Publications by authors named "Christian Righini"

49 Publications

[A thyroid-like low-grade nasopharyngeal papillary adenocarcinoma].

Ann Pathol 2021 Jan 22. Epub 2021 Jan 22.

Clinique universitaire d'oto-rhino-laryngologie et de chirurgie cervico-faciale, pôle PALCROS, hôpital Nord Michallon, CHU de Grenoble Alpes, CS 10217, 38043 Grenoble cedex 9, France; Pôle médecine, université de Grenoble Alpes, domaine de la Merci, 38700 La Tronche, France; Unité Inserm UJF/U823, centre de recherche Albert-Bonniot, Grenoble, France.

Thyroid-like low-grade nasopharyngeal papillary adenocarcinoma is a rare histopathological entity. Patients usually complain of nasal obstruction and epistaxis. Diagnosis is confirmed on endonasal biopsy using immunohistochemical studies. Surgery is the treatment of choice and this pathology exhibits no metastasizes nor recurrence after treatment.
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http://dx.doi.org/10.1016/j.annpat.2020.08.006DOI Listing
January 2021

Locoregional control, progression-free survival and morbidity rates in N3 head and neck cancer patients with low primary tumour burden: A 301-patient study.

Clin Otolaryngol 2020 Nov 16;45(6):877-884. Epub 2020 Sep 16.

Radiation oncology, Centre François Baclesse / ARCHADE, Caen, France.

Objectives: In patients with N3 head and neck squamous cell carcinoma (HNSCC), N3 disease is associated with high regional relapse and metastatic risks. Patients with resectable N3 disease have better prognosis although their metastatic risk may be similar as in patients with unresectable disease. Neoadjuvant chemotherapy has been associated with lower metastatic rates, but N3 patients may die of rapid locoregional progression. We assessed outcomes with the three modalities in patients with low primary burden to better assess the specific prognosis of N3 disease.

Methods: This retrospective multicentric study included T0-2 N3 HNSCC patients. Outcomes and morbidity in upfront neck dissection (uND) vs non-surgical groups were analysed and oncological outcomes and morbidity compared between patients undergoing chemoradiation or neoadjuvant chemotherapy in patients with initially unresectable N3 nodes.

Results: Of 301 patients, 142 (47%) underwent uND, 68 (23%) neoadjuvant chemotherapy and 91 (30%) chemoradiation. The 24- and 60-month incidence of locoregional relapse was 23.2% [18.3%; 28.4%] and 27.4% [21.8%; 33.3%]; it was lower in patients undergoing uND (P = .006). In patients with non-surgical treatments, success rates were 57.8% [49.4%; 66.3%] after chemoradiation and 38.1% [29.6%; 46.7%] after neoadjuvant chemotherapy (P = .001). Overall morbidity was more frequent in patients undergoing uND (68.8%) (P < .001).

Conclusion: uND improved locoregional control but increased morbidity and showed no survival benefit. Success rates were better after chemoradiation versus neoadjuvant chemotherapy. Neoadjuvant chemotherapy did not reduce metastatic rates but non-responders to chemoradiation had poor PFS and survival rate, suggesting that predictive criteria are warranted.
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http://dx.doi.org/10.1111/coa.13615DOI Listing
November 2020

Consensus on resectability in N3 head and neck squamous cell carcinomas: GETTEC recommendations.

Oral Oncol 2020 07 23;106:104733. Epub 2020 Apr 23.

Radiation Oncology, Centre François Baclesse/ARCHADE, Caen, France. Electronic address:

Background: Among patients with T0-2 N3 head and neck squamous cell carcinomas (HNSCC), those undergoing upfront neck dissection have better oncological outcomes. However, there is no consensual definition of disease resectability of N3 nodes, leading to major treatment attrition and interpretation biases between studies. We established a Delphi method-based consensus to define resectability and impact on decision-making for upfront neck dissection in N3 patients.

Methods: The Delphi method was designed as recommended by the French Haute Autorite de Sante among head and neck surgeons from university hospitals and cancer centers, using a 24-item questionnaire. Strong and relative agreements were subsequently established, and recommendations were written. The resulting recommendations were assessed by 30 independent surgeons.

Results: N3 nodes with intraparenchymal brain invasion, foramen invasion, skull base erosion, nodes requiring bilateral XII cranial nerve sacrifice, retropharyngeal N3 node or a node above the plan of soft palate are major contraindications to neck dissection. When neck dissection requires unilateral sacrifice of the IX or X or XII cranial nerves or cervical nerve roots, upfront neck dissection may be performed, based on a case-by-case assessment of other patient and tumor estimates.

