Prospective, open-label, randomized, phase III study of two dose-dense regimens MVAC versus gemcitabine/cisplatin in patients with inoperable, metastatic or relapsed urothelial cancer: a Hellenic Cooperative Oncology Group study (HE 16/03).

BACKGROUND: The combinations of methotrexate, vinblastine, Adriamycin, cisplatin (Pharmanell, Athens, Greece) (MVAC) or gemcitabine, cisplatin (GC) represent the standard treatment of advanced urothelial cancer (UC). Dose-dense (DD)-MVAC has achieved longer progression-free survival (PFS) than the conventional MVAC. However, the role of GC intensification has not been studied. We conducted a randomized, phase III study comparing a DD-GC regimen with DD-MVAC in advanced UC. PATIENTS AND METHODS: One hundred and thirty patients were randomly assigned between DD-MVAC: 66 (M 30 mg/m(2), V 3 mg/m(2), A 30 mg/m(2), C 70 mg/m(2) q 2 weeks) and DD-GC 64 (G 2500 mg/m(2), C 70 mg/m(2) q 2 weeks). The median follow-up was 52.1 months (89 events). RESULTS: The median overall survival (OS) and PFS were 19 and 8.5 months for DD-MVAC and 18 and 7.8 months for DD-GC (P = 0.98 and 0.36, respectively). Neutropenic infections were less frequent for DD-GC than for DD-MVAC (0% versus 8%). More patients on DD-GC received at least six cycles of treatment (85% versus 63%, P = 0.011) and the discontinuation rate was lower for DD-GC (3% versus 13%). CONCLUSIONS: Although DD-GC was not superior to DD-MVAC, it was better tolerated. DD-GC could be considered as a reasonable therapeutic option for further study in this patient population. Clinical Trial Number ACTRN12610000845033, www.anzctr.org.au.

Pathological characteristics, biochemical recurrence and functional outcome in radical prostatectomy patients on statin therapy.

INTRODUCTION: We assessed the pathological characteristics of the radical prostatectomy specimen, the rate of biochemical failure and the functional outcome after surgery, in terms of incontinence and erectile dysfunction rate, in patients on statin medication. MATERIALS AND METHODS: A total of 588 patients with a mean age 65.2 years (SD = 5.7 years) participated in the study. All patients were contacted and interviewed. RESULTS: Users who had been on statin medication for more than 2 years had lower levels of preoperative serum PSA (p = 0.034), a 2.76 times greater likelihood of being staged as pT3a to pT3b rather than pT2a to pT2c, and a 5.39 times greater likelihood of having a postoperative Gleason score equal to seven or more. Positive surgical margins and urinary incontinence were not significantly associated with statin use. The probability of erectile dysfunction was significantly greater for statin users. CONCLUSION: Statin medication was associated with a statistically significantly lower PSA value and an increased rate of high Gleason score and pathologic stage in patients receiving medication for more than 2 years. Statins were found to be an independent predictor of recurrence. Lastly, statin users were more likely to present with preoperative and postoperative erectile dysfunction.

Docetaxel and cisplatin with granulocyte colony-stimulating factor (G-CSF) versus MVAC with G-CSF in advanced urothelial carcinoma: a multicenter, randomized, phase III study from the Hellenic Cooperative Oncology Group.

PURPOSE: The combination of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) represents the standard regimen for inoperable or metastatic urothelial cancer, but its toxicity is significant. We previously reported a 52% response rate (RR) using a docetaxel and cisplatin (DC) combination. The toxicity of this regimen compared favorably with that reported for MVAC. We thus designed a randomized phase III trial to compare DC with MVAC. PATIENTS AND METHODS: Patients with inoperable or metastatic urothelial carcinoma; adequate bone marrow, renal, liver, and cardiac function; and Eastern Cooperative Oncology Group performance status < or = 2 were randomly assigned to receive MVAC at standard doses or docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2) every 3 weeks. All patients received prophylactic granulocyte colony-stimulating factor (G-CSF) support. RESULT: Two hundred twenty patients were randomly assigned (MVAC, 109 patients; DC, 111 patients). Treatment with MVAC resulted in superior RR (54.2% v 37.4%; P =.017), median time to progression (TTP; 9.4 v 6.1 months; P =.003) and median survival (14.2 v 9.3 months; P =.026). After adjusting for prognostic factors, difference in TTP remained significant (hazard ratio [HR], 1.61; P =.005), whereas survival difference was nonsignificant at the 5% level (HR, 1.31; P =.089). MVAC caused more frequent grade 3 or 4 neutropenia (35.4% v 19.2%; P =.006), thrombocytopenia (5.7% v 0.9%; P =.046), and neutropenic sepsis (11.6% v 3.8%; P =.001). Toxicity of MVAC was considerably lower than that previously reported for MVAC administered without G-CSF. CONCLUSION: MVAC is more effective than DC in advanced urothelial cancer. G-CSF-supported MVAC is well tolerated and could be used instead of classic MVAC as first-line treatment in advanced urothelial carcinoma.

