Randomized Phase II trial assessing estramustine and vinblastine combination chemotherapy vs estramustine alone in patients with progressive hormone-escaped metastatic prostate cancer.

Based on the results of combined data from three North American Phase II studies, a randomised Phase II study in the same patient population was performed, using combination chemotherapy with estramustine phosphate (EMP) and vinblastine (VBL) in hormone refractory prostate cancer patients. In all, 92 patients were randomised into a Phase II study of oral EMP (10 mg kg day continuously) or oral EMP in combination with intravenous VBL (4 mg m(2) week for 6 weeks, followed by 2 weeks rest). The end points were toxicity and PSA response in both groups, with the option to continue the trial as a Phase III study with time to progression and survival as end points, if sufficient responses were observed. Toxicity was unexpectedly high in both treatment arms and led to treatment withdrawal or refusal in 49% of all patients, predominantly already during the first treatment cycle. The mean treatment duration was 10 and 14 weeks, median time to PSA progression was 27.2 and 30.8 weeks, median survival time was 44 and 50.9 weeks, and PSA response rate was only 24.6 and 28.9% in the EMP/VBL and EMP arms, respectively. There was no correlation between PSA response and survival. While the PSA response in the patients tested was less than half that recorded in the North American studies, the toxicity of EMP monotherapy or in combination with VBL was much higher than expected. Further research on more effective and less toxic treatment strategies for hormone refractory prostate cancer is mandatory.

[Cystic lymphangioma in the adrenal gland: a case report]. / Le lymphangiome kystique de la surrénale: à propos d'une observation.

Cystic lymphangioma of the adrenal gland are rarely encountered tumoural formations with no clinical expression. Pre-operative diagnosis is difficult. Echography and CT scan are essential exploratory techniques, diagnosis is histological. Usually surgical exploration is indicated due to uncertain diagnosis. We report a new case of cystic lymphangioma of the adrenal gland and a review of recent literature.

Remission of erythrocytosis and hypertension after treatment of a giant renal cyst.

Giant renal cysts measuring more than 15 cm in greatest diameter are uncommon and the association with erythrocytosis and hypertension is very rare. We present a case of a 22-year-old man with an incidental giant left renal cyst associated with hypertension and polycythemia that was treated by drainage and laparoscopic excision, followed by resolution of both hypertension and erythrocytosis.

[Bilateral adrenal pheochromocytomas in von Hippel-Lindau disease]. / Phéochromocytomes surrénaliens bilatéraux au cours de la maladie de von Hippel-Lindau.

The pheochromocytoma is a medullo-adrenal tumor which develops at the cost of the chromaffin cells. It appears in 11-19% of cases of von Hippel-Lindau's disease (VHL), is often bilateral, and the symptomatology is often crude: arterial hypertension is frequently isolated and unstable, and the classic triad of headache, palpitations and sweating is quite rarely observed. We report four observations of bilateral pheochromocytomas in patients with von Hippel-Lindau's disease (three with phenotype IIA and one with phenotype IIB). The tumor was bilateral during the diagnosis in three cases; in the fourth patient, the attack on the contralateral adrenal gland came two years after the first adrenalectomy. All the patients had undergone an adrenalectomy by open surgery after a short preparation of 48 hours; replacement therapy was begun in each patient. Morbidity was low, and the patients submitted to a prolonged follow-up in order to screen for the onset of future lesions of VHL.

[Recanalization of pelvic ureter in prostatic neoplastic obstruction: endoscopic and radiologic approach]. / Reperméabilisation de l'uretère pelvien pour obstacle néoplasique prostatique: approche endoscopique et radiologique.