Conclusion: Consensual contraindications to neck dissection in patients with T0-2 N3 HNSCC were defined among French head and neck surgeons as concerns skull base invasion, retropharyngeal nodes and bilateral XII cranial nerve sacrifice. This consensus should allow more reliable comparisons between surgical and non-surgical strategies in N3 patients.
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http://dx.doi.org/10.1016/j.oraloncology.2020.104733DOI Listing
July 2020

A prospective multicentre REFCOR study of 470 cases of head and neck Adenoid cystic carcinoma: epidemiology and prognostic factors.

Eur J Cancer 2020 May 11;130:241-249. Epub 2020 Mar 11.

Sorbonne University, APHP, Department of ENT-Head and Neck Surgery, Tenon Hospital, 4 Rue de La Chine, 75020, Paris, France. Electronic address:

Background: Adenoid cystic carcinoma (ACC) accounts for 1% of malignant head and neck tumours [1] and 10% of salivary glands malignant tumours. The main objective of our study is to investigate the prognostic factors influencing the event-free survival (EFS) of patients with ACC.

Patients And Methods: A multicentre prospective study was conducted from 2009 to 2018. All 470 patients with ACC whose survival data appear in the REFCOR database were included in the study. The main judgement criterion was EFS. Both a bivariate survival analysis using log-rank test and a multivariate using Cox model were performed using the R software.

Results: Average age was 55 years. Females accounted for 59.4% of the cohort. The body mass index (BMI) was normal in 86% of cases. Tumours were located in minor salivary glands in 60% of cases. T3/T4 stages represented 58%; 89% of patients were cN0. histological grade III was observed on 21% of patients. The EFS and overall 5-year survival rates were 50% and 85%, respectively. After adjustment, the most significant pejorative prognostic factors were age ≥65 years (hazard ratio [HR] = 1.67), BMI<16.5 (HR = 2.62), and lymph node invasion cN (HR = 2.08).

Conclusion: Age, BMI and N stage are the three main clinical prognostic factors determining EFS identified in this prospective series of patients with ACC. Such findings open new research perspectives on the influence of these components on initial patient care.
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http://dx.doi.org/10.1016/j.ejca.2020.01.023DOI Listing
May 2020

Should a neck dissection be performed on patients with cN0 adenoid cystic carcinoma? A REFCOR propensity score matching study.

Eur J Cancer 2020 May 30;130:250-258. Epub 2020 Jan 30.

Sorbonne University, APHP, Department of ENT-Head and Neck Surgery, Tenon Hospital, 4 rue de la chine, 75020, Paris, France. Electronic address:

Background: Patterns of nodal involvement in adenoid cystic carcinoma (ACC) of the head and neck have not been sufficiently assessed to guide a decision of prophylactic neck dissection (ND). The objective of this study is to analyse the influence of ND on event-free survival (EFS) for patients with cN0 ACC.

Patients And Methods: A multicentre prospective study was conducted between 2009 and 2018. Patients presenting cN0 non-metastatic ACC on any site, and who received surgery on the tumour, were included. EFS was the main judgement criterion. A comparative survival analysis between the groups that received a ND versus those that did not was performed, using a propensity score. Analyses were carried out using the R software.

Results: Between 2009 and 2018, 322 patients with cN0 ACC were included, out of which 58% were female. The average age was 53 years. Tumours were in minor salivary glands in 58% of cases, and 52% had T3/T4 stages. ND was performed on 46% of patients. Out of them, seven had histological lymph node invasion, out of which six had tumour infiltration in the mucosa of oral cavity. After propensity score, the median EFS for N0 patients with ND was 72 months (95% Confidence Interval (CI) [48-81]), compared to 73 months (95% CI [52-85]) for patients without ND (HR = 1.33; 95% CI [0.82-2.16]; p = 0.2).

Conclusion: ND of cN0 patients does not provide any benefit on EFS, which suggests that its application on such patients is not necessary.
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http://dx.doi.org/10.1016/j.ejca.2019.12.026DOI Listing
May 2020

Head and neck cancer during pregnancy.

Head Neck 2019 10 22;41(10):3719-3732. Epub 2019 Jul 22.

Service de Radiothérapie, Centre François Baclesse, Caen, France.

Background: The incidence of cancer during pregnancy is low but is slightly increasing. Data on incidence and etiology of head and neck (HN) cancers in pregnant women are rare. We evaluated the frequency, tumor type, associated factors, and specific biomarkers in HN cancers occurring in pregnant (and peripartum) women.

Methods: A systematic literature search was performed on PubMed, for any HN tumor site occurring in pregnant women.

Results: Sixty cases of HN cancers occurring during pregnancy were identified. Most of them were oral cavity cancers. Relationships with oncogenic viruses, hormonal disturbance, and shift in maternal immunity profile were identified.

