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Biomedical subjects

P Vielh

Publications and source records attributed to P Vielh.

At least 19 recordsLinked to original sources

Fine needle aspiration cytology: a survey of current European practice.

Fine needle aspiration cytology (FNAC) is practised widely throughout Europe. The majority of countries have dedicated cytopathologists as well as histopathologists practicing cytology. Despite this, FNAC is performed mostly by clinicians and radiologists except in the larger centres with dedicated staff with a special interest in cytopathology. The advent of One-Stop diagnostic services and image-guided procedures are prompting further development of FNAC clinics where cytopathologists take their own samples, issue reports in the same clinical session and take extra material for ancillary tests to complete the diagnosis. The volume of FNAC work varies accordingly; in dedicated centres FNAC represents up to 80% of the workload whilst, in the majority of countries, it represents one quarter or less. Hence, the rate of inadequate FNAC varies widely, depending on the local sampling policies and the organ, but does not exceed 25% in any of the countries. The most sampled organs are breast and thyroid, followed by lymph nodes. Most countries have dedicated training in cytopathology for pathology trainees, the duration varying between 6 months and 2 years of the total training time. This discussion, focusing on European practices, highlights the heterogeneity of FNAC activity but also its success in many centres where it is practiced to a high standard, particularly in breast, thyroid and lymph node pathology. The relatively high rate of inadequate material in some centres reflects local policies and calls for greater uniformity of FNAC practice, particularly specimen sampling. To achieve this, the future direction should concentrate on specialist training, to include performing as well as interpreting FNAC, as part of the curriculum. Current emphasis on web-based training may not provide first hand experience of the FNAC procedure and should be supplemented by attending FNAC clinics and developing the technique to its full potential.

Biopsy, Fine-Needle↗

Molecular prognostic factors in resectable non-small cell lung cancer.

Lung cancer retains the leading position in cancer-related deaths in the western countries. Non-small cell lung cancer (NSCLC) comprises more than 80% of lung cancers, and complete surgical resection of primary tumors in early-stage disease is the only potentially curative treatment. One area of intense research on early-stage NSCLC is the identification of molecular markers to complement TNM staging to fully assess the prognosis of patients and to define innovative strategies. Numerous prognostic factors have been identified in patients with early-stage NSCLC that might enable classification of such patients into different subsets corresponding to different risks of recurrence following complete resection. Most of the markers are proteins that can be detected by immunohistochemistry assays based on the antigen-antibody reaction. The present review aims at providing a panorama on classical as well as new prognostic markers. Of special interest are some molecular factors, already or currently tested from a prognostic point of view, that might also become good candidates for predicting treatment efficacy.

Biomarkers, Tumor↗

Cytopathology in France.

In France, organization of the cytopathology seems to be quite different from that specifically regulated in the USA and in some other European countries. The aim of this article is to underline these specificities and to describe the solutions we advocate concerning new technologies, teaching, quality assurance, national guidelines em leader, to make our current practice compatible with the international recommendations. Moreover, we highlight the peculiar status of French cytotechnologists' and comment on the recent dramatic decrease of the medical demography in France, the consequence of which may promote a controlled transfer of competence.

Facility Regulation and Control↗

[Standards, options and recommendations for the composition of anatomic and surgical pathology reports or cytopathology reports in oncology].

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 practice guidelines according to the definitions of the Standards, Options and Recommendations project for the content of the anatomic and surgical pathology or cytopathology reports in field of oncology. METHODS: Data were identified either by searching on Medline or via members of the expert groups personal references lists. When the guidelines were defined, the document was submitted to 49 independent reviewers, and to the medical committees of the 20 French Cancer Centres. RESULTS: The main recommendations for the composition of the anatomic and surgical pathology or cytopathology reports in oncology are 1/ The reports must contain the identification of the pathologist, of the patient and of the specimen, a gross description for the surgical specimen, eventually a microscopic description, the diagnosis, all the elements essential for establishing the prognosis and for the clinical care, and a conclusion. 2/ The reports could contain some comments. 3/ The reports must be brief, precise, clear, homogeneous and ideally standardised, in order to be comprehensible for all the clinicians and the pathologists.

Cytodiagnosis↗

Comparative image and flow cytometric TUNEL analysis of fine needle samples of breast carcinoma.

