Characterization of midazolam metabolism using human hepatic microsomal fractions and hepatocytes in suspension obtained by perfusing whole human livers.

Isolated human hepatocytes provide a useful model for studying xenobiotic metabolism. However, in vitro studies using human hepatocytes are scarce due to the limited availability of this material. A new methodology is described for obtaining hepatocytes from a whole adult human liver. This procedure is based on (i) the rapid and intense in situ washing step of the organ with Eurocollins then glucose supplemented HEPES buffer (10 mM, pH 7.4) at 4 degrees in order to both minimize the warm ischemic period and remove erythrocytes, and (ii) a perfusion of collagenase solution (0.05% in 10 mM HEPES buffer at 37 degrees) throughout the portal vein according to a recirculated model. All perfused buffers are oxygenized. Hepatocyte viability averaged 85% as determined by Trypan Blue dye exclusion. The ability of these hepatocytes to catalyze certain metabolic transformations such as Phase I and Phase II reactions has been particularly investigated using the benzodiazepine drug, midazolam, as a substance probe. Freshly isolated human hepatocytes in suspension retained the ability to metabolize midazolam to its different hydroxylated derivatives--mainly the 1-hydroxy-midazolam--which was further conjugated with glucuronic acid. For a better understanding of the cytochrome P-450 mediated reactions, we studied the metabolism of midazolam in microsomal fractions prepared from twelve human livers. It was concluded that human microsomes (i) exhibited a Type I binding spectrum upon midazolam addition (Ks = 3.3 microM) and (ii) intensively metabolized the drug to its different derivatives. Furthermore, and since we demonstrated that midazolam was predominantly transformed by a single cytochrome P-450 enzyme, we could attribute the large inter-individual variations in midazolam metabolism to differences in human liver cytochrome P-450 content.

[Growth fraction (Ki67), ploidy balance and proliferation index in tumors of the urogenital tract and breast]. / Fraction de croissance (Ki67), balance de ploidie et index de prolifération dans les tumeurs du tractus urogénital et du sein.

The practical applications of computer-assisted image analysis systems are multiple in oncology. The computerized system of image analysis referred to as SAMBA (TITN) is particularly relevant to analyse coloured images resulting from immunostaining or histochemical procedures assessed either on tissue sections of any type or cytological preparations (imprints, smears). The SAMBA analysis of positive Ki67 surfaces in tissue sections from breast, endometrial, ovarian, cervical or urinary bladder samples enables a multiparametric evaluation of the growth fraction (GF) in intraepithelial, borderline or invasive proliferations. Moreover, the SAMBA analysis after Feulgen staining procedures provides a parametric evaluation of the nuclei densitometry and morphological features and of the chromatin texture, which serve to compute the ploidy balance (BP) and the proliferation index (PI). In benign tumors, GF and PI are low and tumor cells are diploid with an overall high positive PB values. In malignant tumors, GF, PI and the percentage of aneuploid cells increase with tumor grade and stage whereas PB decreases. In borderline proliferations, FC, PI and PB intermediate values are recorded. These new criteria of prognosis should be assessed routinely in pathology departments and the results from these new investigations are likely to be soon implicated in the selection of patient therapy.

[Cystectomy followed by cecocystoplasty: functional and oncologic results. An experience of 101 cases]. / Cystectomies suivies de caecocystoplasties: résultats fonctionnels et carcinologiques. Une expérience de 101 cas.

From 1979 to 1992, 101 radical cystectomy with caecoplasty were performed by the same operator (MR). Mean age of the patients was 62 years with a sex-ratio: 10 males/1 female. The indications were: Transitional Cell Carcinoma in 89 cases, neurologic bladder in 5 cases, interstitial cystitis in 3 cases tuberculosis bladder in 3 cases and lymphoma in one case. The operative mortality was 3% and postoperative morbidity was 8%. The surgical procedure consisted of performing a neo-bladder with ileocaecal segment. The technique of ureterocaecal implantation changed during the study period. On a functional point of view, 28 ureterocaecal stenosis were reported (15%). It were rare (2.4%) with the last ureterocaecal anastomosis technique. The diurnal continence rate was 100%. The nocturnal continence rate was only 25%. On uroflowmetric point of view, the detubularization permitted to obtain low pressure bladders with 15% rate of atonic bladder. Transverse taeniamyotomy of the caecum permitted to increase the uroflowmetric performance of the bladder without atonic risk. The 5 and 10 year overall actuarial survival rate were respectively 5% and 30%. Tumoral stage was a significant prognostic factor. An adjuvant chemotherapy was performed in 28 patients. The 5 year actuarial survival rate of the patients with a chemotherapy was 82% versus 28% for the patients without chemotherapy (p < 0.01). Caecocystoplasty after radical cystectomy was a reliable technique in our experience.

