Sildenafil Vs. Tadalafil for The Treatment of Benign Prostatic Hyperplasia: A Single-arm Self-controlled Clinical Trial.

PURPOSE: To compare the efficacy and adverse events of sildenafil monotherapy for benign prostatic hyperplasia (BPH) with its FDA-approved counterpart, tadalafil. MATERIALS AND METHODS: In this single-arm self-controlled clinical trial, 33 patients were enrolled. All patients underwent a 6-week treatment with sildenafil, followed by a 4-week washout period and finally a 6-week treatment with tadalafil. Patients were examined on each appointment and post-void residual (PVR) urine, International Prostate Symptom Score (IPSS) and Quality of life index (IPSS-QoL index) were recorded subsequently. Efficacy of each drug regimen was then evaluated by comparing these outcome parameters. RESULTS: Both sildenafil and tadalafil were shown to improve PVR (both p < .001), IPSS (both p < .001) and IPSS- QoL index (both p < .001) significantly. Sildenafil was more effective than tadalafil in reducing PVR (mean difference (95%CI) = 9.91% (4.11, 15.72), p < .001) and ameliorating IPSS-QoL index (mean difference (95%CI) = 19.3% (4.47, 34.41), p = .027). Moreover, although not significant, sildenafil reduced IPSS more than tadalafil (mean difference (95%CI) = 3.33% (-0.22, 6.87), p = .065). Concurrent erectile dysfunction did not affect responsiveness to therapy with either sildenafil or tadalafil but age was inversely related to post-treatment IPSS in both sildenafil (B = 0.21 (0.04, 0.37), p = .015) and tadalafil (B = 0.14 (0.02, 0.26), p = .021) regimens with a more prominent role in responsiveness to sildenafil (ß = 0.31) compared to tadalafil (ß = 0.19). CONCLUSION: Considering the significantly better improvement of PVR and IPSS-Qol index with sildenafil, this drug can be nominated as a suitable alternative for tadalafil as a BPH treatment, especially in younger patients who don't have any contraindications.

Influence of cytotoxic T lymphocyte antigen 4 genetic variants on acute rejection in kidney transplant patients: precision medicine perspective.

Background: The most effective and common treatment for end-stage renal disease is kidney transplantation.The personalized approach to kidney transplantation, which utilizes precision medicine principles, determines distinctive genomics characteristics of candidates/recipients that must be taken into account. Cytotoxic T lymphocyte associated protein 4 (CTLA4) may be a suitable candidate gene for studying allograft rejection. The aim of this study was to understand whether we can consider two common variants of the CTLA4 gene as a risk factor of transplant rejection in a group of Iranian population. Methods: Totally, 169 kidney transplant recipients, including acute rejections (N=39) and non-rejection (N=130) groups who underwent transplantation were included in this study. The genotyping of rs5742909 (-318C/T) and rs231775 (+49A/G) variants of the CTLA4 gene were performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Results: The AG genotype frequency of rs231775 variant was the same in both patients with and without a history of rejection while, none of those groups had homozygote genotype. In rs5742909, both CT and TT frequencies of patients with rejected transplant were lower than patients with a normal outcome. Conclusions: The results of the presented study suggest that rs231775 and rs5742909 of CTLA4 genetic variants are not linked to acute rejection who underwent kidney transplantation. So, these variants cannot be considered as risk factors of acute allograft rejection in a group of Iranian renal transplantation recipients. However, the transplantation precision medicine may be an important area for the improvement of patients outcome as the precision medicine has already entered clinical practice in kidney transplantation.

Kallikarein-related peptidase 3 common genetic variant and the risk of prostate cancer.

Kallikarein-related peptidase 3 (KLK3) gene polymorphisms seem to play a role in susceptibility to prostate cancer (PC). The purpose of this study was to investigate the association between rs2735839 polymorphism of KLK3 gene and risk of PC in an Iranian population. In this case-control study, rs2735839 was genotyped in 532 patients with PC and 602 controls with benign prostate hyperplasia (BPH) using polymerase chain reaction-restriction fragment length polymorphism assay. The frequency of GG, AG, and AA genotypes of KLK3 polymorphism was 24.6% and 76.2%, 46.6% and 21.7%, and 28.8% and 2.1%, in patients with BPH and PC, respectively (P < 0.001). The frequency of G allele in patients with BPH and PC was 47.9% and 87%, respectively (odds ratio: 7.31; confidence interval: 5.88-9.10; P < 0.001). Patients with AG and GG genotypes had a higher total serum level of prostate-specific antigen (PSA) compared to those with AA genotype (P < 0.001). Patients with this polymorphism had higher risk of tumor with higher grade (P = 0.23), advanced stage (P = 0.11), perineural invasion (P = 0.07), and vascular invasion (P = 0.07) compared to those without it but this difference was not statistically significant. Based on our results, KLK3 gene polymorphism was associated with the risk of PC. Higher levels of PSA in the presence of KLK3 polymorphism in patients with PC indicated that rs2735839 polymorphism could be a risk factor for increased levels of PSA.

