Publications by authors named "Emile Reyt"

33 Publications

Multicenter assessment of exclusive endoscopic endonasal approach for the treatment of 53 olfactory neuroblastomas.

Head Neck 2018 05 22;40(5):1000-1007. Epub 2018 Jan 22.

Otorhinolaryngology, Head and Neck Surgery Department, University Hospital Rangueil-Larrey, Toulouse, France.

Background: Given the particularities of olfactory neuroblastoma (ONB) and the lack of studies on the subject, a multicenter collaborative study was conducted to assess treatment strategy.

Methods: Fifty-three patients with ONB were included from the French Rare Head and Neck Cancer Expert Network (REFCOR) database: 16T1, 8T2, 19T3, and 10T4. All cases were treated endoscopically with skull base removal and repair in 26 cases (49%) and without external craniotomy.

Results: The overall survival (OS) and disease-free survival (DFS) rates at 5 years were 87% and 71%, respectively, with mean follow-up of 45.4 ± 26.5 months. The complication rate was 18.8% with 4 cases of meningitis. Pathological analysis showed positive margins in 26.8%, notably on the dura-mater and periorbita, without impairment of OS or DFS. Forty-eight patients received adjuvant radiotherapy on T ± N. Ten patients had a recurrence (18.9%). Six patients died of their disease. Prophylactic neck irradiation seemed to reduce the recurrence rate.

Conclusion: Exclusively endoscopic treatment proved efficient and reliable in a large controlled series.
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http://dx.doi.org/10.1002/hed.25064DOI Listing
May 2018

Spontaneous Cerebrospinal Fluid Rhinorrhea: Association with Body Weight and Imaging Data.

J Neurol Surg B Skull Base 2017 Oct 8;78(5):419-424. Epub 2017 Jun 8.

Joseph Fourier University, UFR Medecine, Grenoble, France.

 Spontaneous cerebrospinal fluid rhinorrhea (SCSFR) might be the only clinical manifestation of idiopathic intracranial hypertension (IIH), which has been historically related to overweight. Our goal was to search for an association between SCSFR and increased body weight on the one hand and SCSFR and imaging findings suggestive of IIH on the other hand.  We retrospectively collected clinical and radiological data of patients operated on endoscopically for SCSFR in our institution from 1993 to 2013. Analyzed factors were body mass index (BMI), extended sphenoid sinus pneumatization on computed tomography, and empty sella and distention of the optic nerve sheath on magnetic resonance imaging.  There were 15 patients: 8 females/7 males; mean age 50 years. Primary surgical success rate was 86.7%. Regarding body weight, 80% were overweight (BMI ≥ 25) versus 32% in the French general population (  < 0.001). Among patients with SCSFR, 20% were obese (BMI ≥ 30) versus 15% in French individuals without SCSFR (  = 0.483). Increased pneumatization of sphenoid sinuses was observed in 92.9 versus 27.5% in the general population (  < 0.0001). Empty sella was found in 46.2 versus 3% in the general population (  < 0.00001). Dilation of the optic nerve sheath was observed in 46.2 versus 15% in the general population (  < 0.01).  We found statistically significant associations between SCSFR and overweight, increased pneumatization of sphenoid sinuses, empty sella, and dilation of optic nerve sheath, but not with obesity, which did not have any additional impact of CSF leak than did overweight.
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http://dx.doi.org/10.1055/s-0037-1603731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5582967PMC
October 2017

Multicenter prospective micro-costing study evaluating mandibular free-flap reconstruction.

Eur Arch Otorhinolaryngol 2017 Feb 27;274(2):1103-1111. Epub 2016 Oct 27.

Epidemiology and Biostatistics Unit, Centre Antoine-Lacassagne, 33 Avenue de Valombrose, 06189, Nice, France.

Free-flap mandibular reconstruction is a highly specialized procedure associated with severe complications necessitating re-interventions and re-hospitalizations. This surgery is expensive in terms of health workers' time, equipment, medical devices and drugs. Our main objective was to assess the direct hospital cost generated by osseocutaneous free-flap surgery in a multicentric prospective micro-costing study. Direct medical costs evaluated from a hospital perspective were assessed using a micro-costing method from the first consultation with the surgeon until the patient returns home, thus confirming the success or failure of the free-flap procedure. The mean total cost for free-flap intervention was 34,009€ (5151-119,604€), the most expensive item being the duration of hospital bed occupation, representing 30-90% of the total cost. In the event of complications, the mean cost increased by 77.3%, due primarily to hospitalization in ICU and the conventional unit. This surgery is effective and provides good results but remains highly complex and costly.
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http://dx.doi.org/10.1007/s00405-016-4360-3DOI Listing
February 2017

Near-infrared fluorescence imaging-guided surgery improves recurrence-free survival rate in novel orthotopic animal model of head and neck squamous cell carcinoma.

Head Neck 2016 04 25;38 Suppl 1:E246-55. Epub 2015 Jun 25.

INSERM U823, Grenoble Cedex, France.

Background: Appropriate animal models are required to test novel therapeutics for head and neck squamous cell carcinoma (HNSCC) such as near-infrared (NIR) imaging-guided surgery.

Methods: We developed an optimized animal model of orthotopic HNSCC (in female athymic NMRI (Naval Medical Research Institute) nude mice) with a prolonged survival time. Resection of the orthotopic tumors was performed 30 days after implantation with or without the aid of a miniaturized clinical grade NIR optical imaging device, after systemic administration of a fluorescent RGD-based probe that targets αv β3 integrin.

Results: NIR optical imaging-guided surgery increased the recurrence-free survival rate by 50% through the detection of fluorescent cancer residues as small as 185 µm; these fragments could remain unidentified if resection was performed exclusively under unaided visual guidance.

