Search

The COVID-19 pandemic has caused significant confusion about healthcare providers' and patients' pandemic-specific risks related to surgery. The aim of this systematic review is to summarize recommendations for sinus and anterior skull base surgery during the COVID-19 pandemic.PubMed/MEDLINE, Google Scholar, Scopus and Embase were searched by two independent otolaryngologists from the Young Otolaryngologists of IFOS (YO-IFOS) for studies dealing with sinus and skull base surgery during COVID-19 pandemic. The review also included unpublished guidelines edited by Otolaryngology-Head and Neck Surgery or Neurosurgery societies. Perioperative factors were investigated including surgical indications, preoperative testing of patients, practical management in operating rooms, technical aspects of surgery and postoperative management. The literature review was performed according to PRISMA guidelines. The criteria for considering studies or guidelines for the review were based on the population, intervention, comparison, outcome, timing and setting (PICOTS) framework.15 International publications met inclusion criteria. Five references were guidelines from national societies. All guidelines recommended postponing elective surgeries. An algorithm is proposed that classifies endonasal surgical procedures into three groups based on the risk of postponing surgery. Patients' COVID-19 status should be preoperatively assessed. Highest level of personal protective equipment (PPE) is recommended, and the use of high-speed powered devices should be avoided. Face-to-face postoperative visits must be limited.Sinus and skull base surgeries are high-risk procedures due to potential aerosolization of SARS-CoV-2 virus. Protection of health care workers by decreasing exposure and optimizing the use of PPE is essential with sinus and anterior skull base surgery.

Head and Neck Squamous Cell Carcinomas (HNSCC) are characterized by a large heterogeneity in terms of the location and risk factors. For a few years now, immunotherapy seems to be a promising approach in the treatment of these cancers, but a better understanding of the immune context could allow to offer a personalized treatment and thus probably increase the survival of HNSCC patients. In this context, we evaluated the infiltration of FoxP3+ Tregs on 205 human formalin-fixed paraffin-embedded HNSCC and we assessed its prognostic value compared to other potential prognostic factors, including HPV infection. First, we found a positive correlation of FoxP3+ Treg infiltration between the intra-tumoral (IT) and the stromal (ST) compartments of the tumors (p &lt, 0.0001). A high infiltration of these cells in both compartments was associated with longer recurrence-free (ST, RFS, p = 0.007, IT, RFS, p = 0.019) and overall survivals (ST, OS, p = 0.002, ST, OS, p = 0.002) of HNSCC patients. Early tumor stage (OS, p = 0.002) and differentiated tumors (RFS, p = 0.022, OS, p = 0.043) were also associated with favorable prognoses. Multivariate analysis revealed that FoxP3+ Treg stromal infiltration, tumor stage and histological grade independently influenced patient prognosis. In conclusion, the combination of these three markers seem to be an interesting prognostic signature for HNSCC.

To review the current literature about the epidemiology, clinical presentation, diagnosis, and treatment of laryngopharyngeal reflux (LPR).PubMed, Cochrane Library, and Scopus.A comprehensive review of the literature on LPR epidemiology, clinical presentation, diagnosis, and treatment was conducted. Using the PRISMA statement, 3 authors selected relevant publications to provide a critical analysis of the literature.The important heterogeneity across studies in LPR diagnosis continues to make it difficult to summarize a single body of thought. Controversies persist concerning epidemiology, clinical presentation, diagnosis, and treatment. No recent epidemiologic study exists regarding prevalence and incidence with the use of objective diagnostic tools. There is no survey that evaluates the prevalence of symptoms and signs on a large number of patients with confirmed LPR. Regarding diagnosis, an increasing number of authors used multichannel intraluminal impedance-pH monitoring, although there is no consensus regarding standardization of the diagnostic criteria. The efficiency of proton pump inhibitor (PPI) therapy remains poorly demonstrated and misevaluated by incomplete clinical tools that do not take into consideration many symptoms and extralaryngeal findings. Despite the recent advances in knowledge about nonacid LPR, treatment protocols based on PPIs do not seem to have evolved.The development of multichannel intraluminal impedance-pH monitoring and pepsin and bile salt detection should be considered for the establishment of a multiparameter diagnostic approach. LPR treatment should evolve to a more personalized regimen, including diet, PPIs, alginate, and magaldrate according to individual patient characteristics. Multicenter international studies with a standardized protocol could improve scientific knowledge about LPR.

Objectives To investigate the role of laryngopharyngeal reflux (LPR) in the development of benign lesions of the vocal folds (BLVF). Methods PubMed, Cochrane Library, and Scopus were searched by three independent investigators for articles published between January 1990 and November 2018 providing substantial information about the role of LPR in the development of nodules, polyps, cysts, Reinke's edema, and sulcus vocalis. Inclusion, exclusion, diagnostic criteria and clinical outcome evaluation of included studies were analyzed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. Results Of the 155 relevant publications, 42 studies were included. Thirty-five were clinical studies and seven were experimental research studying the impact of reflux on vocal fold tissue. Only seven clinical studies utilized objective LPR diagnoses (pH monitoring), suggesting an association between LPR and the development of nodules, polyps, and Reinke's edema. These studies were characterized by a substantial heterogeneity due to discrepancies in inclusion/exclusion criteria, diagnostic methods, and clinical outcome evaluation. The few basic science studies on this topic support that LPR creates an environment that may predispose to BLVF through changes in defense mechanisms of the vocal folds, cell-to-cell dehiscence, inflammatory reaction of the vocal folds, and reaction to phonotrauma. Conclusions Caustic mucosal injury from LPR could cause increased susceptibility of the vocal fold mucosa to injury and subsequent formation of nodules, polyps, or Reinke's edema. However, the heterogeneity and the low number of high-quality studies limit the ability to draw definitive conclusions. Future clinical and experimental studies are needed to better identify the role of reflux in development of BLVF. Laryngoscope, 129:E329-E341, 2019.