Association of XPC Gene Polymorphisms with Prostate Cancer Risk.

BACKGROUND: Defective DNA repair capacity caused by inherited polymorphisms could be associated with cancer susceptibility. One of the major repair pathways is Nucleotide Excision Repair (NER). We investigated Xeroderma Pigmentosum complementation group C (XPC) polymorphisms (Lys939Gln, PAT) with the risk of prostate cancer. METHODS: 154 confirmed prostate cancer patients and 205 Benign Prostate Hyperplasia (BPH) controls were recruited in this survey. The genotypes were determined by PCR-Restriction Fragment Length Polymorphism (RFLP) method. RESULTS: Our results indicated that there were no significant differences between the BPH group and patient group for the XPC Lys939Gln in this pathway. However, deletion/insertion (D/I) and insertion/insertion (I/I) of XPC PAT polymorphism in this pathway could decrease the risk of prostate cancer and act as a protective factor. CONCLUSIONS: In this study, XPC Lys939Gln gene polymorphism was not associated with the risk of developing prostate cancer in Iranian patients. There are no association between different alleles of this polymorphism and grades and stages of tumors, but our results indicated the significant association between XPC PAT and reduction of prostate cancer risk in this group of patients. For more significant results, further samples are required.

Genetic Polymorphism of MMP2 Gene and Susceptibility to Prostate Cancer.

BACKGROUND AND AIMS: The polymorphic genetic variants of matrix metalloproteinase (MMPs) can play critical roles in development and progression of cancer. The purpose of this study was to investigate if any association exists between MMP2 -1306/T and risk of prostate cancer (PCa). METHODS: This case-control study comprised a total number of 241 subjects, including 102 patients with PCa and 139 controls with benign prostatic hyperplasia (BPH). MMP2 genotypes were detected by RFLP. RESULTS: There is no significant difference between different genotypes of MMP2 polymorphism and risk of developing PCa (p = 0.08). Although these genotypes increased the risk of developing PCa 79% (CT vs. CC) and 54% (TT vs. CC), none had a significant effect (p = 0.09 and p = 1 respectively). There were no significant differences in genotype frequencies between patients with low and high degrees of PCa (p = 0.4). Therefore, this polymorphism cannot be considered as a protective factor for PCa metastasis. It seems that MMP2 polymorphism has no protective effect on the grading of the tumor (p = 0.8). Our results indicated that MMP2 polymorphism had no role in the vascular invasion of PCa. CONCLUSION: We found no association between MMP2 polymorphism and cancer risk, overall or by grade, stage or age of diagnosis. Finally, there was no association between the different genotypes and PSA plasma levels among cases or controls. Further evaluations with larger samples from our population may illuminate the effects of polymorphisms on PCa risk and thus help early diagnosis, follow-up and prognostic determinations for PCa patients.

Pediatric kidney transplant with laparoscopic donor nephrectomy.

OBJECTIVES: To evaluate outcomes and complications with pediatric living-donor kidney transplant, mostly performed with laparoscopic donor nephrectomy. MATERIALS AND METHODS: In the 25 years between February 1987 and December 2012, there were 493 children aged ≤ 17 years who received a kidney transplant. Demographic characteristics, graft and patient survival, rejection episodes, and complications were recorded. Analysis was performed for 3 sequential periods (1987-1994, 1995-2002, and 2003-2012). RESULTS: The mean patient age was 13 ± 4 years (age range, 2.5-17 y). There were 290 males (59%). Glomerulonephritis was the most common cause of end-stage renal disease. Preemptive kidney transplant was performed in 412 patients (84%). Donor nephrectomy was performed laparoscopically in 445 patients (90%). The 5-year graft and patient survival were improved from 1987-1994 to 2003-2012. The overall death-censored graft survival was 96% at 1 year, 78% at 5 years, and 66% at 10 years after transplant. The overall patient survival was 96% at 1 year, 83% at 5 years, and 75% at 10 years after transplant. CONCLUSIONS: Kidney transplant is available for most pediatric patients and has acceptable graft and patient survivals. Laparoscopic donor nephrectomy improves donor satisfaction and morbidity, and may provide excellent graft outcomes in children.

Endothelial nitric oxide synthase Glu298Asp polymorphism as a risk factor for prostate cancer.