Conclusion: NIR optical imaging-guided surgery showed an improved HNSCC tumor resection quality in our optimized orthotopic animal model. © 2015 Wiley Periodicals, Inc. Head Neck 38: E246-E255, 2016.
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http://dx.doi.org/10.1002/hed.23980DOI Listing
April 2016

Role of near-infrared fluorescence imaging in head and neck cancer surgery: from animal models to humans.

Eur Arch Otorhinolaryngol 2015 Oct 13;272(10):2593-600. Epub 2014 Aug 13.

Albert Bonniot Institute, CRI INSERM/UJF U823, BP170, 38042, Grenoble Cedex 9, France,

Complete resection of head and neck cancers with negative surgical margins improves the prognosis of the disease and decreases the recurrence rate. Near-infrared fluorescence-guided surgery of head and neck cancer is a rapidly evolving field that represents an invaluable tool for tumor detection and resection. Here, we present a literature review of the principles of near-infrared fluorescence imaging and its use in head and neck cancer surgery. We discuss important studies in both animal models and humans that have been carried out up to this point. We also outline the important fluorescent molecules and devices used in head and neck fluorescence imaging-guided surgery. Although near-infrared fluorescence-guided surgery for head and neck cancers showed efficacy in animal models, its use in humans is limited by the small number of fluorescent probes that are approved for clinical use. However, it is considered as a novel surgical aid that helps delineate tumor margins preoperatively and could spare patients from the added morbidity that is associated with additional surgery or chemoradiation. In addition, it is a useful tool to detect sentinel lymph nodes as well as metastatic lymph nodes.
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http://dx.doi.org/10.1007/s00405-014-3224-yDOI Listing
October 2015

[Rare tumors of the head and neck; on behalf of the REFCOR, the French Network of rare head and neck tumors].

Bull Cancer 2014 May;101(5):411-23

Hôpital Tenon, service ORL-CCF, 4 rue de la Chine, 75970 Paris cedex 20, France.

Malignant tumors of the upper aerodigestive tract may be rare by their histology (sarcoma, variants of conventional squamous cell carcinomas) and/or location (sinuses, salivary glands, ear, of various histologies themselves). They represent less than 10% of head and neck neoplasms. The confirmation of their diagnosis often requires a medical expertise and sometimes biomolecular techniques complementary to classical histology and immunohistochemistry. Due to their location, their treatment often requires a specific surgical technique. Radiation therapy is indicated based on histoclinical characteristics common to other head and neck neoplasms but also incorporate grade. Further, the technique must often be adapted to take into account the proximity of organs at risk. For most histologies, chemotherapy is relatively inefficient but current molecular advances may allow to consider pharmaceutical developments in the coming years. The REFCOR, the French Network of head and neck cancers aims to organize and promote the optimal management of these rare and heterogeneous diseases, to promote research and clinical trials.
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http://dx.doi.org/10.1684/bdc.2014.1956DOI Listing
May 2014

A rationale for chemoradiation (vs radiotherapy) in salivary gland cancers? On behalf of the REFCOR (French rare head and neck cancer network).

Crit Rev Oncol Hematol 2014 Aug 16;91(2):142-58. Epub 2014 Feb 16.

Radiation Oncology, Centre Antoine Lacassagne, Nice 06200, France. Electronic address:

Background: Salivary gland carcinomas constitute a heterogeneous group of tumors, with over 20 histological subtypes of various prognoses. The mainstay of treatment is surgery, with radiotherapy advocated for unresectable disease or postoperatively in case of poor prognostic factors such as high grade, locally advanced and/or incompletely resected tumors. Concurrent chemotherapy is sometimes advocated in routine practice based on criteria extrapolated from squamous cell carcinomas of the head and neck, on radioresistance of salivary gland tumors and on results obtained in the metastatic setting. The aim of this review was to identify situations where chemotherapy is advocated.

Material And Methods: A search of literature was performed with the following key words: parotid, salivary gland, neoplasm, cancer, malignant tumor, chemoradiation, chemotherapy, radiotherapy and treatment. Case report and studies published before 2000 were not included.

Results: Platinum-based regimens were the most frequent. Other regimens were reported and seemed dependent on histology. The level of evidence for the concurrent delivery of chemotherapy with radiation therapy is supported by a low level of evidence. Prescribing chemotherapy mostly relies on poor prognostic factors similar to those used to indicate high dose radiotherapy. Protocols vary with histology.

Conclusion: The rationale for adding chemotherapy to radiotherapy remains to be demonstrated prospectively. Although the type of systemic treatments used may be adapted on histology, the strongest rationale remains in favor of cisplatin.
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http://dx.doi.org/10.1016/j.critrevonc.2014.02.002DOI Listing
August 2014

[Pathologists and the French network of expertise on rare cancers ENT: The REFCORpath].

Ann Pathol 2014 Feb 22;34(1):64-9. Epub 2014 Feb 22.

Service ORL-CCF, hôpital Tenon, AP-HP, université Paris-VI, 4, rue de la Chine, 75020 Paris, France.

Aerodigestive tract tumors are very diverse, either in terms of location, or histologically. Also, this heterogeneity poses particular problems for the histological diagnosis but also for the establishment of the most appropriate treatment. Thus, the network REFCOR (réseau d'expertise français sur les cancers ORL rares/French expert network on rare ENT cancers) was created to better understand these issues, by proposing an epidemiological and diagnostic approach with research collaborations. This network is dedicated to all primary malignant tumors of the salivary glands, ear, nasal cavity and sinuses and all head and neck malignancies other than conventional squamous cell carcinoma. The REFCORpath network consists of expert pathologists and offers, through a network of scanned images, a second opinion or even a third.
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http://dx.doi.org/10.1016/j.annpat.2014.01.006DOI Listing
February 2014

Multicenter study to assess endoscopic resection of 159 sinonasal adenocarcinomas.

Ann Surg Oncol 2014 Apr 22;21(4):1384-90. Epub 2013 Nov 22.

Otorhinolaryngology, Head and Neck Surgery Department, University Hospital Rangueil-Larrey, Toulouse, France.