The assessment of apoptosis in solid tumors is of interest because of its biological role in tumor evolution and response to therapy. A commonly used method for apoptosis measurement is the TUNEL 3' end-labeling technique, which has shown wide variations in results when applied to solid tumors. Thirty-one fine needle breast carcinoma samples were analyzed by fluorescent TUNEL assay and DNA content using image analysis and flow cytometry. TUNEL positivity, seen both in cells with apoptotic morphology and in a subset of morphologically normal cells, was categorized into five staining patterns and quantitated. Values for patterns of TUNEL-positive cells were compared with TUNEL positivity measured by flow cytometry. Flow cytometric quantitation showed a mean of 24.3% positive cells, which correlated (P < 0.02) with total positive cells (all patterns) measured by image (22.4%). Image analysis quantitation of morphologically apoptotic cells (4.2%) did not correlate with flow cytometric TUNEL positivity and the majority of TUNEL-stained cells were morphologically normal (17%). Image analysis allows discrimination of TUNEL-positive morphologically apoptotic and nonapoptotic cells, which are included in the total number of TUNEL-positive events measured by flow cytometry.

Apoptosis↗

Critical clinicopathologic analysis of 23 cases of fine-needle breast sampling initially recorded as false-positive. The 44-year experience of the Institut Curie.

BACKGROUND: Because false-positive cytologic diagnoses in breast tumors are rare, few cases have been reported, although their consequences may be highly detrimental to the patient. The authors report the Institut Curie's experience, by using a multidisciplinary approach. METHODS: Of 9334 benign breast tumors examined preoperatively for cytologic diagnosis by fine-needle sampling (FNS), the 23 (0.25%) FNS cases considered to be false-positive were retrospectively reviewed and analyzed. RESULTS: Tumors were situated close to the nipple in 7 cases and away from the nipple in 16 cases. Tumor stage was T0 for 1 case, T1 for 18 cases, and T2 for 4 cases. Radiologically, six tumors were classified as malignant, seven as indeterminate or suspicious, and nine as benign. Three of six tumors studied by flow cytometry were DNA aneuploid. Based on a multidisciplinary clinicopathologic review, 20 FNS cases were finally classified as false-positive, and the remaining 3 tumors with malignant FNS and subsequent benign histology were classified as true-positive, because local and/or metastatic progression was observed in the short term. CONCLUSIONS: The authors' review suggests two categories of false-positive cases: the first in which cytologic benign patterns are overdiagnosed, and the second in which atypical morphologic criteria were present. Nevertheless, as shown by the malignant course in three cases, patients with malignant preoperative FNS and corresponding benign histology always require close clinical follow-up. Finally, surgical overtreatment rate could be decreased if all radiologically benign tumors with positive/suspicious FNS were subject to intraoperative frozen section examination.

Adult↗

Fine-needle sampling of primary neuroendocrine carcinomas of salivary glands: cytohistological correlations and clinical analysis.

Fine-needle samplings of nine examples of primary neuroendocrine carcinoma of salivary glands were evaluated for their cytologic characteristics and were correlated with the corresponding histological sections. Consistent cytological findings were dispersed or loose clusters of poorly differentiated small- to intermediate-sized cells and occasional smudged nuclei. Mild to moderate nuclear pleomorphism, scant or absent cytoplasm, and nuclear molding were also observed. Rosette-like patterns and multinucleated cells were occasionally seen. Immunostaining of one recent case showed positivity for chromogranin and keratin. The differential diagnosis of primary and metastatic tumors with neuroendocrine features of the salivary glands is discussed.

Adult↗

Cost-effectiveness of monolayers and human papillomavirus testing compared to that of conventional Papanicolaou smears for cervical cancer screening: protocol of the study of the French Society of Clinical Cytology.

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.

Cost-Benefit Analysis↗

Mutation status of genes encoding RhoA, Rac1, and Cdc42 GTPases in a panel of invasive human colorectal and breast tumors.

PURPOSE: The constitutive activation of Ras proteins by point mutation is the most frequently observed oncogene activation in human malignancies. The goal of this study was to investigate whether the constitutive activation of RhoA, Rac1, and Cdc42 proteins by point mutations, which can lead to experimental transformation of cultured cells, actually occurred in a panel of invasive colorectal and breast tumors. METHODS: We performed denaturing gradient gel electrophoresis and sequencing of transcripts amplified by reverse transcription and PCR for RhoA; we used direct sequencing of PCR-amplified genomic DNA to search for mutations in coding exons of the Rac1 and Cdc42 genes. RESULTS: Although mutations of the Kras4B and the p53 genes were detected using these methods, no mutation was found in the coding sequences of RhoA, Rac1, and Cdc42 genes, in primary as well as in associated metastasis. CONCLUSIONS: Point mutations in the coding sequences of genes encoding RhoA, Rac1, and Cdc42 GTPases do not occur at high frequency in invasive breast and colorectal tumors.

Adenocarcinoma↗

[Standards, options and recommendations: practice guidelines for difficult diagnosis in surgical pathology or cytopathology in cancer patients].

