Immunosuppressive protocols after laryngeal transplantation: a systematic review.

BACKGROUNDS: Larynx transplantation has been successfully performed four times, in 1998, 2010, 2015 and 2023 remained the ultimate goal of voice, feeding and breathing rehabilitation. OBJECTIVE: Immunosuppressive protocols used during the previous successful larynx allotransplantation are detailed. MATERIAL AND METHODS: A systematic review of the literature on PUBMED/Medline, Cochrane and Embase was conducted. Articles relating to actual human larynx transplantations were included. RESULTS: Bibliography search gathered N = 10 publications related to the performance and follow-up of human laryngeal transplantations. N = 8 publications were included corresponding to N = 3 actual human larynx transplantations performed in 1998 and 2010 in the USA and in 2015 in Poland. Immunosuppression protocols, induction and maintenance strategies, rejection monitoring and history of all the three previous laryngeal grafts were detailed. CONCLUSIONS: Beyond the surgical prowess, larynx transplantation is feasible and associated with a reasonably successful outcome when compared to other solid organ transplants. Immunosuppressive regimen protocols and technologies for the monitoring of the organ viability have evolved. SIGNIFICANCE: The reevaluation of this surgical option serves as the reminder of the critical necessity to implement a meticulous immunosuppression protocol when transplanting this inherently immunogenic composite organ, the larynx.

Three-dimensional reconstruction of King Henri IV's paranasal sinuses and mastoid cells.

PURPOSE: The preserved head of King Henri IV of France (life 1553-1610, reign 1589-1610) has survived to the present day thanks to high-quality embalming and favorable conservation conditions. The aim of this study was to examine Henry IV's upper resonant cavities and mastoids using an original and innovative forensic three-dimensional segmentation method. METHODS: The paranasal sinuses and mastoid cells of King Henri IV of France were studied by cross-referencing available biographical information with clinical and flexible endoscopic examination and computed tomography (CT-scan) imaging. The paranasal sinuses and mastoid cells were delineated and their volumes were assessed using ITK-SNAP 4.0 software (open-source). Graphical representations were created using Fusion 360® (Autodesk Inc., San Rafael, CA, USA) and MeshMixer® (Autodesk Inc., San Rafael, CA, USA). RESULTS: Paranasal sinus tomodensitometry revealed abnormalities in shape and number. Henri IV of France suffered from sinus aplasia. Neither the left sphenoid nor left frontal sinus contrasted sharply, and a remarkable pneumatization of the right clinoid processes extended throughout the height of the right pterygoid process. The total volumes of Henri IV's mastoid air-cells were estimated at 27 and 26 mL, respectively, for the right and left sides, exceeding the normal mean and the maximum of modern subjects by a wide margin. No sign of chronic ear or sinus condition was found. CONCLUSIONS: An innovative method has been developed in forensic medicine to establish hypotheses about the growth and respiratory conditions of the face.

Over 132 Years Ago, the Inaugural Immunotherapy Treated Its First Head and Neck Cancer Patient.

Immunotherapy in oncology has a more extensive history than is commonly perceived. Rooted in the observations and experiences of multiple physicians in the late 19th century, immunological interventions are currently integral to the oncological therapeutic repertoire. This article seeks to delineate the evolution of cancer immunotherapy, tracing its inception in 1891 with the pioneering work of an American surgeon, William B. Coley, who achieved the first documented cure of a cancer case involving a malignant head and neck tumor. The narrative extends to encompass successive historical breakthroughs and prospective developments in this dynamic field.

Hypothesis of a CD137/Eomes activating axis for effector T cells in HPV oropharyngeal cancers.