Conclusion: Carcinogenesis of HN cancers in pregnant women may be led by different cancer type-specific hallmarks. Relevance of these etiological factors with respect to treatments and birth control recommendations is being investigated by the REFCOR in an ambispective study.
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http://dx.doi.org/10.1002/hed.25877DOI Listing
October 2019

Surgery or Radiotherapy of the Primary Tumor in T1-2 Head and Neck Squamous Cell Carcinoma with Resectable N3 Nodes: A Multicenter GETTEC Study.

Ann Surg Oncol 2019 Oct 1;26(11):3673-3680. Epub 2019 Jul 1.

ENT, Service ORL, Chirurgie cervico-maxillo-faciale et audiophonologie, CHU de Poitiers, 2 rue de la Milétrie, 86000, Poitiers, France.

Background: The prognosis of advanced nodal (N3) squamous cell carcinoma of the head and neck (HNSCC) is poor. We investigated whether surgery or radiotherapy of early (T1-2) primary stage HSNCC is preferable to limit the overall morbidity after upfront neck dissection (uND) for N3 disease.

Methods: This retrospective multicentric Groupe d'Étude des Tumeurs de la Tête Et du Cou study included patients undergoing uND and surgery or radiotherapy of their primary. Prognostic factors were evaluated using propensity score matching to account for biases in performing surgery depending on primary site and stage.

Results: Of 189 T1-2, N3 HNSCC patients, 70 (37.0%) underwent uND: 42 with surgery of their primary and 28 with radiotherapy only. Radiotherapy alone was more frequent in patients with hypopharyngeal primaries. All local (N = 3) and regional (N = 10) relapses (included 2 locoregional relapses) occurred within the first 2 years. There were 16 distant metastatic failures. Five-year locoregional relapse and survival incidences were 15.7% and 66.5% and were similar regardless of the treatment of the primary. The overall morbidity rate was 65.2% and was similar after weighting by the inverse propensity score (p = 0.148). The only prognostic factor for morbidity was the radicality of the uND. Prolonged parenteral feeding was not more frequent in patients only irradiated to their primary (p = 0.118). Prolonged tracheostomy was more frequent after surgery of the primary.

Conclusions: In patients with T1-2, N3 HNSCC undergoing uND, radiotherapy and surgery of the primary yield similar oncological outcomes. Morbidity was related to the extent of neck dissection.
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http://dx.doi.org/10.1245/s10434-019-07589-0DOI Listing
October 2019

Gold nanoclusters as a contrast agent for image-guided surgery of head and neck tumors.

Nanomedicine 2019 08 17;20:102011. Epub 2019 May 17.

Cancer Targets & Experimental Therapeutics, Institute for Advanced Biosciences (IAB), University of Grenoble Alpes- INSERM U1209 - CNRS UMR 5309, Grenoble, France. Electronic address:

With the objective to evaluate the potential of ultra-small gold (Au) nanoclusters (NCs) for optical image-guided surgery, we synthesized and characterized AuNCs shelled by zwitterionic or pegylated ligands. The toxicity of the different AuNCs was evaluated on the Head and Neck Squamous Cell Carcinoma (HNSCC) CAL-33 and SQ20B cell lines in vitro. The safer AuNCs were administrated intravenously to mice for the determination of the pharmacokinetic properties. Biodistributions were performed on orthotopic CAL-33 HNSCC-bearing mice. Finally, the AuNCs were used for image-guided surgery, allowing the increase of the survival time vs. control animals, and the number of animals without any local recurrence.
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http://dx.doi.org/10.1016/j.nano.2019.04.014DOI Listing
August 2019

Lemierre Syndrome: Clinical Update and Protocol for a Systematic Review and Individual Patient Data Meta-analysis.

Hamostaseologie 2019 Feb 2;39(1):76-86. Epub 2018 Aug 2.

Center for Thrombosis and Haemostasis, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.

Lemierre syndrome usually affects otherwise healthy adolescents or young adults and occurs at an overall rate of 1 to 10 cases per million person-years with an estimated fatality rate of 4 to 9%. Diagnostic criteria remain debated and include acute neck/head bacterial infection (often tonsillitis caused by anaerobes at high potential for sepsis and vascular invasion, notably ) complicated by local vein thrombosis, usually involving the internal jugular vein, and systemic septic embolism. Medical treatment is based on antibiotic therapy with anaerobic coverage, anticoagulant drugs and supportive care in case of sepsis. Surgical procedures can be required, including drainage of the abscesses, tissue debridement and jugular vein ligation. Evidence for clinical management is extremely poor in the absence of any adequately sized study with clinical outcomes. In this article, we illustrate two cases of Lemierre syndrome not caused by and provide a clinically oriented discussion on the main issues on epidemiology, pathophysiology and management strategies of this disorder. Finally, we summarize the study protocol of a proposed systematic review and individual patient data meta-analysis of the literature. Our ongoing work aims to investigate the risk of new thromboembolic events, major bleeding or death in patients diagnosed with Lemierre syndrome, and to better elucidate the role of anticoagulant therapy in this setting. This effort represents the starting point for an evidence-based treatment of Lemierre syndrome built on multinational interdisciplinary collaborative studies.
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http://dx.doi.org/10.1055/s-0038-1654720DOI Listing
February 2019

Clinical characteristics and prognostic factors of sinonasal undifferentiated carcinoma: a multicenter study.