Human papilloma virus (HPV) infection has been well-established as a risk factor in head and neck squamous cell carcinoma (HNSCC). The carcinogenic effect of HPV is mainly due to the E6 and E7 oncoproteins, which inhibit the functions of p53 and pRB, respectively. These oncoproteins could also play a role in the Warburg effect, thus favoring tumor immune escape. Here, we demonstrated that the pro-inflammatory cytokine macrophage migration inhibitory factor (MIF) is expressed at higher levels in HPV-negative patients than in HPV-positive patients. However, the secretion of MIF is higher in HPV-positive human HNSCC cell lines, than in HPV-negative cell lines. In-HPV positive cells, the half inhibitory concentration (IC50) of MIF inhibitor (4-iodo-6-phenylpyrimidine (4-IPP)) is higher than that in HPV-negative cells. This result was confirmed in vitro and in vivo by the use of murine SCCVII cell lines expressing either E6 or E7, or both E6 and E7. Finally, to examine the mechanism of MIF secretion, we conducted proton nuclear magnetic resonance (1H-NMR) experiments, and observed that lactate production is increased in both the intracellular and conditioned media of HPV-positive cells. In conclusion, our data suggest that the stimulation of enzymes participating in the Warburg effect by E6 and E7 oncoproteins increases lactate production and hypoxia inducible factor 1α (HIF-1α) expression, and finally induces MIF secretion., SCOPUS: ar.j, info:eu-repo/semantics/published

Backgroung For a long time, laryngopharyngeal reflux disease (LPRD) has been treated by proton pump inhibitors (PPIs) with an uncertain success rate. Aim To shed light the current therapeutic strategies used for LPRD in order to analysis the rationale in the LPRD treatment. Methods Three authors conducted a PubMed search to identify papers published between January 1990 and February 2019 about the treatment of LPRD. Clinical prospective or retrospective studies had to explore the impact of medical treatment(s) on the clinical presentation of suspected or confirmed LPRD. The criteria for considering studies for the review were based on the population, intervention, comparison, and outcome framework. Results The search identified 1355 relevant papers, of which 76 studies met the inclusion criteria, accounting for 6457 patients. A total of 64 studies consisted of empirical therapeutic trials and 12 were studies where authors formally identified LPRD with pH-monitoring or multichannel intraluminal impedance-pH monitoring (MII-pH). The main therapeutic scheme consisted of once or twice daily PPIs for a duration ranged from 4 to 24 wk. The most used PPIs were omeprazole, esomeprazole, rabeprazole, lansoprazole and pantoprazole with a success rate ranging from 18% to 87%. Other composite treatments have been prescribed including PPIs, alginate, prokinetics, and H2 Receptor antagonists. Conclusion Regarding the development of MII-pH and the identification of LPRD subtypes (acid, nonacid, mixed), future studies are needed to improve the LPRD treatment considering all subtypes of reflux.

Head and neck squamous cell carcinomas (HNSCC) are one of the most prevalent cancers worldwide. Active human papillomavirus (HPV) infection has been identified as an important additional risk factor and seems to be associated with a better prognosis in non-drinker and non-smoker young patients with oropharyngeal SCC. The better response of the immune system against the HPV-induced HNSCC is suspected as a potential explanation for the better prognosis of young patients. To further assess this hypothesis, our review aims to shed light the current knowledge about the impact of HPV infection on the immune response in the context of HNSCC, focusing on the innate immune system, particularly highlighting the role of macrophages, Langerhans and myeloid cells, and on the adaptative immune system, pointing out the involvement of T regulatory, T CD8 and T CD4 lymphocytes. In addition, we also review the preventive (HPV vaccines) and therapeutic (checkpoint inhibitors) strategies against HPV-related HNSCC, stressing the use of anti- CTLA4, PD-L1, PD-L2 antibodies alone and in combination with other agents able to modulate immune responses., SCOPUS: re.j, info:eu-repo/semantics/published

We report the clinical features of 3 patients in France who had parotitis (inflammation of the parotid salivary glands) as a clinical manifestation of confirmed coronavirus disease. Results from magnetic resonance imaging support the occurrence of intraparotid lymphadenitis, leading to a parotitis-like clinical picture.

Summary Purpose To study the usefulness of voice quality as therapeutic outcome in laryngopharyngeal reflux disease. Material and methods A total of 80 patients with reflux finding score (RFS) > 7 and reflux symptom index (RSI) > 13 were treated with pantoprazole, diet, and lifestyle recommendations for 3 months. The therapeutic effectiveness was assessed with RSI; RFS; Voice Handicap Index; blinded Grade, Roughness, Breathiness, Asthenia, Strain, and Instability (GRBASI); aerodynamic and a panel of acoustic measurements before and after treatment. A correlation analysis between symptoms, videolaryngostroboscopic signs, and acoustic measurements was conducted. Results Compared to baseline, means of RSI, RFS, Voice Handicap Index, perceptual dysphonia, and roughness significantly decreased. Significant improvements of phonatory quotient, percent jitter, percent shimmer, Relative Average Perturbation, Pitch Perturbation Quotient, Phonatory F0 Range, Amplitude Perturbation Quotient, smooth Amplitude Perturbation Quotient, and Peak-to-Peak Amplitude Variation were found at the end of treatment. Studies of correlation did not identify relevant correlation between videolaryngostroboscopic signs, especially vocal folds edema, and objective voice quality evaluations. Conclusion Voice quality assessments can help to better understand voice disorders and can be used as indicators of the treatment effectiveness in patients with laryngopharyngeal reflux-related symptoms.