Chronic Human Papilloma Virus (HPV) infection is supplanting alcohol and tobacco intoxications as the leading cause of oropharyngeal cancer in developed countries. HPV-related squamous cell carcinomas of the oropharynx (HPV + OSC) present better survival and respond better to radiotherapy and chemotherapy. Regulatory T cells (TREG) are mainly described as immunosuppressive and protumoral in most solid cancers. However, TREG are paradoxically associated with a better prognosis in HPV + OSCs. The transcription factor FoxP3 is the basis for the identification of TREG. Among CD4 + FoxP3 + T cells, some have effector functions. A medical hypothesis is formulated here: the existence of a CD137 (4.1BB)-Eomesodermin (Eomes) activated pathway downstream of TCR-specific activation in a subpopulation of CD4 + FoxP3 + T cells may explain this effector function. Evidence suggest that this axis may exist either in CD4 + FoxP3 + T cells or CD8 + T cells. This pathway could lead T cells to strong antitumor cytotoxic activity in a tumor-specific manner. Furthermore, CD137 is one of the most expected targets for the development of agonist immunotherapies. The identification of CD137 + Eomes + FoxP3+/- T cells could be a key element in the selective activation of the most anti-tumor cells in the HPV + OSC microenvironment.

Validity and reliability of the Group for Learning Useful and Performant Swallowing (GLUPS) tool.

INTRODUCTION: To validate the Group for Learning Useful and Performant Swallowing (GLUPS), a clinical tool dedicated to videofluoroscopy swallowing study (VFSS). METHODS: Forty-five individuals were recruited from January 2022 to March 2023 from the Department of Otolaryngology Head and Neck Surgery of University Hospital Saint-Pierre (Brussels, Belgium). Subjects underwent VFSS, which was rated with GLUPS tool by two blinded otolaryngologists and one speech-therapist. VFSS were rated twice with GLUPS within a 7-day period to assess test-retest reliability. RESULTS: Twenty-four patients and twenty-one controls completed the evaluations. The internal consistency (α = 0.745) and the test-retest reliability (rs = 0.941; p = 0.001) were adequate. GLUPS reported a high external validity regarding the significant correlation with the Penetration-Aspiration Scale (rs = 0.551; p = 0.001). Internal validity was adequate, because GLUPS score was significant higher in patients compared to controls (6.21 ± 4.42 versus 2.09 ± 2.00; p = 0.001). Interrater reliability did not report significant differences in the GLUPS sub- and total score among the independent judges. The mean GLUPS score of individuals without any evidence of VFSS abnormalities was 2.09/23 (95% CI 1.23-2.95), which supported that a GLUPS score ≥ 3.0 is suggestive of pathological VFSS. CONCLUSIONS: GLUPS is a clinical instrument documenting the abnormal findings of oral and pharyngeal phases at the VFSS. GLUPS demonstrated high reliability and excellent criterion-based validity. GLUPS may be used in clinical practice for the swallowing evaluation at the VFSS.

Performance of Non-EPI DW MRI for Pediatric Cholesteatoma Follow-Up.

OBJECTIVE: To evaluate the accuracy, sensitivity, and specificity of nonecho planar (non-EPI) diffusion-weighted (DW) magnetic resonance imaging (MRI) to detect residual cholesteatoma in children. STUDY DESIGN: Retrospective study. SETTING: Tertiary comprehensive hospital. METHODS: Children operated on for a first-stage cholesteatoma procedure from 2010 to 2019 were included. MRIs were performed with non-EPI DW sequences. Initial reports were collected, indicating the presence or absence of hyperintensity suggestive of cholesteatoma. Three hundred twenty-three MRIs were correlated with the subsequent surgery (66%) or year-later MRI (21%), or were considered accurate if performed 5 years or more after the last surgery (13%). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of each imaging procedure for the detection of cholesteatoma were calculated. RESULTS: Two hundred twenty-four children with mean age of 9 ± 4 years old presented with cholesteatoma. MRIs were performed 27 ± 24 months after surgery. Residual cholesteatoma was diagnosed in 35%. The sensitivity, specificity, PPV, and NPV of MRI were 62%, 86%, 74%, and 78%, respectively. Accuracy, sensitivity, and specificity increased significantly over time (multivariate analysis). The mean delay after last surgery was of 30 ± 2.0 months for accurate MRI (true positive or negative) versus 17 ± 2.0 months for nonaccurate (false positive or negative) MRIs (p < .001). CONCLUSION: However, long the delay after the last surgery, the sensitivity of non-EPI diffusion sequence MRI in children has limitations for the detection of residual cholesteatoma. Surveillance for residual cholesteatoma should incorporate findings at primary surgery, surgeon experience, a low threshold for second-look procedures, and routine imaging.

