Atif Akdas

Duration of androgen suppression in the treatment of prostate cancer

BACKGROUND The combination of radiotherapy plus long-term medical suppression of androgens (> or = 2 years) improves overall survival in patients with locally advanced prostate cancer. We compared the use of radiotherapy plus short-term androgen suppression with the use of radiotherapy plus long-term androgen suppression in the treatment of locally advanced prostate cancer. METHODS We randomly assigned patients with locally advanced prostate cancer who had received external-beam radiotherapy plus 6 months of androgen suppression to two groups, one to receive no further treatment (short-term suppression) and the other to receive 2.5 years of further treatment with a luteinizing hormone-releasing hormone agonist (long-term suppression). An outcome of noninferiority of short-term androgen suppression as compared with long-term suppression required a hazard ratio of more than 1.35 for overall survival, with a one-sided alpha level of 0.05. An interim analysis showed futility, and the results are presented with an adjusted one-sided alpha level of 0.0429. RESULTS A total of 1113 men were registered, of whom 970 were randomly assigned, 483 to short-term suppression and 487 to long-term suppression. After a median follow-up of 6.4 years, 132 patients in the short-term group and 98 in the long-term group had died; the number of deaths due to prostate cancer was 47 in the short-term group and 29 in the long-term group. The 5-year overall mortality for short-term and long-term suppression was 19.0% and 15.2%, respectively; the observed hazard ratio was 1.42 (upper 95.71% confidence limit, 1.79; P=0.65 for noninferiority). Adverse events in both groups included fatigue, diminished sexual function, and hot flushes. CONCLUSIONS The combination of radiotherapy plus 6 months of androgen suppression provides inferior survival as compared with radiotherapy plus 3 years of androgen suppression in the treatment of locally advanced prostate cancer. (ClinicalTrials.gov number, NCT00003026.)

An international field study of the EORTC QLQ-PR25: A questionnaire for assessing the health-related quality of life of patients with prostate cancer

AIM To evaluate the psychometrics of the EORTC QLQ-PR25, a questionnaire assessing the health-related quality of life of prostate cancer patients. METHODS The QLQ-PR25 and the QLQ-C30 were administered to 642 prostate cancer patients from 13 countries treated with curative or palliative intent. The QLQ-PR25 assesses urinary, bowel and sexual symptoms and functioning, and the side-effects of hormonal treatment. RESULTS Five hundred and nine patients were available for the final analysis. Multitrait scaling analyses confirmed the hypothesised scale structure of the QLQ-PR25. Internal consistency reliability was good (coefficient alpha=0.70-0.86) for the urinary symptoms and sexual function scales, but lower for the bowel function and side-effects of hormonal treatment scales (alpha<0.70). The module discriminated clearly between clinically distinct patient subgroups, and was responsive to changes in health status over time. CONCLUSION In general, the QLQ-PR25 demonstrates acceptable psychometric properties and clinical validity. Some caution should be used in interpreting the bowel function and side-effects of hormonal therapy scales; results can be reported at the individual item and scale level.

Reactive Oxygen Species Production by the Spermatozoa of Patients With Idiopathic Infertility: Relationship to Seminal Plasma Antioxidants

PURPOSE We attempted to determine reactive oxygen species production by the spermatozoa of patients with idiopathic infertility and healthy donors, and observe whether increased production was due to decreased seminal plasma reactive oxygen species scavengers. MATERIALS AND METHODS Reactive oxygen species production by spermatozoa and seminal plasma antioxidants was assayed in 18 patients with idiopathic infertility and 10 controls. Reactive oxygen species formation and seminal plasma antioxidants were measured by luminol and lucigenin dependent chemoluminescence, and enzymatic methods, respectively. RESULTS Higher reactive oxygen species production was observed in 16 of the 18 patients (88.8%, p < 0.0001 versus controls). Seminal plasma superoxide dismutase, catalase, glutathione peroxidase and total sulfhydryl group levels in infertile patients were significantly lower than in controls. CONCLUSIONS Decreased seminal plasma antioxidant activity and increased reactive oxygen species production can be responsible for idiopathic male infertility.

