Is There a Role for Genetic Information in Risk Assessment and Decision Making in Prostate Cancer?

OBJECTIVES: Prostate cancer is a neoplasm with a variable natural history and clinical behavior. There is much debate on the use of inherited genetic information in clinical application including risk assessment and treatment decisions. This study was performed to evaluate the relationship between clinical parameters of prostate cancer (PSA, Gleason score, and metastasis) and expression of NKX3.1, AMACR, TMPRSS2-ERG, ERG, and SPINK1 genes. METHODS: Newly diagnosed cases of prostate cancer were selected for this study. Thirty four tissue samples were obtained via open radical prostatectomy and 9 samples were obtained via needle biopsy. Each tissue sample was sectioned into two parts, one used for detection of malignant changes and Gleason score determination, and the other immersed in RNA later solution (Qiagen). The expression of NKX3.1, AMACR, TMPRSS2-ERG, ERG, and SPINK1 genes were assessed by real-time PCR assay. Correlation between expression of each gene and PSA level, Gleason score, and presence of metastasis were examined. RESULTS: A total number of 43 specimens were studied, from which 9 were obtained from patients with metastatic prostate cancer. The expression of five examined genes had no correlation with PSA level and Gleason score. The expression of AMACR decreased in metastatic prostate cancer (P = 0.02). The expression of other genes showed no difference between metastatic and non-metastatic tumors (P > 0.1). CONCLUSIONS: Genetic information combined with clinical data can be useful in risk assessment and treatment planning. Based on the results of the current study, the decreased expression of AMACR was a sign of poor prognosis.

Relationship Between Perineural Invasion in Prostate Needle Biopsy Specimens and Pathologic Staging After Radical Prostatectomy.

BACKGROUND: Prostate cancer is the second most common malignancy among men worldwide and the sixth cause of cancer-related death. Some authors have reported a relationship between perineural invasion (PNI), Gleason score, and the invasion of peripheral organs during prostatectomy. However, it is not yet clear whether pathological evidence of PNI is necessary for risk stratification in selecting treatment type. OBJECTIVES: The clinical and pathological stages of prostate cancer are compared in patients under radical prostatectomy and in patients without perineural invasion. PATIENTS AND METHODS: This cross-sectional study was conducted using a sample of 109 patients who attended a tertiary health care center from 2008 to 2013. The selection criteria were PNI in prostate biopsy with Gleason scores less than six, seven, and eight to ten. The participants were enrolled in a census manner, and they underwent clinical staging. After radical prostatectomy, the rates of pathological staging were compared. The under-staging and over-staging rates among those with and without perineural invasion in biopsy samples were compared. RESULTS: The concordance between Gleason scores according to biopsy and pathology was 36.7% (40 subjects). The concordance rate was 46.4% and 33.3% among those with and without PNI, respectively. The concordance rates were significantly varied in different subclasses of Gleason scores in patients without PNI (P = 0.003); the highest concordance rate was a Gleason score of 7 (63.6%) and the lowest was a Gleason score of eight to ten (25%). However, there were no significant differences in patients with PNI (P > 0.05). CONCLUSIONS: Although the presence of PNI in prostate biopsy is accompanied by higher surgical stages, PNI is not an appropriate independent factor in risk stratification.

Postchemotherapy Retroperitoneal Lymph Node Dissection in Patients With Nonseminomatous Testicular Cancer: A Single Center Experiences.

BACKGROUND: Testicular cancer accounts for about 1 - 1.5% of all malignancies in men. Radical orchiectomy is curative in 75% of patients with stage I disease, but advance stage with retroperitoneal lymph node involvement needs chemotherapy. All patients who have residual masses ≥ 1 cm after chemotherapy should undergo postchemotherapy retroperitoneal lymph node dissection (PC-RPLND). OBJECTIVES: Treatment of advanced nonseminomatous testicular cancer is usually a combination of chemotherapy and surgery. We described our experience about postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) in our center. PATIENTS AND METHODS: In a retrospective cross-sectional study between 2006 and 2011, patients with a history of postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) in Imam Khomeini hospital were evaluated. All patients had normal postchemotherapy serum tumor markers and primary nonseminomatous cancer. We reviewed retrospectively clinical, pathological, and surgical parameters associated with PC-RPLND in our center. RESULTS: Twenty-one patients underwent bilateral PC-RPLND. Mean age was 26.3 years (ranged 16 - 47). Mean size of retroperitoneal mass after chemotherapy was 7.6 cm. Mean operative time was 198 minutes (120 - 246 minutes). Mean follow-up time was 38.6 months. Pathologic review showed presence of fibrosis/necrosis, viable germ cell tumor and teratoma in 8 (38.1%), 10 (47.6%) and 3 (14.28%) patients, respectively. One patient in postoperative period of surgery and three patients in two first years after surgery were expired. Of 17 alive patients, only two (11.8%) had not retrograde ejaculation. CONCLUSIONS: PC-RPLND is one the major operations in the field of urology, which is associated with significant adjunctive surgeries. In appropriate cases, PC-RPLND was associated with good cancer specific survival in tertiary oncology center.