Objectives To investigate the therapeutic benefit of proton pump inhibitors (PPIs) over placebo in patients with laryngopharyngeal reflux (LPR) and to analyze the epidemiological factors of heterogeneity in the literature. Methods An electronic literature search was conducted to identify articles published between 1990 and 2018 about clinical trials describing the efficiency of medical treatment(s) on LPR. First, a meta-analysis of placebo randomized controlled trials (RCTs) comparing PPIs versus placebo was conducted according to diet. The heterogeneity, response to PPIs, and evolution of clinical scores were analyzed for aggregate results. Second, a systematic review of diagnosis methods, clinical outcome of treatment, and therapeutic regimens was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Results The search identified 1,140 relevant publications, of which 72 studies met the inclusion criteria for a total of 5,781 patients. Ten RCTs were included in the meta-analysis. The combined relative risk was 1.31 in favor of PPIs and increased to 1.42 when patients did not receive diet recommendations. Randomized controlled trials were characterized by a significant heterogeneity due to discrepancies in clinical therapeutic outcomes, diagnosis methods (lack of gold standard diagnostic tools), and therapeutic scheme. The epidemiological analysis of all articles supports the existence of these discrepancies in the entire literature. In particular, many symptoms and signs commonly encountered in LPR are not assessed in the treatment effectiveness. The lack of diagnosis precision and variability of inclusion criteria particularly create bias in all reported and included articles. Conclusion This meta-analysis supports a mild superiority of PPIs over placebo and the importance of diet as additional treatment but demonstrates the heterogeneity between studies, limiting the elaboration of clear conclusions. International recommendations are proposed for the development of future trials. Laryngoscope, 129:1174-1187, 2019.

Introduction To analyze the epidemiological characteristics of placebo controlled randomized trials (RCTs) that evaluated the effectiveness of medical treatments over placebo in laryngopharyngeal reflux (LPR). Material and methods PubMed, Cochrane database, and Scopus were assessed for subject headings using the PRISMA recommendations. Placebo RCTs published between 1990 and 2018 describing clinical evolution throughout LPR treatment were extracted and analyzed for evidence-based level, number of patients, inclusion and exclusion criteria, gender, age, symptoms and signs used as therapeutic outcomes, and treatment schemes. Results The database search identified 15 placebo RCTs with a total of 763 patients. The mean age of patients was 48.59 years and 52.68% of patients were female. Among the 15 placebo RCTs, 9 have demonstrated a partial or total superiority of a medical treatment over placebo. Most of authors based the LPR diagnosis on symptoms and signs without additional examination. Our analysis reveals an important heterogeneity between studies with regard to the diagnosis criteria, treatment schemes and signs and symptoms used as therapeutic outcomes. Many commonly reported signs and symptoms related to LPR were not used as therapeutic outcomes. Half of the authors did not prescribe diet and behavioral changes along the treatment. Conclusion The controversy in the RCTs about the superiority of medical treatment over placebo in LPR disease is probably due to discrepancies in the diagnosis method, exclusion criteria, therapeutic schemes and the lack of comprehensive tools for the assessment of signs and symptoms. In this context, the LPR Study Group of Young-Otolaryngologists of the International Federations of Oto-Rhino-Laryngological Societies developed two new instruments to precisely assess signs and symptoms throughout the treatment. These two instruments could be used in future trials comparing medical treatment over placebo in LPR disease.

Macrophage migration inhibitory factor (MIF) is a pleiotropic inflammatory cytokine involved in many cellular processes and in particular carcinogenesis. Here, we review the experimental and clinical published data on MIF and its pathways in breast cancer. Experimental data show that MIF is overexpressed in breast cancer cells (BCC) due, at least partly, to its stabilization by HSP90 and upregulation by HIF-1á. MIF interacts with its main receptor CD74 and its co-receptor CXCR-4, both overexpressed, promoting cell survival by PI3K/Akt activation, a possible link with EGFR and HER2 pathways and inhibition of autophagy. Besides these auto- and paracrine effects on BCC, MIF interacts with BCC microenvironment by several mechanisms: immunomodulation by increasing the prevalence of immune suppressive cells, neo-angiogenesis by its link to HIF-1, and finally BCC transendothelial migration. Clinical studies show higher levels of MIF in breast cancer patients serum compared to healthy volunteers but without obvious clinical significance. In breast cancer tissue, MIF and CD74 are overexpressed in the cancer cells and in the stroma but correlations with classical prognostic factors or survival are elusive. However, an inverse correlation with the tumor size for stromal MIF and a positive correlation with the triple receptor negative tumor status for stromal CD74 seem to be showed. This set of experimental and clinical data shows the involvement of MIF pathways in breast carcinogenesis. Several anti-MIF targeted strategies are being explored in therapeutic goals and should merit further investigations., SCOPUS: re.j, info:eu-repo/semantics/published

Glucocorticoids (GCs) are used in the treatment of cancer to induce programmed cell death in the transformed cells of the hematopoietic system and to reduce side effects. Additionally, GCs are described as an inhibitor of certain chemotherapy or radiation-induced apoptosis and also an inhibitor of cancer progression by downregulating or upregulating the expression of several genes. The present study used immunofluorescence to investigate the presence of the glucocorticoid receptor (GR) in MCF-7 cells, and the cell culture growth was determined by cell counting the number of cells following exposure to GC and/or dexamethasone (Dex). The presence and immunoreactivity of the GR were confirmed, and treatment with Dex (10-8-10-7 M) caused an inhibitory effect (30-35%) on the proliferative activity of the MCF-7 cells. This growth inhibitory effect was possibly produced by the pro-apopotic effect of Dex. Since Dex is administered systematically prior to breast cancer chemotherapy, the possible interactions between these drugs require further investigation., SCOPUS: ar.j, info:eu-repo/semantics/published

