The dawn of robotic surgery in otolaryngology-head and neck surgery.

Transoral robotic surgery (TORS) utilizing the da Vinci robotic system has opened a new era for minimally-invasive surgery (MIS) in Otolaryngology-Head and Neck Surgery. Awareness of the historical steps in developing robotic surgery (RS) and understanding its current application within our field can help open our imaginations to future of the surgical robotics. We compiled a historical perspective on the evolution of surgical robotics, the road to the da Vinci surgical system, and conducted a review of TORS regarding clinical applications and limitations, prospective clinical trials and current status in Japan. We also provided commentary on the future of surgical robotics within our field. Surgical robotics grew out of the pursuit of telerobotics and the advances in robotics for non-medical applications. Today in our field, cancers and diseases of oropharynx and supraglottis are the most common indications for RS. It has proved capable of preserving the laryngopharyngeal function without compromising oncologic outcomes, and reducing the intensity of adjuvant therapy. TORS has become a standard modality for MIS, and will continue to evolve in the future. As robotic surgical systems evolve with improved capabilities in visual augmentation, spatial navigation, miniaturization, force-feedback and cost-effectiveness, we will see further advances in the current indications, and an expansion of indications. By promoting borderless international collaborations that put 'patients first', the bright future of surgical robotics will synergistically expand to the limits of our imaginations.

Compared characteristics of current vs. past smokers at the time of diagnosis of a first-time lung or head and neck cancer: a cross-sectional study.

BACKGROUND: Active smoking at the time of diagnosis of a first head & neck (H&N) or lung cancer is associated with a worse cancer outcome and increased mortality. However, the compared characteristics of active vs. former smokers at cancer diagnosis are poorly known. METHODS: In 371 subjects with a first H&N or lung cancer, we assessed: 1) socio-demographic features; 2) lifelong types of smoking; 3) alcohol use disorder identification test (AUDIT); 4) cannabis abuse screening test (CAST); and 5) Mini International Neuropsychiatric Interview (MINI). Using a multivariable regression model, we compared the profile of current smokers and past smokers. RESULTS: Current smokers more frequently exhibited H&N cancer (OR 3.91; 95% CI [2.00-6.51]; p <  0.0001) and ever smoking of hand-rolled cigarettes (OR 2.2; 95% CI [1.25-3.88]; p = 0.007). Among subjects with lung cancer (n = 177), current smoking was primarily associated with ever smoking of hand-rolled cigarettes (OR 2.88; 95% CI [1.32-6.30]; p = 0.008) and negatively associated with age (OR 0.92; 95% CI [0.89-0.96]; p <  0.001). Among subjects with H&N cancer (n = 163), current smokers exhibited a significantly greater AUDIT score (OR = 1.08; 95% CI [1.01-1.16]; p = 0.03). CONCLUSION: At the time of diagnosis of the first lung or H&N cancer, current smoking is highly associated with previous type of smoking and alcohol drinking patterns. TRIAL REGISTRATION: NCT01647425 ; Registration date: July 23, 2012.

Comparison of endoscopic and external resections for sinonasal instestinal-type adenocarcinoma.

Endoscopic sinus surgery (ESS) is considered as a valid option in the management of nasal adenocarcinoma (ADC). Comparative studies with open approaches are still required. A monocentric retrospective study was carried out from May 2002 to December 2013, including 43 patients with intestinal-type adenocarcinoma of the ethmoid sinus. Non-resectable tumours or recurrences were excluded. Before 2008, open approach with lateral rhinotomy (LR) was performed as the gold standard of treatment. From 2008, ESS was systematically used as a first-line option as long as a complete resection was achievable. Adjuvant radiation therapy was delivered (RT) for all the patients. LR and ESS were performed in, respectively, 23 and 20 patients. The two groups were comparable in terms of age, occupational dust exposure, histopathological subtypes, and T stage based on the pathological assessment of the specimen (10 pT2, 26 pT3, 2 pT4a, and 5 pT4b). The tumour origin was mainly located in the olfactory cleft with the involvement of the cribriform plate in 60 % of patients. No major complication was observed in ESS group with a reduced hospital stay (5.6 vs 7.6 days). The disease-free survival was not different between LR and ESS groups over a mean follow-up period of 6.6 years. Even for local advanced stages with skull base involvement, we confirm the reliability and the advantages of ESS in terms of oncological outcomes and morbidity. We advocate complete excision of the olfactory cleft to ensure an appropriate control of the tumoral origin.