Purpose: This study was designed to assess the efficacy and morbidity of the endoscopic endonasal approach for the treatment of sinonasal adenocarcinomas.

Methods: This was a retrospective, multicenter study of nine French tertiary referral centers, including untreated patients. All patients were operated by an endoscopic approach. Tumors were classified according to the UICC 2002. Demographic, therapeutic, histological, morbidity data, and the course of the disease were recorded. Survival rates were obtained using the Kaplan-Meier method.

Results: A total of 159 patients were included with a mean age of 69 years. There were 19T1, 62T2 (1M1), 36T3 (1N1), 26T4a, and 16T4b (1N2a-1N2c). The mean duration of hospitalization was 4.4 days. The histologic outcomes showed that the olfactory cleft, the posterior and anterior ethmoid sinus, and the sphenoid, maxillary, and frontal sinuses were invaded in 95, 64, 55, 19, 7, and 3 % of cases, respectively. Histologic margins were positive in 17 % (1T1, 4T2, 3T3, 2T4a, and 8T4b). In total, 130 patients received adjuvant radiotherapy on the primary tumor site (58 Gy), 24 cases were not irradiated, and 5 refused treatment. The mean follow-up was 32.5 ± 24 months. The complication rate was 19 %: 6 epistaxis, 3 meningitis, 6 CSF leaks, 2 dacryocystitis, and 8 septoplasties. The recurrence rate was 17.6 % (28 cases) within 23 ± 21 months. Eleven patients underwent a second surgical procedure. Nine patients died of their disease (3T2, 2T3, 4T4b). The global and disease-specific, recurrence-free survival rate at 3 years was 74 and 84 % respectively.

Conclusions: The endoscopic approach seems to be efficient to remove sinonasal adenocarcinoma with low morbidity.
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http://dx.doi.org/10.1245/s10434-013-3385-8DOI Listing
April 2014

Lemierre syndrome: study of 11 cases and literature review.

Head Neck 2014 Jul 17;36(7):1044-51. Epub 2013 Dec 17.

Department of Otolaryngology, Grenoble University Hospital, Boulevard de la Chantourne, BP 217, 38043, Grenoble Cedex 09, France.

Background: Lemierre syndrome is a rare but serious illness that associates throat infection and thrombosis of the internal jugular vein (IJV) or one of its tributaries with subsequent distant septic emboli. The purpose of our study was to review the pathogenesis, clinical presentation, and treatment of this disease.

Methods: Patients with confirmed Lemierre syndrome were included in our retrospective monocentric study. All patients had bacteriologic analyses as well as radiologic imaging.

Results: There were 11 patients in our study (from 1998-2012). Fusobacterium necrophorum was responsible for the infection in 45% of cases. Surgical drainage of pharyngeal, cervical, or mediastinal abscesses was carried out in 8 cases. All patients received broad-spectrum antibiotics. Six patients were admitted to the intensive care unit (ICU). One patient (9%) died.

Conclusion: Treatment with broad-spectrum antibiotics is the primary choice of treatment of Lemierre syndrome. Surgery is indicated in case of abscess formation.
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http://dx.doi.org/10.1002/hed.23410DOI Listing
July 2014

Induction chemotherapy followed by either chemoradiotherapy or bioradiotherapy for larynx preservation: the TREMPLIN randomized phase II study.

J Clin Oncol 2013 Mar 22;31(7):853-9. Epub 2013 Jan 22.

Head and Neck Department, Centre Oscar Lambret, 3 rue Combemale, Lille, France 59020.

Purpose: To compare the efficacy and safety of induction chemotherapy (ICT) followed by chemoradiotherapy (CRT) or bioradiotherapy (BRT) for larynx preservation (LP).

Patients And Methods: Previously untreated patients with stage III to IV larynx/hypopharynx squamous cell carcinoma received three cycles of ICT-docetaxel and cisplatin 75 mg/m(2) each on day 1 and fluorouracil 750 mg/m(2) per day on days 1 through 5. Poor responders (< 50% response) underwent salvage surgery. Responders (≥ 50% response) were randomly assigned to conventional radiotherapy (RT; 70 Gy) with concurrent cisplatin 100 mg/m(2) per day on days 1, 22, and 43 of RT (arm A) or concurrent cetuximab 400 mg/m(2) loading dose and 250 mg/m(2) per week during RT (arm B). Primary end point was LP at 3 months. Secondary end points were larynx function preservation (LFP) and overall survival (OS) at 18 months.

Results: Of the 153 enrolled patients, 116 were randomly assigned after ICT (60, arm A; 56, arm B). Overall toxicity of both CRT and BRT was substantial following ICT. However, treatment compliance was higher in the BRT arm. In an intent-to-treat analysis, there was no significant difference in LP at 3 months between arms A and B (95% and 93%, respectively), LFP (87% and 82%, respectively), and OS at 18 months (92% and 89%, respectively). There were fewer local treatment failures in arm A than in arm B; salvage surgery was feasible in arm B only.

Conclusion: There is no evidence that one treatment was superior to the other or could improve the outcome reported with ICT followed by RT alone (French Groupe Oncologie Radiothérapie Tête et Cou [GORTEC] 2000-01 trial [Induction CT by Cisplatin, 5FU With or Without Docetaxel in Patients With T3 and T4 Larynx and Hypopharynx Carcinoma]). The protocol that can best compare with RT alone after ICT is still to be determined.
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http://dx.doi.org/10.1200/JCO.2012.42.3988DOI Listing
March 2013

Sphenoid sinus fungus ball.

Eur Arch Otorhinolaryngol 2013 Mar 1;270(3):893-8. Epub 2012 Aug 1.

Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital of Grenoble, PO Box 217, 38043, Grenoble Cedex 9, France.