Accuracy of ChatGPT in head and neck oncological board decisions: preliminary findings.

OBJECTIVES: To evaluate the ChatGPT-4 performance in oncological board decisions. METHODS: Twenty medical records of patients with head and neck cancer were evaluated by ChatGPT-4 for additional examinations, management, and therapeutic approaches. The ChatGPT-4 propositions were assessed with the Artificial Intelligence Performance Instrument. The stability of ChatGPT-4 was evaluated through regenerated answers at 1-day interval. RESULTS: ChatGPT-4 provided adequate explanations for cTNM staging in 19 cases (95%). ChatGPT-4 proposed a significant higher number of additional examinations than practitioners (72 versus 103; p = 0.001). ChatGPT-4 indications of endoscopy-biopsy, HPV research, ultrasonography, and PET-CT were consistent with the oncological board decisions. The therapeutic propositions of ChatGPT-4 were accurate in 13 cases (65%). Most additional examination and primary treatment propositions were consistent throughout regenerated response process. CONCLUSIONS: ChatGPT-4 may be an adjunctive theoretical tool in oncological board simple decisions.

Influence of Otolaryngological Subspecialties on Perception of Transoral Robotic Surgery: An International YO-IFOS Survey.

BACKGROUND: To investigate perception, adoption, and awareness on the part of otolaryngology and head and neck surgeons (OTO-HNS) of transoral robotic surgery (TORS). METHODS: Several items assessed: awareness/perception; access to TORS; training; indications and advantages/hurdles to TORS practice. A subanalysis was performed to assess differences according to the identified otolaryngological subspecialties. RESULTS: A total of 359 people completed the survey. Among subspecialties, while for otolaryngologists 30/359 (8.4%) and H&N surgeons 100/359 (27.9%) TORS plays an effective role in hospital stay, laryngologists frequently disagreed (54.3%). There was a lower incidence among rhinologists and otologists (1.9%). Pediatric surgeons (0.8%) reported a positive response regarding the adoption of robotic surgery, and head and neck specialists expressed an even greater response (14.2%). Low adherence was related to perceived cost-prohibitive TORS, by 50% of H&N surgeons. CONCLUSIONS: Perception, adoption, and knowledge about TORS play a key role in the application of the robotic system, significantly varying across subspecialties.

Management of 80 sinonasal undifferentiated carcinomas. Retrospective multicentre study of the French Network of Rare Head and Neck Cancers (REFCOR).

OBJECTIVES: Sinonasal undifferentiated carcinoma (SNUC) is a rare and aggressive disease requiring multimodal treatment, and multiple new entities once included in the spectrum of SNUC, such as SWI/SNF-deficient carcinomas, are emerging. We aimed to provide new data regarding the role of chemotherapy and surgery and the prognostic factors of disease-free survival. METHODS: This study was based on data from the REFCOR database and included patients with SNUC treated with curative intent from 2007 to 2021 across 22 centres in France. RESULTS: A total of 80 patients were included in the analysis. Among the entire cohort, the 5-year disease-free survival (DFS) and overall survival (OS) rates were 58% and 63%, respectively. Of 100% of the patients treated with irradiation, 29% underwent surgery, 56% neoadjuvant chemotherapy (82% had either a partial or a complete response) and 76% chemoradiotherapy. No treatment modality was associated with a better OS or DFS, including surgery (p = 0.34). There was a trend for a better DFS for the patients treated with chemotherapy (neoadjuvant or concomitant, p = 0.062). Overall survival at 3 years was 58% for SWI/SNF deficient group and 86% for non deficient group (p = 0.14). The locoregional relapse rate without distant metastases was 21% in the exclusive radiotherapy group and 26% in the surgery group. Grade 3 or higher toxicities concerned 9%, 32% and 29% of patients for surgery, radiotherapy and chemotherapy respectively. CONCLUSION: In the management of localised SNUC among all patients treated with irradiation, surgery yielded no benefit, whereas the addition of chemotherapy tended to improve disease-free survival.