Int Forum Allergy Rhinol 2018 09 23;8(9):1065-1072. Epub 2018 Jun 23.

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

Background: Sinonasal undifferentiated carcinoma (SNUC) is a very rare entity with a poor prognosis. Due to the lack of studies on the subject, evidence is lacking concerning its management.

Methods: A multicenter collaborative study was conducted to assess treatment strategy, oncological outcome, and prognostic factors.

Results: Definitive analyses focused on 54 patients with a majority of advanced stage; the 3-year overall survival (OS) and 3-year recurrence-free survival (RFS) rates were, respectively, 62.4% and 47.8%. During the follow-up, 18 patients (33.3%) died, 10 (18.5%) developed metastases, 7 had lymph-node involvement (13%), and 12 (22.2%) showed recurrence or local progression. In univariate analyses, treatment modalities associated with improved RFS were induction chemotherapy (p = 0.02) and intensity-modulated radiotherapy (p = 0.007). In the multivariate analyses, only induction chemotherapy (p = 0.047, hazard ratio [HR] = 0.39) was significantly associated with improved RFS.

Conclusion: Multimodal therapies including induction chemotherapy and intensity-modulated radiotherapy may improve the prognosis of SNUC; surgery might improve local control. Further multicenter studies are required.
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http://dx.doi.org/10.1002/alr.22143DOI Listing
September 2018

Facial nerve tractography: A new tool for the detection of perineural spread in parotid cancers.

Eur Radiol 2018 Sep 9;28(9):3861-3871. Epub 2018 Apr 9.

Department of Neuroradiology and MRI, Grenoble Alpes University Hospital - SFR RMN Neurosciences, F-38043, Grenoble, Cedex 9, France.

Objectives: To determine whether facial nerve MR tractography is useful in detecting PeriNeural Spread in parotid cancers.

Methods: Forty-five participants were enrolled. Thirty patients with surgically managed parotid tumors (15 malignant, 15 benign) were compared with 15 healthy volunteers. All of them had undergone 3T-MRI with diffusion acquisition and post-processing constrained spherical deconvolution-based tractography. Parameters of diffusion-weighted sequences were b-value 1,000 s/mm, 32 directions. Two radiologists performed a blinded visual reading of tractographic maps and graded the facial nerve average pathlength and fractional anisotropy (FA). We also compared diagnostic accuracy of tractography with morphological MRI sequences to detect PeriNeural Spread. Non-parametric methods were used.

Results: Average pathlength was significantly higher in cases with PeriNeural Spread (39.86 mm [Quartile1: 36.27; Quartile3: 51.19]) versus cases without (16.23 mm [12.90; 24.90]), p<0.001. The threshold above which there was a significant association with PeriNeural Spread was set at 27.36 mm (Se: 100%; Sp: 84%; AUC: 0.96, 95% CI 0.904-1). There were no significant differences in FA between groups. Tractography map visual analyses directly displayed PeriNeural Spread in distal neural ramifications with sensitivity of 75%, versus 50% using morphological sequences.

Conclusions: Tractography could be used to identify facial nerve PeriNeural Spread by parotid cancers.

Key Points: • Tractography could detect facial nerve PeriNeural Spread in parotid cancers. • The average pathlength parameter is increased in case of PeriNeural Spread. • Tractography could map PeriNeural Spread more precisely than conventional imaging.
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http://dx.doi.org/10.1007/s00330-018-5318-1DOI Listing
September 2018

Malnutrition and refeeding syndrome prevention in head and neck cancer patients: from theory to clinical application.

Eur Arch Otorhinolaryngol 2018 May 22;275(5):1049-1058. Epub 2018 Mar 22.

Otolaryngology Department, Grenoble Alpes University Hospital, Grenoble, France.

Purpose: The goal of this review is to raise awareness about refeeding syndrome (RFS) and to give a comprehensive presentation of recent guidelines and latest scientific data about nutritional management among head and neck cancer (HNC) patients while focusing on RFS prevention.

Methods: A review of literature for nutritional assessment and RFS management was conducted. Electronic searches of Medline, Cochrane, PubMed and Embase databases for articles published in peer-reviewed journals were conducted from February to September 2017 using the keywords: "nutrition assessment", "head and neck cancer", "refeeding syndrome" and "guidelines". Articles, reviews, book references as well as national and international guidelines in English and French were included.