Effect of drugs on crystal adhesion to injured urothelium.

The normal urothelium is covered by a glycosaminoglycan (GAG) layer which acts as a barrier to the adhesion of crystals. Destruction of the GAG layer increases the number of adhered crystals, and it is therefore assumed that it promotes crystal growth and stone formation. Intravesical instillation of pentosanpolysulfate, an exogenous glycosaminoglycan, after destruction of this layer reduces the adhesion of crystals to the urothelium. Intramuscular administration of carbenoxolone sodium following the experimental destruction of the GAG layer increases the rate of healing of the layer and reduces the number of adhered crystals.

Oral estramustine and oral etoposide for hormone-refractory prostate cancer.

OBJECTIVES: Estramustine and etoposide have been shown to inhibit the growth of prostate cancer cells in experimental models. An in vivo synergism of the two agents, when administered to patients with metastatic prostate cancer refractory to hormone therapy, has been reported. To confirm these results, we administered this combination to a large number of patients with hormone-refractory prostate cancer (HRPC). METHODS: Fifty-six patients with metastatic HRPC were treated with oral estramustine 140 mg three times a day and oral etoposide 50 mg/m2/day for 21 days. Therapy was discontinued for 7 days and the cycle was then repeated. Therapy was continued until evidence of disease progression or unacceptable toxicity occurred. To control for the possible interference of an antiandrogen withdrawal effect, all patients discontinued antiandrogen therapy and were not enrolled in the study unless there was evidence of disease progression. RESULTS: Forty-five percent of 33 patients with measurable soft tissue disease demonstrated an objective response, which included five complete and ten partial responses. Among 52 patients with osseous disease 17% showed improvement and 50% showed stability of bone scan. Thirty patients (58%) demonstrated a decrease of more than 50% in pretreatment prostate-specific antigen (PSA) levels. The median survival of all patients was 13 months. Good pretreatment performance status, measurable disease response, improvement or stability of bone scan, and PSA response were important predictors of longer survival. CONCLUSIONS: We conclude that the combination of estramustine and etoposide is an active and well-tolerated oral regimen in HRPC.

Does free to total ratio of prostate-specific antigen alter decision-making on prostatic biopsy?

OBJECTIVES: For patients with prostate specific antigen (PSA) values of 4-10 ng/mL, some urologists perform prostatic biopsies depending upon the findings of digital rectal examination (DRE) and transrectal ultrasonography (TRUS), and others perform biopsies on most of these men regardless of the findings of DRE and TRUS. The purpose of this study was to examine whether the information given by the measurement of the ratio of free to total (F/T) PSA can alter decision-making on prostatic biopsy. METHODS: One hundred and two (102) men with PSA values between 4 and 10 ng/mL, were included in this study. All men were examined with DRE and TRUS; a F/T PSA ratio was also measured, and six prostatic biopsies were taken from each patient. RESULTS: In 102 men who were biopsied, 22 (21.5%) prostatic carcinomas were identified. Among these 22 cancer patients, 13 had abnormal findings in DRE and/or TRUS and would have been biopsied and diagnosed anyway. If we use only the F/T PSA ratio (cut-off value 0.20) to decide whom to biopsy, we would have diagnosed 16/22 cancers; the difference between these two procedures was not statistically significant (P = 0.17). If we decide to biopsy those patients who have abnormal findings in DRE and/or TRUS and those who have a F/T PSA ratio < 0.20, we would diagnose 20/22 cancers (P = 0.05) and at the same time, reduce the unnecessary biopsies from 80 to 41 (48%). With a PSA value between 4 and 10 ng/mL and no findings in DRE and TRUS and at the same time with a F/T PSA ratio > or = 0.20, we would have to perform biopsies in 20.5 men to find one cancer. On the other hand, in patients with suspicious findings in DRE and/or TRUS and a F/T PSA ratio < 0.20, in every two men that we biopsy we would find one cancer. CONCLUSION: We believe that among patients with PSA values between 4 and 10 ng/mL after performing DRE and TRUS, the additional information of F/T PSA ratio can help since it increases the number of cancers detected and reduces the number of unnecessary biopsies.

Treatment of patients with metastatic urothelial carcinoma and impaired renal function with single-agent docetaxel.