Unusual Presentation of Renal Cell Carcinoma in Crossed Ectopic Kidney.

INTRODUCTION: Crossed renal ectopia is a rare anomaly and ninety percent of crossed ectopic kidneys are fused to their ipsilateral mate. Based on autopsy findings, the incidence has been estimated to be one in 2000 individuals. CASE PRESENTATION: We hereby report on a 53-year-old woman with two episodes of painless gross hematuria. Imaging revealed left side fused crossed renal ectopia and filling defect within the pyelocaliceal of crossed kidney. CONCLUSIONS: The patient underwent surgery applying a midline incision. The left kidney showed a lump pattern embedded in lower pole of the right kidney. Left sided nephrectomy was performed while temporary right renal artery was clamped temporarily. Histopathological evaluation revealed clear cell carcinoma with severe nuclear atypia (Fuhrman grade 4/4). However, local recurrence was not detected during the 18-month follow up after surgery.

Comparison of the Efficacy of Two Brands of Triptorelin (Microrelin and Diphereline) in Reducing Prostate-Specific Antigen and Serum Testosterone in Prostate Cancer: A Double-Blinded Randomized Clinical Trial.

BACKGROUND: Gonadotropin-releasing hormone (GnRH) agonists initiate androgen deprivation in treating prostate cancer (PC). Triptorelin is a synthetic GnRH and many of its market brands such as Diphereline have been introduced so far. OBJECTIVES: We compared the efficacy of a sustained-release formulation of Triptorelin (Microrelin), domestically produced in Iran, and compared it with Diphereline in a double-blinded randomized clinical trial. PATIENTS AND METHODS: Patients were randomly assigned to Group A (Microrelin S.R. 3.75 mg, Pooyesh Darou, Iran) and Group B (Diphereline S.R. 3.75 mg, IPSEN, France). Each patient received monthly intramuscular injections. Prostate-specific antigen (PSA) and circulatory testosterone were measured at baseline and after one, 3, and 6 months. RESULTS: Each group contained 40 patients. In Group A, PSA was reduced from 75.78 ± 72.43 ng/mL to 1.93 ± 1.40 ng/mL after 6 months and testosterone was reduced from 3.50 ± 1.12 nmol/L to 0.81 ± 0.05 nmol/L. There was no significant difference between the efficacy of Microrelin and Diphereline. Two patients in the Microrelin Group and one patient in the Diphereline Group failed to reach medical castration (testosterone < 1.7 nmol/L), which illustrates that the power of Microrelin and Dipherelin in initiating medical castration is about 95% and 97.5%, respectively. CONCLUSIONS: Our study showed that Microrelin is as effective as Diphereline in reducing PSA and testosterone and can be recommended to initiate medical castration in patients with PC.

Transition Zone Prostate-specific Antigen Density Could Better Guide the Rebiopsy Strategy in Men With Prostate Inflammation at Initial Biopsy.

OBJECTIVE: To assess the role of transition zone prostate-specific antigen density (TZPSAD) in determining rebiopsy strategy in men with prostate inflammation at initial biopsy. MATERIALS AND METHODS: Analysis was performed on data derived from transrectal ultrasound-guided prostate biopsy registry containing 2461 men who underwent biopsy between March 2005 and January 2015. Eligible patients were divided into 2 groups based on the presence of chronic inflammation in prostate. Group 1 consisted of 920 patients with histopathologic evidence of chronic inflammation and group 2 consisted of 1287 patients with no evidence of inflammation. Receiver operating characteristic curve analysis was performed to evaluate the accuracy of PSA, PSA density (PSAD), and TZPSAD for detecting prostate cancer (PCa) in each group. Patients who underwent rebiopsy during the study period were further assessed to determine factors that may predict the presence of PCa on subsequent biopsies. RESULTS: In group 1 patients, at 90% sensitivity for detecting PCa, PSAD and TZPSAD showed 19.7% and 37.8% specificity at cutoff values of 0.10 and 0.27 ng/mL/mL respectively, whereas in group 2 patients, PSAD and TZPSAD revealed 29.8% and 31.4% specificity, respectively. Chronic inflammation at initial biopsy was associated with a significant decrease in the likelihood of cancer detection during rebiopsy (odds ratio, 0.42; 95% confidence interval, 0.18-0.99). TZPSAD was found to be capable of sparing 39.8% of unnecessary rebiopsies in group 1 patients, whereas it spared 20.5% of unnecessary rebiopsies in group 2 patients. CONCLUSION: Applying TZPSAD is advantageous in determining rebiopsy strategy in patients with proven inflammation of prostate at initial biopsy.

