[Vacuum-assisted stereotactic biopsy: experience of the regional cancer center of Caen]. / Macrobiopsies assistées par le vide: expérience du CRLCC François Baclesse de Caen.

PURPOSE: To report our experience with macrobiopsy under stereotaxy. MATERIALS AND METHODS: Retrospective study of 248 procedures in 236 patients for microcalcifications in 95% of cases. The macrobiopsies were performed under Mammotome for lesions graded ACR 3, ACR 4 and ACR 5 in 8.4%, 81.6% and 14.8% of cases respectively. RESULTS: From a technical point of view, 91% of procedures had no technical problem. The image guided excision was complete in 68% of cases with lesions less than 1 cm in size and in 6% of cases for lesions larger than 1 cm. The rate of a misdiagnosis of ductal carcinoma in situ for patients with invasive carcinoma was 27% whereas the rate of a misdiagnosis of atypical ductal hyperplasia in patients with ductal carcinoma in situ was 25% knowing that patients with atypical ductal hyperplasia for which all microcalcifications had been fully removed by macrobiopsy and without risk factors did not undergo surgery. CONCLUSION: Even if macrobiopsy of microcalcifications is a reliable method, its main limitation remains the risk of misdiagnosis of borderline lesions.

Immunohistochemical study of cell cycle regulatory proteins in intraductal breast carcinomas--a preliminary study.

The aim of this study was to assess the levels of cell cycle regulatory proteins p21waf1 (p21), p53, Cyclin A, Cyclin D1 and Ki-67 to see whether they correlated with recurrence-free survival (RFS). From 1982 to 1996, 50 patients aged less than 51 years underwent lumpectomy followed by radiotherapy for a pure ductal carcinoma in situ (DCIS). For each case, the following immunohistochemical stains were carried out: Ki-67, Cyclin A, Cyclin D1, p53 and p21waf1 (p21). The percentage of positive nuclei was assessed. Multiple combinations of these factors were performed; in particular, we called the sum of Ki-67 and Cyclin A a global proliferation factor (GPF). Correlations with classical clinicopathological data were assessed. After a multivariate analysis, only GPF, Van Nuys Prognostic Index (VNPI) grade and mitotic index were independent predictive factors of recurrence in the whole population. In the population with close surgical margins, when the GPF level was less than the 25th percentile or more than the 75th percentile recurrence was low. In this preliminary study, GPF seems to be of interest to help in the decision process in the post-surgical management of the patient.

Cancer of the esophagus and associated lesions: detailed pathologic study of 100 esophagectomy specimens.

One hundred surgical specimens from patients with esophageal cancers were studied in detail. The characteristics of the cancers were similar to those described in the literature. Subserial sectioning of the specimens permitted determination of the type, number, and extent of noncancerous mucosal lesions and their exact location in relation to the carcinomas. Ninety-five per cent of the resected esophagi contained at least one focus of intraepithelial neoplasia, for the most part adjacent to the invasive carcinoma; in 14 per cent of the cases, intraepithelial carcinomas were detected at some distance from the invasive carcinomas. The invasive carcinomas involved an average of 20 per cent of the mucosal surface and the intraepithelial neoplasias, 5 per cent. The noncancerous mucosal lesions were analyzed, and their extent was evaluated. Esophagitis, parakeratosis, atrophy, dyskeratosis of the epithelium, and hyperplasia and metaplasia of the mucosal gland ducts were encountered. The exact significance of these lesions in esophageal carcinogenesis is not known. The mucosal abnormalities associated with preoperative irradiation are defined. The results of iodine and toluidine blue testing are presented.

Prevalence survey of precancerous lesions of the oesophagus in a high-risk population for oesophageal cancer in France.

The prevalence of precancerous lesions of the oesophagus and their association with alcohol drinking, tobacco smoking and some dietary factors were examined in an endoscopic survey carried out in Lower Normandy, France, a high-risk area for oesophageal cancer. The study included 134 male volunteers of 35-64 years of age. In 124 of the volunteers oesophageal biopsies were evaluable. At histology, the prevalence of chronic oesophagitis, epithelial atrophy and dysplasia was 63%, 1.6% and 4.8%, respectively. The prevalence of these precancerous lesions was significantly associated with cigarette smoking and frequent consumption of butter.