OBJECTIVES: To evaluate the efficacy and toxicity of single-agent docetaxel in patients with metastatic urothelial carcinoma and impaired renal function. METHODS: Eleven consecutive patients previously untreated for metastatic disease with renal impairment (median serum creatinine level of 2.6 mg/dL) were treated with intravenous docetaxel 100 mg/m2 for 1 hour every 21 days. Granulocyte colony-stimulating factor was administered at a dose of 5 microg/kg/day subcutaneously from days 5 to 14. RESULTS: Five of 11 patients achieved a partial response, with time to progression of responding patients ranging from 5 to 22 months or more. The median overall survival rate was 11 months. Renal function improved in 5 of 8 patients with tumor-related renal impairment. Toxicity was primarily hematologic, with 5 patients developing grade 3 or 4 neutropenia; nonhematologic toxicities were manageable. CONCLUSIONS: Our preliminary data indicate that single-agent docetaxel therapy may represent an effective therapeutic alternative for patients with advanced urothelial carcinoma and renal insufficiency precluding cisplatin-based combination chemotherapy.

Extracorporeal shockwave lithotripsy in patients with distal ureteral calculi does not influence the prostate specific antigen value.

BACKGROUND AND PURPOSE: Distal ureteral calculi can be treated with extracorporeal shockwave lithotripsy (SWL) in situ, which has a high rate of success. As the prostate is in vicinity of this part of the ureter, it is possible that the shockwaves may pass through the prostate also. We evaluated the effect of SWL on the serum concentration of prostate specific antigen (PSA). PATIENTS AND METHODS: A total of 44 men with distal ureteral calculi located a maximum of 20 mm from the ureteral orifice and without any history of recent urinary tract infection, benign prostatic hyperplasia, or prostate cancer underwent SWL with the Dornier HM-4 lithotripter. Their serum PSA values were measured 5 minutes before SWL as well as 3 hours and 1, 7, and 30 days afterward. The differences of these PSA values were estimated. From a control group of 10 healthy donors, two consecutive PSA values were obtained 30 days apart. RESULTS: Of these patients, 93% (41/44) were stone free within 1 month according to plain radiographs and ultrasonography. No statistically significant difference was observed between the PSA concentration before and after treatment or between the patients who underwent SWL and the control group. CONCLUSION: Treatment of distal ureteral calculi with SWL does not affect the serum PSA concentration.

Shockwave lithotripsy in unrecognized pregnancy: interruption or continuation?

A 32-year-old woman underwent SWL of a 4 x 6-mm calculus in the distal third of the right ureter, receiving 2100 shocks at a maximum intensity of 18 kV. Approximately 1 month later, it was discovered that she had been 10 weeks pregnant at the time of SWL. She chose to continue the pregnancy and delivered a normal infant at term. We do not advocate SWL in pregnancy, but further research is mandatory to determine if this procedure can ever be performed safely during pregnancy.

Malakoplakia of the testis.

Malakoplakia of the testis presenting as painless enlargement of the testis in an 80-year-old man is described. The literature is reviewed.

The necessity of prophylactic antibiotics during extracorporeal shock wave lithotripsy.

In this study we treated 340 patients with renal and ureteric stones. They all underwent ESWL with the HM-4 lithotriptor. The patients were divided into two groups, the first one including 250 patients and the second 90. The first group consisted of patients with sterile urine prior to ESWL. These patients did not receive any antibiotic prophylaxis, while 5.2% of them developed infectious problems which were followed by significant bacteriuria in only 2% of the cases. The 90 patients of the second group had urinary tract infection on the preoperative cultures and received antibiotic treatment. Of these patients 27.8% developed infectious problems which were followed by significant bacteriuria in 21.1% of the cases. Evaluating the above results, we estimate that the administration of prophylactic antibiotics in the case of patients with sterile urine before ESWL is not required while it may prove to be useful in the case of patients with urinary tract infection prior to ESWL.

Distal ureteral calculi: ureteroscopy vs. ESWL. A prospective analysis.

Two groups of 50 consecutive patients each, with distal ureteric calculi, were treated by ureteroscopy or in situ ESWL (Dornier HM-4 lithotriptor) in order to establish the effectiveness of ESWL at the distal portion of the ureter. In comparison to ureteroscopy, ESWL for distal ureteral calculi was performed on an outpatient basis, required less time, patients had more rapid convalescence and the procedure was simpler and safer. The overall success rate was 100% for ureteroscopy and 92% for ESWL. Our observations showed that in situ ESWL with the Dornier HM-4 lithotriptor is the method of choice for the treatment of distal ureteral calculi.

Leiomyoma of the bladder: a case report.

A case of leiomyoma of the urinary bladder in a 20-year-old man is reported. The patient presented with severe frequency and perineal burning at the end of urination along with microscopic haematuria. Enucleation of the tumour was performed because transurethral biopsy revealed leiomyoma. The prognosis of these tumours is excellent.

Experience in 3,500 patients with urinary stones treated with the Dornier HM-4 bath-free lithotriptor.

