Biomedical subjects
Publications and source records attributed to V Molinié.
BHD, TP53, and HNF1beta on chromosome 17 were studied in 92 cases of renal cell carcinoma (46 chromophobe, 19 clear cell, 18 oncocytoma, and nine papillary). Six, thirteen, and zero cases had, respectively BHD, TP53, and HNF1beta mutations, (84% mutations involved chromophobe), suggesting a role for BHD and TP53 in chromophobe subtype.
Thickening of the gallbladder wall may result from a large spectrum of pathological conditions, intrinsic as well as extrinsic to the biliary tract, and may have different appearances. Accurate diagnosis is usually established after a correlation of imaging findings, laboratory data and clinical history. US remains the initial imaging modality for the evaluation of acute right upper quadrant pain. CT and MRI are complementary to US and have an increasing role in assessing a thickened-wall gallbladder.
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CONTEXT: The "Standards, Options and Recommendations" (SOR) collaborative project was initiated in 1993 by the Federation of the French Cancer Centres (FNCLCC), with the 20 French Regional Cancer Centres, several French public university and general hospitals, as well as private clinics and medical speciality societies. Its main objective is the development of serviceable clinical practice guidelines in order to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review, followed by critical appraisal by a multidisciplinary group of experts. Draft guidelines are produced, then validated by specialists in cancer care delivery. OBJECTIVES: Produce clinical practice guidelines for the radiotherapy of prostate cancer using the methodology developed by the Standards, Options and Recommendations project. METHODS: The FNCLCC and the French Urology Association (AFU) designated the multidisciplinary group of experts. Available data were collected by a search of Medline and lists selected by experts in the group. A first draft of the guidelines was written, they validated by independent reviewers. RESULTS: The main recommendations are: 1/ a minimal dose of 70 Gy must be used, whatever the prognostic factors; 2/ it appeared that patients with favourable prognostic indicators (stage T1-2, PSA < or = 10 micrograms/L and Gleason score < or = 6) do not benefit from a dose escalation effect for doses over 70-74 Gy; 3/ patients with intermediate prognosis are the ones who benefit most from the dose escalation effect over 74 Gy, provided they receive exclusive radiation therapy; 4/ whenever possible, patients should be included in controlled trials designed to assess the effects of dose escalation and hormonotherapy.
The Transnational Training Programme in Cervical Cytology (CYTOTRAIN) is a 3-yr project funded by the European Commission to harmonize training and quality standards in cervical screening across the European Union. The aim of the program is to develop new approaches in initial and continuing vocational training, particularly in the area of life-long learning with the aim of meeting national, regional, and local needs. We present a new approach to training in cervical cytology, using an interactive program of cytological images. The method used to prepare the program and the problems encountered are described. The authors have the feeling that giving details of the organizational and management structure adopted for the project implementation might help other pathologists realize more or less similar CD-ROM training programs in their own field of activity.
The French Society of Clinical Cytology is conducting a study to compare the cost-effectiveness of monolayers and human papillomavirus (HPV) testing with that of conventional Papanicolaou (Pap) smears for cervical cancer screening. The protocol of this study is presented. It includes 3,000 women who will be evaluated by the three methods (conventional Pap smears, or monolayers with or without HPV testing) and by the reference method: colposcopy followed, in cases with abnormalities, by cervical biopsy. Efficacy or performance of the methods will be compared on the basis of sensitivity. Cost comparisons and cost-effectiveness modeling will be based on the costs associated with methods themselves and also the costs of "false positives." This will require specific collection of data concerning the costs of the three methods, as these costs have not previously been accurately documented. Patient recruiting and data collection started in September 1999 and will be complete in June 2000. The first results are expected to be available in spring 2001.
A case of transverse testicular ectopia with supernumerary vas deferens and cyst of the ejaculatory duct is reported. The reports relevant to these malformations were reviewed and their embryologic etiology discussed.