Immune profile modulation of blood and mucosal eosinophils in nasal polyposis with concomitant asthma.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is frequently associated with asthma. Mucosal eosinophil (EO) infiltrate has been found to correlate with asthma and disease severity but not necessarily in every patient. Other multifactorial immune processes are required to determine disease endotypes and response to treatment. OBJECTIVE: To evaluate EO immunomodulation for migration and survival in accordance with inflammatory protein profiles and asthmatic status in CRSwNP. METHODS: Ninety-three patients (47 with asthma) with CRSwNP were included. Each patient was staged clinically according to symptom severity and polyp size. Nasal secretions were collected to establish a cytokine profile. The EOs were purified from blood samples and nasal polyps to delineate specific immunophenotypes by flow cytometry and determine in vitro EO survival in relation to asthmatic status. RESULTS: The CRSwNP in patients with asthma was characterized by eosinophilia and a high level of interleukin (IL)-5 in nasal secretions. Although EOs exhibited activation profiles after mucosal migration, there was relative down-expression of IL-5 receptor-α (IL-5Rα) on nasal EOs in patients with asthma. The EO culture with IL-5 and IL-9 showed an antiapoptotic effect in patients with asthma through IL-5Rα modulation. CONCLUSION: Mucosal eosinophilia seems to be induced by EO nasal trapping through modulation of adhesion receptors. In patients with asthma, EO involvement is enhanced by the antiapoptotic synergistic action of T-helper cell type 2 cytokines on IL-5Rα expression. This study shows for the first time that IL-9 is involved in EO homeostasis in CRSwNP and could explain the low benefit of anti-IL-5 therapy for some patients with asthma and nasal polyposis.

European Laryngological Society: ELS recommendations for the follow-up of patients treated for laryngeal cancer.

It is accepted that the follow-up of patients who had treatment for laryngeal cancer is a fundamental part of their care. The reasons of post-treatment follow-up include evaluation of treatment response, early identification of recurrence, early detection of new primary tumours, monitoring and management of complications, optimisation of rehabilitation, promotion smoking and excessive alcohol cessation, provision of support to patients and their families, patient counselling and education. Controversies exist in how these aims are achieved. Increasing efforts are being made to rationalise the structure and timing of head and neck cancer follow-up clinics. The aim of this document is to analyse the current evidence for the need to follow up patients who have been treated for LC and provide an up to date, evidence-based statement which is meaningful and applicable to all European Health Care Systems. A working group of the Head and Neck Cancer Committee of the ELS was constituted in 2009. A review of the current published literature on the management and follow-up of laryngeal cancer was undertaken and statements are made based on critical appraisal of the literature and best current evidence. Category recommendations were based on the Oxford Centre for Evidence-Based Medicine. Statements include: length, frequency, setting, type of health professional, clinical assessment, screening investigations, patient's education, second primary tumours, and mode of treatment considerations including radiotherapy, chemo-radiation therapy, transoral surgery and open surgery. It also addresses specific recommendations regarding patients with persistent pain, new imaging techniques, tumour markers and narrow band imaging.

Influence of EGF and pro-NGF on EGFR/SORTILIN interaction and clinical impact in head and neck squamous cell carcinoma.

