[Prognostic value of erythrocyte polyamines levels in renal cell carcinoma. Prospective study in 418 cases]. / Valeur pronostique des polyamines érythrocytaires dans le cancer du rein. Etude chez 418 patients.

OBJECTIVES: Polyamines: Spermine (Spm) and Spermidine (Spmd), are essential for cell proliferation and differentiation. A measurement of erythocytes polyamines (EPA) was developed in our institution. Our objective was to evaluate this marker as a new prognostic factor in renal cell carcinoma. PATIENTS AND METHODS: A blood sample was prospectively taken before surgery, among 418 patients who had an enlarged nephrectomy (n=318) or a partial nephrectomy (n=100) to quantify EPA rates by using the HPLC technique. The qualitative and quantitative variables have been compared using chi(2) and Student statistical analyses. The survivals have been normalized by the Kaplan Meier and Cox methods. RESULTS: The average age of our population was 64 years (21-88). The average decline was 41 months (1-214). The median size of tumors was 6.5cm (1-24). The median rate of Spm and Spmd were respectively 4.7 (1-83) and 9 (2-86)nmol/8.10(9) erythrocytes. Spm and Spmd were linked to the T stage (p=0.001), and the ECOG (p=0.001 and 0,008). Spm was not linked at N and M stages but at the Fuhrman grade (p=0.001). Spmd was linked to the N, M stages (p=0.04). With univariate analysis, the tumor diameter, the TNM stage, the Fuhrman grade as well as Spm and Spmd (p<0.0001) were predictors of specific survival. With multivariate analysis, some prognostic factors remained independent: the TNM stage, the ECOG and Spmd, a continuous variable (p=0.0001), pushing the rank of Fuhrman out of the model. When Spm and Spmd were dichotomized in quantitative variables, they were both independent factors. CONCLUSION: The EPA is a new prognostic tool, before surgery, which will be tested for its integration into prognostic normograms.

Polyamine contents in current foods: a basis for polyamine reduced diet and a study of its long term observance and tolerance in prostate carcinoma patients.

Polyamine contents were assessed by mass spectrometry in 233 current foods and beverages. In order to reduce gut polyamine uptake, a polyamine reduced diet (PRD) and partial intermittent intestinal tract decontamination (PIITD) with neomycin or nifuroxazide was proposed as nutritional therapy to 33 prostate carcinoma patients, 30 of whom with hormone refractory prostate cancer (HRPC). Mean PRD observance was 22 +/- 19 (median: 16; range: 3-72) months. 10, 8 and 3 patients were respectively on PRD for more than 30, 36 and 64 months. No diet toxicity was observed. 8 patients had moderate intestinal intolerance due to PIITD which was interrupted. No significant differences in body weight, blood counts or serum protein levels were observed during the follow-up of patients under PRD. Performance status and pain scores were relatively stable during the trial with improved pain scores at 6 months. A PRD associated with intermittent PIITD is a safe and well observed nutritional regimen and long term observance is possible.

Polyamine-reduced diet in metastatic hormone-refractory prostate cancer (HRPC) patients.