Results: The prevalence of malnutrition is high in HNC patients and a large number of them will need artificial nutritional support or refeeding intervention. RFS is characterized by fluid and electrolyte imbalance associated with clinical manifestations induced by rapid refeeding after a period of malnutrition or starvation. Regarding risk factors for malnutrition and RFS, HNC patients are particularly vulnerable. However, RFS remains unrecognized among head and neck surgeons and medical teams. Practical data are summarized to help organizing nutritional assessment and refeeding interventions. It also summarizes preventive measures to reduce RFS incidence and morbidity in HNC population.

Conclusion: Nutritional assessment and early refeeding interventions are crucial for HNC patients care. As prevention is the key for RFS management, early identification of patients with high risks is crucial and successful nutritional management requires a multidisciplinary approach.
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http://dx.doi.org/10.1007/s00405-018-4935-2DOI Listing
May 2018

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

Cricoarytenoid Joint Ankylosis: Classification and Transoral Laser Microsurgical Treatment.

J Voice 2019 May 4;33(3):375-380. Epub 2018 Jan 4.

Division of Otolaryngology, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama.

Objective: This study aimed to describe a graduated approach for effective transoral mobilization of cricoarytenoid joint ankylosis (CJA) in the context of the Bogdasarian system of classifying posterior glottic web-based stenosis (PGWS).

Study Design: This is a retrospective cohort study through data from medical records and operative notes. A consecutive series of 23 patients who underwent reconstructive transoral laser microsurgery for PGWS with a significant degree of CJA (Bogdasarian grade III-IV) was included in the study.

Methods: Techniques necessary to remobilize their cricoarytenoid joints were reviewed in the context of the extent of scar tissue found.

Results: Arytenoids with CJA were successfully mobilized by resection of the fused portion of the cricoid and arytenoid cartilages achieving respiratory improvements as well as decannulation of tracheostomy-dependent patients. The majority (83%) of patient's voices improved. All patients tolerated a full diet after the procedures. Cases with Bogdasarian grade III PGWS with minor unilateral fixation should be classified as IIIa. If the fixation is severe, the case should be classified as a grade IIIb. Grade IVa would indicate that both sides were mildly to moderately ankylosed, and grade IVb involves ankylosis of both joints with subtotal or complete fusion of at least one; it presents the greatest surgical challenge.

Conclusion: We provided effective transoral techniques for the re-mobilization of cricoarytenoid joint, along with a classification of CJA that aims to standardize the severity of disease in the context of the existing and widely accepted Bogdasarian scale.
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http://dx.doi.org/10.1016/j.jvoice.2017.11.020DOI Listing
May 2019

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

CXCL-8/IL8 Produced by Diffuse Large B-cell Lymphomas Recruits Neutrophils Expressing a Proliferation-Inducing Ligand APRIL.

Cancer Res 2017 03 6;77(5):1097-1107. Epub 2016 Dec 6.

Albert Bonniot Institute, INSERM U1209/University Grenoble-Alpes, La Tronche, France.

Tumor-infiltrating neutrophils have been implicated in malignant development and progression, but mechanisms are ill defined. Neutrophils produce a proliferation-inducing ligand APRIL/TNFSF13, a factor that promotes development of tumors from diverse origins, including diffuse large B-cell lymphoma (DLBCL). High APRIL expression in DLBCL correlates with reduced patient survival, but the pathway(s) dictating APRIL expression are not known. Here, we show that all blood neutrophils constitutively secrete APRIL, and inflammation-associated stimuli, such as TNF, further upregulate APRIL. In a significant fraction of DLBCL patients, tumor cells constitutively produced the ELC-CXC chemokine CXCL-8 (IL8), enabling them to recruit APRIL-producing blood neutrophils. CXCL-8 production in DLBCL was unrelated to the cell of origin, as APRIL-producing neutrophils infiltrated CXCL-8 DLBCL from both germinal center (GC) and non-GC subtypes. Rather, CXCL-8 production implied events affecting DNA methylation and acetylation. Overall, our results showed that chemokine-mediated recruitment of neutrophils secreting the tumor-promoting factor APRIL mediates DLBCL progression. .
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http://dx.doi.org/10.1158/0008-5472.CAN-16-0786DOI Listing
March 2017

Toll-Like Receptor 9 Stimulation Induces Aberrant Expression of a Proliferation-Inducing Ligand by Tonsillar Germinal Center B Cells in IgA Nephropathy.

J Am Soc Nephrol 2017 Apr 5;28(4):1227-1238. Epub 2016 Dec 5.