During a 3-year period, hundreds of patients underwent ESWL treatment with the Dornier HM-3 and HM-4 lithotriptors operating at our institution. Our experience in 3,500 patients treated with the HM-4 bath-free lithotriptor is reported. Patients with radiolucent or cystine stones, stones larger than 3 cm or staghorn calculi, multiple stones with a total burden of more than 3 cm and those not amenable to follow-up were excluded from the study. The overall stone-free rate was 70.7% and 81% at 1 and 3 months, respectively. The stone-free rates at 1 and 3 months were further determined by the exact location of each stone within the urinary tract. Stone-free rates at 3 months ranged from 90.84% for renal pelvic stones to 71.08% for lower calyceal stones, while the stone-free rates for ureteral calculi ranged from 80.85% for upper third unstented ureteral stones to 92.92% for lower ureteral stones. The overall complication rate was 6.02% with a 1.2% post-ESWL intervention rate (ureteroscopy or placement of percutaneous nephrostomy or stent).

Early repair of injury to the ureter or bladder after hysterectomy.

In the present study we investigated the effectiveness of early diagnosis, repair of injuries to the ureter and urinary bladder sustained during hysterectomy, as compared to the results of delayed intervention. There were 46 ureteral injuries and 20 vesicovaginal fistulas in 55 patients. In 14 cases of ureteral injury an endoscopic approach management was employed. There was complete healing in 18 vesicovaginal fistulas while there was a single case of a ureteral injury that required nephrectomy because of stenosis. This study shows that early repair of urological injuries after hysterectomy has considerable advantages and the results are equally comparable with those of delayed intervention. In most cases of ureteral injury an attempt of an endoscopic repair is warranted before proceeding to open surgery.

Transrectal needle aspiration versus transperineal needle biopsy in diagnosis of prostatic carcinoma.

Fine-needle aspiration of the prostate was compared to transperineal biopsy in 86 patients with suspected prostatic carcinoma. Aspiration was found to have a sensitivity of 98.6% while no complications were seen. Initial core needle biopsy compared to the final histological diagnosis in this study showed a sensitivity of 84.5%. Fine-needle aspiration of the prostate is a safe, inexpensive and accurate diagnostic method in prostatic carcinoma. Our findings suggest that prostatic aspiration should be used more widely as an initial diagnostic procedure for suspected prostatic cancer.

Extracorporeal shock wave lithotripsy monotherapy for bladder stones.

This report presents our initial experience in 36 patients with bladder stones, treated by extracorporeal shock wave lithotripsy. Minute fragmentation and uncomplicated evacuation occurred in 26 patients (72%). Mean treatment duration was 55 minutes. Mean number of shock waves was 3600 and electrical discharge averaged 24 kV per shock wave. No morbidity, during or after treatment, was encountered in these patients. The treatment was performed without the use of anaesthesia on an outpatient basis.

Contribution of transcutaneous ultrasonography to the evaluation of urethral strictures.

The aim of our study was to investigate the accuracy and sensitivity of ultrasound in detecting urethral strictures. Between 1992 and 1994, 117 patients with stricture of the anterior urethra were evaluated by retrograde urethrography, ultrasonography and urethroscopy.

Serum selenium levels in healthy adults and its changes in chronic renal failure.

In this study the serum selenium levels of 500 healthy Greeks and 225 patients with chronic renal failure (CRF) were measured using Watkinson's method. The patients were treated either conservatively or by peritoneal dialysis or haemodialysis. We found that the levels were in an intermediate position compared to those of other Europeans. Selenium levels were also found to increase significantly with age. No difference was detected between male and female patients. A statistically significant drop was observed in CRF patients compared to age matched controls. This drop was smaller in patients treated conservatively than in those treated by peritoneal dialysis. A further drop was observed in patients under haemodialysis.

One-session bilateral ureteroscopy: is it safe in selected patients?

The aim of this study was to investigate the possibility to perform bilateral ureteroscopy in one session and to determine the procedure's indications and complication rate. Twenty-two patients underwent bilateral ureteroscopy in one session. Eighteen patients had bilateral lithiasis of the lower ureteral third, three patients had unexplained haematuria and one had unexplained bilateral hydronephrosis. The rigid ureteroscope was used in cases with stones and the flexible one in cases with haematuria and hydronephrosis. Ureteral catheters were placed in all patients. The overall stone-free rate was 83.3%. The procedure failed to confirm a diagnosis in 2 patients with unexplained haematuria. Follow-up included IVU and retrograde cystogram 3 months after the procedure and a renal scan one year later. No major complication was observed. It is concluded that bilateral ureteroscopy in one session can be performed safely in selected patients. The method does not yield major complications and saves patients from a second procedure and a second anaesthesia.