Management of epithelial cancer of the ovary, fallopian tube, primary peritoneum. Long text of the joint French clinical practice guidelines issued by FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY, endorsed by INCa. (Part 2: systemic, intraperitoneal treatment, elderly patients, fertility preservation, follow-up).

Adjuvant chemotherapy by carboplatin and paclitaxel is recommended for all high-grade ovarian and tubal cancers (FIGO stages I-IIA) (grade A). After primary surgery is complete, 6 cycles of intravenous chemotherapy (grade A) are recommended, or a discussion with the patient about intraperitoneal chemotherapy, according to her risk-benefit ratio. After complete interval surgery for FIGO stage III, hyperthermic intraperitoneal chemotherapy (HIPEC) can be proposed, in accordance with the modalities of the OV-HIPEC trial (grade B). In cases of postoperative tumor residue or in FIGO stage IV tumors, chemotherapy associated with bevacizumab is recommended (grade A).

Management of epithelial cancer of the ovary, fallopian tube, and primary peritoneum. Long text of the Joint French Clinical Practice Guidelines issued by FRANCOGYN, CNGOF, SFOG, and GINECO-ARCAGY, and endorsed by INCa. Part 1: Diagnostic exploration and staging, surgery, perioperative care, and pathology.

An MRI is recommended for an ovarian mass that is indeterminate on ultrasound. The ROMA score (combining CA125 and HE4) can also be calculated (grade A). In presumed early-stage ovarian or tubal cancers, the following procedures should be performed: an omentectomy (at a minimum, infracolic), an appendectomy, multiple peritoneal biopsies, peritoneal cytology (grade C), and pelvic and para-aortic lymphadenectomies (grade B) for all histologic types, except the expansile mucinous subtypes, for which lymphadenectomies can be omitted (grade C). Minimally invasive surgery is recommended for early-stage ovarian cancer, when there is no risk of tumor rupture (grade B). For FIGO stages III or IV ovarian, tubal, and primary peritoneal cancers, a contrast-enhanced computed tomography (CT) scan of the thorax/abdomen/pelvis is recommended (grade B), as well as laparoscopic exploration to take multiple biopsies (grade A) and a carcinomatosis score (Fagotti score at a minimum) (grade C) to assess the possibility of complete surgery (i.e., leaving no macroscopic tumor residue). Complete surgery by a midline laparotomy is recommended for advanced ovarian, tubal, or primary peritoneal cancer (grade B). For advanced cancers, para-aortic and pelvic lymphadenectomies are recommended when metastatic adenopathy is clinically or radiologically suspected (grade B). When adenopathy is not suspected and when complete peritoneal surgery is performed as the initial surgery for advanced cancer, the lymphadenectomies can be omitted because they do not modify either the medical treatment or overall survival (grade B). Primary surgery (before other treatment) is recommended whenever it appears possible to leave no tumor residue (grade B).

[Part II drafted from the short text of the French guidelines entitled "Initial management of patients with epithelial ovarian cancer" developed by FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY and endorsed by INCa. (Systemic and intraperitoneal treatment, elderly, fertility preservation, follow-up)]. / Partie 2 rédigée à partir de la synthèse de la recommandation nationale de bonnes pratiques cliniques intitulée « Conduites à tenir initiales devant des patientes atteintes d'un cancer épithélial de l'ovaire ¼ élaborée par FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY et labélisée par l'INCa. (Traitement systémique et intrapéritonéal, personnes âgées, préservation de la fertilité et suivi).

Adjuvant chemotherapy with carboplatin and paclitaxel is recommended for all high-grade ovarian or Fallopian tube cancers, stage FIGO I-IIA (grade A). After a complete first surgery, it is recommended to deliver 6 cycles of intravenous (grade A) or to propose intraperitoneal (grade B) chemotherapy, to be discussed with patient, according to the benefit/risk ratio. After a complete interval surgery for a FIGO III stage, the hyperthermic intra peritoneal chemotherapy (HIPEC) can be proposed in the same conditions of the OV-HIPEC trial (grade B). In case of tumor residue after surgery or FIGO stage IV, chemotherapy associated with bevacizumab is recommended (grade A). For BRCA mutated patient, Olaparib is recommended (grade B).