Head and Neck Squamous Cell Carcinoma (HNSCC) remains a cancer with a poor prognosis, with a 5-year survival rate of less than 50%. Although epidermal growth factor receptor (EGFR) is almost always overexpressed, targeted anti-EGFR therapies have modest efficacy and are mainly used in palliative care. Growth factors such as Nerve Growth Factor (NGF) and its precursor proNGF have been shown in our laboratory to play a role in tumor growth and aggressiveness. Interestingly, an interaction between Sortilin, a proNGF receptor, and EGFR has been observed. This interaction appears to interfere with the pro-oncogenic signaling of EGF and modulate the membrane expression of EGFR. The aim of this study was to characterize this interaction biologically, to assess its impact on clinical prognosis and to analyze its role in the cellular trafficking of EGFR. Using immunohistochemical staining on tumor sections from patients treated at our university center and PLA (Proximity Ligation Assay) labeling, we showed that Sortilin expression is significantly associated with reduced 5-year survival. However, when Sortilin was associated with EGFR, this association was not found. Using the Cal-27 and Cal-33 cancer cell lines, we observed that proNGF reduces the effects of EGF on cell growth by inducing the internalization of its receptor. These results therefore suggest a regulatory role for Sortilin in the degradation or renewal of EGFR on the membrane. It would be interesting in future work to show the intracellular fate of EGFR and the role of (pro)neurotrophins in these mechanisms.

Effectiveness of Geriatric Assessment-Driven Interventions on Survival and Functional and Nutritional Status in Older Patients with Head and Neck Cancer: A Randomized Controlled Trial (EGeSOR).

This study assesses the efficacy of Geriatric Assessment (GA)-driven interventions and follow-up on six-month mortality, functional, and nutritional status in older patients with head and neck cancer (HNC). HNC patients aged 65 years or over were included between November 2013 and September 2018 by 15 Ear, Nose, and Throat (ENT) and maxillofacial surgery departments at 13 centers in France. The study was of an open-label, multicenter, randomized, controlled, and parallel-group design, with independent outcome assessments. The patients were randomized 1:1 to benefit from GA-driven interventions and follow-up versus standard of care. The interventions consisted in a pre-therapeutic GA, a standardized geriatric intervention, and follow-up, tailored to the cancer-treatment plan for 24 months. The primary outcome was a composite criterion including six-month mortality, functional impairment (fall in the Activities of Daily Living (ADL) score ≥2), and weight loss ≥10%. Among the patients included (n = 499), 475 were randomized to the experimental (n = 238) or control arm (n = 237). The median age was 75.3 years [70.4-81.9]; 69.5% were men, and the principal tumor site was oral cavity (43.9%). There were no statistically significant differences regarding the primary endpoint (n = 98 events; 41.0% in the experimental arm versus 90 (38.0%); p = 0.53), or for each criterion (i.e., death (31 (13%) versus 27 (11.4%); p = 0.48), weight loss of ≥10% (69 (29%) versus 65 (27.4%); p = 0.73) and fall in ADL score ≥2 (9 (3.8%) versus 13 (5.5%); p = 0.35)). In older patients with HNC, GA-driven interventions and follow-up failed to improve six-month overall survival, functional, and nutritional status.

Mucoepidermoid carcinoma of salivary glands: A French Network of Rare Head and Neck Tumors (REFCOR) prospective study of 292 cases.

BACKGROUND: To describe the characteristics of the largest European study of MEC of salivary glands and to determine the prognostic factors for overall and disease free survival. PATIENTS AND METHODS: Patients with MEC were prospectively included in the Réseau d'Expertise Français sur les Cancers ORL Rares (REFCOR, French Network of Rare Head and Neck Tumors) database between 2009 and 2015. RESULTS: A total of 292 patients were included. Tumors were classified as low grade in 175 cases (60%), intermediate in 39 (13%) and high grade in 78 (27%). Median follow-up was 26 months. The 5-year OS and DFS rates were respectively 83% and 69%. In multivariate analysis, age (p = 0.004), diabetes (p = 0.02) and advanced stage (p = 0.03) were found to have a significant negative impact on OS. Diabetes (p = 0.001), alcohol consumption (p = 0.003) and advanced stage (p = 0.001) were found to have a significant negative impact on DFS. Compare to low grade, high grade tended to have a negative impact on OS (p = 0.05) and had a significant effect on DFS (0.002) while intermediate grade had no significant influence on survival. The surgical treatment had a positive impact on both OS (p = 0.00005) and DFS (p = 0.0005). Postoperative radiotherapy had no impact in multivariate analysis. CONCLUSION: Advanced clinical stage, high grade tumor, high age, the impossibility of carrying out a complete surgical resection, and diabetes are the main prognostic factors in this prospective series of patients with MEC. Such findings open new research perspectives on the influence of these components on initial patient care.

