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We investigated the ability of a 20-core prostate biopsy protocol to enhance the prostate cancer diagnosis rate.We compared the diagnosis rate of prostate biopsies in 2 groups of consecutive patients, including group 1-10 cores and group 2-20 cores. The prostate specific antigen range in the 2 groups was 3 to 30 ng/ml and biopsies were performed because of increased prostate specific antigen (more than 3 ng/ml) and/or abnormal digital rectal examination. To analyze the results we divided each group into 3 subgroups according to prostate specific antigen, including group 1-3 to less than 6 ng/ml, group 2-6 or greater to less than 10 ng/ml and group 3-10 or greater to up to 30 ng/ml. Multivariate analysis was performed to assess the difference in the diagnosis rate among the subgroups according to the number of cores taken.The percent of positive biopsies was 39.7% in group 1 and 51.7% in group 2. Multivariate analysis confirmed that the number of biopsies taken was a factor that independently and significantly correlated with the prostate cancer diagnosis. The 20-core biopsy protocol was more efficient than the 10-core protocol in the 3 subgroups with 47.2% vs 28.1% of patients diagnosed in group 1 (OR 3.26, p = 0.001), 40.5% vs 36.1% in group 2 (OR 2.37, p = 0.009) and 69.8% vs 39.7% in group 3 (OR 2.01, p = 0.015).The 20-core biopsy protocol was more efficient than the 10-core biopsy protocol, especially in patients with prostate specific antigen between 3 and 6 ng/ml. Nevertheless, it is mandatory to confirm whether detected tumors are clinically significant on pathological examination of the radical prostatectomy specimens.

Treatment of corneal epithelial diseases induced by limbal stem cell deficiency is an important challenge in ocular surface reconstruction. Since the 1990s, corneal stem cells have been localized in the limbus. This new concept completely changed the way we consider ocular surface reconstruction, with new diseases now found to be isolated in the ocular surface. Limbus insufficiency syndromes are specific depending on their origin (congenital or acquired), their expression (unilateral or bilateral, partial or total), their progression (acute or chronic), and the mechanism involved (burn, infection, chronic inflammation, etc.). Some of these diseases are local diseases and others are systemic diseases. Clinically, limbus insufficiency is a switch of the normal corneal epithelial phenotype (expression of a specific keratin, avascularity, and transparency of the corneal matrix) in an opaque and fibrovascularized cornea. In terms of cellular biology, a phenotype is a terminal expression of a cell differentiation process. This process is the outcome of the interaction between the genome of a cell or a group of cells with their microenvironment. In limbus insufficiency, epithelial cells and corneal matrix are destroyed, and it is the destruction of these two components that leads to limbus insufficiency syndrome.

To study the pathologic features of radical prostatectomy (RP) specimens of patients operated on the basis of a potentially "Insignificant" prostate cancer (Ca P) characterized by one single focus (less than 3mm) of moderately differentiated adenocarcinoma - Gleason scoreor =6, out of 6-10 biopsies and to determine which characteristics, if any, are predictive of the presence of a "non significant" prostate cancer in the specimen characterized by a low volume (0.5 ml) moderately differentiated organ confined, cancer (Gleason score less than 6).PSA, biopsy features, and surgical specimens of a series of 56 patients submitted to RP for "insignificant Ca P" on TRUS prostate biopsies between 1988 and 2004 were compared regarding the number of tumor foci, Gleason grade and score, tumor volume determined by the cylinder method, as well as extraprostatic extension (EPE) and positive surgical margins (P.SM.).70% of the patients had multifocal microfocal cancer apart from the index tumor. The presence of grade 4 was ignored by the biopsy in 50% of the cases, however the primary grade was correctly evaluated in more than 70% of the biopsy sets. 42% of the patients had a cancer volume less than 0.5 ml and 29% met the definition of insignificant/unimportant cancer characterized by a moderately differentiated (Gleason scoreor =6) of low volume (less than 0.5 ml) however no feature accurately predictive of insignificant cancer could be individualized. In this whole series, only 8% of the patients had EPE. When the pre-operative PSA was10 ng/ml, 98% of the patients had an organ confined tumor.Patients diagnosed with prostate cancer on the basis of one single focus less than 3 mm of moderately differentiated (Gleasonor =6) prostate cancer have 30% of chances of harboring an insignificant tumor in their prostate and are therefore, at risk of being overtreated, however there is at this time no specific feature able to identify these patients pre operatively.

Some studies imply that increasing the number of prostate biopsy cores may improve the cancer detection rate. We performed a prospective study to evaluate pain and morbidity after an extensive transrectal ultrasound guided 10-core biopsy protocol.A total of 289 consecutive men with abnormal digital rectal examination findings and/or increased prostate specific antigen underwent extensive prostate biopsy involving 6 sextant and 4 peripheral biopsies. Each received an information leaflet a few days before the procedure. A single dose of fluoroquinolone and a rectal enema were administered before biopsy. In no case was the procedure performed using anesthesia. Immediately after biopsy patients were asked to complete a self-administered nonvalidated questionnaire evaluating the degree of pain and/or discomfort using a visual analog scale. In another questionnaire they listed the side effects noticed during month 1 after biopsy.Although 48% of the 275 men who completed the initial questionnaire reported anxiety before the procedure, 78.8% of them were completely reassured by the information brochure. Of the 275 patients 47.6% described the procedure as painful, including only slightly painful (analog visual scale 3 or less) in 67.9%, while 33.8% described it as uncomfortable but not painful and 18.6% thought that it was neither painful nor uncomfortable. Of the 115 patients who engaged in sexual intercourse during month 1 after the procedure 78.3% noticed hematospermia an average of 10.9 days in duration. Of the 164 men who completed questionnaire 2, 74.4% noticed hematuria an average of 2.7 days in duration, 3.7% noticed pyrexia and 1.2% noticed acute prostatitis. In the 59 patients (36%) who reported delayed perineal pain it was slight in 64.4%, moderate in 30.5% and severe in 5.1%. No patient required hospitalization.Although minor complications are common, the extensive 10-core prostate biopsy protocol is associated with few major complications. The occurrence and intensity of pain and discomfort are in the range reported after the standard 6-core biopsy protocol.

Purpose: We evaluated improvement in the rate of prostate cancer detection when using an extensive biopsy protocol involving peripheral cores.Materials and Methods: We prospectively evaluated 303 consecutive men who underwent transrectal ultrasound guided biopsy due to elevated prostate specific antigen (PSA) and/or abnormal digital rectal examination. Ten biopsies were performed, including at least 5 at the base and middle of each lobe. In addition to standard biopsy at a 45-degree angle, a more peripheral 30-degree angle biopsy was obtained. At the apex only 1 standard biopsy was done. However, when prostate volume was greater than 50 cm.3, an additional peripheral biopsy was obtained at the apex.Results: The complication rate in this biopsy protocol was 1% (3 patients). Prostate cancer was detected in 118 of the 303 men (38.9%). Overall this extensive protocol resulted in 6.6% improvement in the detection rate. Improvement was 6.5% in men with PSA 10 ng./ml. or less and 7% in those with PSA greater tha...