The objective of this retrospective study is to present a large series of patients with sphenoid sinus fungus ball (SSFB) and describe clinical manifestations, diagnostic workup, surgical treatment, and eventual complications of this disease. We included patients operated on for this disease over a 14-year period. All patients benefited from mid-to-long-term follow-up. There were 28 patients (18 females, 10 males, mean age 64 years). Main symptoms were posterior rhinorrhea and headache. Less common symptoms were alteration of vision or ocular mobility and cacosmia. Preoperative diagnosis was based on nasal endoscopy and CT scanning. MRI was performed in case of suspicion of a tumor, an intraorbital or intracranial invasion. Treatment consisted in endoscopic transnasal or transethmoidal sphenoidotomy with removal of the fungus ball. Specimens were sent to pathology and mycology to confirm diagnosis. Postoperative complications consisted of two cases of epistaxis and two other cases of bacterial superinfection of the operated sphenoid cavity. No recurrence of the fungus ball was seen after a mean follow-up of 13 months. To conclude, SSFB is a relatively uncommon entity, usually due to Aspergillus infection. Although not invasive, if left untreated, it can lead to long-term serious complications. Preoperative nasal endoscopic examination and CT scan are the standard tools for diagnosis. Endoscopic sphenoidotomy with removal of the fungus ball is the current treatment because it has proven effective and has a low morbidity and recurrence rate.
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http://dx.doi.org/10.1007/s00405-012-2121-5DOI Listing
March 2013

Role of radiotherapy in the treatment of nasoethmoidal adenocarcinoma.

Arch Otolaryngol Head Neck Surg 2010 Feb;136(2):143-6

Otorhinolaryngology Department, Rouen University Hospital, France.

Objective: To assess the efficacy of radiotherapy in the treatment of nasoethmoidal adenocarcinoma.

Design: Multicenter, retrospective study.

Setting: Eleven French hospitals.

Patients: The medical records of 418 patients who presented with nasoethmoidal adenocarcinoma from January 1, 1976, through December 31, 2001, were evaluated. A total of 324 patients were treated with a combination of surgery and radiotherapy, and 55 were treated with surgery only.

Main Outcome Measures: Survival rates, disease recurrence, and postoperative complications.

Results: The 5-year Kaplan-Meier survey revealed survival rates of 64.5% for the surgery-only group and 70.8% for the combined-treatment group. In the surgery-only group, 28 patients (51%) had disease recurrence (24 local, 2 regional, and 2 distant). Of the 55 patients in the combined-treatment group, 31 patients (56%) had disease recurrence (29 local, 1 regional, and 1 distant). Immediate postoperative complications in the combined-treatment group were hemorrhages in 2 patients, meningitis in 3 patients, and cerebrospinal fluid leakage in 4 patients, but no deaths occurred. In the surgery-only group, 1 patient had meningitis, 2 had cerebrospinal fluid leaking but no hemorrhage, and 5 died postoperatively.

Conclusion: The results of this retrospective study suggest that radiotherapy can be used to treat nasoethmoidal adenocarcinoma, but its usefulness should be confirmed with further prospective studies.
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http://dx.doi.org/10.1001/archoto.2009.212DOI Listing
February 2010

Computed tomography measurements for airway stent insertion in malignant airway obstruction.

J Bronchology Interv Pulmonol 2010 Jan;17(1):22-8

*Clinique d'Oto-Rhino-Laryngologie, Pôle tête et cou et Chirurgie réparatrice §Clinique de Pneumologie, Pôle de Médecine Aiguë et Communautaire ∥Pôle Imagerie ¶Département d'Anesthésie Réanimation ♯Département de Pharmacie, CHU de Grenoble †InsermU823, Epidémiologie des cancers et affections graves, Institut Albert Bonniot ‡Université Joseph Fourier, Grenoble, France.

Background: Metallic airway stents for malignant airway obstruction are considered safe, yet are not without complications. This study reviews the role of computed tomography (CT) airway measurements for planning stent placement in malignant airway obstruction before the actual therapeutic procedure to avoid invasive diagnostic evaluation before the stent placement and to reduce complications.

Methods: This study is a retrospective review of information from a stent order database and medical records of patients receiving stents for malignant airway obstruction at a university hospital over a 12-year period. CT scans were used to determine stent diameter by calculating mean diameters of healthy adjacent zones (proximal and distal), stent length (length of diseased airway), and location and number of potential stents. Results of CT planning before bronchoscopy were judged by complication rates.

Results: Patient population consisted of 69 patients, 61.7±14.0 years old, 40 males, in whom 92 stents were inserted. The most frequent cause of airway obstructions was tracheobronchial cancer (32). All patients had nitinol stent placement; 66 stents were covered and 26 were uncovered. Follow-up time was 1 to 1067 days (median: 35 days). Complication rate was 10.1% and mainly involved the patients with tracheal obstruction (6). Complications included stent fractures (2), migration (2), granuloma (1), and infectious tracheitis (2). One early death within 24 hours after the procedure was not related to stent placement. Five patients required follow-up therapeutic bronchoscopy to treat the complications.

Conclusions: These results suggest that prestent planning by noninvasive method of obtaining CT scan provides optimal stent size and position, possibly avoiding a diagnostic bronchoscopy and reducing complications. Further prospective study is needed to confirm these results because of limitation of this study's design.
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http://dx.doi.org/10.1097/LBR.0b013e3181ccadbeDOI Listing
January 2010

An acute ischemic stroke secondary to sphenoid sinusitis.

Ear Nose Throat J 2009 Nov;88(11):E23-8

Department of Otorhinolaryngology-Head and Neck Surgery, Albert Michallon University Hospital, Grenoble, Cedex 09, France.