Polyamine (PA) deprivation is effective in prostate carcinoma models. We have assessed the observance by patients, tolerance and side effects of a PA-reduced diet (PRD) and intestinal decontamination (ID), in order to reduce PA dietary and intestinal bacterial pools, in metastatic, hormone-refractory prostate cancer (HRPC) patients. A total of 13 volunteers (mean age, 67+/-10 years) with metastatic HRPC were proposed for PRD and ID (0.75 g/day of oral neomycin every other week). The mean time from HRPC diagnosis to the start of the diet was 12+/-8 months. Of the total 13, seven patients had received prior chemotherapy or Estramustine phosphate. PRD was obtained after HPLC assessment of PA contents in current foods and given 5 days a week. Toxicity, performance and pain status were assessed according to the World Health Organisation and EORTC scales. Prostatic specific antigen (PSA), blood counts, ionograms, transaminases and erythrocyte PA spermidine (Spd) and spermine (Spm; assessed by HPLC) were evaluated regularly. Mean observance was 8+/-7 months (range, 2-26 months). One case of grade II toxicity to neomycin was observed. Cancer-specific survival (after the diet) was 14+/-7 months, and two patients are still alive. All the other patients have died of their cancer at 12+/-6 months (range, 4-20 months). Cancer-specific survival after hormonal escape was 27+/-11 months (range, 9-45 months). Performance status was improved during the regimen and deteriorated 3 months after stopping. Pain score was improved (1.3 versus 0.6; P =0.04) during the diet and increased (2.1 versus 0.3) 3 months after stopping. Erythrocyte Spd (11.6+/-7 versus 7.7+/-2 nmol/8 x 10(9) erythrocytes; P =0.036) and Spm (7+/-6 versus 3.9+/-1.6 nmol/8 x 10(9) erythrocytes; P =0.036) levels were significantly reduced at 3 months. One patient had a >50% reduction in PSA, three patients had PSA stabilization for 6 months. PSA progression was observed in all other patients. No significant modification of other studied biological parameters was noted. Reducing PA dietary intake and ID is a well-observed and tolerated regimen and seems to be beneficial for patient quality of life and pain control. Patients with low initial PSA can experience durable stabilization. These encouraging results in such an aggressive disease certainly warrant further investigation.

Pretherapeutic erythrocyte polyamine spermine levels discriminate high risk relapsing patients with M1 prostate carcinoma.

BACKGROUND: Androgen deprivation is currently the standard treatment for patients with metastatic prostate carcinoma. Few reliable prognostic markers are able to select, at diagnosis, patients who will respond favorably and durably to hormone ablation. Circulating polyamines, markers of cell proliferation that are elevated in prostate carcinoma, have been evaluated as a prognostic tool. METHODS: Eighty-eight patients with untreated, M1 classified prostate carcinoma who received endocrine therapy between 1988 and 1993 were included in this study. Performance status, hemoglobin, alkaline phosphatases, prostate specific antigen, Gleason tumor grade, extent of disease by bone scan, and circulating erythrocyte spermidine and spermine were correlated with observed progression free and cause-specific survivals. Multiple correspondence analysis and ascending hierarchical classification were performed to determine significant pretreatment prognostic factors. RESULTS: Pretreatment performance status, alkaline phosphatase, hemoglobin, and erythrocyte spermine levels were correlated with progression, with hemoglobin and erythrocyte spermine level being the most significant independent variables (P < 0.00001 and P < 0.0001, respectively). With regard to cause specific survival, only hemoglobin and spermine erythrocyte levels were significant independent variables (P < 0.0001 and P < 0.0005, respectively). Patients with spermine levels of less than 9 nmol/8.10(9) had a statistically better outcome than patients with 9 nmol/8.10(9) or more erythrocytes. Erythrocyte spermine was the best sole determinant of progression. A test combining spermine with performance status or hemoglobin improved each variable's predictive values. CONCLUSIONS: Circulating erythrocyte spermine levels, extracted from a blood sample, can discriminate, at diagnosis, patients with hormone-refractory from those with hormone-responsive metastatic prostate carcinoma.

[Dose adaptation during training of intracavernous self-injections of prostaglandin E1]. / Adaptation de la dose lors de l'apprentissage des auto-injections intracaverneuses de prostaglandine E1.

OBJECTIVE: Dose adaptation in self-administered intracavernous PGE1 injections is poorly defined in learning protocols and its degree of difficulty depends on the aetiology of the erectile dysfunction. The authors tried to standardize this phase by studying the results and complications of a protocol using an identical initial dose of PGE1 regardless of the aetiology of erectile dysfunction. MATERIAL AND METHODS: 101 patients consulting for erectile dysfunction participated in a learning protocol of self-administered intracavernous PGE1 injections, consisting of 3 injections systematically starting with 10 micrograms of PGE1, following assessment of the aetiology. RESULTS: For an efficacy of 58.4%, 79.2% and 88.1% after one, two or three injections, respectively, the prolonged erection rate (> or = 6 hours) was 2.7% after the first injection and 0% after the other injections. However, erection durations of 2 to 6 hours have frequently been reported in neurological patients. Discontinuations during the learning phase were only observed in patients presenting with tumescence without rigidity after one injection (5.4%) or two injections (21%). CONCLUSION: In the light of these results and to minimize prolonged erections and discontinuations, while ensuring efficacy, PGE1 dose adaptation can be simply performed by starting with 10 micrograms in all patients except for neurogenic patients (5 micrograms) with an increase to 20 or 30 micrograms in the case of failure.