To perform a multivariate analysis to investigate the usefulness of eight preoperative variables as predictors of final pathological stage (pT), positive surgical margins (PSM) and biological progression after radical prostatectomy (RP).In 143 patients undergoing RP for T1-T2 prostate cancer, the respective values of age, clinical stage, preoperative prostate-specific antigen (PSA), prostate-specific antigen density (PSAD), number of positive biopsies (NPB), Gleason score, length of tissue core invaded by cancer (LTI) and topography (uni/bilaterality) of positive biopsies for predicting extracapsular extension, PSM and biochemical failure (PSAor =0.05 ng/ml) were evaluated retrospectively. Univariate and multivariate analyses were applied to define the statistical significance of each variable. Actuarial survival without biological progression was calculated using the Kaplan-Meier method (log-rank test).In this series, 44.8% of patients had extracapsular extension with 41.3% PSM. The mean PSA was 12.4 ng/ml. In univariate analysis, LTI (p0.0001), NPB (p = 0.0023), PSA (p = 0.0039) and Gleason score (p = 0.0136) were the most powerful variables to predict pT stage; however, in logistic regression analysis, LTI was the most predictive feature. For prediction of PSM, some variables (LTI, NPB and PSA) were found to be of statistical value in univariate analysis, and LTI in combination with NPB and PSA in multivariate analysis. For biological progression, statistical analysis (log rank test) showed PSAD and LTI to be significant predictors.The pathological report regarding the biopsy contains crucial information influencing the prediction of pT stage, PSM and biological progression after RP. LTI, NPB and PSA are the most useful parameters for this purpose.

Resume L'objectif de l'etude est d'evaluer les niveaux d'expression tissulaire et les quantites circulantes de chromogranine A chez les patients ayant un cancer prostatique ou une hypertrophie benigne de la prostate (HBP). Parmi 100 patients ayant eu des biopsies prostatiques, 46 ont un adenocarcinome (groupe I) et 54 une HBP (groupe II). Les quantites de chromogranine A dans le sang circulant sont determinees avec un seuil de positivite de 100 ng mL−1. Une procedure immunohistochimique est appliquee chez tous les patients. L'expression tissulaire de la chromogranine A est cotee de 0 a 3+, selon le nombre de cellules marquees. Lorsque le patient a subi une prostatectomie radicale, le niveau d'expression tissulaire de la piece operatoire est rapporte a celui des biopsies. 17,4 % des patients du groupe I ont un taux serique de chromogranine A superieur a 100 ng mL−1 contre 3,7 % dans le groupe II. La moyenne des taux seriques dans le groupe I est de 66,8 ± 98,8 ng mL−1 et de 38,1 ± 27,8 ng mL−1 dans le groupe II. Dans le tissu sain, seuls 10 % des patients n'ont aucune expression tissulaire de chromogranine A, contre pres de la moitie des patients dans le tissu tumoral. La plus forte immuno-expression tissulaire de chromogranine A est retrouvee dans les prelevements tumoraux (10 % versus 1 %). La presente etude confirme que la chromogranine A est statistiquement plus abondante dans le serum des patients ayant un cancer prostatique que dans le serum des patients ayant une HBP.

To evaluate retrospectively the efficacy of adjuvant radiation therapy (ART) in patients with T1–T2 prostate cancer (CaP) in whom extracapsular cancer (pT3) was detected after radical prostatectomy (RP), together with biochemical failure characterized by a recurrent level of serum prostate-specific antigen (PSA)>0.1 ng/mL. Twenty-two patients with T1–T2 CaP treated by RP who subsequently were found to have pT3 CaP with (13) or without (9) positive surgical margins and/or seminal vesicle invasion, exhibited biochemical failure characterized by a recurrent level of serum PSA, 2–40 (mean: 25) months after RP and were treated with ART (65 Gy). Bone and CT scans were negative in every patient, 15 of whom were submitted to TRUS biopsy (Bx) of the anastomosis (resection site), which was positive in 8. Patients were followed up for between 6 and 60 (mean: 32.5) months. Transient side effects (urgency, proctitis, diarrhea) were experienced by 9 patients after ART. A decrease in serum PSA was observed in 19 patients; however, only 14 of these achieved an undetectable level (

Resume L'utilisation des biopsies multiples systematisees, actuellement recommandee avant tout geste therapeutique, permet de rechercher un cancer prostatique dans des conditions optimales et d'etudier differents parametres d'evolutivite locale et de pronostic. Le prelevement des biopsies et leur analyse histologique doivent repondre a un protocole precis. Apres confirmation de la presence de cancer, le score de Gleason sera evalue et le volume tumoral apprecie sur le nombre de biopsies positives et le pourcentage de tissu tumoral dans chacune de ces biopsies. On notera l'uni ou la bilateralite de la tumeur, et l'on recherchera un eventuel franchissement capsulaire ainsi que l'envahissement des espaces perinerveux. Ces notions peuvent etre resumees sur un tableau synoptique.

BACKGROUND Information regarding the quantity of biopsy material invaded by cancer may supplement the usual criteria for the preoperative staging of patients suffering from clinically localized prostate carcinoma (T1-T2). However, conflicting conclusions have been drawn and this topic needs further investigation. METHODS A total of 170 patients had radical prostatectomy for T1-T2 prostate carcinoma. Patients' mean age (± standard deviation [SD]) was 66.05 ± 6.12 years and mean prostate specific antigen (PSA) level (± SD) was 22.5 ± 21.4 ng/mL (Yang Proscheck). Of the patients, 110 underwent transrectal ultrasound-guided biopsy with removal of 6 cores, from whom we had the percentage of biopsy, material invaded by cancer, the Gleason score, and the preoperative PSA. These parameters were compared with the pathologic features of the surgical specimen (capsule penetration, surgical margins, and Gleason score) and biologic progression (defined as persistent/recurrent postoperative PSA > 0.1 ng/mL). RESULTS The most valid threshold of biopsy material invaded by cancer for predicting surgical margins and capsule status, as well as biologic progression, was 10%. When 10% of one core biopsy invaded by tumor. If; cc 10% of tissue in only 1 of 6 cores of a biopsy was invaded by tumor, the status was pT2, SM−, and P− in 87.5% of the patients. CONCLUSIONS On an individual basis, the percent of tissue containing carcinoma in core biopsies was a factor that lacked the statistical power to predict the status of the capsule and surgical margins, and the biologic progression. The finding of; cc 10% of carcinoma in 1 of 6 cores of a biopsy was correlated with a good prognosis. Cancer 1996;78:1079-84.

