Clinical management of adolescents and young adults suffering from sarcoma in the French Rhône-Alpes region: A prospective exhaustive cohort with 10 years follow up.

INTRODUCTION: Survival of adolescents and young adults (AYA) with sarcoma is lower than in younger patients. The objective of this study was to describe the regional healthcare circuits, the differences in the management between adult, paediatric and mixed units and to assess the prognostic impact of compliance with clinical practice guidelines (CPGs) on overall survival (OS) and on relapse free survival (RFS). MATERIALS AND METHODS: Retrospective analysis of the management and long term follow-up of all 13-25 year old patients with a sarcoma diagnosed in the Rhône-Alpes area between 2000 and 2005. RESULTS: 140 patients satisfied inclusion criteria and were selected. The majority of 13-25 year old patients were treated in paediatric units. Joint management resulted in a higher rate of discussion in multidisciplinary tumour board, inclusion in clinical trials, and fertility preservation. Non-compliance with guidelines was observed in 65% of cases. Overall compliance was not reported to correlate to survival. Compliance of radiotherapy with CPG's seemed associated with a better prognosis for OS (HR = 0.20, 95% CI = [0.10-0.40]; p < 0.0001) and RFS (HR = 0.18, 95% CI = [0.09-0.37; p < 0.0001) as well as compliance of surgery for OS (HR = 0.43, 95% CI = [0.23-0.81]; p = 0.01). Multivariate Cox regression analysis revealed other independent predictors of OS like age at diagnosis, stage and histological subtype. CONCLUSIONS: Management of AYA in joint units seems to improve the quality of care. Compliance of surgery and radiotherapy with CGP's seems to improve survival.

Intraperitoneal free cancer cells in non-gynaecological adenocarcinomas: a reproducibility study.

OBJECTIVE: In recent years, therapeutic approaches including cytoreductive surgery followed by intraperitoneal chemotherapy have proven effective in peritoneal carcinomatosis of colorectal origin. If cytology is to be used to include patients in aggressive treatment regimens, it is necessary to evaluate its performance, particularly in terms of specificity. The aim of this study was to assess interobserver agreement for the detection of intraperitoneal free cancer cells (IFCCs) in patients with non-gynaecological adenocarcinomas. METHODS: Over a 5-year period, 1223 patients were recruited in 19 French surgery departments. Peritoneal samples were examined in 14 dispersed pathology laboratories. Giemsa-stained slides were sent to a control reader blind to the previous diagnosis. Discordant cases, concordant positive results and a random selection of negative concordant cases were reviewed by a panel of seven cytopathologists. The 'final diagnosis' was that of the consensus meetings but took into account locally-processed slides. RESULTS: Gathering dubious cases with negative results, a 95.6% concordance was achieved between local readers and the control reader. IFCCs were ascertained by the panel in 85 cases (7.0%). Eight of 873 colorectal cancers cases viewed locally were falsely positive (0.9%). Radiotherapy and neoadjuvant therapy had no impact on the false-positive rate as assessed by final validation by the panel (P > 0.05). Samples initially considered as dubious were reclassified as negative by the panel in 24 of 25 cases (96.0%). CONCLUSIONS: The panel consensus allowed reclassification of most dubious/equivocal peritoneal cytology cases, whereas clearcut distinction between benign and malignant cases was correctly achieved in almost all cases.

Accuracy of conventional cytology: results from a multicentre screening study in India.