Early Magnetic Resonance Imaging to Diagnose Residual Cholesteatoma in Children and Benefit of Radiological Rereview.

OBJECTIVE: Non-echo-planar diffusion-weighted (DW) magnetic resonance imaging (non-EPI MRI) is the appropriate sequence to detect residual cholesteatoma. In the child, MRI may be clinically useful to determine the timing of the second-look procedure. The aim of this paper was to retrospectively evaluate the performance of early MRI (before the 18th postoperative month) in detecting residual cholesteatoma in children after review by experienced specialized neuroradiologists. STUDY DESIGN: Retrospective study. SETTING: One university center comparative cohort. METHODS: All patients who had a 2-staged procedure for cholesteatoma with an MRI before the second stage from 2010 to 2020 were included and analyzed. Three pediatric neuroradiologists reviewed all the images blinded to the surgical result. RESULTS: N = 141 cholesteatoma events (140 children) were included with a mean age at MRI of 10 (±4) years old. Non-EPI MRIs were performed 10.7 (±3.8) months after the first-stage surgery and 2.2 (±2.6) months before the second-stage procedure. Non-EPI MRI had a 0.57 sensitivity (SE) and 0.83 specificity (SP). MRI was reviewed in 112 cases. The diagnosis was corrected in 17 cases (15.1%) (3 true positives, 7 false negatives, and 7 false positives). SE = 0.63 (p = 0.1) and SP = 0.92 (p = 0.08) after rereading. CONCLUSION: Early MRI's SE is poor but SP is excellent after rereading. Evidence does not support the use of early non-EPI MRI to modify the surgical strategy or to postpone the second look. If performed, early non-EPI MRI should be read by specialized experienced radiologists with all 3 sequences (T1, T2, and non-EPI DW) and apparent diffusion coefficient calculation, especially in cases of otitis media with effusion.

Is drug-induced sleep endoscopy associated with better outcomes after soft tissue surgery for sleep apnea? A systematic review and meta-analysis.

OBJECTIVES: The aim was to estimate the effect of drug-induced sleep endoscopy (DISE) on surgical outcomes after soft tissue surgery for obstructive sleep apnea (OSA). DESIGN AND SETTING: Systematic review and meta-analysis. PARTICIPANTS: Adult patients with OSA and candidates for soft tissue surgery, with and without preoperative DISE, were included. MAIN OUTCOMES MEASURES: A systematic literature search of Medline, Web of Science, and Cochrane databases was performed from inception to December 31, 2021. Studies directly comparing patients with and without preoperative DISE were included. Success rate, change in apnea-hypopnea index (AHI), change in minimum SpO2 and change in Epworth Sleepiness Scale (ESS) score were extracted. Random-effect models were used to pool estimates. RESULTS: Seven out of 619 articles were included, representing 791 patients (389 in the DISE group and 402 in the no DISE group). DISE was neither associated with a higher success rate (pooled OR 1.34, 95% CI 0.69-2.59, p = 0.39) after soft tissue surgery for OSA, nor a significant change in AHI (-4.69 events/hour, 95% CI -11.10 to 1.72, p = 0.15), minimal SpO2 (mean increase of 2.02%, 95% CI -0.26 to 4.29, p = 0.08) and ESS (mean difference of 1.29, 95% CI -0.48 to 3.05, p = 0.15) when compared to patients without preoperative DISE. CONCLUSIONS: Soft tissue surgery does not give better results after DISE compared to when DISE is not performed. However, given the overall low level of evidence of included studies, future well-conducted studies should confirm or overturn these results and clarify the added value of DISE.