Objective To evaluate whether a single positive prostate biopsy in six systematic transrectal ultrasonography (TRUS)-guided biopsies is predictive of a small tumour volume in a subsequent radical prostatectomy (RP) specimen. Patients and methods Of 158 patients submitted to RP for T1–T2 prostate cancer, 15.2% had one positive biopsy. The rate of positive margins (M+) and extracapsular involvement (C+) were assessed on the RP specimen in those with one positive biopsy (group I) and in those diagnosed by more than one positive biopsy (group II). The percentage of those with post-operative biological progression (P+), having a prostate-specific antigen (PSA) level>0.1 ng/mL, was evaluated in both groups. The Gleason scores in biopsies and specimens were also compared. Fifteen patients diagnosed by a single positive biopsy were management conservatively. Results The percentage of patients who were categorized C+, M+ and P+ was 29.2, 16.7 and 26% in group I and 70, 46.5 and 49.5%, respectively, in group II. All patients with

Objective To compare retrospectively the efficacy of radical perineal and retropubic prostatectomy in patients with T1, T2 cancer of the prostate. Patients and methods From January 1991 to January 1993, 71 patients with T1, T2 carcinoma of the prostate aged 52–74 years underwent radical retropubic prostatectomy (36) or radical perineal prostatectomy (35); this was preceded by endosurgical lymphadenectomy. The two groups were identical with regard to age (64 vs 66 years), clinical stage (Tla 17% vs 25%, T2 82% vs 74%), mean and median pre-operative prostate-specific antigen (PSA) (20 vs 26, 11 vs 15 using the YANG polyclonal assay n

Objectives To determine if methodic analysis of systematic echo-guidedbiopsies associated with prostatic-specific antigen (PSA) and PSA density can accurately predict the actual pathologic stage of prostate cancer (Ca P). Methods One hundred patients with clinically localized (T1,T2) Ca P who underwent radical prostatectomy (RP) were preoperatively staged by digital rectal examination (DRE), measurement of serum PSA (Yang Pros-check) and PSA density (PSAD), and transrectal echo-guided systematic biopsies (three in each lobe aiming to sample prostatic capsule) to evaluate T stage, Gleason grade, number of positive biopsies, and presence of cancer in the periprostatic tissues. Radical prostatectomy specimens were processed following the McNeal method. The PSA levels were measured every month for 2 years. Results Extracapsular disease was detected on the specimen in 45% of the patients,persistent/recurrent detectable PSA in 47% (mean follow-up 18 months). Clinical stage T2 B, presence of Gleason grade 4, PSA > 25 ng/mL, PSAD > 0.6, number of positive biopsies > 66% of the total number of cores taken had a positive predictive value (PPV), respectively, of 72%, 66%, 80%, and 87%. Periprostatic tissue was evaluable on the core biopsies in 77% of the cases. Presence of cancer in the periprostatic fat on the core biopsies had a PPV of 94% for extracapsular disease/biological recurrence. Conclusions The presence of extracapsular cancerous tissue on prostatic core biopsies accurately predicts extracapsular extension of Ca P. Therefore, care should be taken when performing prostate biopsies to sample the prostate capsule and surrounding tissues to obtain a more accurate staging of the disease. The second best predictor of extracapsular disease is the percentage of positive biopsies.

OBJECTIVE Testicular differentiation can occur in the absence of the Y chromosome giving XX sex-reversed males. Although Y chromosomal sequences can be detected in the majority of male subjects with a 46,XX karyotype, several studies have shown that approximately 10% of patients lack Y material including the SRY gene. The aim of this study was to see if the classification of XX sex-reversed individuals into three groups, Y-DNA-positive phenotypically normal XX males, Y-DNA-negative XX males with genital ambiguities and Y-DNA-negative true hermaphrodites can be applied to our cases. DESIGN Endocrinological and genetic studies were conducted in 20 XX sex-reversed patients. PATIENTS Twenty patients with various phenotypes were studied. They were between 20 days and 35 years old. Ten presented ambiguous external genitalia (Prader's stages II to IV). After laparotomy or gonadal biopsy, the diagnosis was 46,XX true hermaphroditism in five, and XX male in 15. MEASUREMENTS Blood samples were obtained from all patients for hormonal and molecular studies. Basal levels of testosterone, oestradiol and pituitary gonadotrophins were measured by RIA. In addition, two stimulation tests were performed: gonadotrophin stimulation with GnRH and testicular stimulation with hCG. Several Y-specific DNA sequences of the short arm of the Y chromosome were analysed by Southern blot and polymerase chain reaction methods. RESULTS In this study, three categories of XX sex-reversed individuals were observed: phenotypically normal males with or without gynaecomastia, males with genital ambiguities, and true hermaphrodites. Endocrinological data were similar in XX males and in true hermaphrodites. Testosterone levels exhibited normal (n = 9) or decreased (n = 11) values. The hCG response was low. FSH and LH were elevated in 13 patients. Molecular analysis in ten patients showed varying amounts of Y material including the Y boundary and SRY. Ten patients with various phenotypes lacked Y chromosomal DNA. There was no relation between Leydig cell function (as indicated by testosterone levels before or after hCG stimulation) and the presence of Y chromosome material. CONCLUSION Although the presence of Y-specific DNA generally results in a more masculinized phenotype, exceptions do occur. In the Y-DNA-negative group, complete or incomplete masculinization in the absence of SRY suggests a mutation of one or more downstream non-Y, testis-determining genes.

Treatment of corneal epithelial diseases induced by limbal stem cell deficiency is an important challenge in ocular surface reconstruction. Since the 1990s, corneal stem cells have been localized in the limbus. This new concept completely changed the way we consider ocular surface reconstruction, with new diseases now found to be isolated in the ocular surface. Limbus insufficiency syndromes are specific depending on their origin (congenital or acquired), their expression (unilateral or bilateral, partial or total), their progression (acute or chronic), and the mechanism involved (burn, infection, chronic inflammation, etc.). Some of these diseases are local diseases and others are systemic diseases. Clinically, limbus insufficiency is a switch of the normal corneal epithelial phenotype (expression of a specific keratin, avascularity, and transparency of the corneal matrix) in an opaque and fibrovascularized cornea. In terms of cellular biology, a phenotype is a terminal expression of a cell differentiation process. This process is the outcome of the interaction between the genome of a cell or a group of cells with their microenvironment. In limbus insufficiency, epithelial cells and corneal matrix are destroyed, and it is the destruction of these two components that leads to limbus insufficiency syndrome.

Objectives To investigate the hypothesis that Northern Africans differ from Caucasians with regard to their PCa characteristics, using our 1988–2006 database we retrospectively reviewed the preoperative and pathological features of consecutive patients subjected to radical prostatectomy (RP) for localized prostate cancer (PCa) and stratified according to their ethnic origin. Methods In 727 consecutive patients (616 Caucasians; 61 Blacks originating from Central Africa and the French West Indies; 50 Northern Africans from Morocco, Algeria, Tunisia), we preoperatively analyzed and compared age, clinical stage of the tumour, prostate-specific antigen (PSA), transrectal ultrasound prostate volume, PSA density (PSAD), biopsy Gleason score, number of positive cores (NPC), and percentage of tissue core invaded by cancer (PTIC); postoperatively, we determined the status of the capsule, seminal vesicles, and margins of the RP specimen, as well as Gleason score and prostate weight. Statistical analyses (chi-square test and ANOVA) were performed to compare the results between the three groups of patients. A multivariate analysis was carried out to test the independence of variables. Results Black patients were the youngest at the time of surgery (by 3–4 yr) and had the highest rates of final Gleason score≥8. The Northern Africans had more favourable features than did Caucasian and Black patients: mean PTIC was 7.1% versus 14.6% and 12.5%, respectively ( p =0.005), mean NPC was 26.4% versus 34.7% and 36.4%, respectively ( p =0.034), rates of biopsy and final Gleason score≥8 were significantly lower ( p =0.02 and p =0.028, respectively), and there were positive margins in 26% versus 36% and 35.6%, respectively ( p >0.05). Conclusions This study showed that a French Black population is the most likely of those studied to have unfavourable PCa characteristics at the time of RP. Albeit in a limited series, we show for the first time that Northern Africans have significantly better features in this regard than Caucasians and Blacks. Although Northern Africans did not have a better pathological stage outcome, they did have a more favourable Gleason score.

