Etude de la dissémination des cellules tumorales liée à l’acte chirurgical dans les carcinomes épidermoïdes des voies aérodigestives supérieures

Metastasis is defined as the development of secondary tumor sites related to the ability of tumor cells to detach from primary tumor, to implant in another organ and to proliferate. From the primary site, a micrometastatic dissemination can occur through the release in blood stream or lymph system of isolated tumor cells or of small cell clusters. These micrometastases can proliferate and grow into metastases. The detection of isolated or microclustered tumor cells, the evaluation of the prognosis value, and their metastatic potential encounter difficulties. In this study, we focused mainly on the metastatic process related to surgery in epidermoid cancers of the upper aerodigestive tract (CEVADS in french). Indeed, in this type of cancers, the best method to establish diagnosis is the biopsy assessed by the anatomo-pathological analysis of a sample. The main physical barrier preventing cells from migrating is the membrane of the malignant tissue. During surgery, these barriers are destroyed, facilitating the invasion of the vascular system. Therefore tumor cells can locate in vessels and proliferate at distance from the primitive site, thus forming secondary tumors.Generally, metastases are detected by imaging or serology at a very advanced stage of cancer disease. The aim of this study was to detect isolated or disseminated cells (CTCs) of CEVADS in blood stream by three different approaches: 1) the study of molecular markers for the diagnosis of node involvement of epidermoid carcinomas of the upper aerodigestive tract using quantitative PCR in realtime and OSNA. 2) Screening of tumoral cells disseminated in Redon drains after cervical curettage 3) Detection of circulating tumor cells after surgery for epidermoid carcinomas of stage III and IV VADS. This protocol will allow to validate the detection of CTCs in clinic setting and to develop prospective studies for the diagnosis and prognosis of CTCs of CEVADSPar définition, une métastase est la formation de foyers tumoraux secondaires liée à la capacité des cellules tumorales à se détacher de la tumeur primitive, de s’implanter dans un autre organe et de proliférer. A partir du foyer primitif, il peut y avoir une dissémination micrométastatique c’est-à-dire la libération dans le sang ou le réseau lymphatique de cellules tumorales isolées ou de petits amas cellulaires . Ces micrométastases peuvent proliférer et donner naissance à des métastases. La difficulté est de déceler ces cellules tumorales isolées ou en micro-amas, et également d’évaluer leur valeur pronostique, ainsi que leur potentiel métastatique. Dans cette étude, nous allons nous intéresser plus particulièrement au processus métastatique lié à l’acte chirurgical dans les cancers épidermoïdes des voies aérodigestive supérieures (CEVADS). En effet, dans ce type de cancers, la meilleure méthode pour établir un diagnostic est l’analyse anatomo-pathologique du prélèvement réalisé par biopsie. La principale barrière physique empêchant les cellules tumorales de migrer est la membrane du tissu atteint. Lors de la chirurgie, ces barrières sont détruites, ce qui facilite l’invasion du système vasculaire. Les cellules tumorales peuvent ainsi se loger dans les vaisseaux et proliférer à distance du site primitif pour former des tumeurs secondaires. Généralement, les métastases sont détectées par imagerie ou sérologie à un stade très avancé du cancer. L’objectif de cette étude est de détecter la présence de cellules isolées ou disséminées (CTCs) de CEVADS dans la circulation sanguine a travers trois axes de recherche des métastases : 1) Etude des marqueurs moléculaires pour le diagnostic d’envahissement ganglionnaire des carcinomes épidermoïdes des voies aérodigestives supérieures réalisée par PCR quantitative en temps réel et en OSNA. 2) Recherche des cellules tumorales disséminées dans les drains de Redon après curage cervical 3) Recherche des cellules tumorales circulantes après acte chirurgical pour carcinomes épidermoïdes des VADS stade III et IV. Ce protocole nous permettra de valider la recherche des CTCs en situation clinique et par la suite de développer des études prospectives diagnostiques et pronostiques des CTCs des CEVADS

Study of the scattering of the tumoral cells connected to the surgical act in carcinomas epidermoides ways superior aerodigestives