[Cancer of the esophagus induced in the Wistar rat by ethyl-N-butyl-nitrosamine]. / Cancer de l'oesophage induit chez le rat Wistar par l'éthyl-N-butyl-nitrosamine.

OEsophageal papillomas and carcinomas have been induced in Wistar rats using Ethyl-N-Butyl-Nitrosamine. None of those lesions were observed in a previous experiment on the same rats strains, with ethanol and apple brandy. Experimentally induced tumours in the rat are different from oesophageal cancers and associated mucous lesions in man. Both upper digestive mucosae are only similar in regards to their response to carcinogens.

[Absence of effect of ethanol and apple brandy on the upper digestive tract and esophagus of the Wistar rat. Part of a research project to assess etiological factors of cancer of the esophagus in the west of France (author's transl)]. / Absence d'effet de l'éthanol et des eaux de vie de cidre sur le tractus digestif supérieur et l'oesophage du rat Wistar. Suite des recherches concernant les facteurs étiologiques du cancer de l'oesophage dans l'ouest de la France.

Epidemiological studies have shown the role of alcohol in esophageal cancer in the West of France. Experiments were undertaken on Wistar rats to study the effect of locally consumed alcoholic beverages on the esophagus. Neither histological modifications, precancerous lesions nor cancer were observed in the animals. There was no significant excess of benign or malignant tumours in treated animals when compared with controls.

[Evaluation of predictive factors, particularly the Van Nuys index, of local recurrence in ductal carcinoma in situ of the breast: study of 166 cases with conservative treatment and review of the literature]. / In process citation.

Ductal carcinoma in situ (DCIS), a non metastazing lesion of the breast is more frequently observed due to the improvement of mammography and widespread use of screening. The most important risk of this disease is local recurrence. In about half of cases, it occurs as an infiltrating carcinoma. In a series of 166 DCIS treated by lumpectomy plus radiotherapy, we have studied clinico-pathological factors for the prognosis of local recurrences and particularly the Van Nuys Index criteria (nuclear grade, necrosis, size, margin width). After median follow up of 75 months, 21 recurrences were observed with 10 corresponding to an infiltrating carcinoma and one of them died. The size of DCIS evaluated on pathological documents (histological slides and shames), the Van Nuys Prognostic Index (VNPI) and the mitotic index were the main prognostic factors of local recurrence. We discuss these results and confront them to a review of the literature focalised on the delicate problem of the decision of conservative treatment. A multidisciplinary approach (Breast : Surgeon, Radiologist, Pathologist and Radiotherapist), a standardisation of pathological criteria (size, margin width) and the continuation of randomised trials are necessary to fine the best attitude of conservative therapy.

[Flow cytometry in ORL cancers]. / Cytométrie en flux dans les cancers ORL.

The possibility to perform flow cytometry was examined in a series of 167 patients with primary untreated head and neck carcinoma referred to our Institution from February 1989 to January 1992. In all cases, flow cytometry was carried out on frozen tumour samples. The Cox model was used including age, tumour size, nodal status on clinical assessment, topography, treatment, malignancy grade, S phase fraction and ploidy as independent variables and overall survival as dependent variable. In this study, ploidy could be assessed in only 73% of cases and S phase fraction and G2M in 65% of the population studied. No correlation could be evidenced between ploidy or SPF with other clinical, pathologic characteristics or clinical outcome. We conclude that flow cytometry should remain a research tool until the method has proved to be relevant in clinical routine, and until the yield of the technique can be improved.

[A method for the histologic study of the entire esophagus]. / Méthode pour l'étude histologique de l'oesophage in toto.

The authors describe a method for sampling and embedding of oesophagectomy specimens which permits the study of the entire oesophagus with a minimum number of sections. Good localization of the lesions is achieved, and the simplicity of this method (accordion fold) makes it suitable for routine use.

Lymphocyte-rich classical Hodgkin lymphoma (LRCHL): clinico-pathological characteristics and outcome of a rare entity.