We evaluated the ability of an extended, 32-core repeat transrectal ultrasound prostate biopsy protocol to improve the characterization of low volume, well differentiated disease in men with a diagnosis of potentially insignificant microfocal prostate cancer, as defined by 1 single focus positive core of 10 with less than 5 mm of Gleason score 6 or less tumor on primary biopsy.A total of 35 consecutive patients, who were 62 to 75 years old, had a median serum prostate specific antigen of 8 ng/ml (range 0.5 to 14) and a diagnosis of minimal prostate cancer, and were willing to consider observation with delayed treatment at progression, were offered repeat saturation prostate biopsy with a median of 32 cores (range 18 to 36) under local anesthesia. This biopsy was to determine whether more extensive prostate sampling would confirm or disprove the initial diagnosis of microfocal, well differentiated prostate cancer.The procedure was aborted in 1 patient because of massive rectal hemorrhage. Another patient had acute prostatitis with gram-negative sepsis. Of 34 evaluable biopsy sets 11 (32%) were negative for cancer, suggesting that tumor detected at the primary biopsy was probably of low volume and amenable to observation with delayed treatment. Of the biopsies 23 (68%) were positive, 17 were at multiple sites and 7 were upgraded to Gleason score 7 or greater. These patients were then considered to have significant tumors and were offered active treatment.This study is to our knowledge the first to describe the clinical use of prostate saturation biopsies for re-evaluating potentially insignificant prostate cancer. Of patients with minimal disease on standard 10-core biopsy, results show that this technique may be helpful for distinguishing the 30% who probably have minimal disease based on negative repeat saturation biopsy from the 70% who almost certainly have a significant tumor, as characterized by multiple positive cores, with or without an increased Gleason score. The latter patients should be offered active therapy.

Activating somatic point mutations in exons 7, 10, and 15 of the FGFR3 gene are frequently observed in urothelial cell carcinoma (UCC) (1)(2). These mutations have been found primarily in superficial papillary pTa tumors and were absent in carcinoma in situ (3). Given the high frequency of FGFR3 mutations and the possible implication of this receptor in the development of UCC, it was important to develop a simple, fast, and reliable method to identify these mutations in greater detail as a potential tool for the diagnosis and follow-up of UCC patients. Ten different FGFR3 mutations have been described in UCC, but 4 of them (R248C, S249C, G372C, and Y375C) account for >95% of cases (2). These mutations therefore represent an excellent target for assays, such as allele-specific PCR (AS-PCR), that depend on the specific detection of point mutations. The general principle underlying the AS-PCR technique is to design a mutation-specific primer that produces the preferential amplification of a specific mutant allele (4). We compared the results obtained with this assay with those obtained by direct sequencing in a series of 95 DNA samples extracted from UCC tumors. We also analyzed matching tumors and voided urine from 20 patients. Our results demonstrate the sensitivity, specificity, and reliability of this technique for detecting FGFR3 mutations in both tumors and urine from patients with UCC. Ninety-five primary tumor samples were collected from patients admitted to the Department of Urology of Hospitals Henri Mondor (Creteil) and CHRU (Besancon) and who had received no previous treatment. Patients gave written informed consent, and we collected matched tumors and blood samples. Tumors from each patient were snap-frozen and stored at −80 °C. DNA from tumor samples was extracted as described previously (5). DNA was extracted from the blood with use of the QIAamp system …

The retro vesical septum (DENONVILLIERS) can be dissected and separated of the prostate and the bladder. The neurovascular bundles bound laterally this septum and it must be removed during radial prostatectomy. The aim of this study was to know if this septum is crossed by nerves.Dissection of cadaver--histological study of recto-vesical fascia.Nerves are present coming from the neurovascular bundle to the septum and end in the prostate.These anatomical observations conduct to recommend to remove systematically the recto-vesical septum during radical prostatectomy for cancer.

Objectives. To evaluate the correlation between the overexpression of mutant protein p53 and disease recurrence and progression in patients treated with bacillus Calmette-Guerin (BCG) intravesical therapy for T1G3 bladder cancer. Methods. We analyzed the outcome of 29 consecutive patients treated for T1G3 bladder tumor with transurethral resection. Patients previously treated for a bladder tumor, those who underwent incomplete resection, and those in whom no assessment of the muscle cell layer was possible were excluded from the study. p53 overexpression was determined using monoclonal p53-DO7 antibody, with a 20% cutoff for definition of positivity. After the initial transurethral resection, all patients were treated with Pasteur BCG (75 mg in 50 mL saline), weekly for 6 weeks. The correlation between p53 overexpression and disease recurrence and progression was assessed by the Fisher exact test. Results. The median follow-up was 36.7 months (range 1 to 108). Of the 29 patients, 18 (62.1%) were p53 positive and 11 (37.9%) were p53 negative. Both groups were similar according to age, tumoral substage (T1a/T1b), association with carcinoma in situ, multifocality, and length of follow-up. The recurrence rate was 54.4% in the p53-negative group versus 38.9% in the p53-positive group ( P = 0.47). The progression rate was 18.2% in the p53-negative group versus 33.3% in the p53-positive group ( P = 0.67). Conclusions. These findings suggest that overexpression of p53, as determined immunohistochemically, has no predictive value for recurrence and progression in T1G3 bladder cancers treated with intravesical BCG.

The aim of this study was to evaluate the usefulness of gadolinium-enhanced time-of-flight magnetic resonance venography (MRV) in the diagnosis of bland thrombosis/tumoral invasion in the preoperative assessment of renal cell carcinoma. Preoperative precontrast and enhanced GRE fast low-angle shot (FLASH) images of 36 patients with renal adenocarcinoma were reviewed and compared with pre- and post-contrast T1-weighted images. All patients underwent surgery, and MR findings were blindly and prospectively compared with surgical and pathologic data, considered the standard. Renal vein and vena cava were involved in 17 and 9 patients, respectively; right atrial extension was present in one patient. Precontrast spin-echo (SE) and FLASH images were 88 % sensitive and 100 % specific in the detection of venous involvement, respectively, and enhanced FLASH images 100 % sensitive and 96 % specific. The nature of thrombus (neoplastic or bland) was more accurately assessed (McNemar's, p < 0.05) with FLASH-enhanced MR images (sensitivity 89 %; specificity 96 %) than with SE and precontrast FLASH images (sensitivity 79 %; specificity 94 %). Our data suggest that use of Gd-enhanced MRV might improve preoperative assessment of vascular involvement in renal carcinoma.