CONTEXT: The "Standards, Options and Recommendations" (SOR) collaborative project was initiated in 1993 by the Federation of the French Cancer Centres (FNCLCC), with the 20 French Regional Cancer Centres, several French public university and general hospitals, as well as private clinics and medical specialty societies. Its main objective is the development of serviceable clinical practice guidelines in order to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review, followed by a critical appraisal by a multidisciplinary group of experts. Draft guidelines are produced, then validated by specialists in cancer care delivery. OBJECTIVES: Produce clinical practice guidelines for the brachytherapy of prostate cancer using the methodology developed by the Standards, Options and Recommendations project. METHODS: The FNCLCC and the French Urology Association (AFU) first designated the multidisciplinary group of experts. Available data were collected by a search of Medline and lists selected by experts in the group. A first draft of the guidelines was written, they validated by independent reviewers. RESULTS: The main recommendations are: 1/Brachytherapy with permanent seeds alone is a possible curative treatment for prostate cancer patients with the following prognosis factors: tumour stage T1 or T2a (TNM 1992), Gleason score < or = 6 and PSA < 10 micrograms/L. 2/Combined treatment with brachytherapy and hormonal therapy could be more efficient than brachytherapy alone for prostate cancer patients with Gleason score > 7 and/or PSA > 10.3/Combination of brachytherapy and external beam radiation therapy can be proposed to prostate cancer patients with intermediate prognosis. 4/Before and after seed implantation, risks of infection must be prevented by appropriate antibiotic therapy (recommendation). 5/Brachytherapy must not be performed within 2 months of transurethral prostate resection. 6/The height of the urethra receiving more than 200% of the prescribed dose must be reported. The portion of the rectum receiving 100 and 120% of the prescribed dose must be limited to 10 and 5 mm length, respectively.
OBJECTIVE: Hemophagocytic syndrome has been defined as the combination of a proliferation of cytologically benign, actively phagocytic macrophages in bone marrow, spleen, or lymph nodes in association with fever, cytopenia, splenomegaly, and hypertriglyceridemia. Hepatic dysfunction is often present but the nature of the hepatic lesions and related manifestations have not been fully characterized. The aim of this study was to ascertain the features of hepatic involvement in hemophagocytic syndrome. METHODS: Thirty patients with hemophagocytic syndrome were retrospectively studied. Inclusion criteria included: 1) bone marrow with hemophagocytic histiocytosis, 2) clinical or biological signs of hepatic involvement, and 3) available liver specimen. RESULTS: The association of fever, jaundice, and hepatomegaly or splenomegaly was present in 50% of the patients. Median value for serum alanine transaminase activity was five times the upper limit of normal values (range, 0.3-125), for serum alkaline phosphatase activity 2.7 upper limit of normal values (range, 0.2-47.7), for total bilirubin 136 micromol/L (range, 4-681 micromol/L), and for factor V 70% (range, 19-145%). Sinusoidal dilatation with hemophagocytic histiocytosis were found in the biopsy specimen in all patients. An underlying condition potentially responsible for altered immune function (lymphoma, leukemia, liver transplantation) was identified in 29 patients. Liver biopsy was diagnostic for the underlying condition in 15 patients (including eight cases with nonspecific bone marrow biopsy findings). High serum bilirubin, elevated serum alkaline phosphatase activity, low factor V level, and lack of treatment for the underlying disease were associated with a poor prognosis. CONCLUSIONS: Hemophagocytic syndrome should be suspected in immunodeficient patients with fever, jaundice, and hepatosplenomegaly. Hepatic lesions are characterized by nonspecific sinusoidal dilatation with hemophagocytic histiocytosis and in 50% of the patients by alterations specific to the underlying condition. Liver biopsy is a useful diagnostic procedure in patients with this clinical presentation.
Prostatic intraepithelial neoplasia (PIN) is the histologic lesion most strongly associated with prostate cancer and has been postulated to be a pre-malignant lesion. However, much of the natural history of PIN remains unknown. A more fundamental understanding of the relationship between PIN and invasive tumors at the molecular level is critically needed and represents an important future challenge for investigators. The importance of their recognition are based on the correlation between their presence and the existence of prostatic adenocarcinomas. It seemed significant to us to point out the criteria of the diagnosis and the action to be taken in front of the discovery of such lesions on biopsies in prostate sufferers.
Low cost, high-quality consumer-type digital cameras are now available on the market to be used for taking macrophotographs and microphotographs by simply fixing the camera over the eyepiece of a conventional light microscope using an adaptator. The quality of the images obtained is as good as obtained with more expensive materials using Tri CCD cameras. Using the JPEG format for compression, the image file size is approximately 180 Ko. We present a low cost approach we have tested for one year in our pathology department.
