Jérôme R. Lechien

Human papillomavirus DNA strongly correlates with a poorer prognosis in oral cavity carcinoma.

The prevalence of human papillomavirus (HPV) in a clinical series of 162 patients with oral squamous cell carcinoma (OSCC) was studied. Furthermore, we analyzed the correlation between the immunohistochemical expression of p16, p53, epidermal growth factor receptor (EGFR), and HPV status to predict survival in OSCC patients.

Pharmacological inhibition of macrophage migration inhibitory factor interferes with the proliferation and invasiveness of squamous carcinoma cells

Recent clinical observations and experimental studies of our group indicate that macrophage migration inhibitory factor (MIF) may contribute to tumor progression in head and neck squamous cell carcinomas (HNSCC). The present study was undertaken to examine the effects of the irreversible MIF inhibitor 4-iodo-6-phenylpyrimidine (4-IPP) on proliferation and invasiveness of the squamous carcinoma cell line SCCVII. Cell counting, crystal violet assay and flow cytometry were used to analyze the effects of 4-IPP on SCCVII cell growth. The impact of 4-IPP on cell invasiveness was assessed by Boyden chamber assay. Knockdown of the MIF receptor CD74 was achieved by transduction with lentiviral vectors encoding anti-CD74 shRNAs. As shown by immunofluorescence staining, SCCVII cells express both MIF and CD74. Decreased MIF immunoreactivity as a result of exposure to 4-IPP suggested a covalent modification of the cytokine. 4-IPP inhibited SCCVII cell proliferation and invasiveness. Moreover, the cytostatic effect of 4-IPP was enhanced by CD74 knockdown. The inhibitory effects of 4-IPP on cell proliferation and invasiveness strongly suggest that MIF is involved in proliferative activity and invasive properties of squamous carcinoma cells. In conclusion, MIF inhibition may open possibilities for target-directed treatment of head and neck squamous cell carcinoma.

Voice outcomes of laryngopharyngeal reflux treatment: a systematic review of 1483 patients

The aim of this study is to explore voice quality modifications in laryngopharyngeal reflux (LPR) disease and to understand better the pathophysiological mechanisms underlying the development of communicative disability. Biological Abstracts, BioMed Central, Cochrane database, PubMed and Scopus were assessed for subject headings using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) recommendations. Relevant studies published between January 1990 and December 2015 describing the evaluation of voice quality in LPR disease were retrieved. Issues of clinical relevance, such as LPR diagnosis method, treatment efficacy and outcomes, were evaluated for each study. We determined the grade of recommendation for each publication according to the Oxford Centre for Evidence-Based Medicine evidence levels. The search identified 145 publications, of which 25 studies met the inclusion criteria for a total of 1483 LPR patients. Data were extracted by 2 independent physicians who identified 16 trials with a IIb evidence level, 7 trials with a IIa evidence level and 2 RCTs with a Ib evidence level where 4 patient-based instruments and 5 clinician-based instruments were used. The main voice assessment outcomes reported were hoarseness assessments by physicians or patients, followed by acoustic parameters; 15 and 14 articles, respectively, demonstrated significant improvements in subjective and objective voice assessments after treatment. The methodology used to measure acoustic parameters (i.e. sustained vowel duration, the sample portion choice for measurement, etc.) varied from one study to another. The majority of studies indicated that voice quality assessments (especially acoustic parameters) remain an interesting outcome to measure the effectiveness of treatment, but further studies using standardised and transparent methodology to measure acoustic parameters are necessary to confirm the place of each tool in the LPR disease evaluation.

Involvement of CD74 in head and neck squamous cell carcinomas

AbstractPurpose While macrophage migration inhibitory factor (MIF) has been extensively studied in the context of inflammation and inflammatory disorders, less work has been devoted to its involvement in cancer, notably in neoplastic progression. In a previous study, we have found evidence that MIF plays a role in head and neck squamous cell carcinomas (HNSCC). The current investigations were undertaken in order to estimate the importance of the MIF receptor, CD74 in the progression of HNSCC.Methods and resultsIn a cohort of 46 cases of oral cavity carcinomas, immunohistochemical staining revealed an increase in CD74 expression during progression from benign lesions to carcinoma. As shown by cell culture experiments using squamous carcinoma cell line (SCCVII) transduced with anti-CD74 shRNA, the amount of cell-produced VEGF was lower in SCCVII CD74KD cell line compared with control SCCVII CD74sc cell line, suggesting that CD74 could be implicated in angiogenesis in vivo. Furthermore, knockdown of CD74 decreased proliferation of SCCVII cells in vitro. The migration of SCCVII cells, as well as the cell secretion of matrix metallopeptidase 9, was also negatively affected by CD74 knockdown. These observations in vitro were confirmed in an orthotopic mouse model of SCC where tumors produced by SCCVII CD74KD cell inoculation were found to grow more slowly than tumors generated by SCCVII CD74sc cells.ConclusionThe clinical observations and experimental data reported here suggest that CD74, as well as MIF, plays a pivotal role in HNSCC progression.