[Diagnostic value of recording nocturnal erections]. / Valeur diagnostique de l'enregistrement des érections nocturnes.

The recording of tumescence and rigidity during nocturnal erections is considered to be the reference examination to differentiate between the organic or psychogenic origin of erectile dysfunction. However, its diagnostic value is more doubtful in the absence of normal rigidity values. 170 consecutive patients were submitted to this type of recording (RigiScan, Dacomed, USA). With the exception of patients suffering from multiple sclerosis, all patients with erectile dysfunction considered to be psychogenic obtained a rigidity > or = 60%. 59% of these patients were detected by this method (sensitivity: 59%, specificity: 87%). In contrast, no conclusion can be drawn from a pathological nocturnal recording (32% of psychogenic patients) and finally, in view of the aetiologies of this series, this examination was considered to be useful in 29% of patients.

Observations with an S-adenosylmethionine decarboxylase inhibitor in rats with prostatic adenocarcinoma.

CGP 48664A (2-(4-aminoiminomethyl)-2,3-dihydro-1H-inden-1-ylidene dihydrochloride, CAS 149400-88-4) is a new potent inhibitor of S-adenosylmethionine decarboxylase with antitumor properties. In view of the eminent clinical problems in the treatment of non hormone dependent prostatic cancer, the antiproliferative potency of this compound was tested in Dunning MAT-LyLu rat prostatic adenocarcinoma. The compound proved inefficient in preventing the growth of this tumor, even at a near toxic dose. A reason for the lacking effect is presumably the inadequate accumulation of the drug in the tumor cells due to the excessive growth rate of the MAT-LyLu xenografts. Tumor growth seems not to be accompanied by a proportionally rapid vascularization of the tumor mass. CGP 48664A was found to be a potent inhibitor of polyamine oxidase. This property of the drug may have contributed to the activation of the phagocytic capacity of peritoneal macrophages from tumor-bearing rats.

[General practitioners' approach to urination disorders in men over the age of 50. A survey of 250 physicians in Brittany]. / Le médecin généraliste face aux troubles mictionnels de l'homme de plus de 50 ans. 250 médecins interrogés en Bretagne.

A questionnaire was set to 250 general practitioners in the Brittany region, to determine the impact of information campaigns concerning benign prostatic hyperplasia (BPH) and prostatic cancer on their everyday approach to disorders of micturition in men over the age of 50 years. 225 questionnaires were interpretable. 75% of general practitioners systematically investigated the presence of disorders of micturition. In the presence of such symptoms, 76% of general practitioners conducted further investigations to exclude prostatic cancer. 89% of general practitioners performed first-line digital rectal examination, and 34% of them systematically performed this examination once a year. The investigations most frequently performed after digital rectal examination concerned the state of urine (50%) but only 30% of general practitioners used reagent dip-sticks and 43% ordered urine cultures. Other investigations consisted of transrectal ultrasonography (31%) an PSA assay (26%). 3% of PSA assays were ordered before digital rectal examination. Renal and vesical ultrasonography occupied 5th place, although distension of the upper urinary apparatus was a source of concern for 51% of general practitioners. In the presence of symptomatic BPH, general practitioners readily prescribed medical treatment (96%). They assessed the results of this treatment on the course of disorders of micturition (95%), digital rectal examination (91%), and PSA (50%). General practitioners are familiar with disorders of micturition after the age of 50 years. However, 25% of them do not systematically question patients about these symptoms. Digital rectal examination is now performed more frequently, although systematic examination of the prostate is rare (34%). PSA assay is not the doctor's first priority (3rd place in the list of examinations). Two examinations are rarely used and should be developed: reagent dip-sticks (30%) and renal and vesical ultrasonography (5th place). Only 4% of general practitioners did not prescribe any treatment in the case of uncomplicated BPH, which is not in line with current recommendations. There is certainly a need for better information of general practitioners, but this information is only valid when a consensus has been reached among urologists.