Impact of the expression of epidermal growth factor, transforming growth factor alpha, and epidermal growth factor receptor on the prognosis of superficial bladder cancer

OBJECTIVES To investigate the correlation of epidermal growth factor receptor (EGFR) expression and its ligands EGF and transforming growth factor-alpha (TGF-alpha) with disease outcome in a cohort of patients with superficial bladder cancer. METHODS Tumor samples of 21 patients with transitional cell carcinoma of the bladder were analyzed by immunohistochemistry for expression of EGFR, EGF, and TGF-alpha. Disease-related events were recorded during a routine clinical follow-up and analyzed for possible correlation with the expression status of the above-mentioned proteins. RESULTS All Stage pT1 transitional cell carcinomas expressed EGFR, and 10 of 21 (48%) tumors showed focal areas of strong EGF and/or TGF-alpha expression. Of these, 80% with EGF positivity (8 of 10) had recurrences, whereas only 9% of patients without EGF staining (1 of 11) did so. The same pattern was observed with TGF-alpha. A strong association was confirmed between EGF/TGF-alpha positivity and tumor recurrence (P <0.005). We also found that EGF and TGF-alpha were expressed in stroma and/or around the vessels of tumor tissue in 48% and 38% of the tumors, respectively. No association was found between the recurrence rate/vascular invasion and the stromal/vascular wall expression of the growth factors. CONCLUSIONS Expression of EGF and TGF-alpha is correlated with tumor recurrence. Also, there is the ability of vessel walls to express EGF and TGF-alpha in superficial bladder cancer. Further clarification of the impact of this expression on angioinvasion of tumor cells may be helpful in understanding the nature of local invasion and metastasis.

Lack of effect of intrarectal lidocaine for pain control during transrectal prostate biopsy: a randomized prospective study.

INTRODUCTION AND OBJECTIVES Transrectal ultrasound guided biopsy is an essential part in the diagnosis of prostate cancer. Although this procedure is well tolerated by most patients, sometimes it can result in some uneasiness. In this randomised double-blind placebo controlled study, we evaluated the effectiveness of intrarectal lidocaine during TRUS guided biopsy. MATERIALS AND METHODS 100 consecutive eligible patients who had elevated total prostate specific antigen (tPSA) and/or abnormal digital rectal examination (DRE) were included into this study. Patients were randomised into two groups. Group I received 20 cc of 2% intrarectal lidocaine 20 minutes before transrectal ultrasound guided biopsy and Group II received same amount of serum physiologic. Pain was assessed using a 10 point modified visual analog scale. RESULTS Mean patient age was 65.5+/-2.5 and 64.5+/-11.5 years, mean tPSA was 12.3+/-3.6 and 11.3+/-1.7 ng/ml, mean biopsy duration was 6.8+/-2.5 and 6.6+/-2.2 minutes, mean pain score during transrectal ultrasound guided biopsy was 4.8+/-2.2 and 4.4+/-2.1 in Groups I and II, respectively. No statistically significant difference was observed with respect to age, tPSA, mean biopsy duration and pain score between these groups. There was only one patient who could not tolerate the procedure at all, and he was paradoxically in the lidocaine group. CONCLUSION The use of intrarectal lidocaine is not superior to placebo during transrectal prostate biopsy for pain control.

Epidemiological case-control study on the etiology of bladder cancer in Turkey

A case-control study of 194 patients with bladder cancer and the same number of age- and sex-matched hospital controls were interviewed to estimate the role of various factors on the etiology of bladder cancer in Turkey. There was a significant difference between the case and control groups on cigarette smoking (p less than 0.001), alcohol intake (p less than 0.001), Turkish coffee consumption (p = 0.01), and artificial sweeteners (p less than 0.05). The risks for alcohol and tobacco users increased in correlation with the duration of exposure. The risk of bladder cancer increased directly with the quantity and frequency of alcohol intake. Alcohol and coffee drinking was found to be a promoting factor when adjusted to smoking habits (p less than 0.05). No statistical comparisons could be made to clarify the risks attributed by occupation and place of residence due to small figures in each group. However, in farmers, there was a significant difference between the cases and controls on the use of artificial fertilizers and insecticides (p less than 0.01). People who were exposed to unspecified chemical substances were more prone to develop bladder cancer (p less than 0.001). We conclude that both personal habits and exogenous carcinogens play a role in the etiology of bladder tumors.