[Part I drafted from the short text of the French Guidelines entitled "Initial management of patients with epithelial ovarian cancer" developed by FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY and endorsed by INCa. (Diagnosis management, surgery, perioperative care, and pathological analysis)]. / Partie 1 rédigée sur la base de la recommandation nationale de bonnes pratiques cliniques en cancérologie intitulée « Conduites à tenir initiales devant des patientes atteintes d'un cancer épithélial de l'ovaire ¼ élaborée par FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY et labélisée par l'INCa. (Explorations diagnostiques et bilan d'extension, chirurgie, soins périopératoires et anatomopathologie).

Faced to an undetermined ovarian mass on ultrasound, an MRI is recommended and the ROMA score (combining CA125 and HE4) can be proposed (grade A). In case of suspected early stage ovarian or fallopian tube cancer, omentectomy (at least infracolonic), appendectomy, multiple peritoneal biopsies, peritoneal cytology (grade C) and pelvic and para-aortic lymphadenectomy are recommended (grade B) for all histological types, except for the expansive mucinous subtype where lymphadenectomy may be omitted (grade C). Minimally invasive surgery is recommended for early stage ovarian cancer, if there is no risk of tumor rupture (grade B). Laparoscopic exploration for multiple biopsies (grade A) and to evaluate carcinomatosis score (at least using the Fagotti score) (grade C) are recommended to estimate the possibility of a complete surgery (i.e. no macroscopic residue). Complete medial laparotomy surgery is recommended for advanced cancers (grade B). It is recommended in advanced cancers to perform para-aortic and pelvic lymphadenectomy in case of clinical or radiological suspicion of metastatic lymph node (grade B). In the absence of clinical or radiological lymphadenopathy and in case of complete peritoneal surgery during an initial surgery for advanced cancer, it is possible not to perform a lymphadenectomy because it does not modify the medical treatment and the overall survival (grade B). Primary surgery is recommended when no tumor residue is possible (grade B).

Management of epithelial cancer of the ovary, fallopian tube, and primary peritoneum. Short text of the French Clinical Practice Guidelines issued by FRANCOGYN, CNGOF, SFOG, and GINECO-ARCAGY, and endorsed by INCa.

An MRI is recommended for an ovarian mass that is indeterminate on ultrasound. The ROMA score (combining CA125 and HE4) can also be calculated (Grade A). In presumed early-stage ovarian or tubal cancers, the following procedures should be performed: an omentectomy (at a minimum, infracolic), an appendectomy, multiple peritoneal biopsies, peritoneal cytology (grade C), and pelvic and para-aortic lymphadenectomies (Grade B) for all histologic types, except the expansile mucinous subtypes, for which lymphadenectomies can be omitted (grade C). Minimally invasive surgery is recommended for early-stage ovarian cancer, when there is no risk of tumor rupture (grade B). Adjuvant chemotherapy by carboplatin and paclitaxel is recommended for all high-grade ovarian and tubal cancers (FIGO stages I-IIA) (grade A). For FIGO stage III or IV ovarian, tubal, and primary peritoneal cancers, a contrast-enhanced computed tomography (CT) scan of the thorax/abdomen/pelvis is recommended (Grade B), as well as laparoscopic exploration to take multiple biopsies (grade A) and a carcinomatosis score (Fagotti score at a minimum) (grade C) to assess the possibility of complete surgery (i.e., leaving no macroscopic tumor residue). Complete surgery by a midline laparotomy is recommended for advanced ovarian, tubal, or primary peritoneal cancers (grade B). For advanced cancers, para-aortic and pelvic lymphadenectomies are recommended when metastatic adenopathy is clinically or radiologically suspected (grade B). When adenopathy is not suspected and when complete peritoneal surgery is performed as the initial surgery for advanced cancer, the lymphadenectomies can be omitted because they do not modify either the medical treatment or overall survival (grade B). Primary surgery (before other treatment) is recommended whenever it appears possible to leave no tumor residue (grade B). After primary surgery is complete, 6 cycles of intravenous chemotherapy (grade A) are recommended, or a discussion with the patient about intraperitoneal chemotherapy, according to her risk-benefit ratio. After complete interval surgery for FIGO stage III disease, hyperthermic intraperitoneal chemotherapy (HIPEC) can be proposed, in accordance with the modalities of the OV-HIPEC trial (grade B). In cases of postoperative tumor residue or in FIGO stage IV tumors, chemotherapy associated with bevacizumab is recommended (grade A).