Acute isolated sphenoid sinusitis is a relatively uncommon entity. Because its symptoms and clinical findings are nonspecific, it can be easily misdiagnosed. Left unrecognized and untreated, it can lead to several well-known and severe complications, including meningitis, cerebral abscess, cavernous sinus thrombosis, and epidural or subdural empyema. We report the case of a 28-year-old woman with acute sphenoid sinusitis complicated by ischemic stroke in the left caudate nucleus, lentiform nucleus, and posterior part of the internal capsule. The stroke was diagnosed on magnetic resonance imaging. Also, magnetic resonance angiography showed a narrowing of the internal carotid artery and a narrowing of the first part of the left anterior and middle cerebral arteries (A1 and M1 segments). The patient was treated with medical therapy, including antibiotics, and surgical drainage of the sphenoid sinus via an endoscopic approach. Her outcome was good, and she experienced minimal neurologic sequelae. We discuss the possible explanations for this rare complication.
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November 2009

Randomized phase III trial comparing induction chemotherapy followed by radiotherapy to concomitant chemoradiotherapy for laryngeal preservation in T3M0 pyriform sinus carcinoma.

Acta Otolaryngol 2010 ;130(1):150-5

Department of Otolaryngology - Head and Neck Surgery, Saint-Etienne University Hospital Center, Loire Cancer Institute, Saint-Etienne, France.

Conclusions: Conventional radiotherapy with concurrent cisplatin is significantly superior to induction cisplatin fluorouracil chemotherapy followed by radiotherapy in terms of laryngeal preservation in patients with T3 hypopharyngeal carcinoma. Despite a high rate of laryngeal preservation no survival benefit was recorded in this selected population.

Objectives: To compare conventional radiotherapy with concurrent cisplatin to induction chemotherapy with cisplatin fluorouracil followed by conventional radiotherapy. The primary end point was the preservation of the larynx. The secondary end points included toxicity, causes of death, and survival rates.

Patients And Methods: Seventy-one adult patients with previously untreated resectable T3 pyriform sinus squamous cell carcinoma were enrolled in the multicenter prospective randomized phase III trial. They were evaluated for organ preservation, survival rates, and toxic reactions.

Results: The rates of laryngeal preservation at 2 years were 68% for the induction chemotherapy (IC) group and 92% for the chemoradiotherapy (CR) group (p = 0.016). At 2 years, the event-free survival rates were 36% and 41% for the IC group and CR group, respectively.
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http://dx.doi.org/10.3109/00016480902914080DOI Listing
October 2010

Gastro-omental free flap in the reconstruction of the unfavourable hypopharyngeal defects: a functional assessment.

J Plast Reconstr Aesthet Surg 2009 Nov 25;62(11):1367-73. Epub 2008 Nov 25.

Department of ENT-HNS, University Medical Center of Grenoble, Grenoble, France.

Background: Reconstruction flaps following major head and neck cancer surgery should consider the state of tissue at the recipient site. This study presents the cumulative experience of the use of the gastro-omental free flap (GOFF) for pharyngeal reconstruction in cases with unfavourable recipient site conditions.

Methods: The GOFF reconstruction procedure and postoperative follow-up are described in details, and the functional results are analysed retrospectively.

Results: Fifteen patients underwent GOFF reconstruction. Previous treatments included radiotherapy, chemotherapy and surgery. Postoperatively, two patients (13%) developed partial flap necrosis, and four (27%) patients developed fistula and flap stenosis. On the functional level, eight (53%) patients developed oesophageal speech at different levels of audibility, and all patients developed oral alimentation ranging from a mixed diet with supplements to a regular oral diet.

Conclusions: The GOFF is characterised by multiple survival advantages that favour its use in the presence of inhospitable recipient site conditions.
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http://dx.doi.org/10.1016/j.bjps.2008.05.042DOI Listing
November 2009

[Risk factors for cancers of the oral cavity, pharynx (cavity excluded) and larynx].

Presse Med 2008 Sep 27;37(9):1229-40. Epub 2008 May 27.

Clinique ORL, Pôle tête et cou et chirurgie réparatrice, CHU de Grenoble, F-38043 Grenoble, France.

Objective: To review the risk factors for squamous cell carcinoma of the oral cavity, pharynx, and larynx.

Methods: Review of the literature using the Medline digital database (1980-2007). Previously published studies or studies not found in the database were included if relevant. Four types of studies were selected: (1) epidemiological, (2) toxicologic, (3) clinical, and (4) fundamental research. Publications concerning cancer of the nasopharynx were excluded. This work is based upon the ANAES guide for analysis of the literature and rating of guidelines, published in January 2000.

Results: The principal risk factors are tobacco and alcohol. Other risk factors, particularly infectious (viral) or environmental (nutritional and occupational), are also involved. From this analysis we conclude that: (1) most clinical and fundamental publications concern smoking and alcohol use; (2) studies of other risk factors are relatively old, especially those concerning nutritional and occupational factors; (3) most publications have a low level of scientific proof (grade C, levels 3 and 4). These 3 points explain the delay in the analysis of risk factors for upper aerodigestive tract (UADT) cancers.

Conclusions: We must make up for this delay by prospective studies that include very large samples and use thorough and multivariate statistical analyses to estimate the impact of various toxic substances on the incidence of UADT cancer. This demands: (1) awareness on the part of all physicians who manage this type of cancer of the need to ask questions about exposure to risk factors besides than tobacco and alcohol; (2) collaboration between these physicians as well as with general practitioners, epidemiologists, nutritionists, and occupational physicians.
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http://dx.doi.org/10.1016/j.lpm.2008.03.010DOI Listing
September 2008

Cervical cellulitis and mediastinitis following esophageal perforation: a case report.

World J Gastroenterol 2008 Mar;14(9):1450-2

Department of ENT-HNS, University Medical Center of Grenoble, 38043 Grenoble Cedex 09, France.

Unlabelled: Chicken bone is one of the most frequent foreign bodies (FB) associated with upper esophageal perforation. Upper digestive tract penetrating FB may lead to life threatening complications and requires prompt management. We present the case of a 52-year-old man who sustained an upper esophageal perforation associated with cervical cellulitis and mediastinitis. Following CT-scan evidence of FB penetrating the esophagus, the impacted FB was successfully extracted under rigid esophagoscopy. Direct suture was required to close the esophageal perforation. Cervical and mediastinal drainage were made immediately. Naso-gastric tube decompression, broad-spectrum intravenous antibiotics, and parenteral hyperalimentation were administered for 10 d postoperatively. An esophagogram at d 10 revealed no leak at the repair site, and oral alimentation was successfully reinstituted.