To evaluate the clinical, laboratory and histological characteristics of prostate cancer at the time of diagnosis and after radical treatment in various ethnically different patient groups.Prostatic biopsies were performed in 466 consecutive patients because of an abnormal digital rectal examination and/or isolated elevation of PSA (greater than 3 ng/ml). In this series, 40 patients were Black and 426 were Caucasian. The other aspect of the study concerns 320 patients undergoing radical prostatectomy for stage T1 T2 prostatic tumour (25 Black, 295 Caucasian). In the biopsied group, we analysed mean age, mean PSA, mean cancer length on biopsies and mean Gleason score. In the operated group, we studied preoperative characteristics, histological stage, resection margin status, laboratory progression (PSA greater than 0.05 ng/ml) and time to progression.At the time of diagnosis, the mean age was 61.4 years (48-73) for Blacks and 65.2 years (42-87) for Caucasians (p0.05). The median Gleason score was 7 in the two groups. The PSA was 13.4 (1.7-105) ng/ml versus 14.4 (0.4-600) ng/ml, respectively. The mean percentage of invaded tissue on biopsies was 24% versus 18.8% and the mean percentage of positive biopsies was 53% versus 39%, respectively. In the operated group, capsular effraction rates were 39% in Blacks and 48.1% in Caucasians. Positive resection margin rates were 21.7% versus 36.6%, respectively. The laboratory progression rate with a mean follow-up of 33 months (6-126) was identical in the 2 groups (42.1% versus 41.1%), but the time to progression was shorter for Blacks (9 months versus 12.3 months).In this patient series, Black patients had the same laboratory profile as Caucasian patients at the time of diagnosis. However, they were younger at the time of discovery of the disease, had more positive biopsies and more tumour-invaded tissue on biopsies, and Black patients undergoing radical prostatectomy developed laboratory recurrence more rapidly.

Dissection of Denonvilliers' rectovesical fascia allows easy cleavage of the prostatorectal and prostatovesical spaces. Its lateral limit in the "neurovascular pedicles" justifies its resection during radical prostatectomy. The objective of this study was to define the course and to observe the structure of nerves crossing the rectovesical fascia, as the sheaths of these nerves may be invaded by prostatic adenocarcinoma tumour cells.After dissection of a fresh cadavre to define the relations of this fascia with the pedicles, rectovesical fascia biopsies were taken during radical prostatectomies. Transverse sections were performed and examined histologically.Certain nerves, derived from the neurovascular pedicle of the inferior hypogastric plexus, cross the rectovesical fascia to innervate the prostate.This confirms the importance of complete resection of the rectovesical fascia during radical prostatectomy for cancer, not only for surgical reasons, but also to ensure oncologically satisfactory surgery, i.e. with healthy resection margins.

· Background: Immune deposits can be found on the conjunctival basement membrane zone of patients affected by cicatricial pemphigoid using immunofluorescence technique. The purpose of this study was to perform direct immunoelectron microscopy on the conjunctiva of patients with scarring conjunctivitis associated with cicatricial pemphigoid · Methods: Conjunctival and skin biopsies were performed in six patients who presented with presumed autoimmune cicatrizing conjunctivitis associated with cicatricial pemphigoid. Specimens were processed for direct immunofluorescence and direct immunoelectron microscopy. · Results: Direct immunofluorescence was positive in all skin samples and in three of six conjunctival samples. Direct immunoelectron microscopy showed immune deposits in the lamina lucida and the lamina densa of all skin and conjunctival samples. · Conclusions: Direct immunoelectron microscopy can be performed on the conjunctiva. It shows the precise localization of cicatricial pemphigoid target antigens within the conjunctival basement membrane zone.

To study the improvement of prostatic cancer detection provided by ten strictly systematized transrectal prostatic biopsies.This prospective study was conducted in 162 patients submitted to a series of 10 ultrasound-guided transrectal prostatic biopsies due to the presence of elevated PSA and/or an abnormality on digital rectal examination. Five biopsies were taken from different sites in each lobe: 2 biopsies were inserted between the 3 biopsies usually performed in the standard protocol, while maintaining the angle of entry of the needle recommended in this protocol.The complication rate was 1.85% with the 10-biopsy technique. Prostatic cancer was detected in 40.1% of the 162 patients. The percentage diagnostic improvement provided by the 10-biopsy protocol in the overall patient population was +3.1% compared to the standard protocol. The highest percentage diagnostic improvement was observed in the group of patients with PSAor = 10 ng/ml (+4.9%) and in the group of patients with an ultrasound prostatic volumeor = 40 cc (+4%).The most marked diagnostic improvement appears to be related more to sampling of prostatic zones presenting a statistically increased risk of cancer (peripheral zone) than to the increased number of prostatic biopsies performed.

We compare the incidence of positive surgical margins in patients who underwent perineal or retropubic radical prostatectomy for clinically localized (stage T1, T2) prostate cancer.In this retrospective, nonrandomized study we reexamined the specimens of 94 consecutive patients who underwent radical perineal (48) or retropubic (46) prostatectomy for clinically localized prostate cancer (stage T1, T2) and with pathological stage pT2 (intracapsular), pT3A (established extracapsular extension without positive margins) or pT3B (extracapsular extension with positive margins) without lymph node involvement (N0). We assessed the presence or absence of extracapsular cancer with or without positive margins, incisions of the prostatic capsule exposing cancer (surgically induced positive margins) or benign glandular tissue. Patients were followed for 3 to 66 months (mean 25) using an ultrasensitive prostate specific antigen assay with a lower detection limit of less than 0.05 ng./ml.The overall incidence of positive margins in cancer tissue was 56% in the perineal and 61% in the retropubic group, and biochemical failure-free survival was 67% each. However, surgically induced positive margins in patients with organ confined disease were more frequent in the perineal than retropubic group (43 versus 29%, p0.05) and associated with a 37% risk of biochemical failure (prostate specific antigen greater than 0.1 ng./ml.) at mean followup. In addition, capsular incisions exposing benign tissue were more frequent in the perineal than retropubic group (90 versus 37%, p0.05) irrespective of pathological stage.Although overall positive margins and biochemical failure rates are similar or identical for the perineal and retropubic approaches for organ confined prostate cancer, the perineal approach is associated with a significantly higher risk of capsular incisions and surgically induced positive margins and, thus, a higher risk of biochemical failure.

To compare positive resection margin rates in tumour tissue and healthy tissue according to whether total prostatectomy for cancer is performed via a retropubic or transperineal approach.This retrospective, non-randomized study was based on 94 patients suffering from clinically localized cancer (T1-T2) of the prostate operated either via a retropubic (46: group 1) or perineal (48: group II) approach. All slides were reviewed by two pathologists not informed about the clinical course. The frequency of tumour margins associated with extracapsular invasion, capsular incision, without extracapsular extension of the tumour, and finally the incidence of capsular incisions exposing tumour tissue, were determined.While the number of positive resection margins was equivalent in the two groups (61% for group I versus 56% for group II), it was higher in the perineal group (43% versus 29%, p0.05) when the tumour was confined to the gland (pT2). A higher incidence of resection margins in healthy tissue was also observed in group II (90% versus 37%).Transperitoneal prostatectomy is associated with a higher incidence of resection margins in tumour tissue in patients with prostate-confined cancer. Analysis of the resection margins in healthy tissue suggests that the surgical incision is a predisposing factor to their creation.