[Is sentinel node biopsy feasible in endometrial cancer? Results in 26 patients]. / La biopsie du ganglion sentinelle dans les cancers de l'endomètre est-elle faisable? Résultats sur 26 cas.

OBJECTIVES: To evaluate detection rate, topography and false negatives of sentinel lymph node in endometrial cancer. MATERIAL AND METHODS: Twenty-six patients were included. Lymphoscintigraphy was performed the day before surgery. Preoperative detection of the sentinel lymph node was performed with cervical blue dye injection and a gamma probe. Separate pathology examinations were performed for sentinel and non-sentinel lymph nodes. Sentinel lymph nodes were examined with hematoxylin-eosin-safran stain, and immunohistochemistry if negative. RESULTS: Twenty-six patients had a positive lymphoscintigraphy. Preoperative detection was successful in 21 patients (80.8%): the detection rate with isotopic method, 19 cases (73.1%), was superior to the dye detection, 15 cases (57.7%). No isolated lombo-aortic sentinel lymph nodes were observed, and all sentinel lymph nodes were in the ilio-obturator region. Seven patients presented lymphatic spread, and 4 of them had at least one sentinel node. There was one micrometastasis in sentinel node, associated with isolated tumoral cells in pelvic lymphadenectomy. There was no false negative of sentinel node. CONCLUSION: The biopsy of sentinel lymph node is a feasible procedure in endometrial cancer. There was one micrometastatic sentinel node. However there was no isolated lomboaortic sentinel lymph node in this study.

[Recommendations for reforming prostatic specimens. Les Membres du Sous-Comité Prostate du Comité de Cancerologie de l'Association Française d'Urologie]. / Recommandations pratiques pour les prélèvements prostatiques. Les Membres du Sous-Comité Prostate du Comité de Cancerologie de l'Association Française d'Urologie.

The purpose of these recommendations proposed by the members of the <>, is to provide an informative report for the clinician and the pathologist, in the management of patients with prostate cancer. These recommendations are common to the ADSAP and UICC recommendations on prostate cancer. Standardized forms are recommended to be included in every report.

[Value of biopsies in staging of prostatic cancer before radical prostatectomy]. / Valeur des biopsies dans la stadification du cancer de prostate avant prostatectomie radicale.

The diagnosis of prostate cancer is confirmed by histological examination of prostate biopsies. In cases of localized prostate cancer, in which radical prostatectomy can be proposed as curative treatment, these biopsies, directly reflecting the cancer, can provide important prognostic elements, by specifying the tumour staging, allowing better patient selection and guiding surgical techniques in order to improve the postoperative histological results either by decreasing the number of pT3 tumours (extraprostatic) or the positive resection margin rate. Only pejorative elements are a good indicator of extraprostatic spread of the tumour: a Gleason score greater than 7, the presence of extracapsular invasion, perineural invasion, seminal vesicle invasion, 66% of positive biopsies are in favour of extraprostatic tumour. In contrast, the presence of apparently favourable prognostic elements, such as a low Gleason score, one out of six positive biopsies, limited invasion of biopsies cannot confirm the presence of a minimally aggressive, intraprostatic tumour (pT2). Other prognostic criteria may be discovered in the future, which will confirm with greater precision the extraprostatic or intraprostatic nature of localized prostatic tumours.

[Volume and spatial representation of tumors in the core of the prostate gland]. / Volume et représentation spatiale des tumeurs au sein de la glande prostatique.

OBJECTIVES: To describe a method of calculation of prostatic tumour volume allowing spatial representation of the tumour within the prostate gland. METHODS: 60 radical prostatectomy specimens were studied. Each specimen was processed according to the Stanford technique, and each prostatic section was also divided into two parts, anterior and posterior, according to a sagittal plane through the urethra. 5 microns thick serial sections were performed every 3 mm. The tumour surface area was calculated under light microscopy on each slide. The tumour volume between two consecutive slides was considered to be the volume of a truncated cone. The overall volume obtained was then equal to the sum of these various partial volumes. Spatial representation was performed according to two axes for each of the anterior and posterior parts of the prostatic sections: x-axis represented the prostate from the base to the apex, and the y-axis represented the tumour surface area in each prostatic section. RESULTS: The tumour volume ranged from 0.01 cm3, from 0.21 cm3 for pT2A to 1.98 cm3 for pT3C. pT3 tumours corresponded to the largest volumes, but some pT3 had a small volume. pT3 tumours were preferentially located close to Denonvilliers fascia : 40% of posterior tumours were pT3 versus 9% of anterior tumours (p = 0.01). CONCLUSION: The tumour volume on prostatectomy specimens can be evaluated by routine preparations and represents an additional element allowing better assessment of the TNM classification, as well as the predictive value of the information provided by prostatic biopsies.