OBJECTIVE: We conducted a multi-centre cross-sectional study in India to evaluate the accuracy of conventional cytology to detect high-grade squamous intraepithelial lesions (HSIL). SETTING: Cross-sectional studies in Jaipur, Kolkata, Mumbai and Trivandrum, India, during 1999-2003. METHODS: A common protocol and questionnaire were used to test 22,663 women aged 25-65 years with conventional cytology in five cross-sectional studies. Three thresholds were used to define test positivity: atypical squamous cells of uncertain significance (ASCUS), low-grade squamous intra-epithelial lesion (LSIL), or HSIL. All screened women were investigated with colposcopy, and biopsies were taken when necessary. The reference standard for final disease status was histology or negative colposcopy. Data from the studies were pooled to evaluate the test characteristics for the detection of histologically confirmed HSIL. RESULTS: The test positivity rates of cytology were 8.8% at ASCUS, 6.2% at LSIL and 1.8% at HSIL thresholds, and 355 women had histologically confirmed HSIL while 74 had invasive cancer. The pooled sensitivity, specificity, positive and negative predictive values at ASCUS threshold were 64.5%, 92.3%, 11.8% and 99.4% respectively. The corresponding values at LSIL threshold were 58.0%, 94.9%, 15.2% and 99.3%, while at the HSIL threshold they were 45.4%, 99.2%, 46.3% and 99.1%. The sensitivity varied between 37.8-81.3% at ASCUS, 28.9-76.9% at LSIL and 24.4-72.3% at HSIL thresholds. A significantly low sensitivity was observed in women aged 25-39 years (p<0.001). The wide variation in sensitivity across study sites persisted even after age standardisation. CONCLUSION: The sensitivity of cytology varied widely between the study sites. Findings from our study and other reviews indicate that sustained efforts in improving sampling, preparation and reading of cytological specimens and improvements in clinical judgement are essential to achieve concurrently high sensitivity and specificity.

[Standards, options and recommendations: practice guidelines for difficult diagnosis in surgical pathology or cytopathology in cancer patients]. / Standards, options et recommandations: conduite a tenir devant une lésion de diagnostic anatomo-cyto-pathologique difficile en cancérologie.

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993 is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for difficult diagnoses in surgical pathology or cytopathology in cancer patients. METHODS: Data were identified by searching Medline and using the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to 71 independent reviewers. RESULTS: The main recommendations to prevent and reduce the number of difficult diagnoses in surgical pathology or cytopathology are: 1) The development of quality insurance programs with use of written procedures in each pathology laboratory (standard). 2) The knowledge of clinical data in order to explain surgical pathology or cytopathology results (standard). 3) The availability of complementary patient informations (radiologic data . . .) can be useful to explain surgical pathology or cytopathology results (option). The main recommendations to detect lesions associated with difficult diagnosis in surgical pathology or cytopathology are: 1) Tumor types known as potential difficult diagnosis in surgical pathology or cytopathology should be reviewed by a second pathologist. 2) The systematic second reviewing for every case is expensive but has to be done when the difficulty is know (sarcoma, lymphoma . . .) by experienced pathologists. The main recommendations to solve difficult diagnosis in surgical pathology or cytopathology are: 1) Block recuts, use of special techniques (immunocytohistochemistry and molecular biology), additional data from clinicians, second opinion by a local pathologist, or new specimen can be required for establishing the diagnosis (options). 2) Outside second opinion by expert pathologist has to be considered once the other steps did not allow to establish surgical or cytopathology diagnosis (recommendations, expert agreement).

[The "Action Woman Health" program in three Lyons suburbs]. / Le programme "Action Femme Santé" dans trois communes de l'agglomération lyonnaise.

The cervical cancer screening campaign has been led in three cities in Lyons suburbs from October 1st, 1999 to October 31st, 1999. The objectives of this programme whose title was "Action Femme Santé" (Action Woman Health) were to screen cervical cancer systematically for women who accede with difficulties to smear technique, and to settle in an information, screenings and follow-up system. During the three years, 3,127 smears have been declared and have reached about 2,881 women. The rate of detected disorders is about 2.1%. This campaign has succeeded in its goal about the target public but the participation of health professionals was unsatisfactory because of many obstacles. This implementation of the programme and its results, the weak points and strong points to be kept from such experience, are developed.