A Prospective Controlled Study Investigating Odor Identification in Laryngopharyngeal Reflux.

OBJECTIVE: To psychophysically evaluate olfaction in patients with laryngopharyngeal reflux (LPR). STUDY DESIGN: Prospective controlled study. SETTING: Tertiary medical center. METHODS: From January 2021 to January 2022, patients with LPR diagnosed with hypopharyngeal-esophageal multichannel intraluminal impedance-pH monitoring underwent psychophysical evaluation of the sense of smell. Reflux symptoms and findings were assessed with the Reflux Symptom Score (RSS) and Reflux Sign Assessment (RSA). Nasal symptoms were assessed through the Sino-Nasal Outcome Test 22 (SNOT-22). From pre- to posttreatment, patients underwent identification Sniffin' Sticks test and olfactory cleft examination. Clinical outcomes were compared between LPR patients and healthy individuals. RESULTS: In total, 107 patients and 76 healthy individuals completed the evaluations. LPR patients reported significant higher RSS, RSA, and SNOT-22 scores. Psychophysical olfactory evaluations were significantly lower in reflux patients compared with controls, while there were no significant differences in olfactory cleft score. RSS and RSA significantly improved from baseline to 3 months posttreatment. SNOT-22, olfactory cleft endoscopy scale, and psychophysical olfactory evaluations did not change throughout treatment. Patients with higher number of acid pharyngeal reflux events reported lower psychophysical olfactory scores (P = .025). CONCLUSION: LPR disease was associated with low odor identification results in patients without olfactory cleft abnormalities. The sense of smell did not improve after 3-month therapy. Future controlled studies using threshold, discrimination, and identification testing are needed.

Usefulness, acceptation and feasibility of electronic medical history tool in reflux disease.

OBJECTIVES: To investigate usefulness, feasibility, and patient satisfaction of an electronic pre-consultation medical history tool (EPMH) in laryngopharyngeal reflux (LPR) work-up. METHODS: Seventy-five patients with LPR were invited to complete electronic medical history assessment prior to laryngology consultation. EPMH collected the following parameters: demographic and epidemiological data, medication, medical and surgical histories, diet habits, stress and symptom findings. Stress and symptoms were assessed with perceived stress scale and reflux symptom score. Duration of consultation, acceptance, and satisfaction of patients (feasibility, usefulness, effectiveness, understanding of questions) were evaluated through a 9-item patient-reported outcome questionnaire. RESULTS: Seventy patients completed the evaluation (93% participation rate). The mean age of cohort was 51.2 ± 15.6 years old. There were 35 females and 35 males. Patients who refused to participate (N = 5) were > 65 years old. The consultation duration was significantly lower in patients who used the EPMH (11.3 ± 2.7 min) compared with a control group (18.1 ± 5.1 min; p = 0.001). Ninety percent of patients were satisfied about EPMH easiness and usefulness, while 97.1% thought that EPMH may improve the disease management. Patients would recommend similar approach for otolaryngological or other specialty consultations in 98.6% and 92.8% of cases, respectively. CONCLUSION: The use of EPMH is associated with adequate usefulness, feasibility, and satisfaction outcomes in patients with LPR. This software is a preliminary step in the development of an AI-based diagnostic decision support tool to help laryngologists in their daily practice. Future randomized controlled studies are needed to investigate the gain of similar approaches on the traditional consultation format.

Tele-rehabilitation in voice disorders during the pandemic: a consensus paper from the French Society of Phoniatrics and Laryngology.