Division of Nephrology, Department of Internal Medicine, Juntendo University, Tokyo, Japan;

The TNF family member a proliferation-inducing ligand (APRIL; also known as TNFSF13), produced by myeloid cells, participates in the generation and survival of antibody-producing plasma cells. We studied the potential role of APRIL in the pathogenesis of IgA nephropathy (IgAN). We found that a significant proportion of germinal centers (GCs) in tonsils of patients with IgAN contained cells aberrantly producing APRIL, contributing to an overall upregulation of tonsillar APRIL expression compared with that in tonsils of control patients with tonsillitis. In IgAN GC, antigen-experienced IgDCD38CD19 B cells expressing a switched IgG/IgA B cell receptor produced APRIL. Notably, these GC B cells expressed mRNA encoding the common cleavable APRIL- but also, the less frequent APRIL-/ mRNA, which encodes a protein that lacks a furin cleavage site and is, thus, the uncleavable membrane-bound form. Significant correlation between TLR9 and APRIL expression levels existed in tonsils from patients with IgAN. , repeated TLR9 stimulation induced APRIL expression in tonsillar B cells from control patients with tonsillitis. Clinically, aberrant APRIL expression in tonsillar GC correlated with greater proteinuria, and patients with IgAN and aberrant APRIL overexpression in tonsillar GC responded well to tonsillectomy, with parallel decreases in serum levels of galactose-deficient IgA1. Taken together, our data indicate that antibody disorders in IgAN associate with TLR9-induced aberrant expression of APRIL in tonsillar GC B cells.
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http://dx.doi.org/10.1681/ASN.2016050496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5373453PMC
April 2017

Indocyanine green fluorescence angiography for free flap monitoring: A pilot study.

J Craniomaxillofac Surg 2016 Nov 10;44(11):1833-1841. Epub 2016 Sep 10.

INSERM-UJF U823 Team 5, Institut Albert Bonniot, 38706 Grenoble Cedex, France; Maxillofacial Surgery Department, Centre hospitalier Annecy Genevois, 1 avenue de l'hôpital, 74370 Epagny Metz-Tessy, France. Electronic address:

Objective: We evaluated the feasibility and the tolerance of repeated fluorescent indocyanine green angiography in free flap monitoring, and determined the intraoperative predictive values of flap vitality.

Background: The free flap failure rate has been significantly reduced, but free flap loss still occurs and remains a costly disaster. Repeated clinical examinations are commonly used for flap monitoring, but they can be unreliable because of their subjectivity. Laser-induced fluorescence of indocyanine green is a new method for assessing tissue perfusion.

Methods: 20 patients undergoing microsurgical reconstruction were monitored by indocyanine green fluorescence angiography, intraoperatively, and during 4 days after surgery, with 18 injections. Monitoring was made by clinical examination, and then compared to angiographic findings.

Results: The vascular complication rate was 15% (3/20) with 2 cases of venous thrombosis and one case of partial necrosis of the flap skin paddle. Both cases of venous thrombosis were salvaged by secondary surgery. There was no total flap loss. ICG angiography allowed detecting each intra and postoperative complication, earlier than clinical examination. The mean per-operative intensity of fluorescence was significantly lower in flaps with vascular complications (23.8 GL/ms; p = 0.008). The postoperative slope (p = 0.02) and amplitude (p = 0.03) of the fluorescent signal were both significantly lower than for uncomplicated flaps, before surgical revision. These 2 parameters came back to normal values after secondary surgery. There was no adverse effect of ICG despite the repeated injections.

Conclusion: ICG angiography is a feasible and safe technique for the detection of free flap vascular complications.
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http://dx.doi.org/10.1016/j.jcms.2016.09.001DOI Listing
November 2016

Reconstructive transoral laser microsurgery for posterior glottic web with stenosis.

Laryngoscope 2017 03 24;127(3):685-690. Epub 2016 Aug 24.

Division of Otolaryngology, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama, U.S.A.

Objectives/hypothesis: To demonstrate that reconstructive transoral laser microsurgical (R-TLM) techniques can be used for the treatment of symptomatic laryngeal posterior glottic web-based stenosis (PGWS) in a large cohort of patients utilizing a postcricoid mucosal advancement flap (PCMAF).

Study Design: Retrospective cohort review.

Methods: A consecutive series of patients with PGWS who underwent R-TLM using a PCMAF were reviewed for outcomes. After laser excision of the PGWS scar and mobilization of fixed cricoarytenoid joints, a PCMAF was raised using microinstruments and a scanning free-beam CO laser. The flap was advanced and attached over the scar bed using a technique with multiple novel features that make it easy to adopt.