[Cervical cancer screening for high risk women: is it possible? Results of a cervical cancer screening program in three suburban districts of Lyon]. / Le dépistage de masse du cancer du col utérin peut-il atteindre une population à risque? Résultats d'un programme pilote de dépistage de masse du cancer du col utérin dans trois communes de l'agglomération lyonnaise.

Between november 1993 and october 1996, a cervical screening program was proposed for women 25-65-year-old who tend to have little or no medical supervision, in three suburban districts of Lyon. The data and results of the two last Pap-smears have been collected together with details of gynecological follow-up. Both general practitioners and gynaecologists were actively involved. A total of 3,792 women (12.3% of the target) were registered, with a larger proportion of women over 60 (17.7%). According to the "Consensus of Lille", only 403 women (34.4%) had adequate screening (over 50 y: 25.8%, 35-49 y: 39.4%, 25-35 y: 36.5%) and 2,489 women had inappropriate gynaecological follow-up: no smear for 185 women (4.9%) and inadequate schedule of follow-up visits for 476 others (12.5%). Missing data (date or results of Pap smear) were noted for 1,828 patients (48.2%). The screening procedure for women over 50 years was carried out mainly by general practitioner. Of 3,127 registered smears, 62 positive results were found (2.1%). Of these women, 9 were lost to follow-up and 4 did not have appropriate tests. Others results were: 27 negative further investigations, 9 CIN1, 7 CIN2, 3 CIN3, 1 in situ carcinoma and 2 invasive carcinoma. Despite low participation, this pilot study indicates that a procedure can be established to integrate high risk women in cervical cancer screening programme. Active participation of general practitioners is essential.

[The role of the medical corps in a mass screening program for cervical cancer. The program "Female Health Action in 3 urban districts of Lyons]. / La participation du corps médical à une expérience de dépistage de masse du cancer du col utérin. A propos du programme "action femme santé" dans 3 communes de l'agglomération lyonnaise.

A pilot study of cervical cancer screening has been initiated in three districts of Lyons suburbs. This campaign aims to increase women participation, specially for high risk groups, helped by an intensive collaboration of general practitioners and gynecologists. Despite several campaign of information, a low rate of participation (13%) was noted. A survey has been performed on the medical population, notably for their participation, eventual changes, encountered problems and perception of such a screening. At time of survey, only half of the general practitioners and 75% of gynecologist still participated. Complexity of administrative procedures, involvement in an epidemiologic survey, lack of time or non-gynecological practice were important obstacles. Volunteer practitioners, enhanced value of public health and university formation of doctors could be necessary in the future for such mass screening.

Hepatocarcinoma-specific mutant p53-249ser induces mitotic activity but has no effect on transforming growth factor beta 1-mediated apoptosis.

Mutations affecting the p53 gene abrogate its tumor suppressor activity. It is, however, unclear whether such mutations can generate mutant p53 proteins with an intrinsic transforming ability. More importantly, the mechanism(s) by which they exert such activity is unknown. We report here that p53-deficient hepatoma cells (Hep3B) transfected with mutant p53-249ser (codon 249 Arg-->Ser) acquire a new phenotype with an increased in vitro survival and mitotic activity. However, such a phenotypic change is not sufficient to cause a major shift in the poor tumorigenic potential of these cells. This is apparently due to transforming growth factor beta 1-mediated apoptotic death of Hep3B cells which is not affected by the expression of p53-249ser.

Studies of monoclonal antibody BL2-10D1 as a marker for the detection of the urothelial origin of tumors.