Treatment of head and neck cancer in the elderly: European Consensus (panel 6) at the EUFOS Congress in Vienna 2007.

The population in developed countries is growing older, with the number of people over 85 years of age increasing especially rapidly. The incidence of a head and neck cancer increases with age, only a few patients are under 40 years of age and the highest incidence in many sites occurs in patients over 70 years of age. The aging population has increasing amounts of comorbidities. The treatment protocols for head and neck cancer have over the last two decades become intensified as a consequence of larger surgical resections with reconstruction, high dose radiotherapy often in combination with chemotherapy or targeted therapeutic drugs. Should the elderly and old patients be treated similarly to the younger counterparts or should the treatment be altered based on chronologic age? During the EUFOS Congress in Oto-Rhino-Laryngology Head and Neck Surgery in Vienna, Austria 2007, a panel addressed this issue and this is a summary of the conclusions.

The helicase-like transcription factor is a strong predictor of recurrence in hypopharyngeal but not in laryngeal squamous cell carcinomas.

AIMS: To examine the immunohistochemical expression of helicase-like transcription factor (HLTF) in relation to the prognosis of hypopharyngeal (HSCCs) and laryngeal (LSCCs) squamous cell carcinomas, and to characterize the HLTF protein variants expressed in biopsy specimens of head and neck squamous cell carcinoma (HNSCC) as well as the HeLa cell line. METHODS AND RESULTS: HLTF expression was determined by immunohistochemistry on a series of 100 hypopharyngeal (stage IV) and 56 laryngeal SCCs (stages I, II and IV). The HLTF variants were defined using reverse transcriptase-polymerase chain reaction and Western blots in 13 fresh HNSCC biopsies and in HeLa cells. High levels of HLTF expression were associated with rapid recurrence rates in a subgroup of 81 stage IV hypopharyngeal SCCs (with complete follow-up). A 95-kDa HLTF variant truncated at the carboxyl-terminal domain was detected in addition to the 115-kDa full-size protein in HNSCC biopsies, while six variants were observed in HeLa cells. CONCLUSIONS: Our results demonstrate, for the first time, that hypopharyngeal SCCs presenting high levels of HLTF have a worse prognosis. The quantitative determination of HLTF in hypopharyngeal SCCs was an independent prognostic marker alongside tumour node metastasis staging. HNSCCs expressed the truncated HLTF variant lacking the domains involved in DNA repair.

Adhesion/growth-regulatory tissue lectin galectin-1 in relation to angiogenesis/lymphocyte infiltration and prognostic relevance of stromal up-regulation in laryngeal carcinomas.

BACKGROUND: Galectin-1 has been found to modulate lymphocyte invasion in inflammation and to be involved in angiogenesis in models, thus prompting examination of its clinical relevance in laryngeal cancer. PATIENTS AND METHODS: Immunohistochemical processing of tissue sections (n=53) from patients with stage I/II (n=35) and stage IV (n=18) laryngeal squamous cell carcinoma (LSCC) with a specific anti-galectin-1 antibody and monitoring of CD45/CD31 positivity was combined with quantitative morphometric analysis. RESULTS: Lectin presence in the tumor and endothelial cells was positively correlated, while a negative relationship to the number of CD45-positive lymphocytes was demonstrated. No association was seen with the extent of neovascularization. The mean optical density (MOD) of lectin-dependent staining in the tumor stroma was significantly increased compared to normal stroma. CONCLUSION: Galectin-1 was not associated with angiogenesis in the studied cohort while galectin-1 in endothelial cells may negatively influence lymphocyte invasion and the mean optical density for the stromal galectin-1 signal is up-regulated in tumors.

Endoscopic supraglottic laryngectomy: a proposal for a classification by the working committee on nomenclature, European Laryngological Society.