[Cecocystoplasty. Apropos of 14 cases]. / La caeacocystoplastie. A propos de quatorze observations.

Cystoplasty is the ideal method of bringing back normal urinary flow after cystectomy, and the authors have used this procedure in fourteen cases. The cecum is mobIlized with its vascular pedicle. Bowel continuity is readily and safely restored with the aid of suturing forceps (TA 55, GIA). The cecum is carefully cleaned of all fecal matter. Two UCN join the ureters and the cecum, to which the trigone, the cervix vesicae, or the prostatic or membranous urethra is anastomosed, depending on the case. Three benign cystopathies, four recurrent diffuse papillomatoses and seven vesical carcinomas were treated in this way, with excellent results.

[Is iatrogenic vesico-renal reflux a negligible factor in the evolution of recurrent superficial tumors of the bladder?]. / Le reflux vésico-rénal iatrogène est-il négligeable dans l'évolution des tumeurs superficielles récidivantes de la vessie?

The electrocoagulation and resection of superficial tumors of the bladder leads to iatrogenic refluxes. The frequency of subsequent vesical recurrences may thus favor tumoral grafts in the upper urinary tract. Fives cases illustrate this risk. They were treated by ureteral resections and by one bilateral, and two unilateral nephroureterectomies. Should these refluxes be ignored or treated surgically in the event of repeated papillomatous recurrences?

[Cecocystoplasty. Observations apropos 45 cases]. / La caecocystoplastie. Réflexions à propos de quarante-cinq observations.

45 patients underwent urinary diversion by caecocystoplasty following simple or radical cystectomy with or without prostatectomy. The immediate postoperative course of such a major operation was surprisingly simple both in terms of the gastrointestinal tract (due to the use of automatic sutures) and in terms of the urinary tract. Micturition and diurnal continence were perfect. The few cases of incontinence related to high caecal pressure were controlled by perineal reeducation and/or the prescription of oxybutynin. A Peniflow apparatus controls the inevitable enuresis of these neobladders when the trigone has not been preserved. The upper tract is perfectly protected. The authors consider that the caecal reservoir warrants a place of choice in bladder replacement after cystectomy.

[Is intravenous urography indispensable in evaluating a bladder emptying disorder?]. / L'urographie intraveineuse est-elle indispensable dans le bilan d'un trouble de l'évacuation vésicale?

Two patients with disorders of bladder emptying (dysuria, pollakiuria) were treated by endourethral resection after being investigated by ultrasonography without intravenous pyelography. Intravenous pyelography performed subsequently due to persistence and even deterioration of the bladder emptying disorders revealed the diagnosis and allowed treatment of renal tuberculosis. Intravenous pyelography is therefore an essential part of the assessment of patients with prostatic symptoms.

[Stage T1 tumor of the bladder. From research to prognosis]. / Tumeur de vessie stade T1. A la recherche d'un pronostic.

The reserved prognosis of stage T1 (A) bladder tumours is emphasised in relation to a series of 41 cases: 95% of tumours recurred, one third of these recurrent tumours posed a therapeutic problem because of their diffuse nature (15%) or tumour progression (24%). The risk of allowing a limited tumour to progress towards and extensively infiltrating carcinoma justifies the search for a prognostic factor allowing the early recognition of the more aggressive lesions. At the present time, no one prognostic element can indicate with certainty the course of the T1 tumour. All of the data obtained from detailed histological examination of the tumour and the adjacent urothelium and from the early course of the tumour allow a better evaluation of the prognosis. The search for surface antigens (ABO) and, more recently, chromosome analysis and study of the DNA content of the tumour by flow cytometry, may complete this prognostic evaluation.