Results: Fifty-two patients were treated. Of the cases, 42.3% had a tracheostomy at presentation with grade II to IV PGWS, and 46% of cases had grade III to IV PGWS. In all cases, R-TLM was the only treatment approach. No open reconstructions were performed. No airway stents were used. Patients without tracheostomy, regardless of the grade of stenosis, did not require a tracheostomy to undergo this operation. All tracheostomy patients were successfully decannulated. All patients without a tracheostomy had significant improvement of their respiratory symptoms on the Dyspnea Index (mean Δ = 14.75, P value <.01).

Conclusions: RTLM using the PCMAF is a feasible, safe, and effective alternative to open approaches for airway reconstruction for PGWS. This novel transoral technique includes a much simpler endoscopic suturing alternative to knot tying among other new features. It is reproducible and reliable for laryngologists familiar with laryngeal microsurgery.

Level Of Evidence: 4. Laryngoscope, 127:685-690, 2017.
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http://dx.doi.org/10.1002/lary.26212DOI Listing
March 2017

A palm-sized high-sensitivity near-infrared fluorescence imager for laparotomy surgery.

Phys Med 2016 Jan 2;32(1):218-25. Epub 2015 Dec 2.

Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie, UMR 7357, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg/CNRS, 67412 Illkirch, France. Electronic address:

In laparotomy surgery guided by near-infrared fluorescence imaging, the access to the field of operation is limited by the illumination and/or the imaging field. The side of cavities or organs such as the liver or the heart cannot be examined with the systems available on the market, which are too large and too heavy. In this article, we describe and evaluate a palm sized probe, whose properties, weight, size and sensitivity are adapted for guiding laparotomy surgery. Different experiments have been performed to determine its main characteristics, both on the illumination and imaging sides. The device has been tested for fluorescent molecular probe imaging in preclinical procedures, to prove its ability to be used in cancer nodule detection during surgery. This system is now CE certified for clinical procedures and Indocyanine Green imaging has been performed during clinical investigations: lymphedema and surgical resection of liver metastases of colorectal cancers.
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http://dx.doi.org/10.1016/j.ejmp.2015.11.006DOI Listing
January 2016

Schizophyllum commune: an emergent or misdiagnosed fungal pathogen in rhinology?

Med Mycol 2016 Mar 26;54(3):301-9. Epub 2015 Nov 26.

Parasitologie-Mycologie, Assistance Publique-Hôpitaux de Marseille, CHU Timone-Adultes, Marseilles, France Aix-Marseille University, IP-TPT UMR MD3, 13885 Marseilles, France.

Schizophyllum commune is a common basidiomycete fungus that is rarely involved in human disease. The medical records of patients operated on for fungal rhinosinusitis (FRS) in two University Hospitals between 2012 and 2014 were reviewed. Within the two-year survey, six female, and notably no male, patients were diagnosed with S. commune rhinosinusitis. Mean age was 44.6 years at diagnosis (30 to 68 years). Mean time between onset of symptoms and diagnosis was 8.5 months (2 to 12 months). All six patients were immunocompetent and had no particular host factor for FRS. S. commune was identified using MALDI-TOF mass spectrometry and identifications were confirmed via DNA sequence analysis. Chronic invasive fungal rhinosinusitis was diagnosed in three of our six patients. Based on histological findings, antifungal treatment was delivered in association with surgery. The basidiomycete fungus S. commune is an emerging cause of rhinosinusitis probably as a direct consequence of the recent technological progress in fungal identification methods (DNA sequencing and MALDI-TOF mass spectrometry).
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http://dx.doi.org/10.1093/mmy/myv084DOI Listing
March 2016

Parotid gland tumours: MR tractography to assess contact with the facial nerve.

Eur Radiol 2016 Jul 8;26(7):2233-41. Epub 2015 Oct 8.

Department of Neuroradiology and MRI, Grenoble University Hospital - SFR RMN Neurosciences, Grenoble, France.

Objectives: To assess the feasibility of intraparotid facial nerve (VIIn) tractographic reconstructions in estimating the presence of a contact between the VIIn and the tumour, in patients requiring surgical resection of parotid tumours.

Methods: Patients underwent MR scans with VIIn tractography calculated with the constrained spherical deconvolution model. The parameters of the diffusion sequence were: b-value of 1000 s/mm(2); 32 directions; voxel size: 2 mm isotropic; scan time: 9'31'. The potential contacts between VIIn branches and tumours were estimated with different initial fractional anisotropy (iFA) cut-offs compared to surgical data. Surgeons were blinded to the tractography reconstructions and identified both nerves and contact with tumours using nerve stimulation and reference photographs.

Results: Twenty-six patients were included in this study and the mean patient age was 55.2 years. Surgical direct assessment of VIIn allowed identifying 0.1 as the iFA threshold with the best sensitivity to detect tumour contact. In all patients with successful VIIn identification by tractography, surgeons confirmed nerve courses as well as lesion location in parotid glands. Mean VIIn branch FA values were significantly lower in cases with tumour contact (t-test; p ≤ 0.01).