UNLABELLED: Obstruction of the lower ureter by pelvic cancer requires a palliative treatment. Percutaneous derivation is often performed as an emergency. If obstruction is limited to the peri-meatic area (a few mm or a cm) resection of the ureteral orifice can be enough to catheterize the obstructed ureter. Stenting of the ureter can be done even if the obstruction is longer, using the extra vesical repermeabilization. METHODS: A guide wire is passed via the nephrostomy, and ureteral stent is passed over the guide wire. Dye additionned with methylene blue is injected tovisualize the lower extremity of the ureter. A regular resectoscope is placed transuretraly, and resection is conducted using X ray localisation with a C arm and several incidences. The tissue resected first is usually extravesical, in the adipous perivesical tissue. Dissection of this area can be performed bluntly with the tip of the resectoscope until the ureter is reached. At this time, the resectoscope is used to open the lower extremity of the ureter, localized with the C arm. It is important to open widely the ureter, so as to be sure to catheterize easily this opening with a ureteral catheter. A double J can then be passed easily. Tunnel of several cm can be performed using this technique. RESULTS: Seven patients with pelvic cancer with obstruction of the last cm of the pelvic ureter were included in this series. They were recurrent prostate cancer already treated with hormone therapy, stage T3, T4. All procedures were performed under rachianesthesia or general anesthesia according to general status. After this procedure normal miction were obtain in all patients and nephrostomies were removed. This technique is possible for extended pelvic obstruction. Blunt dissection with the endoscope is usualy blood less. This palliative procedure can be done in patients with poor general condition and allows for a better quality of life than nephrostomy or urinary diversions.

Intra-operative electron radiotherapy as a conservative treatment for infiltrating bladder cancer.

The intent of this feasibility study was to evaluate the use of intra-operative electron radiotherapy (IOERT), after transurethral resection (TUR), combined with external beam radiation with concurrent chemotherapy for the conservative treatment of infiltrating bladder cancer. From November 1988 to June 1998, 27 patients with histologically proven non-metastatic infiltrating bladder cancer were included in this protocol. The treatment consisted of: TUR, external beam irradiation (x18 MV:48 Grays (Gy)/24 fractions/5 weeks), with concurrent chemotherapy (cisplatin 30 mg/day for 3 days-two cycles during irradiation), followed by control cystoscopy and cystotomy with IOERT (e 9 MeV:15 Gy). 14 patients received two cycles of neoadjuvant methotrexate, vinblastine and cisplatin (MVC) and folinic acid chemotherapy. Patients were evaluated for toxicity, local control and survival. The 5-year overall and cystectomy-free survival rates were 53.3% +/-11.1% and 48.1%+/-11.4%, respectively. 4 patients developed infiltrating intravesicular recurrence (3 were treated by salvage cystectomy), and an additional patient developed a superficial recurrence. 2 patients subsequently developed regional recurrence in pelvic nodes and 10 patients were found to have distant metastases. The protocol was found to be feasible and associated with acceptable toxicity. Early and late toxicities consisted of 3 cases of bladder mucosal necrosis or ureteral stenosis which resolved with medical management. These preliminary results indicate that IOERT combined with TUR and neoadjuvant external beam radiation with concurrent chemotherapy is feasible. It could be considered as an alternative therapy for infiltrating carcinoma of the bladder, especially in patients unfit for radical surgery, and is well adapted to treat lesions of the fixed portion of the bladder.

Radical nephrectomy with and without lymph node dissection: preliminary results of the EORTC randomized phase III protocol 30881. EORTC Genitourinary Group.

OBJECTIVE: The authors present demographic and surgical data from a randomized phase III trial, instituted by the EORTC Genitourinary Group in 1988, the aim of which was to assess whether complete lymph node dissection in conjunction with radical nephrectomy for renal cell cancer is more effective than radical nephrectomy alone. METHODS: Before surgery, the renal cell carcinoma was staged and judged to be nonmetastatic and resectable. The patients were randomized prior to surgery into those having radical nephrectomy combined with complete lymph node dissection or into those having radical nephrectomy alone. Postoperatively all patients were followed until progression of disease or death. RESULTS: Of the 772 randomized patients, 41 were not eligible. 383 had a complete lymph node dissection together with a radical nephrectomy. 389 had a radical nephrectomy alone. The complication rate did not differ significantly between the two groups. A complete lymph node dissection in 336 patients revealed absence of lymph node metastases in 325 of them. CONCLUSIONS: The present study shows that complete lymph node dissection does not add morbidity to the radical nephrectomy. After proper preoperative staging, the incidence of unsuspected lymph node metastases is low (3.3%).

Differential RNA expression of the pS2 gene in the human benign and malignant prostatic tissue.