Transition zone prostate specific antigen density improves prostate cancer detection in Iranian men.

BACKGROUND: Prostate specific antigen (PSA) as a tumor marker has extensively changed the diagnosis of prostate cancer (PCa). With the advent of PSA, the majority of patients are diagnosed with nonpalpable early stage PCa. However, PSA lacks specificity and many patients undergo unnecessary biopsies due to an elevated serum PSA level. OBJECTIVES: This study aimed to assess the sensitivity and specificity of transition zone PSA density (TZPSAD) in detection of PCa. PATIENTS AND METHODS: This study was performed on 1712 men underwent trans-rectal ultrasound guided prostate biopsy in our institution between March 2008 and March 2013. A total of 1120 men with PSA < 20 ng/mL and normal digital rectal exam were selected for evaluation. Transition zone PSA density was calculated in all patients and the receiver operating characteristic (ROC) curve was used to analyze the accuracy of TZPSAD for the diagnosis of PCa. RESULTS: Among 1120 men who were eligible for enrolment, prostate cancer was detected in 265 patients. Mean serum PSA levels were 9.7 ± 4.3 ng/mL and 8.5 ± 3.7 ng/mL in patients with and without PCa, respectively (P < 0.001). Mean value for TZPSAD was 1.18 ± 1.19 ng/mL/mL in patients with PCa, whereas it was 0.55 ± 0.84 ng/mL in men without cancer (P < 0.001). Optimal cut-off value for TZPSAD was 0.32 ng/mL. At this cut-off value, the sensitivity and specificity values for TZPSAD were 85% and 45%, respectively. Applying the TZPSAD for PCa screening decreased 50% of unnecessary biopsies. CONCLUSIONS: Using TZPSAD as an adjunct to PSA may improve the specificity of PSA in the diagnosis of PCa and decrease the number of unnecessary prostatic biopsies in Iranian men with serum PSA level < 20 ng/mL.

Effects of surgical position on patients' arterial blood gases during percutaneous nephrolithotomy.

PURPOSE: To compare arterial blood gas analysis of patients who underwent percutaneous nephrolithotomy (PCNL) in flank position under ultrasonography guidance with PCNL in prone and supine positions under fluoroscopic guidance. MATERIALS AND METHODS: In a clinical trial, a total of 90 patients with no upper urinary tract abnormalities were candidate for the PCNL. They were assigned into three groups using pseudorandomization method (30 patients in each group). Patients in group 1 underwent ultrasonography-guided PCNL in flank position. Patients in groups 2 and 3 underwent fluoroscopic-guided PCNL in prone and supine positions, respectively. Arterial blood gas was taken just before and 20 minutes after repositioning. RESULTS: The patients' mean age was 40.8 ± 6.9, 39.4 ± 10.6, and 37.2 ± 11.1 years in flank, prone, and supine positions, respectively (P = .69). The mean body mass index was 27.8 ± 3.4, 26.7 ± 4.7, and 28.1 ± 5.1 kg/m² in flank, prone, and supine positions, respectively (P = .21). Arterial oxygen pressure (PaO2) increased significantly in flank (111.7 ± 43.8 to 132.8 ± 58.1 mmHg; P = .01) and prone (118.6 ± 50.2 to 134.6 ± 58.5 mmHg; P < .001) positions and decreased nonsignificantly in supine group (121.7 ± 64.5 to 119.7 ± 60.9 mmHg; P = .23). With surgical positioning, there were no significant changes demonstrated in PaCO2 and serum concentration of HCO3 in the flank, prone, and supine groups. CONCLUSION: We could suggest that flank and prone positions could improve patients' oxygenation during PCNL procedure.

Percutaneous nephrolithotomy with ultrasonography-guided renal access in the lateral decubitus flank position.

PURPOSE: Our aim was to evaluate the safety and efficacy of percutaneous nephrolithotomy (PCNL) with ultrasonography (US)-guided renal access in the lateral decubitus flank position. PATIENTS AND METHODS: From July 2006 to March 2008, 40 patients with renal stones > 2 cm underwent PCNL with US-guided renal access in the lateral decubitus flank position by a single surgeon. We report our technique and the outcomes in detail. RESULTS: Successful access was achieved in 40 patients (100%). Complete stone clearance rate was 85% (34 patients). After surgery, six (15%) patients had stones (6-11 mm) detected by plain abdominal radiography or sonography and were referred for shockwave lithotripsy. The mean stone size was 29 mm (range 22-43 mm). The mean operative time was 45 minutes (range 32-75 min), and the mean hospital stay was 2.8 days (range 2-4 d). Postoperative US did not reveal considerable fluid collection. There were no visceral injuries. Also, there was no significant bleeding that led to transfusion intraoperatively and postoperatively. CONCLUSION: PCNL with US-guided renal access in the lateral decubitus flank position is safe and convenient, and prevents harmful effects of radiation for the surgeon, the surgical team, and the patient.