Chronic Maxillary Rhinosinusitis of Dental Origin: A Systematic Review of 674 Patient Cases

Objectives. The aim of this systematic review is to study the causes of odontogenic chronic maxillary rhinosinusitis (CMRS), the average age of the patients, the distribution by sex, and the teeth involved. Materials and Methods. We performed an EMBASE-, Cochrane-, and PubMed-based review of all of the described cases of odontogenic CMRS from January 1980 to January 2013. Issues of clinical relevance, such as the primary aetiology and the teeth involved, were evaluated for each case. Results. From the 190 identified publications, 23 were selected for a total of 674 patients following inclusion criteria. According to these data, the main cause of odontogenic CMRS is iatrogenic, accounting for 65.7% of the cases. Apical periodontal pathologies (apical granulomas, odontogenic cysts, and apical periodontitis) follow them and account for 25.1% of the cases. The most commonly involved teeth are the first and second molars. Conclusion. Odontogenic CMRS is a common disease that must be suspected whenever a patient undergoing dental treatment presents unilateral maxillary chronic rhinosinusitis.

Incidence des cancers ORL en Belgique en regard des données mondiales et françaises

The squamous cell carcinomas of the upper aerodigestive tracts are frequent neoplasia,with as much as 466,831 and 168,368 cases diagnosed in 2008 among men and women worldwide,respectively. As such, they make up the sixth most frequent neoplasia among men and the eighth among women. Their frequency shows interesting variations covering the last 20 years, with an ascending tendency among women, which is higher in Europe, and a descending tendency in men, maximal in the USA. The comparison with the Belgian official data reveals a striking elevation of incidence of these cancers between both sexes, with important regional differences in Belgium. Finally, when we compare Belgian and French data, these cancers seem more frequent in France in men, but there is an opposite tendency among women, in which the carcinoma of the larynx is most represented in Belgium. Although the limited quality of the data limits the interpretation of these data, they seem to be partly in line with the evolution of the risk factors of these pathologies.

Laryngopharyngeal Reflux and Voice Disorders: A Multifactorial Model of Etiology and Pathophysiology

OBJECTIVE The aim of this paper is to shed light on the pathogenesis and pathophysiological mechanisms underlying the development of hoarseness related to laryngopharyngeal reflux disease (LPRD). MATERIAL AND METHODS PubMed, Embase, and The Cochrane Library were searched for the terms reflux, laryngopharyngeal, laryngitis, voice, and hoarseness. Experimental and clinical studies providing substantial information about the occurrence of voice disorders, laryngeal histologic changes, or any pathophysiological processes related to LPRD were included by two independent investigators. RESULTS Of the 104 studies reviewed, 47 studies that met our inclusion criteria were analyzed. LPRD leads to significant macroscopic and microscopic histopathologic changes in the mucosa of the vibratory margin of the vocal folds. More and more studies suspect that epithelial cell dehiscence, microtraumas, inflammatory infiltrates, Reinke space dryness, mucosal drying, and epithelial thickening are probably responsible for the hoarseness related to reflux and the impairment of the subjective and objective voice quality evaluations. CONCLUSION Future clinical studies examining the pathophysiology of hoarseness related to LPRD should take into consideration all potential mechanisms involved in the development of hoarseness.

Langerhans cell number is a strong and independent prognostic factor for head and neck squamous cell carcinomas