[Retropubic and perineal approach: plea for perineal radical prostatectomy]. / Voies rétropubienne et périnéale: plaidoyer pour la prostatectomie radicale par voie périnéale.

OBJECTIVES: Two surgical approaches are proposed for radical prostatectomy: the retropubic route and the perineal route. We compared the surgical, oncological and functional aspects of these two approaches and present arguments suggesting that the perineal approach is the preferred approach for radical prostatectomy. MATERIAL AND METHODS: 55 retropubic radical prostatectomies were retrospectively compared to 55 perineal radical prostatectomies and performed between March 1992 to December 1995. The clinical TNM, preoperative PSA, results of 6 systematized intrarectal biopsies, operating time, intraoperative bleeding, number of patients transfused and number of packed cell units per patient transfused, medical and surgical complications, catheterization time and length of hospital stay, incidence of urethrovesical anastomosis leak and stenosis, analysis of the prostatectomy specimen, course of PSA, continence and erection were studied. RESULTS: Statistically significant differences were observed for the retropubic and perineal approaches, respectively: preoperative PSA (24 vs 15 ng/mL), intraoperative bleeding (2664 vs 1071 mL), number of patients transfused (91% vs 28%), number of packed cell units per patient transfused (3.9 vs 2.7), medical and surgical complications (56.9 vs 29.1%), anastomotic leak (24.1 vs 7.2%), anastomotic stenosis (31.5 vs 1.8%), duration of catheterization (18 vs 13 days) and length of hospital stay (14 vs 8 days). At 2 years, PSA remained less than 0.5 ng/mL in both groups. CONCLUSION: Even taking the learning period into account, the perineal approach provides the same results as the retropubic approach in terms of functional and oncological parameters, with a simpler postoperative course for patient.

[Improvement over time of oncological results after radical prostatectomy: what are the responsible factors?]. / Amélioration au cours du temps des résultats carcinologiques après prostatectomie radicale: quels en sont les facteurs responsables?

OBJECTIVES: The histological results after radical prostatectomy constitute one of the main prognostic factors. We studied the course of these results over time in order to assess their improvement and to identify the factors responsible. MATERIAL AND METHODS: 175 radical prostatectomies were performed between 1989 and 1996. The preoperative assessment for each patient comprised clinical examination, PSA assay, and histological examination of 6 ultrasound-guided transrectal biopsies. All radical prostatectomy specimens were analysed according to the Stanford technique by the same pathologist: the weight of the prostatectomy specimen, the Gleason score, existence of capsular effraction, seminal vesicle invasion, positive lymph node dissection and the presence of positive surgical margins were studied. The results were studied and compared year by year using Student's test and the Chi-square test. RESULTS: From 1989 to 1996, stages pT1-pT2 increased from 40 to 81.8%, while the positive resection margin rate decreased from 80 to 18.1%. No difference was observed over time for weight and Gleason score. Among the preoperative factors, no difference was observed for age of the patients, number of positive biopsies and Gleason score of these biopsies. Only the mean preoperative PSA level decreased from 52.2 to 12.2 ng/ml (t = 0.0001) and the number of stage T1c tumours increased from 13.3 to 59%. CONCLUSION: The preoperative PSA level is the main factor explaining improvement of the oncological results, especially as the tumours operated between 1988 and 1996 were identical in terms of aggressiveness (Gleason score). This improvement of the results reflects better patient selection, although this selection is performed case by case without exclusive factors.

[The value of prostatic biopsy in tumor mapping]. / Valeur des biopsies prostatiques dans la cartographie tumorale.

