Randomized trial of fenretinide in superficial bladder cancer using DNA flow cytometry as an intermediate end point.

Retinoids have shown a potential activity in preventing tumor recurrence in superficial bladder cancer. We assessed the activity of the synthetic retinoid fenretinide in superficial bladder cancer using DNA flow cytometry and conventional cytology as surrogate biomarkers. A total of 99 subjects with resected superficial bladder cancer (pTa, pT1) were randomized to either fenretinide (200 mg day p.o. for 24 months) or no intervention. Cystoscopy and bladder washing for DNA flow cytometry end points (proportion of DNA aneuploid histograms, hyperdiploid fraction, and percentage of apoptotic cells) and proportion of abnormal cytological examinations were repeated every 4 months for up to 36 months. The primary study end point was the proportion of DNA aneuploid histograms after 12 months. This figure was 48.9% in the fenretinide arm and 41.9% in the control arm (odds ratio, 1.16; 95% confidence interval, 0.44-3.07). There was no difference in any other response biomarker between the two groups up to 36 months, nor was any biomarker able to predict recurrence risk. Recurrence-free survival was comparable between the arms (27 events in the fenretinide arm versus 21 in the control arm; P = 0.36). Twelve subjects in the fenretinide arm complained of diminished dark adaptability, and nine subjects in the fenretinide arm versus one control subject had mild dermatological alterations. We conclude that fenretinide showed a lack of effect on the DNA content distribution and the morphology of urothelial cells obtained in serial bladder washings. Recurrence-free survival was comparable between groups. Because our data are hampered by the lack of predictivity of the selected biomarkers, additional studies are necessary to assess the activity of fenretinide in preventing bladder cancer.

Assessment of DNA flow cytometry as a surrogate end point biomarker in a bladder cancer chemoprevention trial.

Although conventional cytology represents the most widely performed cytometric analysis of bladder cancer cells, DNA flow cytometry has, over the past decade, been increasingly used to evaluate cell proliferation and DNA ploidy in cells from bladder washings. We have investigated whether DNA flow cytometry and conventional cytology of epithelial cells obtained from bladder washings provide reliable surrogate endpoint biomarkers in clinical chemoprevention trials. We used cytometric and clinical data from a chemoprevention trial of the synthetic retinoid Fenretinide on 99 patients with superficial bladder cancer. A total of 642 bladder washing specimens obtained from the patients at 4 month intervals was analyzed. Intra-individual agreement and correlation of flow cytometric DNA ploidy (diploid vs. aneuploid), DNA Index, Hyper-Diploid-Fraction (proportion of cells with DNA content higher than 2C), and conventional cytologic examination, as assessed by kappa statistics and Spearman's correlation test, were poor from baseline through 24 months. Moreover, no correlation was found between DNA ploidy and cytology at each time point. The same results were obtained when the analyses were stratified by treatment group. In addition, the association between the results of bladder washing (by either DNA flow cytometry or cytology) and concomitant tumor recurrence was significant only for abnormal cytology, while neither biomarker was predictive of tumor recurrence at the subsequent visit. During the time of this study only four patients progressed to muscle-invasive bladder cancer, indicating the "low-risk" features of the patient population. We conclude that DNA flow cytometry and conventional cytology on epithelial cells obtained from bladder washings do not appear to provide suitable surrogate endpoint biomarkers during the early stages of bladder carcinogenesis.

[Liquid embolization of the renal artery with absolute ethanol]. / L'embolisation liquide de l'artère rénale avec l'éthanol absolu.

Absolute ethanol is a new agent for use in embolization which has demonstrated excellent efficacy, is simple to manage, and above all is innocuous in case of reflux into the aorta. A part from provoking irreversible occlusion of the complete renal artery circle, embolization with ethanol provokes direct cellular toxic necrosis comparable with a true mummification. This is of fundamental importance during palliative embolization for renal cancer or in all cases of medical nephrectomy for non-neoplastic disease. Results of the use of liquid embolization of the renal artery with absolute ethanol are presented, the technique, described, and mechanisms of action analyzed based on histologic findings.

[Percutaneous dilatation of renal artery stenoses. Apropos of 7 cases]. / Les dilatations percutanées des sténoses de l'artère rénale. A propos de sept observations.

The authors report the results of percutaneous dilatation of renal artery stenoses, performed on 8 occasions in 7 patients. One patient had bilateral stenoses which were operated at two separate occasions. The authors had no complications and they confirm the stability of the results with a follow-up of up to 2 years. In the 4 cases with an isolated unilateral renal artery stenosis, dilatation of the artery led to normalization of the blood pressure within hours of the operation. When there was another cause for hypertension apart from the renal artery stenosis, the dilatation did not cause the blood pressure to return to normal, although the anatomical result was confirmed on arteriography. The authors then review the literature and compare the complications of surgery for renal artery stenoses with those occurring during or after percutaneous dilatation of the renal artery lumen. Because of the quality of the results, the complication rate and the good results obtained with percutaneous dilatation in the literature, the authors conclude that percutaneous dilatation of the renal artery lumen is the treatment of choice for these stenoses. The indication for this operation can be extended, as its aim is not only reduction of hypertension, but also to improve renal function and to avoid the risk of thrombosis on a very narrow stenosis. In this way, the indications for this operation extend to include a population which, up until now, has been excluded from surgery, such as elderly patients, patients with coronary disease, or with renal failure.