BACKGROUND: The endothelial form of nitric oxide synthases (eNOS) seems to have an important role in vascular development, maintenance of the vascular tone and tumor growth in human prostate cancer (PC). The purpose of this study was to investigate the association between grade and stage of disease, age of diagnosis, vascular or perineural invasion, pre-diagnostic plasma prostate-specific antigen (PSA) levels, prostate cancer risk and Glu298Asp polymorphism of the eNOS gene.
 METHODS: Ninety-five prostate cancer patients and 111 benign prostate hyperplasia subjects were included. The Glu298Asp polymorphism of the eNOS gene was determined by polymerase chain reaction and restriction fragment length polymorphism 
 RESULTS: The odds ratio (OR) between the GT and GG polymorphism was 0.76, indicating that the presence of the GT polymorphism decreased the risk of prostate cancer of more than 20% compared to the GG polymorphism. This difference, however, was not statistically significant. The GT polymorphism had an inverse association with cancer grade compared to the reference group (OR=0.47, p value=0.2).
 CONCLUSIONS: These results suggest that prostate cancer development is not associated with the Glu298Asp polymorphism of the endothelial nitric oxide synthase gene in our population. Further studies in larger samples are needed to confirm our results and characterize the molecular mechanisms by which eNOS is involved in the susceptibility to prostate cancer.

Association of G/A polymorphism, rs266882, in AREI region of the prostate-specific antigen gene with prostate cancer risk and clinicopathological features.

PURPOSE: To determine the association of prostate-specific antigen (PSA) 158A/G polymorphism with clinicopathologic characteristics of the disease and prostate cancer (PCa) risk. MATERIALS AND METHODS: Two hundred and six subjects, including 95 patients with PCa and 111 subjects with benign prostatic hyperplasia (BPH), were recruited in this study. Genotyping was performed by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism method. RESULTS: Presence of GG genotype significantly increased the risk of PCa more than 2-fold compared to AG genotype (adjusted odds ratio = 2.4; P = .03). The percentages of G alleles of polymorphisms in patients with PCa were more than that in ones with BPH (odds ratio = 1.2; P = .7). CONCLUSION: The GG genotype of PSA 158A/G polymorphism is a predisposing factor for PCa. But no association was observed between alleles and grade, stage, or age of diagnosis. Similarly, the rs266882 polymorphism was not associated with PSA plasma levels.

Association of angiotensin I converting enzyme polymorphism as genetic risk factor in benign prostatic hyperplasia and prostate cancer.

INTRODUCTION: Angiotensin I converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism is one of the genetic factors found to be related with prostate cancer (PC). We investigated the association between grade and stage of disease, age of diagnosis, vascular or perineural invasion, prediagnostic plasma prostate specific antigen (PSA) levels, and PC risk with I/D polymorphism of the ACE gene. MATERIALS AND METHODS: We recruited 206 subjects in this study, including 95 patients with PC and 111 patients with benign prostatic hyperplasia. RESULTS: The odds ratio between II and DD polymorphisms (reference) was 1.38. It means that the presence of the II polymorphism increased the risk of cancer more than 38% compared with DD polymorphism although still it was not statistically significant. The mean of total PSA in the patients with the II genotype was 20 ng/L more than that in those who had DD polymorphism. The odds ratio (OR) between the D allele and PC development was 1.16, indicating that this allele increased the risk of cancer about 16%. CONCLUSION: We found no association between the ACE polymorphism and cancer risk, overall or by grade, stage, or age of diagnosis. The difference in results for ACE polymorphisms between studies may be minimized by using larger study groups.

Laparoscopic animal surgery for training without sacrificing animals; introducing the rabbit as a model for infantile laparoscopy.

INTRODUCTION: Improvement in laparoscopic skills requires practicing, and it is mostly beneficial when live animal models are considered for use. Apart from pelvic trainer, dogs and rabbits are used as the animal models for training laparoscopic surgeries at our center. Every effort is made to keep the animals alive after surgery. MATERIALS AND METHODS: From January 2007 to January 2010, German shepherd dogs and Angora rabbits were selected as the animal models for laparoscopic skill training. Under general anesthesia, trainees performed several laparoscopic surgeries under the supervision of experienced surgeons. RESULTS: A total number of 72 animals including 54 dogs and 18 rabbits were used for training laparoscopy. In total, some 107 different laparoscopic procedures were performed by trainees including nephrectomy, nephropexy, vesicotomy and vesicorrhaphy, vasectomies, spermatic cord ligation, and unilateral oophrectomy. There were one vascular and two visceral injuries in the rabbit model that were laparoscopically controlled, and conversion to open surgery happened in one case due to the failure in extracting the specimen from the abdominal cavity. Three visceral and six vascular injuries occurred in the canine model. Total mortality was five including three rabbits and two dogs. CONCLUSIONS: The sacrifice of the animal is important to be avoided from both ethical and technical stand points. Dogs and rabbits are good models for laparoscopic training in urology, and it is possible to keep the animals alive after surgery by close monitoring. We also found the rabbit to be a good model for practicing infantile laparoscopic surgery, as it simulates the real surgery in this difficult age group.