Introduction To investigate voice quality (VQ) impairments in idiopathic Parkinson's disease (IPD) and to explore the impact of medical treatments and L-Dopa challenge testing on voice. Methods Relevant studies published between January 1980 and June 2017 describing VQ evaluations in IPD were retrieved using PubMed, Scopus, Biological Abstracts, BioMed Central and Cochrane databases. Issues of clinical relevance, including IPD treatment efficiency and voice quality outcomes, were evaluated for each study. The grade of recommendation for each publication was determined according to the Oxford Centre for Evidence-Based Medicine evidence levels. Results The database research yielded 106 relevant publications, of which 33 studies met the inclusion criteria, for a total of 964 patients with IPD. Data were extracted by 3 independent physicians who identified 21, 11 and 1 trials with IIIb, IIb and IIa evidence levels, respectively. The main VQ assessment tools used were acoustic testing (N = 27), aerodynamic testing (N = 10), subjective measurements (N = 8) and videolaryngostroboscopy (N = 3). The majority of trials (N = 32/33) identified subjective or objective VQ improvements after medical treatment (N = 10) or better VQ evaluations in healthy subjects compared to patients with IPD (N = 22). Especially, our analysis supports that VQ overall improves during the L-Dopa challenge testing, making the VQ evaluation an additional tool for the IPD diagnosis. The methodology used to assess subjective and objective VQ substantially varied from 1 study to another. All of the included studies took into consideration the patient's clinical profile in the VQ analysis. Conclusion The majority of studies supported that VQ assessments remain useful as outcome measures of the effectiveness of medical treatment and could be helpful for the IPD diagnosis based on L-Dopa challenge testing. Further controlled studies using standardised and transparent methodology for measuring acoustic parameters are necessary to confirm the place of each tool in both IPD diagnosis and treatment evaluation.

Head and neck cancers are among the most frequently occurring cancers worldwide. Of the molecular drivers described for these tumors, galectins play an important role via their interaction with several intracellular pathways. In this review, we will detail and discuss this role with specific reference to galectins-1,-3, and-7 in angiogenesis, cell proliferation, and invasion as well as in cell transformation and cancer progression. Furthermore, we will evaluate the prognostic value of galectin expression in head and neck cancers including those with oral cavity, salivary gland, and nasopharyngeal pathologies. In addition, we will discuss the involvement of these galectins in thyroid cancers where their altered expression is proposed as a new diagnostic biomarker., SCOPUS: re.j, info:eu-repo/semantics/published

Background: Hibernoma is a rare soft tissue tumor stem from persistent fetal brown fat tissue. This benign tumor may occasionally occur in head and neck area and, in most cases, is characterized by an asymptomatic slow growth. Case presentation: We presented an uncommon case of hibernoma of the posterior cervical triangle occurring in a 30-year-old man referred to the department of otolaryngology. The patient suffered from a right, very painful, and rapidly growing mass since 3 months. MRI examination reported both an infiltrating mass and a homogenous enhancement of an underlying vascularization after the injection of intravenous contrast. According to the risk of sarcoma, a surgical procedure was made to completely excise the mass that was a hibernoma. Conclusions: Hibernoma may occur with an uncommon clinical presentation imitating malignancy. MRI plays a key role in the differential diagnosis and surgery remains the better therapeutic approach., SCOPUS: ar.j, info:eu-repo/semantics/published

The incidence of papillary thyroid cancer has increased these last decades due to a better detection. High prevalence of nodules combined with the low incidence of thyroid cancers constitutes an important diagnostic challenge. We propose to develop an alternative diagnostic method to reduce the number of useless and painful thyroidectomies using a vectorized contrast agent for magnetic resonance imaging. Galectin-1 (gal-1), a protein overexpressed in well-differentiated thyroid cancer, has been targeted with a randomized linear 12-mer peptide library using the phage display technique. Selected peptides have been conjugated to ultrasmall superparamagnetic particles of iron oxide (USPIO). Peptides and their corresponding contrast agents have been tested in vitro for their specific binding and toxicity. Two peptides (P1 and P7) were selected according to their affinity toward gal-1. Their binding has been revealed by immunohistochemistry on human thyroid cancer biopsies, and they were co-localized with gal-1 by immunofluorescence on TPC-1 cell line. Both peptides induce a decrease in TPC-1 cells' adhesion to gal-1 immobilized on culture plates. After coupling to USPIO, the peptides preserved their affinity toward gal-1. Their specific binding has been corroborated by co-localization with gal-1 expressed by TPC-1 cells and by their ability to compete with anti-gal-1 antibody. The peptides and their USPIO derivatives produce no toxicity in HepaRG cells as determined by MTT assay. The vectorized contrast agents are potential imaging probes for thyroid cancer diagnosis. Moreover, the two gal-1-targeted peptides prevent cancer cell adhesion by interacting with the carbohydrate-recognition domain of gal-1.