Tubeless percutaneous nephrolithotomy: 5 years of experience in 201 patients.

BACKGROUND AND PURPOSE: Our aim was to evaluate the safety, effectiveness, and feasibility of tubeless percutaneous nephrolithotomy (PCNL). PATIENTS AND METHODS: From June 2000 to September 2005, 201 patients with renal stones >2 cm underwent tubeless PCNL by a single surgeon. We report details of the outcomes. RESULTS: The complete stone clearance rate was 91.04% (183 patients). After surgery, 18 patients (8.96%) had stones (mean size = 7 mm) detected on a plain abdominal radiograph or ultrasonographic examination and were referred for shockwave lithotripsy. The mean stone size was 30 mm (range 20-40 mm). The mean operative time was 35 minutes (range 30-60 min), and the mean hospital stay was 3.5 days (range 2-5 days). Postoperative ultrasonography did not reveal considerable fluid collection. There were no visceral injuries. Twenty-two (10.9%) patients received a transfusion, and 16 (7.9%) patients had urinary tract infection. CONCLUSION: In our experience, tubeless PCNL is safe, effective, and feasible without any discomfort for patients.

Impacted upper-ureteral calculi >1 cm: blind access and totally tubeless percutaneous antegrade removal or retrograde approach?

PURPOSE: To compare blind access and totally tubeless percutaneous antegrade removal and pneumatic transurethral ureterolithotripsy for the management of impacted upper-ureteral calculi >1 cm. PATIENTS AND METHODS: Seventy patients (41 male, 29 female) with impacted upper-ureteral calculi >1 cm were selected in randomized order for pneumatic transurethral ureterolithotripsy (35 patients) or blind access and totally tubeless percutaneous nephrolithotomy (PCNL) (35 patients). Ultrasonography and intravenous urography were performed for all patients before surgery. After operation, plain films and ultrasonography were done. RESULTS: In the PCNL group, blind access was achieved from the lumbar notch area in all 35 patients, but in 3 patients, the exposure was not optimal for approaching the ureteropelvic junction (UPJ). So we injected contrast material into the collecting system, and, under fluoroscopic control, another access was achieved. In 33 patients (94.3%), intact removal of the stones was performed. In the other two patients, we fragmented the stones with the Swiss Lithoclast by an antegrade approach. The success rate thus was 100%. The mean operative time was 38 minutes (range 25-48 minutes). In the transurethral lithotripsy group, 12 stones (34.2%) migrated upward to the pelvis of kidney, and 5 stones (14.2%) fragmented incompletely. In these cases, a double- J stent was inserted, and SWL was performed. In follow-up, plain films and ultrasonography showed complete clearance in these patients. Eighteen calculi (51.4%) fragmented completely with the Lithoclast. The mean operative time in this group was 34 minutes (range 20-58 minutes). CONCLUSION: In the presence of moderate to severe hydronephrosis, blind access and totally tubeless PCNL is an effective option for large, impacted upper-ureteral calculi. Flexible ureteroscopy with laser lithotripsy is expensive and not readily available. Pneumatic transurethral ureterolithotripsy has a back-pressure effect and pushes back the calculi to the kidney. Thus, this procedure does not have satisfactory results in the management of these calculi.

Diagnostic application of flexible cystoscope in pelvic fracture urethral distraction defects.

INTRODUCTION: The aim of this study was to evaluate the diagnostic value of antegrade flexible cystoscopy in pelvic fracture urethral distraction defects (PFUDD). MATERIALS AND METHODS: Between 1999 and 2004, a total of 111 patients with PFUDD were evaluated by antegrade flexible cystoscopy. The flexible cystoscope was introduced into the posterior urethra and the area was evaluated for any probable fistula, false passages, or displacement of the posterior urethra. For preventing misalignment, flexible cystoscope was also used during the urethroplasty to open the posterior urethra at its exact distal point. RESULTS: Posterior urethra ended distal to the external sphincter in 16 patients (14.4%). Five (4.5%) and 9 (8.1%) patients had severe displacement of the posterior end of the urethra and bladder neck false passage, respectively. Prostatic urethrorectal fistula was detected in 1 patient. Another 1 patient had bladder rhabdomyoma. CONCLUSION: Flexible cystoscopy is a valuable procedure in the evaluation of the bladder, the bladder neck, and the posterior urethra in patients with urethral distraction defects and complements voiding cystography before the surgery. It is also helpful for showing the exact distal point of the proximal urethra during urethroplasty in cases with displaced posterior urethra.