OBJECTIVES: Prostatic biopsies, a diagnostic tool, are also used as prognostic elements before radical prostatectomy. Their sites within the prostatic gland constitute one of these prognostic criteria. The authors compared the site of positive prostatic biopsies with that of the tumour after radical prostatectomy in order to study the value of this prognostic factor and the way in which it can be improved. MATERIAL AND METHODS: From 1988 to 1996, 166 localized prostatic tumours treated by radical prostatectomy were diagnosed by 6 systematized ultrasound-guided transrectal biopsies and 3 supplementary median biopsies performed from the base to the prostatic apex. The site of positive biopsies was compared to that of the tumour within the prostatic gland. RESULTS: Of the 996 sextant biopsies performed, 331 (33%) were positive, i.e. 1.99 biopsies per prostate. 92 (19%) median biopsies were positive. 331 positive sextant biopsies corresponded to a tumour within the prostate with a specificity of 81.5%, a sensitivity of 39.4%, a positive predictive value (PPV) of 83.3%, a negative predictive value (NPV) of 36.4% and an accuracy of 52%. For 3 median biopsies, the sensitivity was 70.3%, the specificity was 91.6%, the PPV was 61.9%, the NPV was 94%, and the accuracy was 82%. The weight of the prostate (prostates less than and greater than 45 g), influenced these results, as PPV decreased from 90.8% to 76.1% while NPV increased from 32.9% to 37.8%. CONCLUSION: Negative biopsies in a prostatic zone after 6 randomized biopsies do not exclude the presence of tumour in this zone and cannot be used as a prognostic element before radical prostatectomy for the therapeutic management. The presence of negative biopsies in a prostatic zone must be interpreted by taking the prostatic weight into account. 3 median biopsies are more accurate and less influenced by prostatic weight.

[External validation of simple ultrasound rules of Timmerman on 122 ovarian tumors]. / Validation externe des critères de Timmerman sur une série de 122 tumeurs ovariennes.

OBJECTIVE: To study the correlation between the nature of the ovarian tumors presumed according to the ultrasound criteria of Timmerman and the final histological diagnosis. PATIENTS AND METHODS: We made a prospective study during a period of 4 years, concerning consecutive patients having an ovarian tumor, investigated by pelvic ultrasonography using Timmerman's rules estimating their benign or malignant characteristics in order to determine the efficiency of this score. The diagnostic reference was histology. Sensitivity and specificity of these criteria were calculated with their 95% confidence intervals. RESULTS: One hundred and twenty-two patients having adnexal masse were included between January 2002 and December 2005. Among these tumors, 88.5% (108/122) were benign, and 11.5% (14/122) were malignant or borderline. The ultrasound-based rules of classification were applicable for 89.3% (109/122) of them. The sensitivity of these rules was 73% (95% CI [45-100]) and the specificity was 97% (IC 95% CI [94-100]). DISCUSSION AND CONCLUSION: Most adnexal masses can be classified according to the ultrasound simple rules of the score of Timmerman with a good specificity to eliminate their malignant or borderline characteristics. Tumors which cannot be classified according to these rules must be referred to an expert ultrasonographist.

[Sentinel lymph node procedure and uterine cancers]. / Procédure du ganglion sentinelle et cancers utérins.

Lymph node metastases in cervical and endometrial cancer are major prognostic factors. Lymph-nodal involvement determines adjuvant therapy. As imagery is not reliable to diagnose lymph node status, pelvic +/- para-aortic lymphadenectomy remains the gold standard. These surgical procedures are, however, responsible for specific morbidity: lymphocele and lymphedema. Sentinel lymph node procedure could avoid lymphadenectomy and their complications in cervical and endometrial cancer with good negative predictive values. We present actual indications, procedure and results of sentinel lymph node procedures in cervical and endometrial cancer.

Nondissection of pelvic lymph nodes does not influence the results of perineal radical prostatectomy in selected patients.

