Velopharyngeal function after free thoracodorsal artery perforator flap in lateral and superior oropharyngeal cancer.

The purpose of this study was to report our experience with the free thoracodorsal artery perforator flap for reconstruction of the oropharynx and soft palate in head and neck cancer using a retrospective review of the medical charts of all patients undergoing oropharyngeal reconstruction by free thoracodorsal artery perforator flap during the same procedure as cancer resection between January 2011 and April 2013. Evaluation of speech, feeding and the presence of nasal emissions was performed 6 months after treatment in accordance with the Declaration of Helsinki. Nine patients were evaluated. Clear understanding of the patient was reported by the family and the examiner for seven patients, while understanding difficulties were reported for two patients (1 case of flap dehiscence and 1 technical error of flap fixation). The results indicated that, due to its complex anatomy and function, reconstruction of the soft palate remains a delicate procedure. The free thoracodorsal artery perforator flap allows functional soft palate reconstruction, while limiting donor site morbidity.

Intraperitoneal linear polyethylenimine (L-PEI)-mediated gene delivery to ovarian carcinoma nodes in mice.

Linear polyethylenimine (L-PEI) is an efficient transfection agent for ovarian carcinoma cells in vitro and ex vivo. In the present work, we go a step further and evaluate the efficacy of L-PEI in human ovarian tumor nodes developed in mice. PEI/DNA complexes were administered intraperitoneally instead of intravenously to avoid sequestering of complexes in the lung and liver and to allow transfection of nonvascularized tumor nodes. Plasmid biodistribution was studied by PCR and gene expression was characterized using complementary luciferase and beta-galactosidase assays. Intraperitoneal (i.p.) injection of L-PEI/DNA complexes allowed the straightforward distribution of plasmid in the whole peritoneal cavity. Gene expression occurred in many organs, but tumor nodes appeared as preferential sites for transgene expression. The i.p. delivery route allowed repeated injections and administration of large amounts of DNA (up to 400 mug) without signs of toxicity, even for doses well beyond the intravenous lethal dose. Transgene expression was dose-dependent and transient. However, multiple injections allowed its persistence to increase. These results provide encouraging elements towards the development of PEI-based gene therapy protocols for the treatment of advanced stage ovarian carcinoma.

[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.

[Laryngeal schwannoma: a case report and review of the literature]. / Schwannome laryngé: a propos d'un cas et revue de la littérature.

OBJECTIVES: In presenting a case of laryngeal schwannoma, the authors emphasize the difficulties in diagnosing this rare pathology and review treatment options. The recent literature concerning this benign tumour is reviewed. MATERIALS AND METHOD: The authors present a case of laryngeal schwannoma in a 29 year old man, revealed by exertional inspiratory dyspnea. RESULTS: The patient was treated by a conservative surgery with no recurrence after two years follow-up. CONCLUSION: CT scan and magnetic resonance imaging provide essentiel data on the spread of this benign tumour. The possibility of malignant change and recurrence warrant long-term follow-up.

Extranodal lymphoma of the head and neck: a 67-case series.

UNLABELLED: The present study sought to describe clinical presentation in extranodal lymphoma of the head and neck (ELHN), with the aim of improving diagnostic management. MATERIAL AND METHODS: A single-center retrospective observational study was conducted over the period 2001-13. Age, gender, histologic type, location, type of clinical presentation, time interval between symptom onset and histologic diagnosis and presence of specific symptoms were recorded, as were the specialty of the physician initially consulted and of the physician taking the diagnostic sample. RESULTS: Sixty-seven cases of ELHN were diagnosed: 39 male and 28 female patients, with a median age of 68 years. B-cell lymphoma (84%) was more frequent than plasmacytoma (7%) or T-cell lymphoma (6%). Location was mainly palatine tonsil (28%), nasal fossa and sinus (19%), nasopharynx (14%) or parotid (13%). Revelation often involved a mass (33%), and only rarely any specific symptoms (9%). Time interval from symptom onset to diagnosis was short in aggressive lymphoma and longer in low-grade lymphoma (mean 4 and 10 months respectively). The physician initially consulted was an ENT specialist in 67% of cases, and an ENT specialist performed diagnostic sampling in 97% of cases. CONCLUSION: ELHN is a rare pathology (5 cases per year in our department) of highly variable clinical presentation depending on location and histologic type. The ENT physician should be prepared for diagnosis regardless of anatomic location, so as to optimize diagnostic management.

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.