PURPOSE: Proliferation rate is an important determinant of bladder tumor progression. However, this factor has not yet been correlated to bacillus Calmette-Guérin (BCG) therapy response in a selected high-risk population of patients with stage T1 grade G3 bladder cancer. To assess the predictive value of the proliferation rate, an immunoreactivity test with monoclonal antibodies MIB-1 was carried out. The aim of this study was to evaluate the prognostic value of an MIB-1 labeling index by selecting a group of responsive patients prior to intravesical therapy. MATERIALS AND METHODS: After complete transurethral resection, 35 patients with T1G3 bladder carcinoma received 6 weekly installations of BCG (intravesical Pasteur strain: 75 mg in 50 ml course of BCG therapy). After treatment a cystoscopy and randomized biopsies of the bladder mucosa were carried out and all recurrences were systematically resected. All tissue samples were fixed in Bouin's solution, embedded in paraffin and stained with hematoxylin-eosin-safran. Pathologists had sufficient material to perform immunomarking in 25 patients using peroxidase-antiperoxidase (PAP) technique, with antiprotein monoclonal antibody MIB-1 (Immunotech, Marseilles, France) to study MIB-1 expression before BCG therapy. Consensus was obtained from three independent pathologists for all sections. The results were expressed in a percentage of marked nuclei. Ten percent increment thresholds were established from 10 to 60%. Contingency tables were established, chi2 (p1) and Fisher exact test (p2) were performed for each threshold of 10%. RESULTS: Median follow-up was 57.3 months (range 25-144). Of the 25 patients, 8 (32%) did not respond to BCG therapy, 17 (68%) responded positively. With a 20% threshold, there was a statistical difference (p1 = 0.03, p2 = 0.04) between responder (R) and nonresponder (NR) patients. All the 7 patients with less than 20% of nuclear activity positively responded to BCG. At this threshold level, sensitivity was high but specificity low (positive predictive value = 0.44). If we consider other reactivity thresholds there were no statistical differences between R and NR patients (10%) threshold p1 = 0.13, p2 = 0.19; 30% p1 and p2 = 0.20; 40% p1 = 0.82, p2 = 0.61; 50% p1 = 0.57, p2 = 0.55). CONCLUSION: Our study indicates that the proliferation rate, assessed by MIB-1 immunoreactivity in Bouin's solution-fixed primary tissue, could be a useful predictive marker of outcome in T1G3 bladder carcinoma. With a 20% reactivity cut-off, a negative MIB-1 immunomarking appears to predict a positive response to BCG instillations. However, on the other hand, MIB-1 is of limited clinical use because the low specificity of this test cannot predict failure and then select candidates for cystectomies.
OBJECTIVES: Cystectomy is the reference treatment for invasive bladder cancer and superficial tumours with a high risk of recurrence. However, the long-term results of this treatment remain controversial. Progress in anaesthesia-intensive care and surgical techniques appear to have improved the prognosis of this disease over the last two decades. The availability of numerous adjuvant therapies (radiotherapy and chemotherapy) and the development of alternative conservative management therefore require a re-evaluation of the long-term results of cystectomy for bladder cancer performed over the last 20 years. MATERIAL AND METHODS: The case files of 504 consecutive patients undergoing cystectomy for bladder cancer in our department from 1981 to 1997 were reviewed. The operative and postoperative morbidity and actuarial survival by stage were studied. Histological prognostic factors and the influence of adjuvant therapies were also studied. RESULTS: According to the TNM 97 classification, 55% of tumours (on the cystectomy specimen) were intravesical (< T3), and 70% of patients had negative lymph nodes (N0). The perioperative mortality was 1.56%. The overall survival at 2 years, 5 years and 10 years for the total patient population was 83.1%, 52.3% and 46.6%, respectively. The 5-year survival of tumours confined to the bladder (< T3) was 79.4% versus 27.5% when the tumour extended beyond the bladder (> T3). The lymph node status considerably influenced survival. N0, N1 and N2-3 patients had 5-year survival rates of 64%, 48% and 14%, respectively. Neoadjuvant chemotherapy or radiotherapy did not appear to improve survival. CONCLUSIONS: Survival after cystectomy for bladder cancer essentially depends on pathological stage and lymph node status. Patients with a localized tumour have a 5-year survival greater than 80%. Prospective studies are required to determine the real benefit of adjuvant chemotherapy, as its value has not yet been formally demonstrated.
