A. Kostakopoulos

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.

Vesicourethral Anastomotic Strictures after Radical Retropubic Prostatectomy: The Experience of a Single Institution

Objective: Stricture of the vesicourethral anastomosis remains a well-documented complication after radical retropubic prostatectomy. Materials and Methods: We performed a retrospective study of 294 patients with prostate cancer who underwent radical retropubic prostatectomy. Possible correlations between anastomotic stricture formation, tumor stage, positive surgical margins, number of anastomotic sutures, bladder neck preservation, urine leakage, previous prostate surgery and/or intraoperative blood loss were examined. Results: An anastomotic stricture was found in 18 cases (6%) requiring some kind of treatment. In 10 patients (56%), the bladder neck stricture occurred within 3 months after surgery, in 5 (28%) at 4–12 months after surgery and in 3 (16%) more than 12 months after surgery. Intraoperative blood loss (>1,000 ml) was found to be significantly correlated with urinary leakage (p < 0.001) and both correlated with anastomotic stricture formation (p < 0.005). Conclusion: Excessive intraoperative blood loss (>1,000 ml) and urine leakage was found to be significantly correlated to the formation of anastomotic stricture following radical retropubic prostatectomy.

Extracorporeal shock wave lithotripsy for renal stones in children.

The aim of our study is to determine the efficacy and safety of extracorporeal shock wave lithotripsy (ESWL) as a method of treatment of nephrolithiasis in childhood. Between 1986 and 1994, 50 children with renal calculi were treated by ESWL in our department. The age of the children ranged from 8 months to 14 years. Thirty-three of them were boys and 17 girls. The stone location was in the renal pelvis in 38 cases, in the upper renal calyx in 4 cases, in the lower calyx in 2, while 6 children had staghorn calculi. The stone size ranged between 3 and 39 mm. All treatments were performed with Dornier HM4 except 12 children, all older than 10 years, who underwent ESWL with Dornier HM3. All ESWL procedures took place under general anesthesia or sedation with ketamine. The number of shock waves varied between 400 and 2,000 per treatment and the standard maximum generator voltage was 18 kV. The overall stone clearance rate at 1 month was 66%. Fourteen children with large residual fragments underwent a second ESWL procedure 3 months later. With a mean follow-up of 33 months, 41 children (82%) are stone-free. Ten children developed urinary tract infection and 5 Steinstrasse. Twelve children had a pre- and post-ESWL DMSA scan and no permanent impairment of renal function was observed. We conclude that ESWL is the treatment of choice for urinary tract lithiasis in childhood. It is a low-risk method, without serious complications, which yields as high a success rate in children as in adults. We believe that as the stone fragmentation and clearance is much higher in children that in adults, the method must be the initial approach and may be the monotherapy even in staghorn or complex stones.

A Phase II Randomized Study of Topical Intrarectal Administration of Amifostine for the Prevention of Acute Radiation-Induced Rectal Toxicity