Conclusion: Rigid endoscope management of FB esophageal penetration is a simple, safe and effective procedure. Primary esophageal repair with drainage of all affected compartments are necessary to avoid life-threatening complications.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2693698PMC
http://dx.doi.org/10.3748/wjg.14.1450DOI Listing
March 2008

Adenocarcinoma of Ethmoid: a GETTEC retrospective multicenter study of 418 cases.

Laryngoscope 2008 Mar;118(3):437-43

ENT department, Rouen University Hospital, Rouen, France.

Objective: To determine risk factors and evaluate the treatment of ethmoid adenocarcinoma. Epidemiologic data were recorded and compared with the literature.

Materials And Methods: A multicenter and retrospective study. The medical records of 418 patients who had presented with ethmoid adenocarcinoma at 11 French hospitals from 1976 to 2001 were analyzed to determine the clinical characteristics and treatment of the disease.

Results: The gender ratio was 2.8 men per 1 woman. Toxic exposure was classic for this lesion, exposure to wood and leather for most cases. The mean age was 63 years (range 31-91). Symptoms were nonspecific and based on clinical rhinologic signs. Nasal endoscopy after mucosal retraction was found useful to evaluate the extension of the lesion and to perform biopsies. Computed tomography scan and magnetic resonance imagery must be carried out prior to treatment to define extra nasal extension. The survival rate was significantly influenced by the size of the lesion (T4, N+) and extension to brain or dura. Surgery with postoperative radiotherapy remains the treatment of choice. Total excision must be a major priority, as confirmed in our series.

Conclusion: This retrospective study was, to our knowledge, the largest ever reported in the literature. This series confirmed the risk factor of this lesion as well as the lesion's influence on the survival rate. Surgery is the most important part of the treatment. Local recurrences were responsible for the poor prognosis of this lesion.
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http://dx.doi.org/10.1097/MLG.0b013e31815b48e3DOI Listing
March 2008

Course and prognosis of basaloid squamous cell carcinoma of the head and neck: a case-control study of 62 patients.

Eur J Cancer 2008 Jan 21;44(2):244-50. Epub 2007 Dec 21.

Department of ENT-HNS, University Medical Center of Grenoble, 38043 Grenoble Cedex 09, France.

Objective: To describe the natural history and evaluate the prognosis of basaloid squamous cell carcinoma (BSCC) of the upper aero-digestive tract as compared to the usual squamous cell carcinoma (SCC).

Materials And Methods: Sixty-two patients with BSCC and 62 patients with SCC were matched with regards to TNM classification, localisation and therapeutic modalities. Histological criteria, follow-up and 5-year survival were compared among the two groups.

Results: Survival rates were significantly higher in patients with SCC as compared to patients with BSCC. The rate of distant metastasis was six times higher in cases of BSCC, which was the major cause of mortality.

Conclusion: This study reveals that BSCC has distinct histo-pathologic features and an aggressive clinical course, justifying its consideration as a separate entity with poor prognosis. The authors propose to systematically perform a chest CT-scan and FDG-PET to rule out early distant metastasis and to include adjuvant chemotherapy in treatment protocols.
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http://dx.doi.org/10.1016/j.ejca.2007.11.008DOI Listing
January 2008

Osteoplastic maxillotomy approach for infraorbital nerve schwannoma, a case report.

Head Neck 2008 Mar;30(3):401-4

Department of Otorhinolaryngology-Head and Neck Surgery, University Medical Center of Grenoble, Grenoble, France.

Background: Extracranial schwannomas can readily occur in the head and neck region and rarely involve the trigeminal nerve. As a rule, their treatment is surgical and dictated by the location of the tumor and nerve of origin.

Methods: We describe a case of a 14-year-old boy with a mass invading right nasal fossa, maxillary sinus, orbital floor, pterygopalatine fossa, and infratemporal fossa. The diagnosis of a nerve sheath tumor was evoked after angiography showed no vascular blush.

Results: The tumor was removed through a Weber-Fergusson incision with subciliary extension followed by maxillozygomatic osteotomy. This approach showed the tumor to be coming from the infraorbital nerve and allowed complete tumor exposure and removal. Pathology confirmed the diagnosis of a schwannoma.

Conclusion: We describe the osteoplastic maxillotomy approach which we felt most appropriate for removal of the infraorbital schwannoma and discuss other possible surgical options for this type of tumor.
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http://dx.doi.org/10.1002/hed.20702DOI Listing
March 2008

What is the diagnostic value of flexible bronchoscopy in the initial investigation of children with suspected foreign body aspiration?

Int J Pediatr Otorhinolaryngol 2007 Sep 18;71(9):1383-90. Epub 2007 Jun 18.

University Hospital, ENT Department, CHU A. Michallon, Service ORL, 38043 Grenoble, France.

Purpose Of The Study: The diagnosis and early bronchoscopic extraction of a foreign body (Fb) in children are life-saving measures. Many studies have described the manifestation of foreign body aspiration (FbA); however, only a few analyzed the role of flexible bronchoscopy in the diagnosis of FbA. The aim of this work is to define the indications of flexible bronchoscopy in the management algorithm of suspected FbA.

Setting: This study was conducted at a tertiary referral University Medical Center with an outpatient clinic and a 20-bed pediatric emergency unit.

Material And Methods: Between January 2002 and July 2006 children referred with suspected FbA were included in this prospective study. Children with asphyxiating FbA requiring immediate rigid bronchoscopy, were excluded. If there was no convincing evidence of FbA, a diagnostic flexible bronchoscopy was performed under local anesthesia. In the case where a Fb was actually found, extraction was always performed by rigid bronchoscopy.