OBJECTIVES: Retrospective studies have shown that pelvic lymph node dissection can be dispensed with in selected men undergoing radical prostatectomy. We prospectively evaluated the influence of nondissection of pelvic lymph nodes on tumor progression in our first 100 perineal prostatectomies. METHODS: From October 1992 to February 1998, 100 patients underwent radical perineal prostatectomy for localized prostate cancer. Preoperative PSA, the Gleason score of positive biopsies and age at surgery were noted. Forty-three of the 100 patients (group 1) did not undergo pelvic lymph node dissection because their preoperative PSA level was below 10 ng/ml (Hybritech assay, normal value 4 ng/ml) and the Gleason score of their positive biopsies was below 7. These 43 patients were compared with 25 of the 114 patients operated on during the same period by the retropubic approach and who had pelvic node dissection and the same preoperative criteria (PSA <10 ng/ml and a Gleason score of positive biopsies <7; group 2). All prostatectomy specimens were processed according to the Stanford protocol: prostate weight, Gleason score, capsular, seminal vesicle, lymph node and surgical margin status, and tumor volume were studied. Postoperative followup was based on routine serum PSA assays after 1 and 3 months and then half-yearly. Biological progression was defined as PSA level which was detectable postoperatively (>/=0.2 ng/ml). Kaplan-Meier analysis was used to evaluate the likelihood of biochemical recurrence. Results were compared by using Fisher's test, the Mann-Whitney test and the log-rank test. Differences were considered significant when the p value was <0.05. RESULTS: No differences in preoperative characteristics were observed; in groups 1 and 2, mean age was 65.9 and 64.7 years, PSA was 6.7 and 5.11 ng/ml, and the Gleason biopsy score was 5.7 vs. 5.0, respectively. In groups 1 and 2, specimen weight was 44.5 and 54.3 g (p = 0.04), the Gleason score was 6.2 and 5.6, tumor volume was 0.91 and 0.8 ml, 81.4 and 84% of patients were in stage pT2, 13.9 and 12% had extracapsular disease, 4.6 and 0% had seminal vesicle invasion, and 13.9 and 16% had positive surgical margins, respectively. The mean follow-up was 2.74 years (0.27-5.59 years). The actuarial 5-year recurrence-free rate was 78% in group 1 and 80% in group 2 (p>0.05). CONCLUSION: The lack of pelvic lymph node dissection does not influence the intermediate term results of perineal radical prostatectomy in selected patients (preoperative PSA <10 ng/ml and Gleason score for positive biopsies <7).

Value of ultrasound-guided systematic sextant biopsies in prostate tumor mapping.

OBJECTIVE: To determine the value of positive sextant biopsies in assessing the location of prostate tumors within radical prostatectomy specimens and to determine if prostate weight influences the results. METHODS: From 1988 to 1996, 166 radical prostatectomies were performed for localized prostate cancer diagnosed by means of ultrasound-guided sextant biopsies. The location of the biopsies was compared with that of tumor tissue within the radical prostatectomy specimen. RESULTS: Of the 996 biopsies, 331 (33%) were positive. The correspondence between the location of the biopsies and that of tumor tissue in the surgical specimen was found to have a sensitivity of 39.4%, a specificity of 81.5%, a positive predictive value of 83.3%, negative predictive value of 36.4% and an accuracy of 52%. For prostates weighing < and >/= 45 g, the sensitivity was 39.9 and 38.9%, the specificity was 88 and 77.2%, the positive predictive value was 90.8 and 76.1%, the negative predictive value was 34.9 and 39.8%, and the accuracy was 52 and 52%, respectively. CONCLUSION: Negative biopsies do not predict a lack of tumor tissue in the corresponding prostate site after radical prostatectomy, and had less value than positive biopsies for prognostic staging before radical prostatectomy. Results of sextant biopsies are more significant for prognosis before radical prostatectomy when positive. Prostate weight influences the interpretation of the results of sextant biopsies.

The prognostic value of p53 nuclear overexpression and MIB-1 as a proliferative marker in transitional cell carcinoma of the bladder.

BACKGROUND: There is controversy regarding the value of biologic markers as prognostic indicators independent of clinicopathologic parameters in transitional cell carcinoma (TCC) of the bladder. The authors examined the prognostic value of p53 tumor suppressor gene expression and the proliferative marker MIB-1 in TCC of the bladder. METHODS: Fresh frozen samples from 114 TCCs of the bladder and 13 normal bladders were studied by immunohistochemistry, using monoclonal antibodies MIB-1 for proliferation and PAb 1801 for p53 nuclear overexpression. Scores were determined in each case by counting at least 500 nuclei per slide in 3-5 selected regions. Patients were stratified for both markers into two groups for time-event analysis, according to the median number of nuclei stained. Patients with nuclear staining below the median value of the score were considered negative in the statistical analysis. Quantitative immunostaining was analyzed in relation to the time to recurrence, progression, and cancer death, and compared with clinical and pathologic parameters for prognostic significance in univariate and multivariate analysis (stepwise logistic regression). RESULTS: Median nuclear overexpression of p53 was 22% and that of MIB-1 28%. There was a strong association between proliferation and p53 nuclear overexpression (P < 0.0001). Progression free and disease specific survival rate estimates (log rank test) were significantly lower in patients with p53 or MIB-1 scores above 22% and 28%, respectively. Multivariate analysis indicated that stage as well as p53 and MIB-1 immunostaining provided independent prognostic information. CONCLUSIONS: Quantitative immunohistochemical evaluation of nuclear p53 and MIB-1 immunostaining inexpensively provides prognostic indicators in cases of TCC of the bladder.