Renal oncocytoma has several features that overlap with other renal neoplasms, including the eosinophilic subtype of chromophobe cell carcinoma. In fact, strict criteria for renal oncocytoma have not been well defined and remain a matter of controversy. Ultrastructural studies or sophisticated methods such as flow cytometry and cytogenetic techniques can be of great use in distinguishing the two tumors, but are difficult to propose as routine methods because of their limited availability.To further characterize the histologic criteria of these tumors, we undertook a retrospective study to define the utility of routinely available histochemical and immunohistochemical techniques.Twenty-one cases of chromophobe cell carcinoma, eosinophilic subtype, and 103 cases of oncocytoma were tested with histochemical (Perls, periodic acid-Schiff, and Hale's colloidal iron) and immunohistochemical (peanut agglutinin antigen and UEA-1 for lectins; cytokeratin KL1, epithelial membrane antigen, vimentin, S100 protein, and lysozyme) staining.The antibodies tested and the histochemical staining using Hale's colloidal iron allowed eosinophilic chromophobe cell carcinoma to be distinguished by its characteristic reaction pattern. Seventy-six percent of the chromophobe cell carcinomas showed a microvacuolated pattern, and 89% of the renal oncocytomas showed an apical positivity with Hale's colloidal iron staining (P.01). Peripheral cell accentuation reactivity for cytokeratin KL1 was observed in 66% of the chromophobe cell carcinoma cases, and apical cytoplasmic positivity was observed in 37% of the renal oncocytoma cases (P = .01). Significant patterns were observed with anti-epithelial membrane antigen and anti-peanut agglutinin antigen antibodies (P = .05 and P = .01, respectively). Positive reactions for vimentin, S100 protein, lysozyme, and UEA-1 were not significant characteristics.Our study demonstrated that a precise morphologic description associated with simple histochemical and immunohistochemical techniques provides sufficient criteria for a high level of discrimination between the eosinophilic subtype of chromophobe cell carcinoma and renal oncocytoma.

Early diagnosis of prostate cancer is based on determination of serum prostate specific antigen (PSA) and digital rectal examination (DRE). In men with PSA values above 10 ng/ml and where there is a positive DRE, the indication for prostatic biopsy is given. However, there is controversy as to whether men with an intermediate PSA level of 4-10 ng/ml should undergo further evaluation. Since cancer secretes 12 times more serum PSA per volume than benign prostatic hyperplasia, PSA density (PSAD, serum PSA divided by the volume of the entire prostate) has been suggested as an additional diagnostic criterion. In 153 men with prostatism and PSA values between 4 and 10 ng/ml (Hybritech assay), the volume of the prostate was determined by transrectal ultrasonography and 6 systematic biopsies were performed. The groups with positive and negative biopsies respectively were compared according to age of the patient, results of DRE and PSAD. Histological grade of positive biopsies and pathological stage of patients who underwent radical prostatectomy were also compared with diagnostic criteria. Prostate cancer was found in 45 of 153 men (29.4%). Patient's age had no influence on detection rates. The positive predictive value of a PSAD of 0.2 or more was twice the value of a PSAD below 0.2, irrespective of DRE findings. An increasing number of positive biopsies was associated with increasing PSAD and histological grade. Only half of the tumors operated on were still confined to the prostate. Pathological stage could be predicted by the number of positive biopsies. We conclude that PSAD may be useful as a diagnostic parameter in men with prostatism and PSA values of 4-10 ng/ml. The prostate cancers that were detected in this setting are of clinical significance.

Information regarding the quantity of biopsy material invaded by cancer may supplement the usual criteria for the preoperative staging of patients suffering from clinically localized prostate carcinoma (T1-T2). However, conflicting conclusions have been drawn and this topic needs further investigation.A total of 170 patients had radical prostatectomy for T1-T2 prostate carcinoma. Patients' mean age (+/- standard deviation [SD]) was 66.05 +/- 6.12 years and mean prostate specific antigen (PSA) level (+/- SD) was 22.5 +/- 21.4 ng/mL (Yang Proscheck). Of the patients, 110 underwent transrectal ultrasound-guided biopsy with removal of 6 cores, from whom we had the percentage of biopsy, material invaded by cancer, the Gleason score, and the preoperative PSA. These parameters were compared with the pathologic features of the surgical specimen (capsule penetration, surgical margins, and Gleason score) and biologic progression (defined as persistent/recurrent postoperative PSA0.1 ng/mL).The most valid threshold of biopsy material invaded by cancer for predicting surgical margins and capsule status, as well as biologic progression, was 10%. When10% of biopsy material was invaded by cancer, positive surgical margins (SM+) were present in 30.3%, capsular penetration (pT3, pathologic extracapsular involvement) in 27.3%, and biologic progression (P+) in 21.7%. The Gleason score did not improve this prognostic evaluation. The mean quantities of tissue invaded by cancer differed significantly between positive and negative surgical margin groups, between pT2 and pT3 groups, and between P- and P+ groups (no biologic progression/biologic progression). There was statistical significance (log rank test, P = 0.0320 in the survival without biologic postoperative progression between patients withor = or10% of one core biopsy invaded by tumor. Ifor = 10% of tissue in only 1 of 6 cores of a biopsy was invaded by tumor, the status was pT2, SM-, and P- in 87.5% of the patients.On an individual basis, the percent of tissue containing carcinoma in core biopsies was a factor that lacked the statistical power to predict the status of the capsule and surgical margins, and the biologic progression. The finding ofor = 10% of carcinoma in 1 of 6 cores of a biopsy was correlated with a good prognosis.

To evaluate whether the percentage of biopsy tissue invaded by tumour provides any supplementary information to laboratory and/or biopsy data (Gleason, number...) in the preoperative staging of patients with localized prostatic cancer (T1-T2).170 patients with a mean age of 65.05 +/- 6.12 years and a mean PSA of 22.5 +/- 21.4 ng/mL were submitted to radical prostatectomy (RP) for T1-T2 prostatic cancer. 110 patients were submitted to a series of 6 transrectal prostatic biopsies to establish the diagnosis. We evaluated the percentage of biopsy tissue invaded. This parameter, as well as the Gleason score and the preoperative PSA, were studied in comparison with pathological criteria of the operative specimen (capsule status, resection margins) and postoperative PSA.The cut-off value of 10% of invaded biopsy tissue was calculated as being the most discriminant for the prediction of resection margins, capsule status and progression of laboratory parameters. When less than 10% of biopsy tissue was invaded, there were 31.2% positive margins (RM+). 28% of invaded capsules (pT3), and 21.7% of laboratory progression (P+) versus 44.1%, 71.4% and 47%, respectively, when more than 10% of tissue was invaded. The Gleason score of the biopsy did not improve this prognostic evaluation. The mean quantities of invaded biopsy tissue were statistically different between pT3 and pT2, RM+ and RM-and P+ and P-. When only one positive biopsy was invaded by less than 10%, 87.5% of these operated patients remained stable, RM- and pT2.On an individual level, the percentage of invaded tissue does not reflect the degree of extension or progression of localized prostatic cancer. Only a single positive biopsy invaded over less than 10% of its length is statistically correlated with a good prognosis.

To present a new masquerade syndrome showing features of mucosal-associated lymphoid tissue (MALT) lymphoma associated with choroidal white dots and scleritis. Differentials including systemic lymphoma, central nervous system lymphoma, and etiologies of white-dot syndromes and scleritis are discussed.A 42-year-old man who had decreased vision and ocular redness of his right eye for 4 years had a biopsy-proven diffuse anterior and posterior scleritis associated with intense circumferential perilimbal chemosis and ipsilateral yellow-white choroidal dots. A new conjunctival biopsy was performed because of unresponsiveness to high-dose systemic steroid and cyclophosphamide therapy. Immunostains for lymphocyte markers were preformed.A morphologically and immunohistochemically typical, monotypical mu-kappa immunoglobulin light chain secreting B-cell MALT-lymphoma was diagnosed. Eighteen months after completion of radiotherapy, the patient recovered completely, except for the choroidal dots, which remained unchanged.When scleritis, even histologically proven, fails to respond to immunosuppressive therapy, a new biopsy is mandatory to rule out a misdiagnosed MALT lymphoma.