OBJECTIVES Head and neck squamous cell carcinomas (HNSCCs) exhibit great biological heterogeneity and relatively poor prognosis. Tobacco and alcohol consumption is involved in the cause of the majority of these cancers, but over the last several years, Human Papilloma Virus (HPV) infection has increased specifically in oropharyngeal cancers and become an additional risk factor. Here, we evaluated the number of Langerhans cells (LCs) in HNSCC and reporting its prognostic power in comparison to other risk factors. MATERIALS AND METHODS Our clinical series was composed of 25 tumor-free peritumoral epithelium, 64 low-grade dysplasia, 54 high-grade dysplasia and 125 carcinoma samples. HPV was detected by E6/E7 qPCR and p16 immunohistochemistry. CD1a-positive LCs were counted in intra-tumoral and stromal compartments as well as lymph nodes. MIP-3α was assessed in carcinomas using immunohistochemistry. RESULTS Univariate Cox regression analyses demonstrated that high LC number is associated with longer recurrence-free survival in both intra-tumoral and stromal compartments and longer overall survival in stromal compartment. Tobacco and alcohol habits, but not HPV status, are also correlated with poor prognoses in terms of recurrence. Multivariate analyses reported stromal LC number as a strong prognostic factor independent of tobacco, alcohol and HPV status. Moreover, LC number is higher in tumors and invaded lymph nodes than dysplastic lesions but it decreases in HPV-positive cancer patients. Further, LC number correlates with MIP-3α expression. CONCLUSION These findings suggest that LC number is a significant and independent prognostic factor for HNSCC. LC infiltration is increased in cancer lesions but decrease with HPV infection.

Change of signs, symptoms and voice quality evaluations throughout a 3- to 6-month empirical treatment for laryngopharyngeal reflux disease

To assess the usefulness of voice quality measurements as a treatment outcome in patients with laryngopharyngeal reflux (LPR)‐related symptoms.

Reply to the letter “Laryngopharyngeal reflux disease in the elderly”

The authors are thankful for the very interesting comments about our article entitled “impact of age on laryngopharyngeal reflux disease presentation: a multi-center prospective study” [1] in the letter to the editor entitled “laryngopharyngeal reflux disease in the elderly”. We wish briefly to reply to the questions raised by the author of the letter. The author rightly suggested the existence of many conditions or cofactors able to bias the presentation of signs, symptoms, and voice quality evaluations at baseline and throughout proton pump inhibitors (PPIs) trial in elderly patients with laryngopharyngeal reflux (LPR). The first cofactor reported by the author concerns hoarseness caused by localized ischemia and cerebral infarction, which can cause vagitis and hoarseness. According to recent review of the literature, clinical presentations of patients with small infarct(s) mainly include, in decreasing order of frequency, pure motor stroke (50–66%), pure sensory stroke, sensorimotor stroke, ataxic hemiparesis, and dysarthria with motor impediment of one hand [2]. Naturally, hoarseness related to ischemia or cerebral infarction may be part of these clinical presentations but, in most cases, the neurological picture is associated with other neurological signs and symptoms. To conduct our study, the first author (JRL) performed precise anamnesis, clinical examination (ear, nose, and throat, and, if necessary, general examination) and assessment of many exclusion criteria. Precisely, as described in another publication [3], patients were excluded of our study if they met the following conditions: neurological disease affecting voice, psychiatric illness, upper respiratory tract infection within the last month, an antacid treatment already started (i.e., PPI(s), gastroprokinetic, or antihistamine), previous history of cervical surgery or radiotherapy, laryngeal trauma, vocal cord paralysis/paresis, benign vocal fold lesions, pharyngolaryngeal malignancy, seasonal allergies, asthma, chronic obstructive pulmonary disease, PPI hypersensitivity, untreated thyroid disease, prior antireflux surgery, or chemical exposure causing laryngitis. Moreover, active smokers, alcoholics, and pregnant and lactating women were also excluded. With strict application of these exclusion criteria, we aimed to have the “purest” population of LPR subjects. Thus, our patients did not have the other cofactors presented by the author to be able to bias the evaluations (i.e. respiratory tract disease, uncontrolled diabetes, active allergy, or psychiatric disorder). In other words, the implementation of these exclusion criteria led us to exclude a lot of patients where we had a doubt concerning the cause of laryngeal symptoms. The methodology of our study and the comments of the author highlight the difficulty to make the LPR diagnosis. As suggested by the author, and regarding the lack of gold standard for the LPR diagnosis, we think that the best way to select LPR patients involves the evaluation of both signs and symptoms, and the exclusion of a maximum of cofactors able to bias the clinical presentation of LPR. That is why we only had 80 patients in this multi-center trial because LPR diagnosis was only confirmed in these patients regarding the response to PPIs trial or according to positive result of pH impedance metry. Indeed, we prefer to make the LPR diagnosis with empirical therapeutic trial (PPIs), which, combined with adequate exclusion criteria, is quite competitive than pH impedance metry [4]. However, This reply refers to the comment available at https://doi. org/10.1007/s00405-017-4802-6.