Purpose:To investigate the cytoprotective effect of intrarectal amifostine administration on acute radiation-induced rectal toxicity.Patients and Methods:67 patients with T1b–2 N0 M0 prostate cancer were randomized to receive amifostine intrarectally (group A, n = 33) or not (group B, n = 34) before irradiation. Therapy was delivered using a four-field technique with three-dimensional conformal planning. In group A, 1,500 mg amifostine was administered intrarectally as an aqueous solution in a 40-ml enema. Two different toxicity scales were used: EORTC/RTOG rectal and urologic toxicity criteria along with a Subjective-RectoSigmoid (S-RS) scale based on the endoscopic terminology of the World Organization for Digestive Endoscopy. Objective measurements with rectosigmoidoscopy were performed at baseline and 1–2 days after the completion of radiotherapy. The area under curve for the time course of mucositis (RTOG criteria) during irradiation represented the mucositis index (MI).Results:Intrarectal amifostine was feasible and well tolerated without any systemic or local side effects. According to the RTOG toxicity scale, five out of 33 patients showed grade 1 mucositis in group A versus 15 out of 34 patients with grade 1/2 in group B (p = 0.026). Mean rectal MI was 0.3 ± 0.1 in group A versus 2.2 ± 0.4 in group B (p < 0.001), while S-RS score was 3.9 ± 0.5 in group A versus 6.3 ± 0.7 in group B (p < 0.001). The incidence of urinary toxicity was the same in both groups.Conclusion:Intrarectal administration of amifostine seems to have a cytoprotective efficacy in acute radiation-induced rectal mucositis. Further randomized studies are needed for definitive therapeutic decisions.Ziel:Untersuchung des zytoprotektiven Effekts von intrarektal verabreichtem Amifostin zur Verhinderung akuter rektaler Strahlentoxizität.Patienten und Methodik:67 Patienten mit einem Prostatakarzinom im Stadium T1b–2 N0 M0 wurden randomisiert zwei Gruppen zugeteilt: Gruppe A (n = 33) mit und Gruppe B (n = 34) ohne intrarektale Verabreichung von Amifostin vor der Bestrahlung. Zur Behandlung wurde eine Vier-Felder-Technik mit dreidimensionaler konformaler Bestrahlungsplanung eingesetzt. Die Patienten in Gruppe A erhielten 1 500 mg Amifostin intrarektal als wässrige Lösung in einem 40-ml-Klysma. Zwei verschiedene Toxizitätsskalen wurden verwendet, die rektalen und urologischen Toxizitätskriterien der EORTC/RTOG und die auf der endoskopischen Terminologie der WODE (World Organization for Digestive Endoscopy) basierende S-RS-Skala („Subjective-RectoSigmoid scale“). Mittels Rektosigmoidoskopie wurden objektive Messungen vor und 1–2 Tage nach der Beendigung der Strahlentherapie durchgeführt. Der Bereich unter der Kurve (AUC) für den zeitlichen Verlauf einer Mukositis (RTOG-Kriterien) während der Bestrahlung stellte den Mukositis-Index (MI) dar.Ergebnisse:Die intrarektale Verabreichung von Amifostin erwies sich als einfach und gut verträglich und führte zu keinen systemischen oder lokalen Nebenwirkungen. Gemäß der RTOG-Toxizitätsskala zeigten fünf von 33 Patienten der Gruppe A eine Mukositis Grad 1 und 15 von 34 Patienten der Gruppe B eine Mukositis Grad 1/2 (p = 0,026). Der mittlere rektale MI betrug in Gruppe A 0,3 ± 0,1 gegenüber 2,2 ± 0,4 in Gruppe B (p < 0,001), während der S-RS-Score in Gruppe A bei 3,9 ± 0,5 gegenüber 6,3 ± 0,7 in Gruppe B lag (p < 0,001). Toxische Wirkungen an den Harnwegen traten in beiden Gruppen gleich häufig auf.Schlussfolgerung:Die intrarektale Verabreichung von Amifostin scheint bei akuter strahleninduzierter Entzündung der Rektumschleimhaut zytoprotektiv zu wirken. Weitere randomisierte Studien sind erforderlich, um definitive Therapieentscheidungen treffen zu können.

Subcapsular Hematoma due to ESWL: Risk Factors

A study of 4,247 Shockwave lithotripsy treatment was performed to identify and analyze the risk factors for the development of post-extracorporeal shock-wave lithotripsy hematomas. The Dornier HM-3 and HM-4 lithotriptors were used. We recognized 23 hematomas in 23 patients (0.54%). Various factors were examined to identify the certain predisposing risk factors. There was no correlation of sex, age, stone number, stone size, stone location, number of shock waves and voltage used with the occurrence rate of hematoma. We found that patients with pre-existing hypertension and especially those with poor control of it had a significantly increased incidence of perinephric hematoma.

Extracorporeal Shock Wave Lithotripsy in 5 Patients with Aortic Aneurysm

PURPOSE The safety and efficacy of extracorporeal shock wave lithotripsy (ESWL*) in patients with an aortic aneurysm were assessed. MATERIALS AND METHODS Five patients with an aortic aneurysm and symptomatic renal (4) or upper ureteral (1) lithiasis underwent ESWL with either an HM3 or HM4 lithotriptor. RESULTS The procedure was well tolerated in all patients. The stone was fragmented completely in the 4 patients with renal lithiasis, while 1 with ureteral lithiasis also required ureteroscopic extraction of the stone fragments. CONCLUSIONS For patients with symptomatic renal stones and an aortic aneurysm ESWL may be the treatment of choice.

Influence of Digital Examination, Cystoscopy, Transrectal Ultrasonography and Needle Biopsy on the Concentration of Prostate-Specific Antigen

The influence of various prostatic manipulations, including digital rectal examination, cystoscopy, transrectal ultrasonography and transrectal needle biopsy, on the serum prostatic-specific antigen (PSA) levels in 170 men, were examined. We found that digital rectal examination, cystoscopy and transrectal ultrasonography had no significant effect on PSA levels, except for transrectal needle biopsy, which caused an immediate increase of serum PSA in 96.2% of the patients lasting more than 2 weeks in 42.3% of the cases. In conclusion, serum PSA determination after digital rectal examination, after cystoscopy and after transrectal ultrasonography is accurate and reliable. On the other hand, we must wait about 6 weeks after needle biopsy before measuring PSA in the serum of patients with prostatic diseases.

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 procedures 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 ureteoroscope 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.

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.

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.