[Ureter-aorto-iliac prosthesis cross-over and a tumor of the ureter]. / Croisement uretère-prothèse aorto-iliaque et tumeur de l'uretère.

Ureteric stenoses sometimes occur after the insertion of aorto-iliac prostheses. Two cases of neoplastic ureteric stenosis, independent of the ureter-prosthesis crossing are reported, indicating the possibility of such lesions after aorto-iliac prosthetic surgery.

["Wallstent" endoprosthesis in recurrent urethral stricture in men]. / L'endoprothèse "Wallstent" dans les sténoses récidivantes de l'urètre masculin.

Many patients are condemned to repeated urethral dilatations because of the poor efficacy of treatment for male urethral stricture. The authors have recently used a new urethral prosthesis: a metal-reinforced, meshed tube which opens in the urethra and maintains a it open allowing the urothelium to grow over. The prosthesis therefore becomes incorporated in the wall of the urethra. they have implanted this prosthesis in 21 patients with a mean age of 61 years, essentially in the bulbar urethra, for longstanding strictures measuring 5 to 35 mm and unresponsive to currently available treatments. The endoscopic insertion of the prosthesis is performed after dilatation. The mean follow-up is 9 months. The stricture was correctly treated in all patients (three patients required two sessions). The follow-up of these patients is short and the stability of these favourable results needs to be confirmed by a longer follow-up.

[Quantitative renal DMSA scintigraphy after extracorporeal lithotripsy]. / Scintigraphie rénale quantitative au DMSA après lithotripsie extra-corporelle.

This study reports the results of renal DMSA isotope scan before and after EDAP extracorporeal lithotripsy in 106 patients. An isotope scan was performed before lithotripsy and on the fourth day after lithotripsy and again on the 90th day when alterations were observed on the first post-lithotripsy scan. The assessment of any sequelae was based on the scale of colours of the spectrum, which revealed three types of modifications. The analysis of the results is divided into three periods according to the development in our lithotripsy technique: high firing rates had a success rate of only 40%, with renal scars on isotope scans in 2/3 of cases; low frequency firing rates had a 55% success rate and induced minor changes which were virtually always reversible; in contrast, low frequency firing rates during the 3rd period had a 60% success rate with scars on isotope scans in 1/3 of cases. These isotope scan modifications also depended on the site of the stone. In conclusion, lithotripsy definitely induces renal modifications. The renal parenchyma cannot remain indifferent to lithotripsy beyond a certain threshold. A homogeneous multicentre study with a common protocol is necessary to compare the various lithotriptors and to define cautious and coherent indications for each lithotriptor in the treatment of renal stones.

[Our experiences using ureteral stripping in nephro-ureterectomy]. / Notre expérience du stripping urétéral dans la néphro-urétérectomie.

The authors report their experience concerning 25 cases of ureterectomy by stripping, introduced by Dell'Ami. The technique carried out in the department is described. Cases of failures and possible complications are also discussed.

[Functional and urodynamic study of cecocystoplasties with or without detubation]. / Etude fonctionnelle et urodynamique des caecocystoplasties avec ou sans détubulisation.

The authors analyse and compare the clinical and urodynamic results of 16 tubed caecocystoplasties and 5 detubed ileocaecocystoplasties. The urodynamic assessments were performed between 2 months and up to 4 years after the operation. After a period of about 6 months, there was a functional difference between these two types of reservoir. The loss of pressure peaks in detubed reservoirs is not sufficient to ensure complete nocturnal continence. Neovesico-sphincteric synergy is responsible for real sphincteric self-re-education. Rationally, a detubing procedure in bladder replacement is only desirable in the case of a "deficient" sphincter.

[Extra-corporeal lithotripsy (EDAP LT 01) in urinary lithiasis]. / La lithotripsie extra-corporelle (EDAP LT 01) dans la lithiase urinaire.