Bcl-2 and p53 overexpression as associated risk factors in transitional cell carcinoma of the bladder

Bcl-2 and p53 genes are implicated in cell cycle regulation with roles on programmed cell death. Consequently, presence of Bcl-2 and nuclear accumulation of p53 were proposed to confer a growth advantage tumour cells.We have investigated their role as prognostic factors in fresh tumour samples from a cohort of twenty patients with transitional cell carcinoma of the bladder by immunohistochemical analysis in paired specimens.Expression of Bcl-2 was observed in 11 cases (69%) and nuclear p53 accumulation in 9 (45%). In the presence of Bcl-2 protein expression, tumours showed a slightly higher rate of recurrence (55% vs. 40%) and significantly more progression (36% vs. 0%). Recurrence and progression rates were not significantly different in tumours with and without nuclear p53 overexpression (recurrence rates 56% vs. 55% and progression rates 33% vs. 27%, respectively). Grade and stage appeared as important prognosticators since 75% of grade 3 tumours showed recurrence and 50% progressed in contrast to 44% and 13%, respectively, of grades 1 and 2 tumours. Similarly, 50% of Ta-T1 tumours recurred and 20% progressed, while these rates were 75% and 75% for T2–T3 tumours. Also, expression of Bcl-2 and nuclear accumulation of p53 correlated with grade. In grade 3 tumours, 75% showed nuclear p53 overexpression and 80% cytoplasmic Bcl-2 protein. These figures were 25% and 64% for grades 1 and 2 tumours.In conclusion, Bcl-2 protein expression in transitional cell carcinoma appears to be associated with a poorer prognosis and together with nuclear p53 overexpression They are associated with tumour de-differentiation.

Antimicrobial prophylaxis in management of urinary tract stones by extracorporeal shock-wave lithotripsy: Is it necessary?

OBJECTIVES In a prospective randomized study, we evaluated the incidence of urinary tract infections following extracorporeal shock-wave lithotripsy (ESWL) and the necessity of prophylactic antibiotic administration in patients treated with this modality. METHODS A total of 360 consecutive patients with renal and ureteric stones who had sterile urine before ESWL treatment and did not have any increased risk of infection received either a single dose of 400 mg of ofloxacin or no prophylaxis. Patients were followed by simple urine analysis and urine cultures together, with clinical evaluations. RESULTS Only 3 patients (0.8%) had positive urine cultures at 1 week after ESWL. Two of these patients were in the antibiotic prophylaxis group. CONCLUSIONS The incidence of urinary tract infections after ESWL is extremely low, provided that patients have sterile urine before ESWL, and prophylactic antibiotics are not required.

The impact of squamous metaplasia in transitional cell carcinoma of the bladder

The authors report a case of squamous cell carcinoma of the bladder induced by radiation therapy for transitional cell carcinoma, possibly from sites of squamous metaplasia, which were present at the time of initial diagnosis. Although data in the literature are not sufficient at the moment in terms of implication on prognosis, foci of squamous metaplasia during the initial diagnosis of transitional cell carcinoma must be carefully sought and their presence warrants caution in utilizing irradiation in the management of the disease.

Is stent placement necessary after uncomplicated ureteroscopy for removal of impacted ureteral stones

BACKGROUND AND PURPOSE Ureteral stent placement after ureteroscopic lithotripsy has some advantages and disadvantages. In this randomized study, the necessity of ureteral stent placement after uncomplicated ureteroscopy for impacted ureteral stones was assessed. MATERIALS AND METHODS Between 2005 and 2007, 60 evaluable patients were equally randomized to groups with and without stents. Patients underwent ureteroscopic pneumatic lithotripsy for ureteral stones. The operation was completed with or without stent placement according to the randomization order. Excretory urography was performed 3 months after the procedure. All stents were cystoscopically removed at the third postoperative week. Sociodemographic and clinical variables (age, sex, stone location, stone size, operative time, hospital stay, narcotic and nonnarcotic analgesic use), and postoperative complications (fever, pain delaying discharge, emergency department visit, urinary retention, stent-related irritative symptoms) were evaluated. RESULTS Mean stone size was not significantly different in both groups. Mean operative time was significantly longer in the stent group: 30.5 +/- 9.6 vs 43.7 +/- 11.6 minutes. On the operation day and until postoperative day (POD) 5, narcotic (P = 0.004) and nonnarcotic analgesic (P = not significant) use was more frequent in the no-stent group. At POD 5 and later, although narcotic and nonnarcotic analgesic use were frequently necessary in the stent group, both were almost unnecessary in the no-stent patients. Stent-related irritative symptoms were overwhelmingly higher (10% vs 93%) in the stent group. Discharge was delayed (23% vs 10%) and unplanned emergency department visits (20% vs 10%) were exercised almost two times more commonly in the no-stent group. Stone-free rates were identical (n = 29/30; 97%) in both groups. CONCLUSION Routine placement of a ureteral stent is not mandatory in patients without complications after ureteroscopic lithotripsy for impacted ureteral stones. Stent placement can be argued and agreed with the patients preoperatively in the light of the data presented above.