Purpose: Glucocorticoids (GCs) are often administered prior to any chemotherapeutics to prevent the secondary effects of anticancer agents. Glucocorticoid receptors (GRs) are expressed in several types of cancer cells, particularly in several histological types of breast cancer. Activation of GRs is not associated with any specific cellular response. Both proapoptotic and antiapoptotic responses have been observed, depending on the study or the type of breast cancer cells. Therefore, it is of relevance to investigate the possible modulation of apoptotic effect of chemotherapeutic agents when cancerous cells have previously been exposed to GCs. Methods: In vitro cell growth was assayed by counting MCF-7 cells upon exposure to epirubicin (25 nM), 5-fluorouracil (5-FU) (15 µM), and paclitaxel (15 μM), either with or without prior exposure to the GC dexamethasone (Dex) (100 nM). Results: Following preexposure to Dex, the antiapoptotic activity of paclitaxel was significantly reduced by 8.5% (p, SCOPUS: ar.j, info:eu-repo/semantics/published

Whipple procedure has been described since 1935,1 using classic open surgery. With the advent of minimally invasive surgery (MIS), it has been described to be feasible using the latest technology.2 , 3 In this video the authors report a full laparoscopic Whipple procedure, realizing the three anastomoses by intracorporeal handsewn method. A 70-year-old man who presented with adenocarcinoma of the ampulla of Vater, infiltrating the pancreatic parenchyma underwent to a laparoscopic Whipple. Preoperative work-up shows a T3N1M0 tumor. No perioperative complications were registered. The pancreatico-jejunostomy was created in end-to-side fashion using two PDS 3/0 running sutures (Fig. 1), the hepatico-jejunostomy in end-to-side method using two PDS 4/0 running sutures (Fig. 2), and the gastro-jejunostomy in end-to-side method using two PDS 1 running sutures (Fig. 3). Total operative time was 8 h 20 min. Time for the dissection was 6 h 20 min, time for the specimen’s extraction was 20 min, and time for the three laparoscopic intracorporeal handsewn anastomoses was 1 h 40 min. Operative bleeding was 350 cc. Patient was discharged on postoperative day 9. Pathologic report confirmed the moderately differentiated adenocarcinoma of the ampulla of Vater, with perinervous infiltration and lymphovascular emboli, free margins, 2 metastatic lymphnodes on 23 isolated; 8 edition UICC stade: pT3bN1. Laparoscopic Whipple remains an advanced procedure to be performed by laparoscopy as well as by open surgery. All the advantages of MIS, such as reduced abdominal trauma, less postoperative pain, shorter hospital stay, improved patient’s comfort, and enhanced cosmesis are offered using using laparoscopy.

In previous studies we found that several Neurotransmitters and Neuropeptides among them: Glutamate, Dopamine, Gonadotropin-releasing-hormone (GnRH) I and II, Somatostatin, CGRP and Neuropeptide Y, can each by itself, at low physiological concentration (~10 nM) bind its receptors in human T cells and trigger several key T cell functions. These findings showed that the nervous system, via Neurotransmitters and Neuropeptides, can 'talk' directly to the immune system, and stimulate what we coined 'Nerve-Driven Immunity': immune responses dictated by the nervous system. In various human cancers, the immune system of the patients, and their T cells in particular, are not functioning well enough against the cancer due to several reasons, among them the suppressive effects on the immune system induced by: (1) the cancer itself, (2) the chemotherapy and radiotherapy, (3) the ongoing/chronic stress, anxiety, depression and pain felt by the cancer patients. In Head and Neck Cancer (HNC), 5-year survival rate remains below 50%, primarily because of local recurrences or second primary tumors. Two-thirds of HNC patients are diagnosed at advanced clinical stage and have significantly poorer prognosis. Most HNC patients have multiple severe immunological defects especially in their T cells. A major defect in T cells of patients with HNC or other types of cancer is low CD3zeta expression that correlates with poor prognosis, decreased proliferation, apoptotic profile, abnormal cytokine secretion and poor abilities of destructing cancer cells. T cells of cancer patients are often also unable to migrate properly towards the tumor. In this study we asked if Glutamate, Dopamine or GnRH-II can augment the spontaneous migration, chemotactic migration and towards autologous HNC migration, and also increase CD3zeta and CD3epsilon expression, of peripheral T cells purified from the blood of five HNC patients. These HNC patients had either primary tumor or recurrence, and have been already treated by surgery and/or radiotherapy and/or chemotherapy without satisfactory outcomes. We found that Glutamate, Dopamine and GnRH-II, each by itself, at 10 nM, and during 30 min incubation only with the peripheral T cells of the HNC patients increased substantially their: (1) spontaneous migration (up to 4.4 fold increase), (2) chemotactic migration towards the key chemokine SDF-1 (up to 2.3 fold increase), (3) migration towards the autologous HNC tumor removed surgically ~48 h earlier in a pre-planned operation (up to 3.5 fold increase). Each of the Neurotransmitters even 'allowed' the T cells of one HNC patient to overcome completely the suppressive anti-migration effect of his autologous tumor, (4) cell surface CD3zeta expression (up to 4.3 fold increase), (5) cell surface CD3epsilon expression (up to 1.9 fold increase). If the absolutely essential larger scale subsequent studies would validate our present findings, Glutamate, Dopamine and GnRH-II could be used for a completely novel indication: adoptive T cell immunotherapy for some patients with HNC and maybe also other types of cancer. We coin here a novel term-'Neuroimmunotherapy' for this new form of T cell immunotherapy, based on the direct activation of the patient's own T cells by Neurotransmitters. Such 'Neuroimmunotherapy' could be reduced to practice by rather simple, painless and repeated/periodical removal of peripheral T cells from the cancer patients, activating them ex vivo for 30 min by either Glutamate, Dopamine or GnRH-II, and infusing them back to the patients by intravenous and/or intratumoral injection. The 'rejuvenated' Neurotransmitter-treated T cells are expected to have significantly improved abilities to reach and eradicate the cancer, and also combat infectious organisms that cancer patients often suffer from. Since the T cells are autologous, since the Neurotransmitters are physiological molecules, and since the ex vivo 'parking period' is very short, such Neuroimmunotherapy is expected to be very safe.