A case of myospherulosis occurring in the perirenal adipose tissue.

The authors report a case of spontaneous myospherulosis that developed in the right perirenal adipose tissue, presented like an abscess, in an 82-year old man of the A, Rh+ blood group. The patient had a history of chronic lymphocytic leukaemia. Fine needle aspiration and histological examination of the renal cyst allowed the observation of 4- to 7-micron spherules (or endobodies) enclosed in saccular structures (or parent bodies) and accompanied by a foreign body-type response. The walls of the parent bodies were negative for PAS, Gomori's methenamine silver and Giemsa's stain. Immunohistochemical study was positive with anti A antibody specific of A1/A2 blood group and with anti glycophorin A antibody. The authors reviewed the literature concerning this rare lesion: it usually occurs in subcutaneous fat or in the paranasal sinuses, nose and middle ear but, up to now, no previous case has ever been reported in the urinary tract. The only case of visceral myospherulosis previously reported occurred in a cystic teratoma of the ovary. The reported case is also peculiar by the unusual thickness of the parent bodies. The authors also discuss the mechanism of the disease and suggest that, in the present observation, myospherulosis could have been induced by the rupture of a preexisting cyst in the perirenal adipose tissue.

[Pelviscopy: a good solution]. / Pelviscopie: une bonne solution.

With the ongoing evaluation of laparoscopic techniques in urology, the transperitoneal access used initially has been progressively replaced by the much simpler retroperitoneal route. The applicability of these new techniques has now been proven though their application still requires a delicate procedure. A long training period is usually required to be able to perform safe operations of reasonable duration. We present a different technique using a modified vaginal speculum and a laparoscopic optic positioned between the valves of the speculum to give a good visualization and expose the operative field. Several retroperitoneal procedures can be performed with this technique using the video-assisted pelviscope, including nephrectomy, pyeloplasty, lymphadenectomy in the pelvis... This video-assisted surgical technique is an interesting compromise between classical surgery and laparoscopic surgery. It is both simple and safe causing little tissue damage and has the advantage of a short postoperative recovery period.

In vivo, synergestic inhibition of MAT-LyLu rat prostatic adenocarcinoma growth by polyamine deprivation and low-dose cyclophosphamide.

Polyamine deprivation in vivo produces significant tumor growth inhibition of the hormone-resistant, metastatic Dunning Mat-LyLu murine prostatic carcinoma. In order to produce a cytotoxic effect in addition to the cytostatic effect of polyamine deprivation, various chemotherapy regimens, combined with drug-containing polyamine-deficient chow (DC-PDC), were assessed. Triple chemotherapy combining methotrexate, cyclophosphamide and vindesine; and monochemotherapy with high-dose cyclophosphamide (90 mg. kg-1) and low-dose cyclophosphamide (20 mg.kg-1) were studied alone and in combination with DC-PDC. A variant of DC-PDC excluding the polyamine oxidase inhibitor MDL 72527 was also studied in combination with low-dose cyclophosphamide. The triple-chemotherapy regimen alone or in combination with polyamine deprivation was effective on tumor growth inhibition but was also toxic. High-dose cyclophosphamide alone produced significant tumor growth inhibition and an increase in life span. High-dose cyclophosphamide in combination with DC-PDC was also effective on tumor growth but was also toxic. Low-dose cyclophosphamide alone was moderately effective on tumor growth inhibition with a marginal increase in life span. When combined with polyamine deprivation, results with low-dose cyclophosphamide compared favourably with those of high-dose cyclophosphamide alone and prevented the formation of lung metastases. The polyamine oxidase inhibitor does not appear to be mandatory to achieve this effect if DC-PDC is combined with low-dose cyclophosphamide. Polyamine deprivation appears to be an important tool in anticancer therapy, allowing the use of reduced doses of cytotoxic agents with the same antitumoral efficacy.

[Testicular microlithiasis: ultrasonographic diagnosis and semiologic value]. / Microlithiases testiculaires: diagnostic échographique et valeur sémiologique.