BACKGROUND: To investigate the proportion, clinical characteristics and outcome of lymphocyte-rich classical Hodgkin lymphoma (LRCHL) in relation to nodular lymphocyte predominant HL (NLPHL) and classical HL (cHL). PATIENTS AND METHODS: A series of 2743 HL patients of all stages enrolled into three EORTC trials (H7, H8, H34) conducted between 1988 and 2000 and forming an unbiased series of HL patients was studied. RESULTS: Detailed histological classification after panel review was available in 96% of the cases to allow selection of all cases with features potentially compatible with the WHO-definition of LRCHL for this study. Cases with dominance of lymphocytic infiltrate and relative paucity of eosinophils and fibrosis could be selected for re-classification. Twenty-one (0.8%) LRCHL cases were identified of which three were originally classified as NLPHL, seven as nodular sclerosis HL (NSHL) and 11 as mixed cellularity (MCHL), indicating that LRCHL is a rare disease. CONCLUSIONS: Clinical evaluation of the unselected series of patients (n = 2743) showed that LRCHL and NLPHL cases more often presented with favorable features. Clinical outcome adjusted on ab initio patient prognosis did not differ between the three histological entities. These results strongly suggest that LRCHL corresponds to an early stage in the spectrum of cHL rather than a biologically different disease entity.

Variation of flow cytometric DNA measurement in 1,485 primary breast carcinomas according to guidelines for DNA histogram interpretation.

From 1990-1996, 1,485 previously untreated invasive breast carcinomas were sampled by a pathologist for flow cytometric DNA analysis. The aim of the present work was to study the variations of flow cytometric DNA ploidy and S-phase evaluation according to the conditions of DNA histogram interpretation. Results obtained with the American Consensus guidelines of 1993 and the François Baclesse Department of Pathology's own guidelines are presented. According to the percentage of events taken into account to identify a DNA aneuploid peak, the proportion of DNA diploid cases can change from 35-39%. For S-phase evaluation, although the two guidelines were quite different, the results of S-phase cutoff were identical. Whichever guidelines were used, there was a strong relationship between DNA ploidy and/or S-phase and classical clinicopathological factors (T, N, histological type, grade, receptor status, or lymphatic invasion), with the exception of age, whose correlation was discrepant with S phase according to the set of guidelines. Whichever guidelines were used, ploidy and S phase correlated strongly with survival (overall, metastasis-free, or recurrence-free). Hence we recommend the use of the American consensus guidelines, despite minor imperfections, because they are now well-known, allow a high yield in the ratio of assessable S phases, and permit standardization in the technical processing and reporting of S phases, thanks to the use of terciles.

Flow cytometry in primary breast carcinomas. Prognostic impact of proliferative activity.

From 1990 to 1996, 607 previously untreated, node-negative, invasive breast carcinomas were sampled by a pathologist for flow-cytometric DNA analysis. The aim of the present work was to study the correlations between flow cytometric results obtained thanks to the American Consensus (AC) guidelines of 1993 and the established clinico-pathological prognostic factors (T, grade, receptors), and despite a short global follow-up (mean of 4 years), to correlate flow cytometry with the outcome of the patients. In this study S-phase fraction (SPF) correlated strongly with tumor size, histological grade, lack of steroid receptors, histological type and was together with the mitotic activity a paramount prognostic factor even after multivariate analysis. This study compared also the technical criteria proposed by the AC with our own more stringent ones and concluded that the criteria of the AC are relevant and allow, thanks to the use of tertiles in the reporting of SPF values, a comparison of values obtained by different teams. Our review of the literature, focused on series using fresh material, enabled us to show that there is a rather wide agreement concerning the relationship between SPF and prognosis most often after multivariate analysis. This despite the lack of standardization in the design of the studies (implementation of the technical steps or reporting of results). When estimated from fresh or frozen material following AC's guidelines. SPF along with mitotic activity should become a prognostic factor used in the daily practice by oncologists in the management of breast carcinomas.

Expression of p53 in oesophageal squamous epithelium from surgical specimens resected for squamous cell carcinoma of the oesophagus, with special reference to uninvolved mucosa.