Iron accumulation is observed in liver and spleen during hemochromatosis and important neurodegenerative diseases involve iron overload in brain. Storage of iron is ensured by ferritin, which contains a magnetic core. It causes a darkening on T2-weighted MR images. This work aims at improving the understanding of the NMR relaxation of iron-loaded human tissues, which is necessary to develop protocols of iron content measurements by MRI. Relaxation times measurements on brain, liver and spleen samples were realized at different magnetic fields. Iron content was determined by atomic emission spectroscopy. For all samples, the longitudinal relaxation rate (1/T1) of tissue protons decreases with the magnetic field up to 1 T, independently of iron content, while their transverse relaxation rate (1/T2) strongly increases with the field, either linearly or quadratically, or a combination thereof. The extent of the inter-echo time dependence of 1/T2 also varies according to the sample. A combination of theoretical models is necessary to describe the relaxation of iron-containing tissues. This can be due to the presence, inside tissues, of ferritin clusters of different sizes and densities. When considering all samples, a correlation (r2 = 0.6) between 1/T1 and iron concentration is observed at 7.0 T. In contrast the correlation between 1/T2 and iron content is poor, even at high field (r2 = 0.14 at 7.0 T). Our results show that MRI methods based on T1 or T2 measurements will easily detect an iron overloading at high magnetic field, but will not provide an accurate quantification of tissue iron content at low iron concentrations. Copyright © 2014 John Wiley & Sons, Ltd.

Macrophage migration inhibitory factor (MIF) and its receptor CD74 appear to be involved in tumorigenesis. We evaluated, by immunohistochemical staining, the tissue expression and distribution of MIF and CD74 in serial sections of human invasive breast cancer tumor specimens. The serum MIF level was also determined in breast cancer patients. We showed a significant increase in serum MIF average levels in breast cancer patients compared to healthy individuals. MIF tissue expression, quantified by a modified Allred score, was strongly increased in carcinoma compared to tumor-free specimens, in the cancer cells and in the peritumoral stroma, with fibroblasts the most intensely stained. We did not find any significant correlation with histoprognostic factors, except for a significant inverse correlation between tumor size and MIF stromal positivity. CD74 staining was heterogeneous and significantly decreased in cancer cells but increased in the surrounding stroma, namely in lymphocytes, macrophages and vessel endothelium. There was no significant variation according to classical histoprognostic factors, except that CD74 stromal expression was significantly correlated with triple-negative receptor (TRN) status and the absence of estrogen receptors. In conclusion, our data support the concept of a functional role of MIF in human breast cancer. In addition to auto- and paracrine effects on cancer cells, MIF could contribute to shape the tumor microenvironment leading to immunomodulation and angiogenesis. Interfering with MIF effects in breast tumors in a therapeutic perspective remains an attractive but complex challenge. Level of co-expression of MIF and CD74 could be a surrogate marker for efficacy of anti-angiogenic drugs, particularly in TRN breast cancer tumor., Journal Article, Research Support, Non-U.S. Gov't, SCOPUS: ar.j, info:eu-repo/semantics/published

Galectins, a family of endogenous lectins, are multifunctional effectors that act at various sites and can be used in immunohistochemical localization studies of diseased states. Since they form a potentially cooperative and antagonistic network, we tested the hypothesis that histopathological fingerprinting of galectins could refine the molecular understanding of naso-sinusal pathologies. Using non-cross-reactive antibodies against galectin-1, -3, -4, -7, -8 and -9, we characterized the galectin profiles in chronic rhinosinusitis, nasal polyposis, inverted papillomas and squamous cell carcinomas. The expression, signal location and quantitative parameters describing the percentage of positive cells and labeling intensity were assessed for various cases. We discovered that inverted papillomas showed a distinct galectin immunohistochemical profile. Indeed, epithelial overexpression of galectin-3 (p=0.0002), galectin-4 (p, Journal Article, Research Support, Non-U.S. Gov't, SCOPUS: ar.j, info:eu-repo/semantics/published

// Meggy Suarez-Carmona 1,2,* , Pascale Hubert 1,* , Arnaud Gonzalez 3 , Anaelle Duray 4 , Patrick Roncarati 1 , Charlotte Erpicum 2 , Jacques Boniver 1 , Vincent Castronovo 3 , Agnes Noel 2 , Sven Saussez 4 , Olivier Peulen 3 , Philippe Delvenne 1,** and Michael Herfs 1,** 1 Laboratory of Experimental Pathology, GIGA-Cancer, University of Liege, Liege, Belgium 2 Laboratory of Tumor and Developmental Biology, GIGA-Cancer, University of Liege, Liege, Belgium 3 Metastasis Research Laboratory, GIGA-Cancer, University of Liege, Liege, Belgium 4 Laboratory of Anatomy, Faculty of Medicine and Pharmacy, University of Mons, Mons, Belgium * These authors contributed equally to this work ** These authors share last authorship Correspondence: Michael Herfs, email: // Keywords : p63, defensins, (lymph)angiogenesis, prognosis, squamous cell carcinoma Received : January 17, 2014 Accepted : March 19, 2014 Published : March 21, 2014 Abstract Beside a role in normal development/differentiation, high p63 immunoreactivity is also frequently observed in squamous cell carcinoma (SCC). Due to the complexity of the gene, the role of each p63 isotype in tumorigenesis is still confusing. Constitutively produced or induced in inflammatory conditions, human beta-defensins (HβDs) are cationic peptides involved in host defenses against bacteria, viruses and fungi. Here, we investigated both the role of p63 proteins in the regulation of HβDs and the implication of these antimicrobial peptides in tumor (lymph)angiogenesis. Thus, in contrast to TAp63 isotypes, we observed that ΔNp63 proteins (α, β, γ) induce HβD1, 2 and 4 expression. Similar results were observed in cancer tissues and cell lines. We next demonstrated that ΔNp63-overexpressing SCC are associated with both a poor prognosis and a high tumor vascularisation and lymphangiogenesis. Moreover, we showed that HβDs exert a chemotactic activity for (lymphatic) endothelial cells in a CCR6-dependent manner. The ability of HβDs to enhance (lymph)angiogenesis in vivo was also evaluated. We observed that HβDs increase the vessel number and induce a significant increase in relative vascular area compared to negative control. Taken together, the results of this study suggest that ΔNp63-regulated HβD could promote tumor (lymph)angiogenesis in SCC microenvironment.