Testicular microlithiasis corresponds to calcifications in the lumen of seminiferous tubules. This rare condition, primarily diagnosed histologically, is usually discovered on scrotal ultrasonography. The characteristic appearance combines multiple microscopic hyperechoic areas disseminated bilaterally throughout the testicular parenchyma. The coexistence of microlithiasis and testicular neoplasms has been described and raises the problem of the therapeutic approach following incidental discovery on scrotal ultrasonography performed for other reasons. The authors report a case of testicular microlithiasis discovered on ultrasonography performed after testicular trauma.

Is ipsilateral adrenalectomy a necessary component of radical nephrectomy?

Due to the increased use of modern imaging systems during the last few years, kidney tumors are often diagnosed at an earlier and less advanced stage. This fact implies a reevaluation of the operative technique of radical nephrectomy that was recommended 30 years ago. The ipsilateral adrenal involvement during radical nephrectomy for renal cell carcinoma is assessed and the necessity of its extirpation is discussed. Between September 1987 and September 1993, we performed 299 radical nephrectomies for renal cell carcinoma and removed 285 ipsilateral adrenal glands. Eleven adrenal glands (3.8%) were involved with the kidney tumor and 274 (96.2%) were free of disease. In 7 of the adrenal gland involved cases (63.6%) the tumor invaded the gland by direct extension from the superior pole of the kidney. In the other 4 cases the ipsilateral adrenal gland was affected by a metastatic lesion. In all 11 adrenal gland involved cases the tumors were at an advanced stage (the lowest was stage pT3N1). Our results led us to recommend adrenalectomy during radical nephrectomy only when direct extension of the kidney tumor into the gland is suspected (upper pole or large tumors) or when the adrenal is the site of a single metastasis. Macroscopically normal adrenal glands at radical nephrectomy should not be routinely extirpated. Metastatic renal cell carcinoma (not by contiguity) in the ipsilateral adrenal gland should be regarded as a stage M+ (distant metastasis) tumor.

Treatment of the intraoperative penile erection with intracavernous phenylephrine.

A total of 23 patients who had an intraoperative penile erection during endoscopic or penile surgery underwent intracavernous injection of 200 micrograms phenylephrine. Detumescence occurred rapidly in all patients with a single injection. Hemodynamic changes consisted of a transient increase in systolic and diastolic blood pressures (+9%, p < 0.05) without significant change in pulse rate (-5%, p > 0.05). No marked side effect was reported even in elderly patients. Intraoperative penile erection, which seems to be more frequent in patients younger than 50 years, during general anesthesia with propofol or epidural anesthesia, can be treated safely with intracavernous injection of phenylephrine.

[Synchronous bladder metastasis of a clear-cell adenocarcinoma of the kidney]. / Métastase vésicale synchrone d'un adénocarcinome du rein à cellules claires.

Urinary bladder synchronous metastases from renal cell carcinoma are rare, three cases were reported in the literature and we present the fourth. In these four published cases, the bladder metastases followed a left kidney tumor and in three, a brain metastases was also found. A possible retrograde metastatic dissemination through the left genital and vertebral veins has to be taken in consideration. The short survival after the extirpation of the tumor and the bladder metastases implies a less aggressive approach in the presence of a bladder metastases.

[Extracorporeal lithotripsy for urinary calculi: a non invasive technique? Report of 150 patients treated with the Nova lithotriptor]. / La lithotripsie extra-corporelle pour calcul urinaire: une technique non invasive? A propos de 150 patients traités avec le lithotripteur Nova.

The NOVA apparatus is an electrohydraulic lithotriptor not yet available in France. The authors present an evaluation of the first 150 patients treated with this machine. 92.2% of the 185 stones treated were fragmented. 141 patients were reviewed at 1 month and, if necessary, 3 months after the first session; 4/24 patients and 1/3 patients were not reviewed after their second and third treatment session, respectively. Evaluation of the 177 sessions performed (16% of second sessions and 2% of third sessions), 69.11% of patients did not have any residual stones. The success rate was 52% for renal stones; 96% for stones of the lumbar ureter and 50% for pelvic stones. The morbidity was low (10% of renal colic, 5% of obstructive stone) but in combination with second treatment sessions, it generated a risk of being rehospitalised after the first session of 26%. When the procedures performed under anaesthesia before and after ECL (apart from repeated sessions) are added, the risk of this supplementary anaesthetic for a given patient is 18.66%. Lastly, the risk of undergoing another anaesthetic after the 1st ECL was 33%. These data indicate the limits of the "noninvasive" nature of a modern and effective lithotriptor.