BACKGROUND: In previous studies, the authors demonstrated the value of the monoclonal antibody (MoAb) BL2-10D1 in identifying malignant transitional cells. In this study, the authors evaluate the possible diagnostic value of a murine MoAb, BL2-10D1, raised against human bladder cancer in the determination of the urothelial origin of metastases in a series of 29 patients with metastatic bladder or prostatic carcinoma. METHODS: Using an immunoperoxidase method, BL2-10D1 and anti-prostate-specific antigen (anti-PSA) reactivity were studied, using histologic sections from 18 pelvic lymph nodes and 4 other anatomic sites invaded by transitional cell cancer, and from 7 pelvic lymph nodes containing prostatic cancer. RESULTS: All lymph nodes containing metastases of transitional cell carcinoma were positive with BL2-10D1, whereas all metastases of prostatic cancer were negative; the four instances of distant urothelial metastases were positive with BL2-10D1 MoAb. Conversely, anti-PSA reacted only with prostatic metastases. CONCLUSION: Thus, MoAb BL2-10D1 and anti-PSA complement each other in the separation of cancers of prostatic and urothelial origin, and the BL2-10D1 MoAb has potential usefulness in differentiating between urothelial carcinoma and prostate adenocarcinoma. In patients with bladder tumors of uncertain origin, BL2-10D1 may be helpful in confirming that a tumor is a transitional cell carcinoma.

Combination of standard cytology and immunocytology with BL2-10D1 monoclonal antibody for monitoring-treated bladder cancer patients.

Monoclonal antibody BL2-10D1 directed against a tumor-associated antigen of bladder carcinoma was used for monitoring 11 intravesically treated patients. Thirty-three bladder washout specimens were used for standard cytology and immunological staining. Prior to treatment, 9 of 11 cytologic specimens examined with standard cytology were found to be positive. Using BL2-10D1 alone, only 6 were positive but 1 patient negative with standard cytology was positive with the antibody and corresponded to a positive histological control. Thus, before treatment, an increase in positive rate was observed using the combination of the 2 methods from 82 to 91%. At the end of treatment, 9 washout specimens remained positive with standard cytology, whereas 1 case negative in standard cytology was positive in immunocytology. Thus, the positive rate increased from 82 to 91%. One month after the end of treatment, of 11 washout specimens tested, 3 false-negative standard cytologies and 4 false-negative immunocytologies were shown. However, used in combination, the two methods lead to an increase in positive rate from 67 to 89%. In view of these results, BL2-10D1 may be considered as a useful reagent in combination with the standard cytology for the confirmation of the presence of tumor cells before and after immunotherapy.

An image cytometric DNA-analysis in breast neoplasms. Parameters of DNA-aneuploidy and their relationship with conventional prognostic factors.

In this prospective study, an image cytometric DNA-analysis was performed in 86 women with breast neoplasms (72 primary invasive carcinomas and 14 benign lesions). Four DNA ploidy parameters were analysed: histogram type (according to AUER classification), DNA-index, tumor cells with DNA content above the 5n limit and DNA malignancy grade (DNA-MG, calculation according to Böcking). Their correlations with well established prognostic factors in breast carcinomas (tumor size, lymph node status, histologic grade, hormone receptor content) were studied. All but one benign lesions were diploid (13/14 cases), whereas the majority of the primary invasive breast carcinomas were aneuploid (58/72 cases). A predominance of carcinomas with a percentage of cells superior or equal to 1% with DNA content above the 5n limit was observed (54 cases out of 58). Most of the aneuploid tumors had a histogram type III or IV (53 cases) or a high DNA-index (50 cases). Of these 58 aneuploid cases, only 26 tumors had a DNA-MG superior to 1. Interestingly, 26 tumors had the 4 criteria of aneuploidy, 19 had 3 and 9 had 2 and only 4 tumors had one parameter. The DNA-MG was significantly related to hormonal receptors (p less than 0.001) and tumor size (p less than 0.01). The histogram types (Auer classification) and the DNA content above the 5n limit were correlated with histologic grade (SBR or SBRM) (p less than 0.02). Concerning the DNA-index no correlation was observed with well established prognostic factors. On the other hand no significant correlation was found between these new biologic variables and lymph node status.(ABSTRACT TRUNCATED AT 250 WORDS)