In July 1999, the European Laryngological Society (ELS) has accepted a proposal for the classification of different laryngeal endoscopic cordectomies. This is actually a common classification system used as a tool for surgical training, documentation and comparison of results. The same harmonization work is deemed necessary for the treatment of supraglottic lesions. The ELS is proposing a classification of the different laryngeal endoscopic supraglottic partial laryngectomies. This classification comprises four types of supraglottic laryngectomies: Type I, limited excision of small size superficial lesions of the free edge of the epiglottis, the ary-epiglottic fold, the arytenoid, or the ventricular fold or any other part of the supraglottis; Type II, medial supraglottic laryngectomy without resection of the pre-epiglottic space, suitable for T1 lesions of either the suprahyoid or the infrahyoid laryngeal surface of the epiglottis (Type IIa, superior hemi-epiglottectomy or Type IIb, total epiglottectomy, respectively); Type III, medial supraglottic laryngectomy with resection of the pre-epiglottic space, suitable for T1-T2 tumors of the infrahyoid endolaryngeal epiglottis without (Type IIIa) or with (Type IIIb) extension to the ventricular fold, necessitating its excision; finally, Type IV, lateral supraglottic laryngectomy, suitable for tumors of the threefolds' region, which may include the ventricular fold (Type IVa) or the arytenoid (Type IVb), when involved. As in the cases of endoscopic cordectomies, these operations are similarly classified according to the surgical approach used and the degree of resection completed in order to facilitate their use in daily clinical practice.

Helicase-like transcription factor exhibits increased expression and altered intracellular distribution during tumor progression in hypopharyngeal and laryngeal squamous cell carcinomas.

The helicase-like transcription factor (HLTF) belongs to the SWI/SNF family of proteins that use the energy from adenosine triphosphate hydrolysis to remodel chromatin during a variety of cellular processes. HLTF is also involved in DNA repair. Using computer-assisted microscopy, the immunohistochemical expression of HLTF was determined using a series of 100 hypopharyngeal and 56 laryngeal squamous cell carcinomas (SCCs) compared to tumor-free epithelia (60 cases) and dysplasias (92 cases). In hypopharyngeal SCC tumor progression, increased HLTF expression was associated with the percentage of immunopositive epithelial tissue areas (p = 0.02) and the staining intensity of the positive area (p = 0.0005). In the cases of laryngeal lesions, the immunolabeling intensity of HLTF significantly decreased with malignancy (p = 0.01). We also observed a significant shift of HLTF expression from the cytoplasm toward the nuclear compartment (p = 0.0007). Our data reveal an association between the presence of HLTF and neoplastic progression of hypopharyngeal and laryngeal SCCs.

Epithelioid angiomatous nodule of the nasal cavity.

Epithelioid angiomatous nodule (EAN) is a recently described cutaneous vascular lesion with epithelioid features. We report two additional cases occurring in an unusual location in the nasal cavity. The patients were two young adults (17 and 26 years) presenting with recurrent unilateral epistaxis. Computerized tomography scan and endoscopy revealed small tumors that had developed in the nasal septum and the turbinate, measuring 1 and 1.5 cm, respectively. Endoscopic resection was performed. No recurrence was observed in the follow-up. Pathological examination revealed a well-limited but unencapsulated nodule composed of large epithelioid cells with round nuclei. Some tumor cells contained intracytoplasmic vacuoles. Mitotic activity was low without necrotic areas. Tumor cells were strongly immunostained with antibodies to CD34 and CD31. The main differential diagnosis is an epithelioid hemangioma sharing many morphologic features with EAN. We report these cases to inform of a possibly unusual location of EAN.

High level of galectin-1 expression is a negative prognostic predictor of recurrence in laryngeal squamous cell carcinomas.