Erythrocyte polyamines and prognosis in stage D2 prostatic carcinoma patients.

We studied 43 patients with newly diagnosed, untreated, stage D2 prostatic carcinoma, and correlated the initial performance status, hemoglobin, prostate specific antigen levels, tumor Gleason grade, extent of disease on the bone scan, and erythrocyte spermidine and spermine levels with progression. Three patients died of unrelated causes and were excluded from the study, 16 remained in remission with a mean 28 +/- 11 months of followup and 24 had progression (18, or 75%, of whom died of the cancer) with a mean 12 +/- 9 months of followup (p < 0.05 for followup) after initiation of hormonal therapy. Pretreatment performance status, hemoglobin, and erythrocyte spermidine and spermine levels were correlated with progression, hemoglobin and spermine being the most significant independent variables (p = 0.006 and p = 0.001, respectively). Concerning cause-specific survival, only hemoglobin and spermine erythrocyte levels were significant independent variables (p = 0.02 and p = 0.0025, respectively). If confirmed, polyamine erythrocyte levels obtained by a simple blood sample could discriminate at diagnosis patients with a high risk of rapid hormonal relapse who may benefit from a more aggressive primary management.

Polyamine deprivation: a new tool in cancer treatment.

The fact that tumors require polyamines for growth has been demonstrated in vitro and in vivo and widely reported. This finding led to the use of polyamine biosynthetic enzymes as targets for antitumor drug design. Highly efficient in vitro selective inhibitors of ornithine decarboxylase such as DFMO do not produce important antitumoral effects in vivo, due to the ability of tumor cells to uptake extracellular polyamines. A new strategy was developed, combining a systematic blockade of all endogenous and exogenous sources of polyamines in vivo. Sources of exogenous polyamines were eliminated by administration of a polyamine-free diet to the animals and decontamination of their gastrointestinal tract. Important antitumoral effects were obtained with this polyamine deprivation and are presented with two experimental models of tumors (Lewis lung carcinoma, Mat Lylu prostatic carcinoma). Biological parameters, modified in cases of cancer, were restored to normal values in treated animals: blood counts and NK cytotoxic activity. Number of metastases was significantly reduced. Given that in man cancer treatment remains unsatisfactory due to incomplete cell kill, development of resistance to treatment and secondary effects of chemotherapy, we chose to investigate the potential interest of polyamine deprivation in this field. By combining clinically applied cytotoxic drugs with polyamine deprivation, we observed an improvement of their antitumoral efficiency: a considerable retardation of tumor growth paired with a marked increase in life-span of the treated animals. Our observations confirm that polyamines absorbed from exogenous sources, mainly food and gastrointestinal tract, play an important role in tumor growth control. Furthermore, the study shows that polyamine deprivation represents an important potential therapeutic tool in improved management of cancer treatment.

[Medical treatment of prostate cancer]. / Traitement médical du cancer de la prostate.

Hormone dependence of prostate cancer is well known. In 80% of cases with metastases, hormone suppression leads to the reduction of tumour volume and related disorders. However the treatment is generally palliative because malignant process recurs after about around 16 months. Mean survival is less than 3 years in these forms. Lack of response come always together with a poor prognosis, and there is 90% mortality at 2 years. Advanced prostatic cancer should not be treated with hormones if the patient has few symptoms and his quality of life is satisfactory. Symptomatic forms require hormone manipulation. Orchidectomy or LH-RH are recommended. Total androgen ablation (combined treatment) leads rapidly to more relief of symptoms, but its drawbacks and especially high cost indicate that its use should be weighed individually. Estramustine is not a first-lune treatment. Presently, there is no criteria to predict response to treatment.