Five hundred and twenty six extracorporeal lithotripsies have been performed for renal and ureteric stones. Using low frequencies (1.25 to 2.5 cycles per second), extracorporeal lithotripsy was performed without anaesthesia and without premedication in 85% of cases. 91.9% of patients treated were followed and reviewed after one and three months: 292 (55%) were successes, 124 (22.5%) obtained partial results, 122 (22.5%) were failures. The best results were obtained in stones less than 20 mm in diameter. The results could only be improved by a second session of extracorporeal lithotripsy. Scintigraphic scars observed after high frequency lithotripsy and not observed after low frequency lithotripsy were again seen after renewal of the firing head.

[Extracorporeal lithotripsy in urinary calculi using the LT 01 EDAP]. / Lithotripsie extra-corporelle avec le EDAP LT 01 dans la lithiase urinaire.

Three hundred and sixty nine extracorporeal lithotripsies for renal stones have been performed using the EDAP apparatus (ultrasound detection, piezoelectric destruction). In 7.1% of cases, the stone could not be located. By using low frequencies (1.25 to 5 cycles per second), extracorporeal lithotripsy was able to be performed in 82% of cases without anaesthesia and without premedication. 96.5% of patients treated have been followed and reviewed at one and three months: 169 (61%) cases were successful, 59 (21.3%) were partial results and 49 (17.7%) were failures. The best results were obtained in stones less than 20 mm in diameter. A poor result can only be improved by a second session of extracorporeal lithotripsy. The scintigraphic scars observed after high frequency extracorporeal lithotripsy were not observed when low frequencies were used. This new outpatient extracorporeal lithotripsy procedure without anaesthesia currently represents 79% of our primary indications in renal stones.

[New uretero-cystoneostomy in cystocecoplasties. Technique and results]. / Nouvelle urétéro-cystonéostomie dans les cystocaecoplasties. Technique et résultats.

Ureteric reimplantations into an intestinal segment are frequently followed by early, secondary or late stenoses. In UCN, it is essential to perform atraumatic ureteric dissection followed by reimplantation of a short ureter well vascularized by a single superior pedicle, i.e. the simplest UCN, putting the least strain on the ureter both during creation of the diversion and during subsequent healing. The ileal segment of an ileocaecocystoplasty must extend above the right iliac vessels. It is open on the antimesenteric border and its distal border is stripped of a 3 mm band of mucosa. To reach its homologue, the left ureter passes underneath the common root of the sigmoid mesocolon. Each optimally shortened ureter is placed in and fixed to the start and the end of a longitudinal mucosal tunnel, about 3 cm long. The ileum is sutured as a cuff around the orifice of each ureter. A ureteric stent is left in place for a fortnight. The ileum is sutured to the right laterocaval retroperitoneal tissue. This UCN is simple and rapid to perform.

[Value of radiologic examinations in the diagnosis and staging of upper urinary tract tumors]. / Valeur des examens radiologiques dans le diagnostic et la stadification des tumeurs de la voie excrétric urinaire supérieure.

From 1980 to 1991, 109 patients were treated for a tumour of the upper urinary tract. All patients were examined by intravenous urography (IVU) which had a sensitivity of 61%. The combination of IVU + RUP established the diagnosis in 72% of cases. Renal ultrasonography and abdominal computed tomography (CT) were performed in 41 and 67 cases, respectively. The sensitivity of ultrasonography was 40% and that of CT was 72%. CT was more sensitive for tumours of the renal pelvis (78%) than for ureteric tumours (53%) (p < 0.02) and when the tumour diameter exceeded 2 cm (70% vs 45%: p < 0.01). The sensitivity of CT for lymph node extension was 47% with an accuracy of 88%. Preoperative CT staging was compared to pathological staging: CT staging had an accuracy of 56%; in 31% of cases, CT underestimated the parietal extension of the tumour. The sensitivity of CT to assess invasion of the renal parenchyma and of the perirenal fat was 52% and 74%, respectively (p < 0.01). Morphological examinations are able to diagnose a tumour of the upper urinary tract in 3 out of 4 cases. Correct preoperative staging can only be achieved on one half of cases, which constitutes a drawback to the development of conservative treatment techniques.

[Stage M1b prostatic adenocarcinoma: prognostic factors, value of bone scintigraphy]. / Adénocarcinome prostatique de stade M1b: facteurs de pronostic, intérêt de la scintigraphie osseuse.