OBJECTIVES: To establish a consensus protocol for telerehabilitation in speech therapy for voice disorders. METHODS: The study was conducted according to a modified Delphi method. Twenty speech therapist or laryngologist experts of the French Society of Phoniatrics and Laryngology assessed 24 statements of voice telerehabilitation with a 10-point visual analog scale ranging from 1 (totally disagree) to 10 (totally agree). The statements were accepted if more than 80% of the experts rated the item with a score of ≥ 8/10. The statements with ≥ 8/10 score by 60-80% of experts were improved and resubmitted to voting until they were validated or rejected. RESULTS: The French Society of Phoniatrics and Laryngology experts validated 10, 6, and 2 statements after the first, second and third voting round, respectively. Seven statements did not reach agreement threshold and were rejected. The validated statements included recommendations for setting (N = 4), medical/speech history (N = 2), subjective voice evaluations (N = 3), objective voice quality measurements (N = 3), and voice rehabilitation (N = 5). The experts agreed for a follow-up consisting of combined telerehabilitation and in-office rehabilitation. The final protocol may be applied in context of pandemic but could be assessed out of pandemic period for patients located in rural regions. CONCLUSIONS: This Delphi study established the first telerehabilitation protocol of the French Society of Phoniatrics and Laryngology for patients with voice disorders. Future controlled studies are needed to assess its feasibility, reliability, and the patient perception about telerehabilitation versus in-office rehabilitation.

History of Otolaryngology: Globus Pharyngeus as "Globus Hystericus".

Globus pharyngeus is the uncomfortable sensation of a "lump in the throat," and at present it has many recognized pathophysiologic causes. However, until relatively recently, this condition was often labeled "globus hystericus" and was thought to be a manifestation of hysteria or anxiety. In this commentary, we briefly review the history surrounding the initial treatment of globus pharyngeus sensation as a hysterical condition rooted in anxiety/psychological causes; then, we briefly review the emerging evidence that roots globus pharyngeus sensation within a constellation of pathophysiologies that are related to pharyngoesophageal inflammation and irritation rather than psychological disorders.

Voice Quality Outcomes After Transoral CO2 Laser Cordectomy: A Longitudinal Prospective Study.

OBJECTIVE: To evaluate the evolution of voice quality in patients after type I-VI transoral CO2 laser cordectomy (TLC) by using validated voice outcome measures over a 12-month period. STUDY DESIGN: Prospective uncontrolled study. SETTING: Monocenter study. METHODS: Patients with laryngeal carcinoma who were eligible for type I-IV TLC were prospectively recruited from a tertiary medical center. The following outcomes were assessed throughout the 12-month posttreatment period: Voice Handicap Index (VHI), GRBAS (grade of dysphonia, roughness, breathiness, asthenia, strain), maximal phonation time, fundamental frequency (F0), F0 standard deviation, percentage jitter, percentage shimmer, noise-to-harmonic ratio, and speech fluency. Analyses were performed considering 2 groups of cordectomies: type I-III vs IV-VI. RESULTS: A total of 131 patients completed the evaluations, totaling 76 type I-III and 55 type IV-VI cordectomies. In type IV-VI, breathiness and maximal phonation time significantly worsened from pretreatment to 1 month posttreatment (P < .05). In the type I-III cordectomy group, VHI, shimmer, roughness, breathiness, and strain significantly improved from pretreatment to 3 months posttreatment, while VHI, F0 standard deviation, shimmer, jitter, grade of dysphonia, roughness, breathiness, and strain improved from baseline to 6 months. Assessments at 12 months posttreatment revealed significant improvements for VHI, shimmer, jitter, noise-to-harmonic ratio, grade of dysphonia, roughness, breathiness, and strain. In the type IV-VI group, VHI significantly improved from baseline to 3, 6, and 12 months posttreatment. Strain improved at 6 and 12 months while roughness improved from baseline to 12 months. Maximal phonation time significantly worsened over the 12-month evaluation period. CONCLUSION: The effect of TLC on voice quality depends on its type. VHI was identified as the most indicative tool of voice changes irrespective of TLC type.