Impact of sleep position on stone clearance after shock wave lithotripsy in renal calculi.

OBJECTIVES: We evaluated the impact of sleep position on the effectiveness of shock wave lithotripsy (SWL) in renal calculi. PATIENTS AND METHODS: Patients (n = 120) with a single radiopaque renal stone who were candidates for SWL were enrolled. For studying patients' position during sleep, a novel sleep position recorder was designed. Group 1 (n = 60) consisted of patients who slept preferentially on the ipsilateral side of the stone; group 2 (n = 60) comprised patients who slept preferentially on the contralateral side. Treatment effectiveness was defined as the absence of residual stones >3 mm up to 3 months after SWL. RESULTS: The mean (range) percent of sleep on the ipsilateral side of the stone was 61.5% (51-78) and on the contralateral side it was 62.4% (51-81) in groups 1 and 2, respectively (p > 0.05). The overall success rate of SWL was 88.3% (77.4-95.2) and 70.0% (56.8-81.2) in groups 1 and 2, respectively (p = 0.01). Stone clearance increased with an increasing percent of total sleep time on the ipsilateral side of the kidney stone (p = 0.045). CONCLUSIONS: The percent of stone-free patients was higher in the group of patients who slept ipsilaterally relative to the kidney stone compared with patients who slept on the contralateral side.

Laparoscopic retroperitoneal lymph node dissection for stage I nonseminomatous germ cell testis tumors: the first case series in Iran.

PURPOSE: To report laparoscopic retroperitoneal lymph node dissection (RPLND) as an approach for management of low-stage nonseminomatous germ cell testis tumors (NSGCT). MATERIALS AND METHODS: Between August 2002 and December 2008, 19 patients with stage I NSGCT underwent RPLND in our center. RESULTS: Mean operation time was 340 minutes (range, 250 to 360 minutes). Procedure in 2 (10.5%) patients was converted to open. Four (21%) patients had tumors with pure histopathology while other 15 (79%) had mixed histopathology. The mean number of removed lymph nodes was 11 (range, 6 to 14). Pathology revealed lymph node involvement in 8 (42%) patients, including 6 (75%) viable tumors and 2 (25%) teratoma. After on average 47-month follow-up (range, 3 to 70 months), recurrence occurred in 2 (10.5%) patients, who underwent open retroperitoneal lymph node dissection after chemotherapy, and surgical pathology revealed teratoma in one and fibrotic tissue in another. No patient developed systematic metastasis during followup period. CONCLUSION: Our results show that compared with open surgery, RPLND has same oncologic outcome, but lower, and can be recommended for management of patients with low stage NSGCT.

Evaluation of the learning curve for percutaneous nephrolithotomy.

PURPOSE: To determine the number of percutaneous nephrolithotomy (PCNL) operations which are required to achieve competence or excellence. MATERIALS AND METHODS: One hundred and five consecutive PCNL operations performed by a fellow in endourology, with no previous experience in performing solo PCNL, were studied. Operation duration, stone extraction percent, stone-free rate, number of access, tubeless cases, and complications were studied in sequential groups of 15 patients as the surgeon gained experience. RESULTS: Operation duration decreased from the mean of 95.4 minutes in the first to 15th patients to 78.3 minutes in the 31st to 45th patients, and then remained unchanged. Minor complications were only observed in the first to 45th patients. Stone extraction percent increased from the mean of 88.3% in the first to 15th patients to 99.3% in 91st to 105th patients. Percentage of patients with no residual fragments decreased from 53% in the first to 15th patients to 6.7% in the 91st to 105th patients. No statistically significant differences were observed in estimated blood loss or transfusion rate between sequential groups of subjects. CONCLUSION: An improvement in operation duration was observed, and absence of complications was achieved after 45 cases. The improvement in stone clearance was observed up to the last subjects. Competence and excellence were achieved after 45 and 105 operations, respectively.

Some notes on stem cell therapy in cardiovascular diseases.

Cardiovascular diseases have become an increasing clinical issue worldwide. Acute ischaemic injury and chronic cardiomyopathies lead to permanent loss of cardiac tissue and ultimately heart failure. Current therapies widely aim to attenuate the pathological changes that occur after injury and to reduce risk factors of cardiovascular diseases. However, they do not improve the patient's quality of life or the prognosis more than moderate. A new challenge in the treatment of the cardiovascular disease is cellular transplantation or cellular cardiomyoplasty. Different types of stem cells have been used for stem cell therapy. Clinical trials using primary bone-marrow-derived cells and skeletal myoblasts have also shown some encouraging results. An additional clinical and pre-clinical study to further enhance the beneficial effects of cell therapy is necessary. Recent studies have shown that there are various pools of putative resident stem cells in an adult heart, raising the hope that these cells can contribute to the treatment of cardiovascular diseases.