Fluoroscopically guided skinny-needle aspirative biopsy in normal and suspected lymph nodes in urologic cancer.

The authors present their experience with transperitoneal thin-needle biopsy of the retroperitoneal lymph nodes. This method is a means of improving lymphographic diagnosis in suspected lymph node metastases, the small contrast defects serving as a sign. The high rate of false-negative results makes its use unadvisable in patients with negative lymphography where the sample cannot be aimed at but is multiple and randomized.

[Embolization of the inferior mesenteric artery in hemorrhagic bladder neoplasms after failure of hypogastric arteries embolization]. / Embolisation de l'artère mésentérique inférieure dans les tumeurs vésicales hémorragiques ayant résisté à une gastrique bilatérale.

The authors report 3 cases of revascularisation through the inferior mesenteric artery of bladder tumors which had previously been treated by transcatheter occlusion of both hypogastric arteries because hemorrhage. New uncomplicated embolizations of the inferior mesenteric artery are performed in 2 cases and recurrency of the bleeding was stopped.

[Endo-urological techniques. New applications in two cases]. / De nouvelles indications à l'application des techniques endo-urologiques. Présentation de deux cas.

Two new indications for the application of endo-urological techniques are reported. One case involved recanalization of stenosis at the ureterovesical junction, while in the other case a double J ureteral endoprosthesis was extracted by the transnephropyelostomy percutaneous route.

[Percutaneous embolization of renal cancer. Clinical evaluation (author's transl)]. / Embolizzazione percutanea dell'adenocarcinoma renale. Valutazione clinica di tre anni di applicazione.

The authors deal with 17 cases of renal adenocarcinoma treated with preventive embolization, widened nephrectomy and total parenteral nutrition, as well as one case of palliative definitive embolization in a patient who could not be operated. The most remarkable clinical aspects turned out to be in the easier and safer maneuverability under surgery, a decrease in mortality during and after the operation, reduced consumption of blood units, and a better which were treated only with purely surgical therapy.

[Therapeutic occlusion of the hypogastric arteries with isobutyl-2-cyanoacrylate in vesical and prostatic cancer (author's transl)]. / Occlusione arteriosa terapeutica delle arterie ipogastriche con isobutil-2-cianoacrilato nelle neoplasie vescicali e prostatiche.

The authors refer their clinical experience of the use of embolization of the hypogastric arteries in cases of serious haemorrhage of the bladder and prostate. The immediate results in the 14 cases observed are decidedly positive, especially considering the serious conditions of certain neoplastic patients, which ruled out alternative surgical treatment. Nevertheless, even when the embolization technique has been correctly used, the possibility exists that bleeding may start up again after some time, and this is always caused by the revascularization of the neoplasia.

[Therapeutic angiographic occlusion with a modified autologous clot. Case report]. / L'occlusione angiografica terapeutica con coagulo autologo modificato. Contributo casistico.

Therapeutic arterial embolization with autologous clot is readily applied in urology. The procedure is particularly effective in those cases where a temporary blockage of the artery is required, enough to cause a definitive haemostasis in noble parenchymas sensitive to ischaemia. However this method is not limited only to poor risk patients ("life-threatening"); it may be preferable to surgical operation, as in the case studied, of postraumatic, intraparenchymal arterovenous fistula. In their presentation, the authors also take into consideration several technical side-effects, helping towards correct execution.

[The subclavian approach as an alternative to the femoral approach in selective cervicocephalic phlebography (author's transl)]. / L'abord sous-clavier comme alternative de la voie fémorale dans la phlébographie sélective cervico-céphalique.

The authors describe the technique employed for selective catheterization of the main mediastinal trunks and the veins of the brachiocephalic and cervicocephalic regions by means of the subclavian approach. The importance and advantages of this procedure as an alternative to the femoral approach, especially if this is contra-indicated, are emphasized.

Hematuria due to circumaortic left renal vein.

A patient with benign recurrent hematuria underwent selective renal venography, manometric registration of pressure levels in the renal veins, and renal biopsy which indicated the circumaortic left renal veins was responsible for intermittent hematuria and proteinuria.

[Arterial complications during therapeutic vesicorenal embolizations (author's transl)]. / Complications artérielles au cours de deux embolisations thérapeutiques réno-vésicales.

Accidental peripheral occlusion occurred during the course of precutaneous embolization with NBC in two patients. The authors propose some modifications in the technique employed in order to avoid these dangerous incidents.

Multiple sampling for parathyroid hormone by subclavian approach.

Selective venous catheterization with parathyroid hormone assay is a valuable procedure in the diagnosis and treatment of parathyroid tumors. The multiple sampling via the femoral vein is sometimes frustratingly uncertain and time consuming. The technique herein described is simpler, quicker, and less hazardous. It is accomplished via the subclavian approach, a relatively easier anatomic way, and utilizes a short single-curve catheter that gives a high degree of torsion control.