Accumulation of p53 protein has been considered an intermediate biomarker in multistage oesophageal carcinogenesis. The aim of the present study was to investigate p53 expression by immunohistochemistry in 13 thoroughly sampled oesophagectomy specimens from a geographical area with a high oesophageal cancer incidence (Basse Normandie, France). Expression of p53 was looked for in tissue samples of cancer, intraepithelial neoplasia, and uninvolved mucosa. The streptavidin biotin peroxidase complex method was used for p53 immunostaining. p53 expression was found in invasive squamous cell carcinoma in 8 out of 11 cases and in intraepithelial neoplasia in 10 out of 11 cases. In all 13 cases, in uninvolved oesophageal mucosa, expression of p53 was focally present in areas of chronic oesophagitis. Chronic oesophagitis has been regarded by epidemiologists as a precursor lesion for squamous cell carcinoma of the oesophagus. Since oesophageal carcinogenesis is a multistage process, the study of precursor lesions could provide information on the timing of p53 gene abnormalities during oesophageal carcinogenesis. These preliminary data require to be confirmed by molecular analysis of the p53 gene.

A study of the mechanism of the toluidine blue dye test.

Toluidine blue is commonly used by endoscopists as a screening test for squamous cell carcinoma. Little information is available on the mechanism of vital staining as it is not preserved by conventional fixation. By using a simple method to stabilize toluidine blue, the authors were able to study the action of the dye under the light and electron microscope. The findings are reported.

Autopsy findings in 111 cases of esophageal cancer.

Autopsy findings for 111 cases of esophageal cancer are presented. Residual tumor in the esophagus was present in 75% of the cases. Lymph node metastases were found in 74.5% and visceral metastases in 50% of the cases. Autopsy revealed a second primary tumor in 21% of the cases; 12% of these were oropharyngeal-laryngeal (OPL) carcinomas, and 9% were visceral carcinomas or malignant lymphomas. Nonmalignant disease found in association with esophageal cancer was dominated by conditions related to chronic alcoholism. Autopsy findings thus revealed that the patients bore not only esophageal lesions, but also patterns of other associated malignant and nonmalignant diseases which would seem to correspond to a complex pathologic state occurring in association with chronic alcoholism. The time between onset of symptoms and autopsy averaged 10.6 months and between first consultation and autopsy, 6.3 months. The brevity of survival from onset of symptoms would seem to confirm that by the time esophageal cancer manifests clinically, it is already at a stage of development beyond the scope of treatment.

Pararosaniline or acriflavine-Schiff staining of epoxy embedded tissue after periodic acid oxidation in ethanol: a method suitable for morphometric and fluorometric analysis of glycogen.

A method for preparing tissue sections for automatic image analysis of glycogen is described. Large semithin sections of epoxy embedded tissue fixed in glutaraldehyde-osmium were stained with Schiff reagent and acriflavine (fluorescent staining) after resin removal and periodic acid oxidation in ethanol. We found it essential to avoid tissue rehydration before final staining. The Schiff stain permits an assessment of the cellular volume of glycogen, and the acriflavine allows a fluorometric evaluation of glycogen density.

Analysis of the results of the micronucleus test in patients presenting upper digestive tract cancers and in non-cancerous subjects.

A micronucleus test was performed on 75 subjects of whom 38 presented with cancer of the upper digestive tract and 37 were free of disease; the absence of cancerous or pre-cancerous lesions in this latter group was confirmed by endoscopy and vital staining. The daily levels of alcohol and tobacco consumption of the 75 subjects were determined by precise questioning: 78% of the non-cancerous subjects smoked less than 10 g of tobacco per day whereas 79% of the cancer patients smoked 10 g or more daily. The alcohol intake of 78% of the non-cancerous subjects and 63% of the cancer patients was less than 101 ml per day. Only 10% of the cancer patients had combined daily intake levels corresponding to the threshold of sensitivity of the micronucleus test as defined by previous studies. The mean frequency of micronucleated buccal cells was 0.26% in the cancer patients and 0.13% in the non-cancerous subjects. All non-cancerous patients presented a negative test. Only 5% of the cancer patients presented a micronucleated cell frequency above 1% and could thus be considered as positive. It thus appears that the micronucleus test was not significantly positive in our population of 38 cancer patients.