Double immunohistochemical labeling technique applied to different types of cytokeratins in epithelial proliferations of the breast.

The double labeling technique using peroxidase and alkaline phosphatase for immunohistochemistry is well known, but must be adapted according to the antibodies used, fixation, and technical conditions. The technique allows identification on one slide of two antigens that are localized in the same or different cells of the same lesion. The aim of this paper is to describe the adaptation of this technique to cytokeratins of normal mammary tissue and proliferative lesions of the breast.

[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.

[Recurrence of giant-cell fibroblastoma as dermatofibrosarcoma protuberans in the adult]. / Récidive d'un fibroblastome à cellules géantes de l'enfant sous forme de dermatofibrosarcome protubérant à l'âge adulte.

Giant cell fibroblastoma is a rare, subcutaneous tumor of children. Local recurrences frequently occur after surgical excision, occasionally taking the form of dermatofibrosarcoma protuberans. An immunohistochemical study is associated in this case report.

[2002 Standards, Options and Recommendations: good practice for the management and shipment of histological and cytopathological cancer specimens]. / Standards, Options et Recommandations 2002 bonnes pratiques de l'acheminement et de la prise en charge initiale d'un prélèvement en anatomie et cytologie pathologiques en cancérologie (rapport intégral).

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 management and shipment of histological and cytopathological cancer specimens using the methodology developed by the Standards, Options and Recommendations project. METHODS: The FNCLCC designated the 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, then validated by independent reviewers. RESULTS: The main recommendations are: 1/ High-quality transmission of information between professionals is essential to the management of cancer specimens in order to assure high-quality diagnosis and evaluation of prognostic factors; 2/ Written procedures concerning sample shipment, handling, storage, registration, tracking and fixation exist; these procedures, as well as the necessary shipping material, will be sent to all clinical services involved; 3/ When possible, fresh, unfractionated, oriented surgical samples will be submitted to the same histological and cytopathological laboratory; 4/ Samples collected for extemporaneous examination, freezing or cell culture must be shipped immediately under appropriate storage conditions; 5/ Once frozen, samples can be stored in a deep freezer at temperatures of -80 degrees C or below, or kept in liquid nitrogen; 6/ Fixing tissues shortly after sample collection is essential to prevent cell lysis; 7/ Computerised systems will be used to assure correct specimen registration and tracking in histological and cytopathological laboratories.

[Is mammography useful in Paget's disease of the breast?]. / La mammographie est-elle utile dans la maladie de Paget du sein?

PURPOSE: Interest of the mammogram in Paget's disease of the breast, especially for a therapeutic decision in otherwise asymptomatic women with Paget's disease, who would be candidates for conservative treatment. MATERIALS AND METHODS: 61 women with histological Paget's disease of the nipple, treated by mastectomy, were retrospectively analyzed with clinical, radiological and pathological correlations. RESULTS: An underlying carcinoma was found in 60 cases (98.4%), atypical epithelial hyperplasia in one. In the 24 women without breast palpable mass, 17 (71%) had a normal mammogram, 12 (50%) had carcinoma with an invasive component, 14 (58%) had a cancer at a distance from the nipple, 17 (71%) had a multifocal carcinoma. All 37 women with a palpable mass had a pathological mammogram, 36 of them had carcinoma with an invasive component, 35 (95%) a cancer at a distance from the nipple, 31 (84%) a multifocal carcinoma. CONCLUSION: Mammogram is of limited value in management of Paget's disease of the breast for women without breast palpable mass; it can not predict the site of malignancy, nor the invasive component.

[Atypical prostatic leiomyoma: a new case with cytodensitometric analysis]. / Léiomyome à cellules bizarres de la prostate: un nouveau cas avec étude cytométrique.

Atypical prostatic leiomyoma is a very rare benign tumor. We report here a new case with a cytodensitometric analysis. The result of cytodensitometry is a polyploid tumor that is well correlated with the morphology of nuclear multilobulated cells of this tumor. The differential diagnosis is essentially the leiomyosarcoma which is characterized by the absence of mitotic activity.

[An ovarian mucinous borderline tumour with mixed mural nodules]. / Une tumeur ovarienne mucineuse borderline avec des nodules muraux mixtes.