Par définition, une métastase est la formation de foyers tumoraux secondaires liée à la capacité des cellules tumorales à se détacher de la tumeur primitive, de s’implanter dans un autre organe et de proliférer. A partir du foyer primitif, il peut y avoir une dissémination micrométastatique c’est-à-dire la libération dans le sang ou le réseau lymphatique de cellules tumorales isolées ou de petits amas cellulaires. Ces micrométastases peuvent proliférer et donner naissance à des métastases. La difficulté est de déceler ces cellules tumorales isolées ou en micro-amas, et également d’évaluer leur valeur pronostique, ainsi que leur potentiel métastatique. Dans cette étude, nous allons nous intéresser plus particulièrement au processus métastatique lié à l’acte chirurgical dans les cancers epdermoïde des voies aérodigestive supérieures (CEVADS). En effet, dans ce type de cancers, la meilleure méthode pour établir un diagnostic est l’analyse anatomo-pathologique du prélèvement réalisé par biopsie. La principale barrière physique empêchant les cellules tumorales de migrer est la membrane du tissu atteint. Lors de la chirurgie, ces barrières sont détruites, ce qui facilite l’invasion du système vasculaire. Les cellules tumorales peuvent ainsi se loger dans les vaisseaux et proliférer à distance du site primitif pour former des tumeurs secondaires. Généralement, les métastases sont détectées par imagerie ou sérologie à un stade très avancé du cancer. L’objectif de cette étude est de détecter la présence de cellules isolées ou disséminées (CTCs) de CEDVADS dans la circulation sanguine a travers trois axes de recherche des métastases : 1) Étude des marqueurs moléculaires pour le diagnostic d’envahissement ganglionnaire des carcinomes épidermoïdes des voies aérodigestives supérieures réalisée par PCR quantitative en temps réel et en OSNA. 2) Recherche des cellules tumorales disséminées dans les drains de Redon après curage cervical 3)Recherche des cellules tumorales circulantes après acte chirurgical pour carcinomes épidermoïdes des VADS stade III et IV. Ce protocole nous permettra de valider la recherche des CTCs en situation clinique et par la suite de développer des études prospectives diagnostiques et pronostiques des CTCs des CEVADSMetastasis is defined as the development of secondary tumor sites related to the ability of tumor cells to detach from primary tumor, to implant in another organ and to proliferate. From the primary site, a micrometastatic dissemination can occur through the release in blood stream or lymph system of isolated tumor cells or of small cell clusters. These micrometastases can proliferate and grow into metastases. The detection of isolated or microclustered tumor cells, the evaluation of the prognosis value, and their metastatic potential encounter difficulties. In this study, we focused mainly on the metastatic process related to surgery in epidermoid cancers of the upper aerodigestive tract (…). Indeed, in this type of cancers, the best method to establish diagnosis is the biopsy assessed by the anatomo-pathological analysis of a sample. The main physical barrier preventing cells from migrating is the membrane of the malignant tissue. During surgery, these barriers are destroyed, facilitating the invasion of the vascular system. Therefore tumor cells can locate in vessels and proliferate at distance from the primitive site, thus forming secondary tumors. Generally, metastases are detected by imaging or serology at a very advanced stage of cancer disease. The aim of this study was to detect isolated or disseminated cells (CTCs) of CEDVADS in blood stream by three different approaches : 1) the study of molecular markers for the diagnosis of node involvement of epidermoid carcinomas of the upper aerodigestive tract using quantitative PCR in real time and OSNA. 2) Screening of tumoral cells disseminated in Redon drains after cervical curettage 3) Detection of circulating tumor cells after surgery for epidermoid carcinomas of stage III and IV VADS. This protocol will allow to validate the detection of CTCs in clinic setting and to develop prospective studies for the diagnosis and prognosis of CTCs of CEVAD

Étude de la dissémination des cellules tumorales liée à l’acte chirurgical dans les carcinomes epidermoïdes des voies aérodigestives supérieures