Importance Laryngopharyngeal reflux (LPR) is a prevalent disease that is usually treated with diet, lifestyle modifications, and proton pump inhibitor therapy. However, nearly 10% to 30% of patients do not achieve adequate acid suppression even with high doses of proton pump inhibitors. For these patients with resistant disease, fundoplication may be recommended but the success rate of fundoplication surgery on laryngopharyngeal symptoms and findings remains uncertain. Objective To determine whether fundoplication is associated with control of signs and symptoms in patients with LPR. Evidence Review A literature search was conducted on PubMed, Cochrane Library, and Scopus according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline to identify studies published between 1990 and 2018 about the efficacy of fundoplication on clinical outcomes of LPR. Three investigators screened publications for eligibility and exclusion based on predetermined criteria. Study design, patient characteristics, diagnostic method, exclusion criteria, treatment characteristics, follow-up, and quality of the outcome assessment were evaluated. Findings Of the 266 studies identified, 34 met the inclusion criteria, accounting for 2190 patients with LPR (1270 women and 920 men; mean [SD] age at the time of surgery, 49.3 [6.3] years). A weighted mean of 83.0% of patients (95% CI, 79.7%-86.3%) experienced improvement and a weighted mean of 67.0% of patients (95% CI, 64.1%-69.9%) experienced a disappearance of symptoms, but there is a high level of methodological heterogeneity among studies according to diagnostic method, exclusion criteria, and outcomes used to assess the efficacy of fundoplication. A pH study without impedance study was used in most studies but with various inclusion criteria. According to results of an a priori assessment, the clinical outcomes used were overall poor, excluding many symptoms and findings associated with LPR. Conclusion and Relevance The reported studies of fundoplication in LPR disease have important heterogeneity in method of diagnosis, exclusion criteria, symptoms, and signs assessed as therapeutic outcomes; therefore, this systematic review was nonconclusive regarding whether surgery for LPR disease is associated with effective control of sight and symptoms. Otolaryngologists, gastroenterologists, and surgeons must establish a diagnostic criterion standard, clear indications for surgery, and future clinical outcomes to precisely assess the effectiveness of treatment.

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.

We investigated the prevalence of human papillomavirus (HPV) in a clinical series of 72 patients with head and neck squamous cell carcinoma (HNSCC) using a retrospective and prospective study design. The majority of patients were smokers and/or drinkers and were treated with concomitant chemoradiotherapy (CCR). Furthermore, we assessed the impact of HPV positivity on the response to CCR. Paraffin-embedded samples from HNSCC patients (n=72) were evaluated for the presence of HPV DNA using both GP5+/GP6+ consensus PCR and type-specific E6/E7 PCR to detect HPV types 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 67 and 68. The type-specific E6/E7 PCR demonstrated that 20 out of 69 HNSCC patients (29%) presented with high-risk (HR) HPV types and that 5 of the 69 HNSCC patients (7%) presented with low-risk (LR) HPV types. Using the GP5+/GP6+ PCR, we observed that the rate of response was statistically lower in the HPV+ group (P=0.02). Concerning patient outcomes in terms of recurrence and survival, we observed that the prognosis was poorer for HPV+ patients. We showed for the first time that patients with HPV+ HNSCC present with a worse prognosis after CCR. This observation highlights the need for prospective studies with large numbers of patients and a detailed history of tobacco and alcohol consumption before validating HPV as a marker of prognosis following CCR.

Aero-digestive tract squamous intra-epithelial neoplasia is a disease whose genetic and epigenetic features lead to clinical signs and well codified histologic features. This publication aims to review the molecular alterations which have been identified in these lesions, to clarify the clinical manifestations and to discuss the proposed histological classification.

Summary 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.

Head and neck squamous cell carcinoma (HNSCC) represent the sixth most common malignancy diagnosed worldwide. Patient's survival is low due the high frequency of tumor recurrence. Inflammation promotes carcinogenesis as well as the formation of metastasis. Indeed, proinflammatory mediators are known to stimulate the expression of specific transcription factors such as Snai1 and to increase the ability of tumor cells to migrate into distant organs. The atypical interleukin-32 (IL32) was mainly described to exacerbate inflammatory responses in rheumatoid arthritis and inflammatory bowel diseases. IL32 is expressed in various cancers but its role in HNSCC physiology is still unexplored. Here, we analyzed the expression of IL32 and its implication on HNSCC aggressiveness. We showed that patients with tumor expressing high amounts of IL32 exhibit decreased disease-free periods (20.5 mo vs. 41 mo, P = 0.0041) and overall survival (P = 0.0359) in comparison with individuals with weak IL32 tumor expression. This overexpression was negatively correlated with gender (P = 0.0292) and p53 expression (P = 0.0307). In addition, in vitro data linked IL32 expression to metastasis formation since IL32 inhibition decreased Snai1 expression and tumor cell migration in a Boyden chamber assay. Our data provide new insight into the role of IL32 in HNSCC aggressiveness. © 2013 Wiley Periodicals, Inc.