Prognostic factors in soft tissue sarcomas. A multivariate analysis of 109 cases.

Prognostic factors were evaluated in 109 soft tissue sarcomas of the extremities, walls of the trunk, head, and neck. All lesions were graded according to the systems proposed by the National Cancer Institute (NCI) and the French Federation of Cancer Centers (FNCLCC), and a correlation was found between tumor grade and prognosis. Univariate analysis selected the following variables as unfavorable prognostic factors: invasive tumor margins, extra-compartmental status, deep tumors, tumor diameters over 5 cm, inadequate excision, presence of necrosis, high mitotic count, histologically undifferentiated tumors, and blood vessel invasion. These variables were found to be interdependent. Multivariate analysis selected quality of surgery as the most important variable for predicting local recurrences. The factors selected with regard to overall and metastasis-free survival were tumor size, tumor margins, necrosis, and adequacy of excision. These results permitted classification of patients into four prognostic groups: two with good and two with bad prognosis. Five-year survival for the four groups was 100%, 83%, 53%, and 0%; 5-year metastatic rates were 0%, 12%, 67%, and 100%. Similar groups were obtained when the variables of tumor margins and size were combined with an adaptation of the NCI grading (low-grade tumors/high-grade tumors without necrosis/high-grade tumors with necrosis). Comparative analysis showed that patients with tumors of the same histologic grade or type were not necessarily classed in the same prognostic groups. A better clinicopathologic correlation was obtained using a combination of prognostic factors than with histologic grading or typing alone.

Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations.

BACKGROUND: The benefits of preoperative chemotherapy and radiation for esophageal carcinoma are under investigation. A pilot study was undertaken to determine if pathologic assessment of tumor regression correlated with disease free survival. METHODS: Ninety-three resected specimens from patients treated with cis-dichloro-diamino cisplatin and irradiation before surgery were examined on semiserial sections. Patients selected for surgery were all Status 1 according to the World Health Organization (WHO) classification. Histologic typing was based on the WHO classification. Tumor regression grade (TRG) was quantitated in five grades: TRG 1 (complete regression) showed absence of residual cancer and fibrosis extending through the different layers of the esophageal wall; TRG 2 was characterized by the presence of rare residual cancer cells scattered through the fibrosis; TRG 3 was characterized by an increase in the number of residual cancer cells, but fibrosis still predominated; TRG 4 showed residual cancer outgrowing fibrosis; and TRG 5 was characterized by absence of regressive changes. Survival curves were estimated according to the Kaplan-Meier method. A quantification of the relationship between treatment failure and confounding variables (age, tumor location, tumor size, esophageal wall involvement by residual cancer and/or regressive changes, histology, treatment, adequacy of surgery, pathologic lymph node status, and tumor regression grade) was done using Cox's proportional hazards model. RESULTS: Forty-two percent of specimens were TGR 1-2; 20%, TGR 3; and 33%, TGR 4-5. Univariate analysis found that tumor size, pathologic lymph node status, tumor regression grade, and esophageal wall involvement were highly correlated with disease free survival (P < 0.05). After multivariate analysis, only tumor regression (i.e., TRG 1-3 versus TRG 4-5) remained a significant (P < 0.001) predictor of disease free survival. CONCLUSIONS: This study highlights the importance of tumor regression in the survival of patients with esophageal carcinoma treated with preoperative chemoradiotherapy. These findings suggest that tumor regression grade should be considered when evaluating therapeutic results.

[Screening for cancer of the upper aerodigestive tract in a high-risk population]. / Dépistage des cancers des V.A.D.S. dans une population à haut risque.

From the data collected in the Cancer Registry of Calvados, a screening program for neoplastic lesions of the whole upper digestive and respiratory tract was performed in a canton where esophageal cancer incidence is very high. 137 men underwent this examination for mouth, pharyngo-larynx and esophagus. None neoplastic lesion was revealed but histologic and cytologic swabs showed some abnormalities that are now being studied.