Metastasis is defined as the development of secondary tumor sites related to the ability of tumor cells to detach from primary tumor, to implant in another organ and to proliferate. From the primary site, a micrometastatic dissemination can occur through the release in blood stream or lymph system of isolated tumor cells or of small cell clusters. These micrometastases can proliferate and grow into metastases. The detection of isolated or microclustered tumor cells, the evaluation of the prognosis value, and their metastatic potential encounter difficulties. In this study, we focused mainly on the metastatic process related to surgery in epidermoid cancers of the upper aerodigestive tract (…). Indeed, in this type of cancers, the best method to establish diagnosis is the biopsy assessed by the anatomo-pathological analysis of a sample. The main physical barrier preventing cells from migrating is the membrane of the malignant tissue. During surgery, these barriers are destroyed, facilitating the invasion of the vascular system. Therefore tumor cells can locate in vessels and proliferate at distance from the primitive site, thus forming secondary tumors. Generally, metastases are detected by imaging or serology at a very advanced stage of cancer disease. The aim of this study was to detect isolated or disseminated cells (CTCs) of CEDVADS in blood stream by three different approaches : 1) the study of molecular markers for the diagnosis of node involvement of epidermoid carcinomas of the upper aerodigestive tract using quantitative PCR in real time and OSNA. 2) Screening of tumoral cells disseminated in Redon drains after cervical curettage 3) Detection of circulating tumor cells after surgery for epidermoid carcinomas of stage III and IV VADS. This protocol will allow to validate the detection of CTCs in clinic setting and to develop prospective studies for the diagnosis and prognosis of CTCs of CEVADSPar définition, une métastase est la formation de foyers tumoraux secondaires liée à la capacité des cellules tumorales à se détacher de la tumeur primitive, de s’implanter dans un autre organe et de proliférer. A partir du foyer primitif, il peut y avoir une dissémination micrométastatique c’est-à-dire la libération dans le sang ou le réseau lymphatique de cellules tumorales isolées ou de petits amas cellulaires. Ces micrométastases peuvent proliférer et donner naissance à des métastases. La difficulté est de déceler ces cellules tumorales isolées ou en micro-amas, et également d’évaluer leur valeur pronostique, ainsi que leur potentiel métastatique. Dans cette étude, nous allons nous intéresser plus particulièrement au processus métastatique lié à l’acte chirurgical dans les cancers epdermoïde des voies aérodigestive supérieures (CEVADS). En effet, dans ce type de cancers, la meilleure méthode pour établir un diagnostic est l’analyse anatomo-pathologique du prélèvement réalisé par biopsie. La principale barrière physique empêchant les cellules tumorales de migrer est la membrane du tissu atteint. Lors de la chirurgie, ces barrières sont détruites, ce qui facilite l’invasion du système vasculaire. Les cellules tumorales peuvent ainsi se loger dans les vaisseaux et proliférer à distance du site primitif pour former des tumeurs secondaires. Généralement, les métastases sont détectées par imagerie ou sérologie à un stade très avancé du cancer. L’objectif de cette étude est de détecter la présence de cellules isolées ou disséminées (CTCs) de CEDVADS dans la circulation sanguine a travers trois axes de recherche des métastases : 1) Étude des marqueurs moléculaires pour le diagnostic d’envahissement ganglionnaire des carcinomes épidermoïdes des voies aérodigestives supérieures réalisée par PCR quantitative en temps réel et en OSNA. 2) Recherche des cellules tumorales disséminées dans les drains de Redon après curage cervical 3)Recherche des cellules tumorales circulantes après acte chirurgical pour carcinomes épidermoïdes des VADS stade III et IV. Ce protocole nous permettra de valider la recherche des CTCs en situation clinique et par la suite de développer des études prospectives diagnostiques et pronostiques des CTCs des CEVAD

Modification of lymphocyte subsets in patients with rhinoscleroma

PURPOSE: Rhinoscleroma is a rare, chronic, granulomatous disorder of the upper airways. This disease presents some etiopathogenetic aspects that are not yet clear. Infection by Klebsiella rhinoscleromatis is fundamental for the onset of the disease, but it is impossible to reproduce rhinoscleroma experimentally only via infection with the bacteria both in man and in animals. Furthermore, this disease mainly affects blood-related people and occurs in certain geographic areas. In this context, we present a study that brings to light some of the quantitative abnormalities of the lymphocyte subsets. MATERIALS AND METHODS: The study group consisted of 5 patients with rhinoscleroma. The following parameters were studied for each patient: clinical manifestations, histologic examinations, number of leukocytes, lymphocytes, and lymphocyte subsets. RESULTS: In all patients, we noted the following: There was a relative reduction of the CD4+ cells, an absolute increase of the CD8+ cells, and an inversion of the CD4+/CD8+ ratio. There was an absolute increase of the CD56+ cells and cytotoxic cells that coexpress CD8+CD56+ antigens. There was a relative reduction of the CD3+ cells, and the CD19+ cells tended to show an ambiguous behavioral pattern. CONCLUSION: We believe that K. rhinoscleromatis does not play a major role in the etiopathogenesis of rhinoscleroma. However, we do believe that the anomalous behavior of the immune system can favor rhinoscleroma

A rare case of extremely high counts of circulating tumor cells detected in a patient with an oral squamous cell carcinoma