Determine the incidence of prostate cancer in patients consulting for common miction disorders and serum prostatic specific antigen (PSA) between 4 and 10 ng/ml.A total of 153 patients consulted for miction disorders. In 107 of them, the digital examination was abnormal and PSA was between 4 and 10 ng/ml. Transrectal sonography and prostatic biopsies were performed in these 107 patients. We determined the number of cancers detected and assessed the contribution of PSA density (PSAD) to diagnosis. In patients undergoing radical prostatectomy, invasion of the capsule (C+) and positive exeresis section (M+) were recorded.Cancer of the prostate was diagnosed in 29.4% of the patients on the basis of at least 1 of the 6 biopsies. This rate was 47.8% in patients with an abnormal and 21.5% with a normal digital examination. Radical prostatectomy was performed in 32 patients: 50% of them were C+ and 33% M+.Biopsy of the prostate is indicated in patients with an abnormal prostate at digital examination when PSA is between 4 and 10 ng/ml. When the prostate appears to be normal, PSAD may be helpful in determining when to perform a biopsy. Intermediary serum PSA levels do not guarantee favorable pathological characteristics.

To evaluate whether or not a single positive prostatic biopsy out of six systematic ultrasound-guided biopsies, is reliably correlated manner with favourable histopathological features of the tumour on the radical prostatectomy (RP) specimen.In a series of 158 patients undergoing RP for clinically localized prostatic cancer, 15.2% had only one positive biopsy out of 6 systematic biopsies. We compared the rates of capsular effraction (C+) and positive resection margins (RM+), assessed on the operative specimen, in this group of patients with a single positive biopsy (group 1) and in the group (group 2) diagnosed by more than one positive biopsy. The postoperative biological progression rate (P+), defined as an immediate or secondary postoperative elevation of PSA beyond 0.1 ng/ml by polyclonal assay, was also evaluated in the two groups. The Gleason score was evaluated and compared on biopsies and on RP specimens.29.2 of cases were C+, 16.7% were RM+ and 26% were P+ in group 1, versus 70%, 46.5% and 49.5%, respectively, in group 2. All differences were statistically significant. All patients in group 1 with less than 10% of prostatic tissue invaded on the positive biopsy had stage P2, while all patients with 100% of the length of the biopsy invaded by tumour had stage P3. The Gleason score was accurately predicted by the positive biopsy in 39% of cases and was underestimated in 39% of cases.A single positive prostatic biopsy out of six systematic biopsies is a useful predictive factor of local extension, but, in the individual patient, does not guarantee favourable histopathological characteristics of the tumour, nor a favourable course of the disease.

The coexistence of tumours confined to the prostate and laboratory signs of progression is surprising unless we accept the possibility of errors of the pathological examination. In view of the high incidence of laboratory signs of progression after radical prostatectomy, it is important to define the most pejorative histological features in order to improve patient selection.129 radical prostatectomy specimens were studied, 8 out of 129 patients, with an immediate or secondary elevation of PSA while histological examination diagnosed a pT2 intracapsular cancer, were re-evaluated by reviewing the slides and resection of paraffin embedded blocks of prostate. The actuarial survival curves were analysed in 4 groups of patients, defined according to the various pathological characteristics of their tumour.Review of the slides led to the diagnosis of 2 cases of focal capsular effraction and I case of seminal vesicle invasion. Resection of paraffin blocks led to the diagnosis of 2 cases of focal capsular effraction and one positive resection margin. The differences between the 4 survival curves with no laboratory signs of progression (PSA0.1 by highly sensitive polyclonal assay) were statistically significant except between patients whose tumour had extended beyond the capsule and those with positive resection margins.Overall, resection of the blocks corrected the pathological staging in 2.3% of cases and global analysis of factors of poor prognosis can guide the urologist in this decision to administer adjuvant treatment.

Radical prostatectomy is the treatment of choice for organ-confined prostatic cancers (T1-T2). However, it has been reported to improve the long-term survival of patients and achieve its oncological objectives in only one half of patients despite a serious morbidity. Based on a consecutive series of one hundred patients, the authors performed univariate statistical analysis to determine the predictive value of eight preoperative criteria for biological progression and capsular effraction: clinical stage, PSA (using a highly sensitive test derived from the Yang Proscheck and lowering the limit of detection to 0.1 ng/ml), PSA density (PSAD), percentage and topography of positive biopsies, capsular effraction, perineural spaces and Gleason's score. The predictive value for progression of five postoperative histological criteria (Gleason's score, capsule, perineural spaces, seminal vesicles and resection margins) was also studied in the same group of patients. The presence of capsular effraction on the biopsy was shown to have a positive predictive value of 90%. The three preoperative criteria most closely correlated with tumour progression were PSA, PSAD and percentage of positive biopsies (p0.001). Analysis of the combined predictive value of PSAD, percentage of positive biopsies and capsular effraction revealed that progression was always present when two of these criteria were positive. Seminal vesicle invasion on the operative specimen is the most pejorative element for progression. In conclusion, analysis of the histological features of biopsies associated with PSA and PSAD allows a more accurate selection of patients with a high risk of progression and seminal vesicle invasion is so pejorative that it could be detected in subjects with a preoperative PSA greater than 25 ng/ml.

The course of pancreatic beta cell destruction during the prediabetic period of autoimmune diabetic syndromes is not precisely known. We have analyzed the course of insulitis (n = 140) and the beta cell and lymphocytic volume densities by morphometric methods (n = 80) in NOD mice aged 6 to 45 weeks. In the absence of diabetes the mean beta cell density was only slightly reduced with age: 0.64 +/- 0.04% glandular tissue (mean SEM; n = 12) in 6 wk-old mice, 0.52 +/- 0.06% in 45 wk-old mice (n = 12; ns). However, a minority of pancreases were free of insulitis or showed isolated periinsulitis at the end of the 45-wk follow-up period. Invasive insulitis (i.e. mononuclear cells invading the islet area) was detected in 60-85% of mice from the 12th week on. In non overtly diabetic mice, beta cell density was reduced only when insulitis was invasive in more than 40% of islets: 0.30 +/- 0.03%, (n = 11) vs 0.59 +/- 0.04% (n = 34) in moderately invasive insulitis (p0.05). These mice had significant metabolic abnormalities. In diabetic mice, the beta cell density was markedly decreased: 0.02 +/- 0.01% (n = 7; p0.001). On the whole, a lymphocytic infiltrate affecting less than 50% of the islet volume was compatible with a normal beta cell density. Beyond this 50% lymphocytic infiltration threshold, beta cell density was tightly and negatively related to the lymphocytic volume density.(ABSTRACT TRUNCATED AT 250 WORDS)