Evaluation of cellular tumour rejection mechanisms in the peritumoral bladder wall after bacillus Calmette-Guérin treatment.

OBJECTIVE: To compare the immunological status of normal and peritumoral bladder walls, and to characterize immunocompetent cells before and during intravesical instillations of bacillus Calmette-Guérin (BCG). PATIENTS AND METHODS: Twenty-three patients with superficial urothelial bladder carcinoma (stages pTa to pT1, grades 1-3) were treated with six weekly instillations of 150 mg of BCG (Pasteur strain). Biopsies of cystoscopically normal bladder wall were taken before, 3 weeks and 3 months after BCG instillation. The controls comprised bladder biopsy specimens from 13 brain-dead ventilated kidney donors. Local infiltrating cell types, i.e. lymphocyte infiltrates (CD4, CD8, CD20, CD3, interleukin-2-receptor-positive, natural killer, gammadelta), macrophages and dendritic cells, adhesion and costimulatory molecules (ICAM-1 and B7-BB1) and major histocompatibility complex (MHC) class I and class II antigens were assessed using semi-quantitative immunohistochemical analysis. RESULTS: Before BCG the peritumoral bladder wall had fewer macrophages than control bladder wall. BCG treatment restored normal numbers of macrophages and enhanced T helper lymphocytes, B lymphocytes, natural killer cells, activated lymphocytes, dendritic cells, normal MHC class I, adhesion (ICAM-1) and costimulatory (B7-BB1) expression. The enhancement of these immunological variables was transient, with a return to baseline 3 months after BCG instillation. CONCLUSIONS: These results support the concept that there is a host-immune escape associated with bladder cancer. BCG therapy may temporarily restore impaired tumour rejection mechanisms in the peritumoral bladder wall, suggesting a need for maintenance therapy after the first course of BCG.

Low E-cadherin expression in bladder cancer at the transcriptional and protein level provides prognostic information.

We studied E-cadherin down-regulation at the protein level in frozen sections of 111 bladder tumours and 13 normal bladder specimens by means of immunohistochemistry, and at the mRNA level by semi-quantitative RT-PCR in 40 of the same tumours. Results indicate that E-cadherin expression detected by immunohistochemistry correlated with both stage and grade (P < 0.0001 and P < 0.001, respectively). Analysis of recurrence, progression and survival over a mean period of 36 months after surgery in the entire cohort showed that abnormal E-cadherin immunoreactivity correlated strongly with poor outcome (log-rank test: P = 0.001, P = 0.0001 and P = 0.0003, respectively). In multistep logistic regression analysis, only E-cadherin status and stage had significant additional prognostic value (P= 0.008 and OR = 0.2; P= 0.03 and OR = 3.6, respectively). Survival estimates derived from RT-PCR transcript quantification differed significantly for low and high expression (log-rank test: P = 0.0006). These results suggest that the alteration occurs at the transcriptional level and support the clinical and biological relevance of cell adhesion molecules in bladder cancer.

Induction of apoptosis and inhibition of cell proliferation by the lipido-sterolic extract of Serenoa repens (LSESr, Permixon in benign prostatic hyperplasia.

BACKGROUND: To determine the mechanism by which prostate volume increases during the development of BPH and to evaluate the effect of LSESr (Permixon), a phytotherapeutic agent, we investigated apoptosis and cell proliferation in the stroma and epithelium of normal prostate and of BPH tissues from patients treated with or without LSESr. METHODS: MIB-1 staining and the in situ end-labeling assay were used to evaluate the proliferative-apoptotic balance in normal prostates and in BPH tissues. Quantitative assessment was performed using an image analysis system. RESULTS: In normal prostates, there was no significant difference between apoptotic and proliferative indices. Cell numbers and proliferative indices were higher in BPH than in normal prostates, while apoptosis values were similar. In the BPH treated group, LSESr significantly inhibited proliferation and induced cell death in both epithelium and stroma. CONCLUSIONS: Induction of apoptosis and inhibition of cell proliferation are likely to be the basis for the clinical efficacy of LSESr.