Results: Seventy cases (median age: 2 years, males: 44/females: 26) were analyzed. Among the 19 children who underwent flexible bronchoscopy first, 7 (37%) had a Fb. Among the 51 who underwent rigid bronchoscopy first, 43 had a Fb and 8 (16%) had a negative first rigid bronchoscopy. Predictive signs of a bronchial Fb were a radiopaque Fb, foreign body aspiration syndrome (FbAS) associated with unilaterally decreased breath sounds or localized wheezing and obstructive emphysema or atelectasis.

Conclusion: In case of suspected FbA in children, the following management algorithm is suggested: rigid bronchoscopy should be performed solely in case of asphyxia, finding of a radiopaque Fb, or in the presence FbAS associated with unilaterally decreased breath sounds, localized wheezing and obstructive radiological emphysema, or atelectasis. In all other cases, flexible bronchoscopy should be performed first for diagnostic purposes.
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http://dx.doi.org/10.1016/j.ijporl.2007.05.012DOI Listing
September 2007

[Aberrant methylation of tumor suppressor genes in head and neck squamous cell carcinoma: is it clinically relevant?].

Bull Cancer 2007 Feb;94(2):191-7

Service ORL et Chirurgie cervicofaciale.

During malignant transformation, the malignant cell accumulates epigenetic abnormalities that do not alter the DNA sequence but are transmissible during divisions and modify genes expression. The methylation of CpG islands in the tumor suppressor genes (TS genes) promoters inhibits their transcription ; it is a mecanism of gene inactivation as frequent as allelic deletions. The methylation profile (or panel of methylated genes in a tumor), similarly to allelic deletions, varies with the tumor histology. Within head and neck squamous cell carcinoma (oral cavity, larynx and oropharynx), 19 genes have been analysed, among them 5 are frequently methylated, i.e. : p16, ECAD, DAPK, MGMT et TIMP3. The method of methylation analysis, based on a bisulfite treatment followed by a PCR amplification, is sensitive and specific enough to allow the detection of abnormalities in biological fluid that drain the tumor or in circulating tumoral DNA. In the head and neck squamous cell carcinoma, correlation between the methylation profile in tumor and paired saliva is excellent ; thus methylation analysis in saliva is a very promising approach for early cancer detection in high risk patients or for the post treatment follow up and rapid diagnosis of relapse. The methylation signature might also reflect the tumor prognosis and complete the histology to define the diagnosis. Finally, DNA methylation is reversible with demethylating agents, a new avenue for cancer therapy in association with conventional chemotherapy.
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February 2007

Tumor-specific methylation in saliva: a promising biomarker for early detection of head and neck cancer recurrence.

Clin Cancer Res 2007 Feb;13(4):1179-85

Institut National de la Sante et de la Recherche Medicale/Université Joseph Fourier, La Tronche, France.

Purpose: Our goal was to define tumor and saliva gene methylation profile of head and neck squamous cell carcinoma and to evaluate its prognostic significance and its biomarker potential for early detection of relapse.

Experimental Design: We prospectively analyzed 11 genes by methylation-specific PCR on primary tumors, histologically normal adjacent mucosa, and saliva from 90 French patients at diagnosis and during follow-up as well as on 30 saliva specimens from control-matched patients with nonmalignant head and neck pathology. Five additional genes were analyzed on 50 tumors of the series.

Results: Methylation of TIMP3, ECAD, p16, MGMT, DAPK, and RASSF1 was the most frequently observed in tumors and paired saliva samples were analyzed at diagnosis, with an excellent agreement between both samples. At least one of these six genes was methylated in >75% of the samples without additional positive samples when other genes were analyzed. Methylation profile was similar in newly diagnosed and second primary cancers. Aberrant methylation was not associated with a worse prognosis. Ninety percent of normal adjacent mucosa and all control saliva samples were negative. Twenty-two patients were followed after treatment; abnormal methylation was detectable in the saliva of five patients few months before clinical and 2-deoxy-2[(18)F]fluoro-d-glucose-positron emission tomography signs of relapse, allowing curable surgery. Saliva samples were negative for the 17 other patients: 16 were in remission and only 1 relapsed.

Conclusions: Gene methylation in saliva is a promising biomarker for the follow-up and early detection of still curable relapses of head and neck squamous cell carcinoma patients.
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http://dx.doi.org/10.1158/1078-0432.CCR-06-2027DOI Listing
February 2007

Epistaxis and its management: an observational pilot study carried out in 23 hospital centres in France.

Rhinology 2006 Jun;44(2):151-5

Department of Otorhinolaryngology-Head & Neck Surgery Centre Hospitalo-Universitaire, Poitiers, BP 577- 86021, Poitiers Cedex, France.

Objective: The purpose of this study is to describe the treatment of epistaxis in hospital emergency departments and to identify the principal risk factors for more severe episodes of bleeding.

Study Protocol: Prospective cross-sectional epidemiological study

Material And Methods: This study was carried out in 23 hospital centres in France, most of them teaching hospitals. Every patient presenting non-traumatic epistaxis or else associated with hereditary hemangioma during two consecutive and separate 24-hour periods were included.

Results: Fifty patients were included in the study. Nasal bleeding was stopped within 30 minutes for 47 patients. Fourteen patients were hospitalized. The risk factors for severe epistaxis included either copious bleeding or else bleeding for more than 6 hours or patients aged 65 and over. A history of repeated nasal packing and/or taking medication with a known hemorrhagic risk was associated with the amount and duration of bleeding (p < 0.05).

Conclusion: Risk factors for severe epistaxis should be identified as to improve patient care and avoid treatment failure or useless hospitalization.
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June 2006

Use of tubed gastro-omental free flap for hypopharynx and cervical esophagus reconstruction after total laryngo-pharyngectomy.