Based on a retrospective study of 52 patients with prostatic adenocarcinoma and bone metastases (stage M1b), the authors analysed the following prognostic factors at the time of diagnosis: age, general status, bone pain, haemoglobin, local tumour volume, ureteric repercussions, pre and post-treatment PAP and PSA levels, Gleason score, and metastatic spread on bone scan. This study demonstrated two predominant prognostic factors for the appearance of early or late therapeutic escape: tumour differentiation established by the Gleason score (P = 0.003), stage of the disease, i.e. local tumour volume (p = 0.001) and bone mass invaded on bone scan (p = 0.0002). The other prognostic factors can be deduced from these two parameters. Qualitative analysis of the initial bone scan allowed patients with peripheral bone metastases to be distinguished from those with exclusively axial involvement. The two-year survival was 50% in patients with peripheral metastases versus 93% in patients without peripheral metastases (p < 0.05). Although bone metastasis constitutes a decisive prognostic factor, the detection of peripheral bone metastases appears to be a factor of poor prognosis.

[Flow cytometry in bladder lavage fluid for the diagnosis and surveillance of bladder tumors. Preliminary results]. / La cytométrie en flux sur liquide de lavage vésical dans le diagnostic et la surveillance des tumeurs de vessie. Résultats préliminaires.

The authors evaluate the accuracy and practical applications of flow cytometry (FCM) on bladder lavage fluid in the diagnosis and follow-up of bladder tumours. The apparatus used was a Coultronics Epics Profile II cytofluorograph. Two hundred and fifteen samples were obtained with a yield of 86%. The specimens were preserved in ethanol. The staining was performed on whole cells with preservation of the cytoplasm. The analysis of a control group of 45 patients confirmed that the FCM study of ploidy was specific (0.97 for normal bladders and 0.8 for inflammatory lesions). Four aspects were evaluated: Correlation between FCM and the histological type of the tumour: a significant difference was observed between the control group, the invasive tumour group (p < 0.01) and the carcinoma in situ group (< 0.001). A significant difference was observed in the case of high-grade PTA and PT1 tumours. No significant difference was observed between FCM and classical cytodiagnosis when this technique was performed by a trained cytologist. Predictive value of FCM for the recurrence of PTA and PT1 tumours: 40 patients were followed with a mean follow-up of 13 months. The relative risk of recurrence in the case of a tumour with an abnormal FCM was 2 (p < 0.05). FCM and monitoring of conservatively treated tumours: 30 patients with normal endoscopic examination after endoscopic resection of a PTA or PT1 tumour underwent cytometric analysis and cytodiagnosis. In the case of an abnormality on cytometry, randomised bladder biopsies and urography were performed. The positive predictive value for the presence of a lesion not diagnosed by cystoscopy and detected by FCM was 0.38 +/- 0.26. FCM and intravesical chemotherapy: 16 patients with PT1 tumours and abnormal FCM received BCG therapy (11 patients) or mitomycin C instillations (5 patients). A significant difference (p < 0.01) was observed between the 2 treatments in terms of normalisation of cytometry.(ABSTRACT TRUNCATED AT 400 WORDS)

[Ultrasonographic study of adrenal gland tumors (report of 5 cases)]. / Etude échographique des tumeurs de la surrénale (à propos de 5 cas).

The authors study the ultrasound signs of the adrenal gland based on 5 different types of operated adrenal tumours (a lipoma, an adrenal cortical adenoma, a cyst, a corticoadrenaloma, an adrenal metastasis from a renal cell carcinoma). The ultrasonographic morphological criteria of the normal adrenal gland and each type of tumour are recalled and are illustrated by clinical cases. The value of ultrasonography in the investigation of this organ was evaluated in comparison with other imaging techniques. It constitutes a good first-line diagnostic guiding examination, but needs to be completed by other investigations (computed tomography, magnetic resonance imaging, etc.). Ultrasonography can also reveal asymptomatic adrenal tumours ("adrenal incidentalomas") in which the therapeutic decision (surveillance or surgery) must be based on criteria of size and appearance after a complete laboratory and morphological assessment.