Monitoring of gene-expression profiles is assumed to refine tumor characterization of laryngeal squamous cell carcinomas (LSCCs) with a therapeutic perspective. This is especially expected for adhesion/growth-regulatory effectors such as galectins, a class of endogenous lectins. Using computer-assisted microscopy, we investigated the prognostic value contributed by the quantitative determination of the immunohistochemical levels of expression of galectin-1, -3 and -7 in a series of 62 LSCCs including 42 low- and 20 high-stage LSCCs. As galectin-1 may have a key role leading to a tumor escape from immune surveillance, we also investigated whether or not the level of galectin-1 expression correlated with lymphocyte infiltration in LSCCs. The immunohistochemical determination of expression of galectin-1 is of prognostic value in human squamous laryngeal cancers. LSCCs that display high levels of galectin-1 have worse prognoses than laryngeal cancers with low levels of galectin-1 expression. Elevation of galectin-1 levels in laryngeal cancers can contribute to the process of tumor immune escape by killing the activated T-cells and other protumoral activities such as promoting motility or activity of oncogenic H-Ras proteins. The quantitative determination of galectin-1 in LSCCs is an independent prognostic marker when opposed to TNM staging. It has the potential to identify patients unlikely to benefit from T-cell-mediated immunotherapy, although the definitive effector function from its pro- and antitumoral activity profile has not been delineated.

Open partial laryngectomy after failure of (chemo) radiation: indications, oncologic and functional outcomes.

PURPOSE OF REVIEW: Early-stage squamous cell carcinoma of the larynx can be successfully treated with radiotherapy or surgery (transoral or open approaches). Oncologic results are comparable while functional results may be different according to the volume of resection. In some countries radiotherapy is often preferred as primary treatment. In case of recurrence, surgical salvage is the only option. Careful examination, endoscopic assessment, computed tomography or magnetic resonance imaging are necessary to assess superficial and deep extensions into the larynx, including cartilage framework and to restage the tumor. RECENT FINDINGS: The choice between endoscopic and open partial laryngectomy is based on the extension and characteristics of the tumor. Oncologic results of open approaches are encouraging as local control, survival, and laryngeal preservation rates reported in the literature are close to those obtained in nonpreviously treated patients. Functional results are not significantly worse and major complications in the previously irradiated patients undergoing open neck surgery not increased.Supracricoid partial surgery seems to be more and more performed. SUMMARY: With regards to the results, open partial surgery, like in nonpreviously treated patients, is still indicated for the surgical treatment of postradiotherapic recurrent/persistent disease.

Is a chlorine dioxide wiping procedure suitable for the high-level disinfection of nasendoscopes?

BACKGROUND: Nasendoscopes are widely used in the outpatient ENT setting. Their reprocessing requires high-level disinfection (HLD). Recently, a wiping procedure using chlorine dioxide (ClO2) has been proposed as an alternative to HLD traditional procedures. OBJECTIVE: To assess the effectiveness of the HLD wiping procedure versus soaking procedure on a contaminated nasendoscope. METHOD: A nasendoscope was contaminated with four strains of bacteria and Bacillus subtilis spores. After HLD either with the wiping procedure or with the soaking procedure (PA), the reduction of the initial contamination was determined. FINDINGS: The wiping procedure with ClO2 displayed more than 5 log reduction for vegetative bacteria after 30 s contact time (CT) and 4 log reduction on B. subtilis spores after 2 min CT. The soaking procedure with PA displayed similar results on planktonic bacteria after 10 min CT but the log reduction of B. subtilis remained below 4. CONCLUSION: The ClO2 wiping procedure showed bactericidal and sporicidal efficacy on a contaminated nasendoscope in a shorter time compared to the PA soaking procedure. Thus, ClO2 wiping procedure might be considered as an alternative to the traditional HLD procedure for nasendoscopes.

[Organ preservation surgery in pharyngolaryngeal cancer]. / Préservation d'organe et de fonction du pharyngo-larynx dans les cancers des VADS.

Organ preservation surgery is a reasonable name for these types of techniques because it accurately describes the postoperative outcome, which is preservation of the quintessential laryngeal functions: swallowing, respiration without a permanent stoma and speech. In response to the common use of total laryngectomy, the non-surgical approaches have often been referred to as organ preservation strategies. In many institutions, it appears that there are organ preservation strategies and then there is surgery. In our opinion there are both non surgical organ preservation strategies and surgical organ preservation strategies. The key is that in both approaches the goal is to spare the functions of the larynx. In both, the work-ups are very important to analyse 3-dimensional extent of the lesion by nasofibroscopy (laryngeal mobilities), endoscopy and radiology. Organ preservation surgical approach allowed to save the use of radiotherapy for the management of various metachronous second primary tumours.