In order to analyse further the pathophysiology of pentamidine effects on blood glucose regulation, the following experimental models were established in rats: impairment of the renal function, bile duct ligation, inhibition of the P450 cytochrome enzyme system. In otherwise intact rats, 7.5 mg/day pentamidine was well tolerated whereas doses of 15 mg/day induced severe, relapsing and eventually lethal hypoglycaemia within a few days. Induction of a renal insufficiency of graded severity by treatment with gentamycin, subtotal nephrectomy and total bilateral nephrectomy resulted in repetitive, severe (sometimes lethal) hypoglycaemia, alternating with hyperglycaemia, glucosuria and ketonuria in pentamidine-treated rats (7.5 mg/d). No long-standing insulin-dependent diabetes was observed. In the dysglycemic animals, plasma insulin levels were inappropriate to the concomitant glycaemia; no stimulation was obtained by i.v. glucose. Glucagon levels were higher than normal, suppressible by i.v. glucose, responsive to IV arginine and to hypoglycaemia. Dysglycemic events were more frequent and marked in the rats with the most severe renal functional derangement. They were more frequent in the rats treated with pentamidine mesylate than in those treated with the isethionate salt. Control uremic rats (free of pentamidine) remained euglycaemic. The islets of Langerhans displayed severe vascular congestion and degranulation and necrosis of the B cells, while the non B cells (and particularly the A cells) were intact. Exocrine pancreatitis was occasionally observed in the most severely uremic rats. In contrast with uremic rats, neither surgical ligation of choledocus, nor treatment by P450 cytochrome inhibitors (particularly ketoconazole) precipitated dysglycaemia in the pentamidine-treated rats. These experimental data: 1) strengthen the concept of inappropriate insulin release from pentamidine-lesioned islet B cells due to pentamidine accumulation; 2) indicate a predominant role for renal insufficiency in determining the accumulation of this drug; 3) emphasize the clinical importance of renal insufficiency as a risk factor for pentamidine-induced dysglycaemia. Association with ketoconazole does not appear to be a risk factor.

Ten patients were studied who had sexual ambiguity having in common a 46.XX karyotype and testicular tissue. They were aged from one month to 23 years: some of them were followed through puberty. Eight cases were sporadic and two familial. They were divided into two groups according to finding of surgery and histology: 46, XX males with sexual ambiguity and 46 XX true hermaphrodites (TH). They were no differences in phenotypes (except uterus and ovotestis in TH). The endocrinological data were identical in the two groups: testosterone levels were in the normal range during puberty, then decreased in adulthood. Gonadotrophins were above the normal range at mid-puberty. Gonadal biopsies, regardless of the ovarian part of the ovotestis, were identical in two groups, i.e., normal in the youngest patients, then spermatogonia desappeared afterwards and dysgenesis became obvious. In one case, the ovarian zone of the ovotestis was only detected on serial cuts after gonadectomy. Southern blots displayed the presence of Y specific material in tow cases (PABY-SRY-PO.9). Otherwise, in all other patients, there was the lack of any Y sequences without any differences between the two groups. These data suggests that 46, XX males with sexual ambiguity and 46 XX true hermaphrodites may be alternative expressions of two genetic defects: one, a minimal interchange between Yp and Xp, another, a mutation of an autosomal testis determining factor for the patients without Y detectable material.

A case of congenital esophageal stenosis due to tracheobronchial remnants is reported. This is a very rare condition. Only 46 previous cases have been reported in the French and English literature. The cause is thought to be esophageal sequestration of a tracheobronchial anlage before embryologic separation. Esophageal atresia is frequently associated with this rare abnormality. Symptoms generally appear early in infancy, but are sometimes very discrete and diagnosis can be made later in infancy of exceptionally in adulthood. When there is no evidence of gastric reflux and caustic ingestion, symptoms of esophageal obstruction with date back to infancy or childhood are often the only sign suggestive of congenital stenosis. However, the diagnosis can only be established by microscopic examination of the entire esophageal wall, as endoscopic biopsy will not show the heterotopic tissue lying deep under the normal mucosa. The presence of tracheobronchial remnants in the esophageal wall explains why treatment by dilatation is unsatisfactory or impossible. Definitive treatment involves excision of the stenotic segment.

Congenital esophageal stenosis and bronchogenic cyst are secondary to the same dysembryoplastic disorder in spite of different clinical signs. These lesions are revealed during infancy, unusually during adult age. Dysphagia is the most common symptom. Our two cases highlight these topics. Imaging methods displayed, in case 1, a distal stenosis, associated with a proximal dilatation, in case 2, a benign independent mass, without connection with the respiratory tract. A chirurgical excision was carried out in the two cases and the post operative course was uncomplicated. Histologically the two resection specimens showed a respiratory mucosa trapping cartilaginous pieces.

We report a case of necrotic collection in the head of the pancreas infected by Salmonella typhimurium. Treatment associated necrosectomy and antibiotic therapy without cholecystectomy. The course of pancreatic disease was uneventful. Complete sterilization was obtained with quinolone antibiotic therapy.

Four cases of neuroendocrine carcinoma following Bowen's disease are presented. An immunohistochemical study was performed. The four patients, 3 men and a woman, ranging from seventy to eighty-seven years of age, developed a nodular tumor on a preexisting cutaneous lesion. In one of those cases the diagnosis of Bowen's disease was confirmed histologically before the apparition of the nodular tumor. The tumors were localized on the scalp, thorax, dorsum of the hand, and the scrotum. The four tumors were immunohistologically typical of neuro-endocrine carcinoma: there was a positivity for neurofilaments, cytokeratins and neurone-specific enolase. The clinico-pathological characteristics of those 4 neuro-endocrine carcinomas associated with a Bowen's disease, when compared with the 15 similar described in the literature, are identical to the isolated neuroendocrine carcinoma, from a clinical, morphological and evolutional point of view. The majority are seen in patients older than 60 years old and one third of the cases described survived at least 5 years. The coexistence of Bowen's disease and neuroendocrine carcinoma, the association of neuroendocrine and epidermoid cells in other cutaneous tumors, reactivate the controversy concerning the histogenesis of the so-called Merkel cell carcinoma. In fact, the histogenesis of the tumor is still not fully understood.

An immunohistochemical study of 40 primary and secondary malignant melanomas in 27 patients, with routinely-used monoclonal antibodies, demonstrated the antigenic pattern exhibited by these tumors, as well as the frequency of aberrant positivities for epithelial cell markers. The following results were found: 95% of melanomas stained positively for S100 protein and vimentin, which is the characteristic immunohistochemical pattern in melanomas. In most cases, the primary tumor and its metastases in a given patient had the same antigenic phenotype. As for epithelial markers, 10% of melanomas stained positively for KL1 and 27.5% for EMA. Despite this relatively high frequency of KL1 and EMA positivities, in practice, simultaneous positivity for S100 protein and vimentin, confronted with the patient's history and with histologic features, firmly establishes the diagnosis of malignant melanoma in virtually all cases.

Recently, applications of immunohistochemical techniques for the cytoplasmic localization of intermediate filaments has produced advances in tumor diagnosis and characterization. We report a 58-year-old white male with a clinically and histologically typical metastatic malignant melanoma. This case was peculiar because the same neoplastic cells stained for both S-100 protein and keratin on paraffin embedded tissue. These facts illustrate how cautiously we must interpret the positivity of immunohistochemical technics. We thus insist on the importance of the clinical and basic histologic data for the diagnosis, in order to avoid errors.