Conclusions: This study showed the feasibility of intraparotid VIIn tractography to identify nerve contact with parotid tumours.

Key Points: • Diffusion imaging is an efficient method for highlighting the intraparotid VIIn. • Visualization of the VIIn may help to better manage patients before surgery. • We bring new insights to future trials for patients with VIIn dysfunction. • We aimed to provide radio-anatomical references for further studies.
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http://dx.doi.org/10.1007/s00330-015-4049-9DOI Listing
July 2016

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 case study of a primary carcinoma of the petrous bone and a brief literature review.

Head Neck 2015 Apr 25;37(4):E45-8. Epub 2014 Sep 25.

Department of Otolaryngology, Grenoble University Hospital, Grenoble Cedex, France; Joseph Fourrier University, Grenoble, France.

Background: Temporal bone carcinoma is an aggressive tumor with multiple unconfirmed risk factors.

Methods And Results: Herein, we present a rare case of a primary petrous bone carcinoma in a female patient (65 years old) with an irrelevant medical history. She presented a postauricular swelling that revealed a multilocular osteolytic cystic lesion of the mastoid portion of the temporal bone on the CT scan. The patient underwent resection of the lesion and pathological analysis revealed moderately to well-differentiated squamous cell carcinoma. Postoperative radiotherapy was carried out. Until the present time, the patient shows complete remission on regular clinical and radiological follow-up.

Conclusion: Although no widely accepted strategy for managing temporal bone tumors exists, a review of the literature showed that surgery with or without radiotherapy is the treatment of choice. Preoperative assessment and accurate staging are vital in ensuring that the treatment is adequate for each disease stage.
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http://dx.doi.org/10.1002/hed.23819DOI Listing
April 2015

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

FluoSTIC: miniaturized fluorescence image-guided surgery system.

J Biomed Opt 2012 Oct;17(10):106014

Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.

Over the last few years, near-infrared (NIR) fluorescence imaging has witnessed rapid growth and is already used in clinical trials for various procedures. However, most clinically compatible imaging systems are optimized for large, open-surgery procedures. Such systems cannot be employed during head and neck oncologic surgeries because the system is not able to image inside deep cavities or allow the surgeon access to certain tumors due to the large footprint of the system. We describe a miniaturized, low-cost, NIR fluorescence system optimized for clinical use during oral oncologic surgeries. The system, termed FluoSTIC, employs a miniature, high-quality, consumer-grade lipstick camera for collecting fluorescence light and a novel custom circular optical fiber array for illumination that combines both white light and NIR excitation. FluoSTIC maintains fluorescence imaging quality similar to that of current large-size imaging systems and is 22 mm in diameter and 200 mm in height and weighs less than 200 g.
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http://dx.doi.org/10.1117/1.JBO.17.10.106014DOI Listing
October 2012

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

Compliance with fluoride custom trays in irradiated head and neck cancer patients.

Support Care Cancer 2012 Aug 25;20(8):1811-4. Epub 2011 Sep 25.

Department of Radiation Oncology/Institut Universitaire de la Face et du Cou fo J thariat, Cancer Center Antoine-Lacassagne, University Nice Sophia-Antipolis, 33 Av. Valombrose, 06189, NICE Cedex 2, France.

Purpose: The purpose of this study is to assess compliance with fluoride gel custom trays in irradiated head and neck cancer patients.

Methods And Materials: One hundred fifty-five consecutive patients on remission following radiation therapy of head and neck cancers were assessed retrospectively for dental care practices prior to radiation and prospectively for long-term compliance with custom trays from November 2009 to January 2010. A five-item questionnaire was filled in by patients in the waiting room, and a 15-item questionnaire by the physician in charge during the corresponding follow-up visit.

Results: Ten percent of patients were edentulous at inclusion. Among dentate patients, 17% had total extractions. With a mean follow-up of 24 months, 19% of patients used custom trays for over a year. Primary stage, age, and tobacco consumption were correlated with compliance with custom trays. More than half of dentate patients developed carious lesions, and 8% had stage 1-3 osteoradionecrosis of the whole population of edentulous and dentate patients.

Conclusion: Compliance with custom trays was poor in this series. Specific postirradiation dental care follow-up visits and education have demonstrated their utility in the era of 2D irradiation. We currently advocate an 18-month compliance with custom trays in IMRT patients on the basis of the Parsport trial, after which we assess the quality of salivary recovery before recommending prolonged use or interruption. Data with innovative irradiation techniques are however required.
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http://dx.doi.org/10.1007/s00520-011-1279-5DOI Listing
August 2012