The occurrence of mural nodules in serous or mucinous ovarian tumours is not frequent. Mural nodule can be developed in benign, borderline or malignant tumours. They can be benign, malignant or mixed type. Thus the prognosis of the ovarian tumour can be dramatically modified by the presence if these nodules. Eighty-two cases of mural nodules were reported in the literature, among which we account four cases of mixed nodules type. We report an additional case of mixed type mural nodules of anaplastic carcinoma and sarcoma-like developed in an ovarian mucinous borderline tumour at a 60-year-old woman.We give details about the classification, the differential diagnosis and prognosis of theses nodules.

[Pulmonary cystic adenomatoid malformation in an adult patient: an underdiagnosed disease]. / Malformation kystique adénomatoïde pulmonaire de l'adulte : une pathologie méconnue.

Currently, most congenital lower respiratory tract malformations are detected during pregnancy or at birth, thanks to antenatal imaging. However, a pulmonary congenital cystic adenomatoid disease may be found in adulthood. The diagnosis is difficult, due to its rarity. We present the case of a patient whose diagnosis of pulmonary cystic adenomatoid malformation was confirmed when she had tuberculosis. A lobectomy was performed, which enabled identification of tuberculosis and also multiple cysts of adenomatoid malformation. The risk posed by this malformation, i.e. the risk of developing bronchioloalveolar carcinoma and of infection or pneumothorax, is the incentive for proposing formal surgical removal.

Mutations in BHD and TP53 genes, but not in HNF1beta gene, in a large series of sporadic chromophobe renal cell carcinoma.

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.

Expression and localization of alpha v integrins and their ligand vitronectin in normal ovarian epithelium and in ovarian carcinoma.

In an extension of a previous in vitro study [Carreiras et al., Int. J. Cancer 63, 530-536 (1995)] and in an effort to understand the adhesive interactions mediated by integrins within epithelial ovarian tumors, the presence of the alpha v and beta 3 subunits and that of vitronectin (Vn) in ovarian carcinomas at various stages of differentiation and in normal ovarian epithelium were comparatively investigated. The study was performed on material from 34 patients. By immunofluorescence, cryostat sections were analyzed for their expression of alpha v (34 cases), beta 3 (19 cases), and Vn (29 cases). alpha v was expressed in normal epithelium and in highly differentiated tumors as well as in a majority of moderately and poorly differentiated carcinomas with identical staining pattern. beta 3 subunit and Vn were also expressed in normal cases and highly differentiated carcinomas. However, they were lacking in most of the less differentiated tumors. The analysis of cases which were simultaneously tested for the presence of alpha v, beta 3, and Vn revealed that a large proportion of normal ovarian epithelium and highly differentiated tumors simultaneously expressed alpha v, beta 3, and Vn; in contrast, in all moderately and poorly differentiated carcinomas either beta 3 or Vn was absent. The potential role of the alpha v beta 3/Vn system in ovarian epithelium functions is discussed. It is also speculated that modifications of this system in ovarian carcinomas might contribute to tumor progression.

Agreement between chromogenic in situ hybridisation (CISH) and FISH in the determination of HER2 status in breast cancer.

Determination of the HER2/neu (HER2) status in breast carcinoma has become necessary for the selection of breast cancer patients for trastuzumab therapy. Amplification of the gene analysed by fluorescence in situ hybridisation (FISH) or overexpression of the protein determined by immunohistochemistry (IHC) are the two major methods to establish this status. A strong correlation has been previously demonstrated between these two methods. However, FISH is not always feasible in routine practice and weakly positive IHC tumours (2+) do not always correspond to a gene amplification. Our study was performed in order to evaluate the contribution of chromogenic in situ hybridisation (CISH), which enables detection of the gene copies through an immunoperoxidase reaction. CISH was performed in 79 breast carcinomas for which the HER2 status was previously determined by IHC and FISH. The results of IHC, FISH and CISH were compared for each tumour. CISH procedures were successful in 95% of our cases. Whatever the IHC results, we found a very good concordance (96%) between CISH and FISH. Our study confirms that CISH may be an alternative to FISH for the determination of the gene amplification status in 2+ tumours. Our results allow us to think that, in many laboratories, CISH may also be an excellent method to calibrate the IHC procedures or, as a quality control test, to check regularly that the IHC signal is in agreement with the gene status.

Calibration of immunohistochemistry for assessment of HER2 in breast cancer: results of the French multicentre GEFPICS study.