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).

Humans↗

Fine-needle aspiration of metastatic nonlymphomatous tumors to the major salivary glands: a clinicopathologic study of 40 cases cytologically diagnosed and histologically correlated.

BACKGROUND: Metastatic tumors to the salivary glands are common, but documentation in the cytologic literature has been limited. The current study presents the authors' experience with fine-needle aspiration (FNA) in metastatic nonlymphomatous tumors to the salivary glands. METHODS: From a retrospective review of 1675 salivary gland lesions (1535 patients), the authors collected 40 salivary gland lesions (39 patients who had histories of extrasalivary cancer) that were diagnosed cytologically as metastases to the salivary glands and were correlated histologically. RESULTS: FNAs of 34 parotid gland and 6 submandibular gland tumors were performed. The cytologic diagnoses of metastases of squamous cell carcinoma (15 cases), melanoma (12 cases), carcinoma (5 cases), rhabdomyosarcoma (3 cases), and retinoblastoma (2 cases) were confirmed (95%) histologically. Two (5%) FNAs were false-negative. CONCLUSIONS: In patients who had a history of extrasalivary cancer, cytology examination was very helpful and sufficient for adequate patient management.

Adolescent↗

Opposite regulation of tenascin-C and tenascin-X in MeLiM swine heritable cutaneous malignant melanoma.

Interactions between tumour cells and surrounding extracellular matrix (ECM) influence the growth of tumour cells and their ability to metastasise. It is thus interesting to compare ECM composition in tumours and healthy tissues. Using the recently described MeLiM miniature pig model of heritable cutaneous malignant melanoma, we studied the expression of two ECM glycoproteins, the tenascin-C (TN-C) and tenascin-X (TN-X), in normal skin and melanoma. Using semiquantitative RT-PCR, we observed a 3.6-fold mean increase of TN-C RNAs in melanoma compared to normal skin. Both stromal and tumour cells synthesise TN-C. On the contrary, TN-X RNAs decreased 30-fold on average in melanoma. This opposite regulation of TN-C and TN-X RNAs was confirmed at the protein level by indirect immunofluorescence. Whereas pig normal skin displayed a discrete TN-C signal at the dermo-epidermal junction, around blood vessels and hair bulbs, the swine tumour showed enhanced expression of TN-C in these areas and around stromal and tumour cells. In contrast, normal skin showed a strong TN-X staining at the dermo-epidermal junction and in the dermis, whereas this signal almost completely disappeared in the tumour. The results presented here describe a dramatic alteration of the ECM composition in swine malignant melanoma which might have a large influence on tumourigenesis or invasion and metastasis of melanoma cells.

Animals↗

Differential expression of Bax and Bcl-2 in the assessment of cellular dynamics in fine-needle samples of primary breast carcinomas.

The rates of cell proliferation and programmed cell death (apoptosis) reflect tumor cell dynamics and are considered to directly influence biological progression and tumor response to therapy. Bax and Bcl-2 are members of a gene family that influence apoptosis and have been used as surrogate markers in the evaluation of this process. Sixty-three fine-needle tumor samples from an equal number of patients with breast carcinomas were analyzed for Bax, Bcl-2, and DNA content by flow cytometry. The results were correlated with classical clinicopathological parameters. Bax values varied widely among tumors and showed no significant correlation with any of the clinicopathological parameters analyzed. Bcl-2 levels ranged from 4% to 91%, correlated positively with estrogen (P = 0.0004) and progesterone (P = 0.0045) receptor positivity, and were more associated with low S-phase tumor values. In contrast, high S-phase values correlated with estrogen receptor negativity, high grade, and DNA aneuploidy. The study results indicate that Bcl-2 and S-phase analysis of fine-needle samples of breast carcinomas provide a convenient tool for the assessment of these tumors.

Adult↗

Alterations of the DNA repair gene OGG1 in human clear cell carcinomas of the kidney.

The OGG1 gene, which codes for a DNA repair protein with antimutator activity, is located on chromosome 3p25, a frequent site of allelic deletions in many types of human tumors, including renal clear cell cancers. We present the analysis of 99 renal tumors for alterations in the OGG1 gene to determine its association with tumorigenesis. Loss of heterozygosity in the 3p25 region was found for 85% of the informative cases. We detected somatic missense mutations of the OGG1 gene in 4 of the 99 tumor samples. Biochemical analysis of the mutant proteins revealed that a substitution at codon 46 impairs the enzymatic activity. We also describe the occurrence of several polymorphisms as well as aberrantly spliced OGG1 transcripts.

Adenocarcinoma, Clear Cell↗