PURPOSE: The pS2 trefoil protein has been detected in close association with neuro-endocrine differentiation in prostate cancer and prostatic intraepithelial neoplasia. These preliminary results have suggested that pS2 is a candidate as a specific marker for prostate cancer tissue. To ascertain the specificity of pS2 in prostate cancer tissue, we have used an RT-PCR method from prostate biopsies provided from human malignant and benign prostatic hyperplasia (BPH) tissue. MATERIALS AND METHODS: Prostate biopsies were obtained from transrectal biopsies from 153 patients with an abnormal DRE or a PSA more than 4 ng./ml. or symptoms of BPH and a PSA more than 4 ng./ml. Total RNA was extracted from fresh frozen specimens of tissue samples. Detection of pS2 transcript compared with GADPH transcripts was done using RT-PCR. RESULTS: Biopsy results showed that 108 patients had prostate cancer (average Gleason score 6.39+/-0.74) and 45 patients had BPH. PS2 RT-PCR results showed that PS2 RNA expression was negative in 83% of the BPH cases. Conversely, 92% of prostate cancer specimens were positive (Chi-square: 86.09, p<0.001). There was no correlation with tumor stage or the Gleason score. Comparing the expression of pS2 in BPH and localized prostate cancer, we found a sensitivity of 92% and a specificity of 82%. CONCLUSIONS: On this large sample of prostate biopsies from patients at risk of having prostate cancer, pS2 was demonstrated as an interesting marker significantly associated with prostate cancer. Further work on the expression of pS2 according to differentiation and hormonal status is in progress.

Mutations of the VHL gene in sporadic renal cell carcinoma: definition of a risk factor for VHL patients to develop an RCC.

To investigate the nature of somatic von Hippel-Lindau (VHL) mutations, we analyzed 173 primary sporadic human renal cell carcinomas for mutations of the VHL tumor suppressor gene, using polymerase chain reaction (PCR) and single-strand conformational polymorphism analysis (SSCP) of DNA. We detected abnormal SSCP pattern in 73 samples. After sequencing, we identified microdeletions in 58% of cases, microinsertions in 17%, nonsense mutations in 8%, and missense mutations in 17%. Among these mutations, 50% correspond to new mutations. VHL mutations were found only in the nonpapillary renal cell carcinoma (RCC) subtype, as previously reported. To compare somatic and germline mutations, we used the VHL database, which includes 507 mutations. The study of mutational events revealed a significant difference between somatic and germline mutations with mutations leading to truncated proteins observed in 78% of somatic mutations vs only 37% in germline mutations (P < 0.001). We postulated that a specific pattern of VHL mutations is associated with sporadic RCC. This pattern corresponds to mutations leading mainly to truncated proteins with few specific missense mutations. We then analyzed the occurrence of RCC in VHL families, based on the nature of mutations. We observed RCC in at least one member of the VHL families in 77% of cases with mutations leading to truncated proteins versus 55% in cases with missense mutations (P < 0.05). Thus, mutations resulting in truncated proteins may lead to a higher risk of RCC in VHL patients.

[Laparoscopic surgical treatment of simple cysts of the kidney]. / Traitement coeliochirurgical des kystes simples du rein.

OBJECTIVE: To demonstrate the efficacy of laparoscopic treatment of symptomatic renal cysts or cysts suspicious of malignancy. MATERIAL AND METHODS: 10 patients (mean age: 58 years) were operated by laparoscopy either for compressive or symptomatic cysts (7 cases), or for cysts suspicious of malignancy (3 cases). The mean cyst diameter was 7.8 cm. All patients were evaluated by preoperative CT scan. There were 8 Bosniak type I and 3 Bosniak type II cysts. RESULTS: The procedure was performed via an intraperitoneal approach (8 cases) or via a retroperitoneal approach (2 cases). The mean operating time was 92 min and the mean hospital stay was 5.4 days. One patient was operated (conversion to lumbotomy) for uncontrolled haemorrhage of the base of the cyst. The 10 cysts were found to be benign histologically. All 10 patients are asymptomatic (mean follow-up: 8.3 months) with disappearance of the cyst on the follow-up CT scan. CONCLUSION: Laparoscopic treatment of renal cysts is feasible and effective. However, this treatment must be reserved for Bosniak type I and II cysts, associated with a low risk of malignancy.

[Can the prostatic capsule be preserved during cystectomy for bladder tumors: a study of urethral and prostatic involvement in the cystectomy specimens]. / Peut-on préserver la coque prostatique au cours des cystectomies pour tumeur de vessie: étude de l'atteinte urétrale et prostatique sur les pièces de cystectomie.