Objectives Head and neck squamous cell carcinomas (HNSCC), one of the most frequent cancers in the world, are largely infiltrated by inflammatory immune cells. Our aim was to evaluate the number of Foxp3+ T cells in HNSCC, reporting its prognostic power in comparison to other risk factors. Material and methods Our clinical series was composed of 21 tumor-free peri-tumoral epithelia, 49 low grade dysplasia, 43 high grade dysplasia and 110 carcinoma samples including some cases with HPV infection. In vivo experiments were conducted on 80 C3 H/HeN mice which were orthotopically injected with SCCVII CT, E7, E6 and E6/E7 cell lines. Results Foxp3+ T cell infiltration increased with tumor progression from normal epithelia, dysplasia to carcinoma and the increase is more important in HPV+ patients than in negative ones. Animal experiments revealed that E7 oncoprotein expression was significantly associated with an increase in Foxp3+ T cell recruitment in tumor, a delay in tumor onset and improved animal survival. Univariate Cox regression analyses demonstrated that high Foxp3+ T cell number in stromal compartment is associated with longer patient recurrence-free and overall survivals. Foxp3+ T cell number improved the prognostic value of tumor stage. Multivariate analyses reported that stromal Foxp3+ T cell number is a strong prognostic factor independent of classical risk factors such as tobacco, alcohol, and HPV status. Conclusion Foxp3+ T cell number is a significant prognostic factor for HNSCC, improving the tumor stage, and that viral E7 may play a role in the Foxp3+ T cell infiltration to the tumor.

Background Laryngopharyngeal reflux is a prevalent, not well-understood disease affecting a high proportion of patients who seek laryngology consultation. The objective of this prospective case series is to explore the subjective and objective voice modifications in Laryngopharyngeal reflux (LPR), especially the usefulness of acoustic parameters as treatment outcomes, and to better understand the pathophysiological mechanisms underlying the development of voice disorder. Methods Forty-one patients with a reflux finding score (RFS) > 7 and a reflux symptom index (RSI) > 13 were enrolled and treated with pantoprazole 20 mg twice daily for three months. RSI, RFS, Voice Handicap Index (VHI), and Grade, Roughness, Breathiness, Asthenia, Strain and Instability (GRBASI) were assessed at baseline and after three months post-therapy. Acoustic parameters were measured by selecting the most stable interval of the vowel /a/. A study of correlations between acoustic measurements and laryngoscopic signs was conducted in patients with roughness. Statistical analysis was performed using Statistical Package for the Social Sciences (SPSS). Results Significant improvement in RSI, RFS, VHI, jitter, percent jitter, relative average perturbation (RAP), shimmer, percent shimmer, and amplitude perturbation quotient (APQ) was found at 3 months of treatment (p

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.

Macrophage migration inhibitory factor (MIF) is a glycosylated multi-functional protein that acts as an enzyme as well as a cytokine. MIF mediates its actions through a cell surface class II major histocompatibility chaperone, CD74 and co-receptors such as CD44, CXCR2, CXCR4 or CXCR7. MIF has been implicated in the pathogenesis of several acute and chronic inflammatory diseases. Although MIF is a molecule of biomedical importance, a public resource of MIF signaling pathway is currently lacking. In view of this, we carried out detailed data mining and documentation of the signaling events pertaining to MIF from published literature and developed an integrated reaction map of MIF signaling. This resulted in the cataloguing of 68 molecules belonging to MIF signaling pathway, which includes 24 protein-protein interactions, 44 post-translational modifications, 11 protein translocation events and 8 activation/inhibition events. In addition, 65 gene regulation events at the mRNA levels induced by MIF signaling have also been catalogued. This signaling pathway has been integrated into NetPath ( http://www.netpath.org ), a freely available human signaling pathway resource developed previously by our group. The MIF pathway data is freely available online in various community standard data exchange formats. We expect that data on signaling events and a detailed signaling map of MIF will provide the scientific community with an improved platform to facilitate further molecular as well as biomedical investigations on MIF.

Purpose: Despite the advent of concomitant chemoradiotherapy (CCRT), the prognosis of advanced head and neck squamous cell carcinoma (HNSCC) patients remains particularly poor. Classically, HNSCC, especially oropharyngeal carcinomas, associated with human papillomavirus (HPV) exhibits better treatment outcomes than HNSCCs in non-infected patients, eliciting a call for the de-escalation of current therapies. To improve the management of HNSCC patients, we aimed to determine the impact of active HPV infection on patient response, recurrence and survival after CCRT in a population of heavy tobacco and alcohol consumers. Methods: Paraffin-embedded samples from 218 advanced HNSCC patients, mostly smokers and/or drinkers treated by CCRT, were tested for the presence of HPV DNA by surrogate type-specific E6/E7 qPCR and p16 immunohistochemistry. Associations between the response to CCRT and patient outcomes according to HPV status and clinical data were evaluated by Kaplan–Meier analysis and both univariate and multivariate Cox regression. Results: Type-specific E6/E7 PCR demonstrated HPV positivity in 20 % of HNSCC. Regarding HPV status, we did not find any significant relation with response to therapy in terms of progression-free survival or overall survival. However, we observed a significantly worse prognosis for consumers of alcohol and tobacco compared to nondrinkers (p = 0.003) and non-smokers (p = 0.03). Survival analyses also revealed that the outcome is compromised in stage IV patients (p = 0.007) and, in particular, for oral cavity, hypopharynx and oropharynx carcinoma patients (p = 0.001). Conclusion: The risk of death from HNSCC significantly increases when patients are exposed to tobacco and alcohol during their therapy, regardless of HPV status., SCOPUS: ar.j, info:eu-repo/semantics/published

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.