International audienceBACKGROUND:Despite aggressive regimens, the clinical outcome of head and neck squamous cell carcinoma remains poor. The detection of circulating tumor cells could potentially improve the management of patients with disseminated cancer, including diagnosis, treatment strategies, and surveillance. Currently, CellSearch(®) is the most widely used and the only Food and Drug Administration-cleared system for circulating tumor cells detection in patients with metastatic breast, colorectal, or prostate cancer. In most cases of head and neck squamous cell carcinoma, only low counts of circulating tumor cells have been reported.CASE PRESENTATION:A 56-year-old white male with no particular medical history, was diagnosed with a squamous cell carcinoma of oral cavity. According to the imaging results (computed tomography and (18)F-fluorodeoxyglucose positron emission tomography / computed tomography) and panendoscopy, the TNM staging was classified as T4N2M0. A non-interruptive pelvimandibulectomy was conducted according to the multidisciplinary meeting advices and the postoperative observations were normal. The patient complained of a painful cervical edema and a trismus 6 weeks after the surgery. A relapse was found by computed tomography and the patient died two weeks later. The search for circulating tumor cells in peripheral venous blood by using the CellSearch(®) system revealed a very high count compared with published reports at three time points (pre-operative: 400; intra-operative: 150 and post-operative day 7: 1400 circulating tumor cells). Of note, all detected circulating tumor cells were epidermal growth factor receptor negative.CONCLUSION:We report here for the first time a rare case of oral squamous cell carcinoma with extremely high circulating tumor cells counts using the CellSearch(®) system. The absolute number of circulating tumor cells might predict a particular phase of cancer development as well as a poor survival, potentially contributing to a personalized healthcare

Current Approaches to Salvage Surgery for Head and Neck Cancer: A Comprehensive Review

Salvage surgeries of head and neck cancer are often complicated and do not always show decent results. This type of procedure is tough on the patient, as many crucial organs can be affected. A long period of reeducation usually follows the surgery because of the need to rehabilitate functions such as speech or swallowing. In order to lighten the journey of the patients, it is important to develop new technologies and techniques to ease the surgery and limit its damages. This seems even more crucial since progress has been made in the past years, allowing more salvage therapy to take place. This article aims at showing the available tools and procedures for salvage surgeries, such as transoral robotic surgery, free-flap surgery, sentinel node mapping, and many others, that help the work of the medical team to operate or obtain a better understanding of the status of the cancer when taken in charge. Yet, the surgical procedure is not the only thing determining the outcome of the operation. The patient themself and their cancer history also play an important part in the care and must be acknowledged

Photodynamic therapy as salvage treatment for recurrent head and neck cancer

Head and neck cancers often lead to disfiguration or functional impairments after treatment. Local recurrence occurs in around 60% of cases and most of them can not be retreated. Photodynamic therapy (PDT) can be an alternative treatment. In a serie of 10 patients with recurrent squamous cell carcinoma of the head and neck that have failed prior therapies and are unsuitable for conventional curative therapy, PDT treatment has been used. Eight patients have shown complete cicatrisation. Seven patients were cured after the follow up period up to 53 months. Three patients died (one outside etiology). Quality of life was considered as very much for 6 out of 10 patients, quite a bit for 1 patient, a little for 2 patients and not at all for 1 patient. Clinical benefit was evaluated as very much for 6 patients out of 10, quite a bit for 2 patients, a little for 1 patient and not at all for 1 patient. PDT can be proposed to patients with head and neck cancer in palliative situation. It could be a therapeutic solution for selected cases with good outcomes. PDT offers patients a unique chance of remission and increased life expectancy compared with palliative treatments

ICG-induced NIR fluorescence mapping in patients with head & neck tumors after the previous radiotherapy

International audienceBackground: The distinction between tumor and healthy tissues is complicated in the areas previously subjected to radiation therapy (RT). This is related to the fact that tissues can undergo delayed and irreversible deterioration such as inflammation, vascular alteration and fibrosis. The trials related to the fluorescence –guided surgery (FSG) in Head and Neck Squamous Cell Carcinoma (HNSCC) patients, previously subjected to RT, have not yet been reported. The present study addresses for the first time the possibilities of tumor near-infrared (NIR) imaging using Indocynaine Green (ICG) in irradiated areas.Methods: Four patients with histologically confirmed HNSCC were included in this study. All included patients were previously treated with RT with at least 50 Gy. RT-radiation fields from original treatment fully encompassed the second tumor or recurrence. ICG was injected via cephalic vein 45 min before the images were captured using a NIR camera system Artemis. The images were also captured before ICG injection serving as background signal. The fluorescence intensity measurements were carried out using specially designed software.Results: ICG fluorescence clearly demonstrated a significant difference in fluorescence intensity between healthy and tumor tissues in 2 of 4 patients. Histology post-resection analysis confirmed a complete tumor resection with safe surgical margins. No difference between tumor and surrounding healthy tissue was detected in patients with an epidermoid carcinoma developed from sclerohypertrophic lichen.Conclusions: In our pilot study, we clearly established the feasibility of using NIR FGS with ICG to delineate tumor and healthy tissues in irradiated areas in infiltrating lichen-free tumors