OBJECTIVES: To evaluate the frequency of urethral and prostatic lesions on cystectomy specimens for bladder tumour. MATERIAL AND METHODS: This retrospective histological study was based on 260 specimens: radical cystectomies performed in 7 operative sites. The prostate and urethra were analysed in 3 planes (upper, middle and lower thirds). The apex was studied separately. Urethral invasion was identified by continuity of the tumour or by the presence of vesical CIS. RESULTS: Urethral involvement is frequent (30.6% cases) essentially due to contiguous invasion (43/80). CIS is the second pathological association (44 urethral CIS/75 bladder CIS). Prostatic adenocarcinoma was present in 17.8% of cases with a Gleason score > 6 for 30% of lesions. CONCLUSION: The high frequency of urethral and prostatic involvement does not justify preservation of the prostate during cystectomy. A serial prospective study should define the precise criteria able to minimize the risk of conservative surgery.

[Contribution of computed tomography in the staging of upper urinary tract urothelial tumors. Importance of the tumor diameter measurement]. / Apport de la tomodensitométrie dans la stadification des tumeurs urothéliales de la voie excrétrice supérieure. Importance de la mesure du diamètre tumoral.

OBJECTIVES: To demonstrate a correlation between abdominal computed tomography (CT) data and the histological stage of upper urinary tract tumour (UUTT) in order to more accurately define therapeutic indications. MATERIALS AND METHODS: From 1984 to 1995, 51 patients were treated for UUTT and were assessed by preoperative abdominal CT. 41 of the 51 CT scans were considered to be interpretable and were reviewed retrospectively by a single radiologist. The CT stage and tumour diameter were compared to the pathological stage. RESULTS: CT staging had a reliability of 76%, by combining stages Ta-T2, which could not be distinguished. The sensitivity of CT to assess invasion of the renal parenchyma and ureteric or perirenal fat was 100% and 70%, respectively, with a specificity of 82% and 97%. The accuracy can be improved by decreasing the thickness of sections of the tumour. Tumour diameters (d) of pyelocaliceal tumours, measured by CT and pathology, were closely correlated (r2 = 0.83). All UUTTs less than 3 cm in diameter were found to be superficial on histology. CT correctly estimated the size of these small tumours in 14/15 cases. Overall, by setting the limit at 3 cm, CT was able to detect a superficial pyelocaliceal tumour with a specificity of 92% and a PPV of 93%; however, a CT size > or = 3 cm is not predictive of the histological stage of the lesion. CONCLUSIONS: CT is still imprecise for the staging of UUTT, as it cannot distinguish between Ta, T1 and T2 lesions, and is still not sufficiently reliable in the assessment of invasion of the periurothelial fat or of the renal parenchyma. CT measurement of the diameter of pyelocaliceal tumours can provide an argument in favour of the superficial nature of the lesion and therefore guide the therapeutic decision towards a conservative approach.

[Peroperative radiotherapy in the conservative treatment of infiltrating bladder cancers]. / La radiothérapie per-opératoire dans le traitement conservateur des cancers infiltrants de la vessie.

OBJECTIVE: Descriptive analysis of an intraoperative radiotherapy protocol (IOR) in the context of conservative management of invasive bladder cancer. METHOD: From November 1988 to September 1994, 24 patients with invasive bladder carcinoma (20 T2, 3 T3) were included in this protocol consisting of: transurethral resection (TUR), neoadjuvant chemotherapy (M.V.C.) in 14 patients, external irradiation (x 18 MV: 48 Gy/24 F/5 weeks) with concomitant chemotherapy (cisplatin 30 mg/day-3 days-2 cycles during irradiation)-follow-up cystoscopy then surgery with IOR (E 9 MeV: 15 Gy). RESULTS: The global 3-year survival was 69%. An invasive intravesical relapse developed in 3 patients (1 salvaged by cystectomy) and a superficial relapse occurred in 1 patient. One patient developed pelvic lymph node progression and 7 developed distant metastases. The early and late toxicity was acceptable with 3 cases of ureteric necrosis or stenoses resolving after medical treatment. CONCLUSION: This series shows encouraging preliminary results. IOR appears to be a technique well adapted to lesions of the fixed portion of the bladder.