Eur Arch Otorhinolaryngol 2005 May 7;262(5):362-7. Epub 2004 Sep 7.

ENT Department, University Hospital of Grenoble, P.O. Box 217, 38043 Grenoble, France.

In case of total laryngo-pharyngectomy (TLP), replacement of the pharyngoesophageal segment is more often done with jejunal flap; however, in some cases, this flap doesn't represent the best surgical technique of reconstruction. The tubed gastro-omental free flap (TGO) offers an alternative procedure in selective cases. The objective of the study was to assess the TGO as a method of pharyngoesophageal reconstruction. Our study was based on a literature review and a retrospective study of six consecutive cases of TGO reconstruction after TLP. Six patients aged from 52 to 70 years underwent TGO reconstruction after TLP. Five patients had previously received systemic chemotherapy and external irradiation at curative doses, and three had undergone previous surgery. No abdominal complication occurred. Partial necrosis of the gastric flap occurred in one case. Except for this case, the feeding tube could be removed after 15 days. One patient was successfully treated with pneumatic esophageal dilatation for stricture 2 months after surgery. Four patients died of loco-regional tumor evolution or distant metastatic disease. For both of the patients who survived (mean follow-up, 40 months), a normal diet and an esophageal voice were obtained. The TGO offers a safe method of reconstructing the pharyngoesophageal segment in a surgical field compromised of previous multimodal therapy.
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http://dx.doi.org/10.1007/s00405-004-0828-7DOI Listing
May 2005

Primary tracheal schwannoma: one case report and a literature review.

Eur Arch Otorhinolaryngol 2005 Feb 2;262(2):157-60. Epub 2004 Apr 2.

ENT Department, University Hospital, 38043, Grenoble Cedex 09, France.

We report a case of primary tracheal schwannoma causing symptoms of airway obstruction in a 51-year-old woman. There was no history of pulmonary disease. The patient had been coughing and suffering from progressive dyspnea for over 1 year. Medical treatment with bronchodilatators had no effect. Computerized tomography and bronchoscopy demonstrated a polypoid mass located inside the trachea's cervical segment, obstructing 50% of the lumen. A biopsy was not attempted because of the tumor's vascularity to avoid bleeding. Tracheal resection with primary anastomosis was performed. The diagnosis was confirmed with histological analysis. It revealed a benign neurogenic tumor of Schwann's cell origin. Schwannoma of the trachea is extremely rare. Only 23 cases have been reported previously. Most of them occur in adults (19/23, 82.6%) and are located in the lower trachea. They usually have a long natural history, causing symptoms only after they have attained a large size. The treatment of choice is surgical removal.
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http://dx.doi.org/10.1007/s00405-004-0778-0DOI Listing
February 2005

Malakoplakia of the neck.

Arch Otolaryngol Head Neck Surg 2003 Nov;129(11):1240-2

Department of Ear, Nose, and Throat Surgery, Grenoble University Hospital, Grenoble, France.

Malakoplakia that presents in the head and neck is very rare. We describe a 76-year-old man who presented with an inflammatory mass in the lateral aspect of the neck that clinically mimicked a tumoral expansion and was consistent with a cervical malakoplakia. To our knowledge, this is the second case reported with manifestations of this chronic inflammatory disease localized in the neck. Malakoplakia is a rare granulomatous disease that most frequently involves the genitourinary tract and occurs in an immunodeficient host. The symptoms are nonspecific and the diagnosis is based on the histologic findings. In the present case, the biopsy specimen of the cervical mass revealed a collection of numerous von Hansemann cells containing Michaelis-Gutmann bodies, which are pathognomonic of malakoplakia. Bacteriologic analysis identified Escherichia coli. The evolution was favorable after surgical excision and prolonged antibiotic therapy with fluoroquinolones.
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http://dx.doi.org/10.1001/archotol.129.11.1240DOI Listing
November 2003

Chronic hypoxia protects against gamma-irradiation-induced apoptosis by inducing bcl-2 up-regulation and inhibiting mitochondrial translocation and conformational change of bax protein.

Int J Oncol 2003 Oct;23(4):1033-41

Fundamental and Applied Bioenergetics Laboratory, INSERM E02-21, Joseph Fourier University, BP 53X, 38041 Grenoble cedex 9, France.

Malignant tumours contain zones of chronic or acute hypoxia, which influence their prognosis and progression. The goal of our study was to understand the role of hypoxia in radio-resistance in a squamous cell carcinoma cell line of the head and neck (KB-3-1 cells). Cell growth was evaluated by Trypan blue exclusion under chronic hypoxia (3-5% O2) for 4 weeks or under normal conditions (21% O2). Cells were then gamma-irradiated either by X-ray (2-6 Gy) or UV-C radiation (0.001-10 J/cm(2)). Apoptosis was estimated by double staining with orange acridine and ethydium bromide and fluorescence microscopy. DNA content was estimated by FACS analysis. Expression of Bax, Bcl-2 and P53 was assessed by immunofluorescence and Western blotting. ROS production was measured by dichlorofluorescein fluorescence. Cell growth depends on oxygen tension. It decreased by 42 and 70% at 5 and 3% O2 compared to control with a significant cell cycle arrest rather than increased mortality. Hypoxic cells are more radio-resistant (x2.5) than normoxic cells. Under chronic hypoxia, Bcl-2 increased considerably in cells compared to control, while Bax and P53 did not change. After irradiation, in hypoxic cells very weak expression of the pro-apoptotic Bax protein and no translocation of Bax to the mitochondria were observed. In addition, irradiation of control KB-3-1 cells demonstrated a large increase in ROS production (x2) compared to cells irradiated identically under hypoxia. In conclusion, chronic hypoxia: i) seems to slow-down cell growth of KB-3-1 cells without inducing apoptosis, ii) induces Bcl-2 overexpression and prevents radiation-induced apoptosis by inhibiting ROS production and altering Bax subcellular redistribution and conformational changes.
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October 2003