BACKGROUND: Actinomycosis is uncommonly observed in a pelvic localization. The presence of an intrauterine device is an important risk factor. CASE REPORT: A 50-year-old woman presented a tumoral mass in the pelvis with secondary liver involvement. Pathology examination corrected the initial diagnosis of advanced stage pelvic neoplasia to actinomycosis. Rapid improvement was achieved with penicillin. DISCUSSION: Differential diagnosis is difficult but essential in case of pelvic actinomycosis as misdiagnosis can have disastrous surgical consequences. Medical treatment is indicated. Actinomycosis should be entertained as a possible diagnosis in all cases associating a pelvic tumor and inflammation in women wearing an intrauterine device.
UNLABELLED: AN UNUSUAL INFECTION: Actinomycosis, uncommon in a pelvic localization, is a severe condition not well known to gynecologists. It is caused by Actinomyces israeli and is closely associated with long-term use of an intrauterine device. In the pelvic localization, the disease generally presents as a pseudoneoplastic formation. DIFFICULT DIAGNOSIS: Diagnosis is generally not established clinically. Pathology provides positive diagnosis. The germ cannot be isolated easily as it does not survive standard bacteriology sampling. Monoclonal antibodies may be helpful. MEDICAL TREATMENT: Intravenous penicillin G followed by at least 6 months oral penicillin is generally successful in eradicating the infection. Indications for surgery should be limited to diagnostic procedures (pathology specimen), drainage in case of abscess formation, and removal of an obstacle compressing the digestive or urinary tract.
OBJECTIVE: To evaluate the diagnostic accuracy of videomicroscopy image selection for expert consultation in cervical cytology. STUDY DESIGN: One hundred diagnostically difficult cervical cytologic smears were selected and rescreened by a general pathologist who chose, from each slide, four or five fields featuring abnormal cells. Video images were digitized and stored on a 512 x 512-pixel matrix using an image acquisition and transmission system. Five experts each reviewed 20 of the 100 cases, and a sixth reviewed all 100 cases. Diagnoses based on selected digitized images were compared to those based on conventional examination of whole slides. RESULTS: Intraobserver agreement was fair to excellent for all six experts (kappa value: 0.47-0.81); it was complete or acceptable in 68.4-85% of cases. Compared to the reference diagnosis, interobserver agreement was not significantly different whether cases were examined by screening the entire slide or by videomicroscopy of selected fields. The marked discordance in four cases concerned very small cells the significance of which was misinterpreted on videomicroscopy because of poor image quality due to lack of focus setting. CONCLUSION: This exploratory study showed that selection of videomicroscopy images seems as reliable as conventional examination of slides for expert consultation on diagnostically difficult cervical cytologic smear cases.
OBJECTIVES: The objective of this study was to compare the proliferation index (immunolabelling by monoclonal antibody Ki67 - MIB-1) of renal cell carcinomas as a function of the presence or absence of renal vein thrombus. Analysis of the numbers of Ki67-positive nuclei can be used to assess the degree of aggressiveness of the cell populations of these various carcinomas (tumour without thrombus, tumour with thrombus and neoplastic thrombus). METHODS: Twenty three renal cell carcinomas with renal vein thrombus were matched for Furhman grade (1st degree), tumour volume (2nd degree) and the patient's age (3rd degree) with 23 renal cell carcinomas not presenting any vascular embolus on histology. Monoclonal antibody MIB-1 immunolabelling was performed on 69 paraffin-embedded specimens: 23 tumours with thrombosis, the 23 corresponding neoplastic thrombi and 23 tumours without vascular embolus. RESULTS: A correlation between Furhman grade and the percentage of immunolabelled nuclei was observed (mean: 2.67% for low-grade tumours and 14.34% for high-grade tumours). No labelling difference was observed between the two populations of primary tumours (with thrombus/without embolus). Primary tumours presented significantly weaker Ki67 labelling than their corresponding neoplastic thrombus (mean of 2.47% versus 10.3%, p < 0.01). CONCLUSION: This study shows that there is no difference of the proliferation index between tumours with neoplastic venous thrombus and those with no histological vascular embolus. However, a difference of proliferation index was observed between the primary tumour and its corresponding thrombus, which presented a statistically higher immunolabelling. This finding suggests that the thrombus possesses more dividing cells than the primary tumour, i.e. has a shorter doubling time.