, 4.5, 10, 20.7, 18.8, and 16.6 mL/cm H2O), the maximum bladder capacity (82.0, 157.0, 191.0, 272.0, 299.0, and 210.5 mL), and the maximum detrusor pressure (55.0, 33.0, 22.0, 12.5, 16.0, and 12.5 cm H2O) were assessed. The findings significantly improved following the first, second, and third injections, when compared with the previous bladder dynamics (P <.05), but the differences with the fourth were not statistically significant (P >.05). The continence periods were similar under clean intermittent catheterization after all of the injections (P <.05), and no severe side effects were observed. CONCLUSION Repeated onaBoNT-A injections are a safe treatment modality and can be offered as an effective alternative choice, instead of more invasive surgery, in children with neurogenic detrusor overactivity due to myelodysplasia.