AIMS: HER2 protein is over-expressed in 15-30% of breast carcinomas. Immunohistochemistry (IHC) is a common and inexpensive method able to specifically detect HER2 protein. However, lack of standardization of IHC has been considered responsible for discrepancies in HER2 status assessment performed by IHC and fluorescence in-situ hybridization (FISH). This prompted us to perform a multicentric IHC calibration test to achieve a maximum accuracy of HER2-IHC compared with HER2-FISH taken as the reference method. METHODS AND RESULTS: Twelve French laboratories participated in this study, including 119 cases of invasive breast carcinomas for which both fixed and frozen tissues were available. HER2 expression was determined in fixed tissues by individual in-house IHC techniques, using either CB11 (Novocastra, Newcastle, UK) or A0485 (Dako, Glostrup, Denmark) anti-HER2 antibodies. Two cut-off values were used: 10% and 60% of immunostained cells. In 116 of the 119 cases, HER2 gene status could also be determined by FISH on frozen sections, performed in a single laboratory. Results were centralized and compared. When suboptimal concordance between IHC and FISH was observed, IHC was calibrated and a second run was performed. The specificity, sensitivity and accuracy of IHC compared with FISH were noted before and after calibration. Forty-four out of 116 (38%) tumours showed HER2 gene amplification. Accuracy of IHC was complete in the first run for 6/12 laboratories. Calibration, necessary for the six others, relied mainly on the combination of a heat-induced epitope retrieval step with an increase of dilution of the primary antibody. In the second run, HER2 over-expression was found in 46 (40%) and 44 (38%) of the 116 cases, using 10% or 60% of stained cells as cut-offs, respectively. The corresponding accuracy rates were 93% and 95%. CONCLUSIONS: This study showed that a high accuracy of IHC could be obtained for the determination of HER2 status in all laboratories using their in-house IHC technique, provided that a calibration process was performed. Antigen retrieval procedure, high dilutions of anti-HER2 antibody and the use of specific controls were crucial for HER2-IHC calibration. A 95% accuracy rate of IHC, using FISH as gold standard, was obtained by considering immunolabelling HER2-IHC results as a continuous variable, and taking 60% invasive stained cells as the cut-off for HER2 over-expression.

Prognostic value of DNA cytometry in 281 premenopausal patients with lymph node negative breast carcinoma randomized in a control trial: multivariate analysis with Ki-67 index, mitotic count, and microvessel density.

BACKGROUND: The clinical relevance of DNA image cytometry (ICM) and flow cytometry (FCM) remains under investigation in breast carcinoma. The objective of the current work was to study the prognostic value of DNA ICM and FCM in a series of patients randomized in a control trial. A multivariate analysis has been performed including other factors still under investigation such as Ki-67 index, mitotic count, microvessel density, and P53 and Bcl-2 expression. METHODS: Two hundred and eighty-one patients were randomized in the European Organization for Research and Treatment of Cancer 10854 trial comparing surgery followed by one course of perioperative chemotherapy versus surgery alone. Tumor parameters studied were pT, multicentricity, tumor grading according to modified Scarff-Bloom-Richardson, estrogen receptors, mitotic count per 1.7 mm(2), MIB-1, and BCL-2 scores, microvessel density, and p53 expression. ICM DNA parameters studied from paraffin embedded specimens, were DNA ploidy, proliferative index, 2c deviation index, malignancy grade, and Auer-Baldetorp typing. FCM DNA parameters analyzed on the same samples were ploidy and S-phase fraction statistics. The influence of tumor parameters, and DNA parameters on overall survival (OS), disease free survival (DFS), and metastasis-free survival (MFS) was evaluated using the Cox model. Median follow-up was 82 months. RESULTS: For OS, the prognostic parameters retained were pathologic tumor size (pT) and mitotic index (MI). Overall survival was 94% and 68% for tumors pT1/MI less than 10 and pT2-3 MI greater than or equal to 10, respectively. For DFS, age, multicentricity, and grading according to modified Scarff and Bloom were predicting factors with the same relative risk. Disease free survival was 96%, 78% and 68% respectively, when 1, 2, or 3 of those factors were present. For MFS, the only retained predicting factor was MI. MFS was 97% and 73% when MI was less than 10 and MI was greater than or equal to 10, respectively. CONCLUSIONS: Evaluation of proliferative compartment was the most important predicting factor for OS and MFS in the current series of premenopausal lymph node negative patients with breast invasive carcinoma. When working on paraffin embedded tissue, the best way of assessing it was MI count. ICM DNA analysis results were not selected in multivariate analysis. DNA analysis by FCM should be considered as an unsuitable technique when working on paraffin embedded tissue.