An automated approach for real-time informative frames classification in laryngeal endoscopy using deep learning.

PURPOSE: Informative image selection in laryngoscopy has the potential for improving automatic data extraction alone, for selective data storage and a faster review process, or in combination with other artificial intelligence (AI) detection or diagnosis models. This paper aims to demonstrate the feasibility of AI in providing automatic informative laryngoscopy frame selection also capable of working in real-time providing visual feedback to guide the otolaryngologist during the examination. METHODS: Several deep learning models were trained and tested on an internal dataset (n = 5147 images) and then tested on an external test set (n = 646 images) composed of both white light and narrow band images. Four videos were used to assess the real-time performance of the best-performing model. RESULTS: ResNet-50, pre-trained with the pretext strategy, reached a precision = 95% vs. 97%, recall = 97% vs, 89%, and the F1-score = 96% vs. 93% on the internal and external test set respectively (p = 0.062). The four testing videos are provided in the supplemental materials. CONCLUSION: The deep learning model demonstrated excellent performance in identifying diagnostically relevant frames within laryngoscopic videos. With its solid accuracy and real-time capabilities, the system is promising for its development in a clinical setting, either autonomously for objective quality control or in conjunction with other algorithms within a comprehensive AI toolset aimed at enhancing tumor detection and diagnosis.

Enhancing quality of life in head and neck cancer patients: a comparative analysis of 3D exoscope-assisted surgery vs. traditional approaches.

Introduction: The increasing population of survivors of head and neck carcinomas is becoming more conspicuous. Consequently, the pivotal role of quality of life, particularly elucidated through the assessment of dysphagia and dysphonia, is progressively influencing the decision-making process. The current study aims to assess whether VITOM 3D could offer a comparable post-treatment quality of life to traditional approaches for patients with laryngeal cancer and oro-hypopharyngeal cancer. Methods: A case series of laryngeal cancer and oro-hypopharyngeal cancer patients treated either with an exoscopic-assisted surgical setup and with conventional treatments (transoral microsurgery and radio-chemotherapy) at the Otolaryngology Unit of IRCCS San Martino Hospital, Genoa, is presented. The post-treatment quality of life of the two cohorts were compared through the administration of the University of Washington Quality of Life Questionnaire, Voiceik Handicap Index-10, M.D. Anderson Dysphagia Inventory were administrated to both cohorts of patients. Results: In the laryngeal cancer group, a total of 79 patients were included. Of these, 50.1% underwent transoral exoscope-assisted surgery, while 49.9% underwent primary transoral microscopic-assisted surgical approach. No significant differences were observed in terms of the University of Washington Quality of Life Questionnaire and Voice Handicap Index-10 between the two subgroups. Conversely, in the oro-hypopharyngeal cancer group, 43 patients were included. Of these, 37.2% underwent primary transoral exoscope-assisted surgery, while 62.8% received (chemo)radiotherapy. No notable differences were reported in terms of the University of Washington Quality of Life Questionnaire and M.D. Anderson Dysphagia Inventory between the transoral exoscope-assisted surgery and (chemo)radiotherapy subgroups. Conclusions: Assessments of quality of life, conducted through the University of Washington Quality of Life Questionnaire questionnaire, dysphonia evaluations using the Voice Handicap Index-10, and dysphagia assessments employing the M.D. Anderson Dysphagia Inventory questionnaire, demonstrate analogous outcomes between conventional treatment modalities and transoral interventions utilizing the 3D exoscope.

The impact of margins in laryngeal cancer patients treated with transoral laser microsurgery: a systematic review and meta-analysis.

PURPOSE: In laryngeal squamous cell carcinoma (LSCC) treated with transoral laser microsurgery (TOLMS), the status of margins significantly affected local control. When a positive or close margin is present, there is no ubiquitous consensus regarding further treatments. The rationale of the present systematic review and meta-analysis is to investigate the survival impact of the status of the margins in patients affected by LSCC treated with TOLMS. DATA SOURCES: PubMed, EMBASE, and Cochrane Library. METHODS: We performed a systematic search, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Inclusion criteria were: patients affected by LSCC, staged according to the American Joint Committee on Cancer Staging System and treated by TOLMS without any previous treatment; margins status (close, positive, negative) and the adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) of overall survival, disease-specific survival, and disease-free survival has to be reported. RESULTS: Nine studies were deemed eligible for the qualitative analysis, and 3 for the quantitative analysis to investigate the association between margin status and OS. The cumulative number of patients was 3130. The sample size ranged from 96 to 747 patients. The follow-up period ranged from 0 to 201 months. The meta-analysis results show that positive margins have an aHR of 1.30 yet with CI range (0.56 to 2.97). CONCLUSIONS: Our current meta-analysis results are unable to definitively assess the real impact of resection margins on OS. Few authors provide accurate data regarding position and types of margins. Further prospective or high-quality studies are required.

Effectiveness of combined approach to recurrent respiratory papillomatosis (RRP).

PURPOSE: Recent approaches for recurrent respiratory papillomatosis including local injection of bevacizumab and HPV vaccination show promise in reducing the need for frequent surgeries. In this study we propose a new combined approach of surgery, intralesional injection of 25 mg bevacizumab and HPV vaccine that can lead to resolution of RRP. MATERIAL AND METHODS: Our study involved 5 patients treated with a combination of transoral microsurgery, intralesional injection of 25 mg bevacizumab, and HPV vaccination with Gardasil 9 between April 2020 and May 2023. Standard video laryngoscopy was performed to assess the presence of papilloma and Derkay score was used to assess the severity of disease. RESULTS: All 5 patients completed the study successfully and a complete response was achieved by all. The follow-up ranged from 8 to 45 months. The mean total Derkay score before treatment was 41 (range 25 to 52) and after the combined approach was 0 both anatomically and clinically in all patients. CONCLUSIONS: This study demonstrates the effectiveness of a combined treatment approach for RRP involving surgical intervention, intralesional injection of bevacizumab, and HPV vaccination.

Depth of Invasion Assessment in Laryngeal Glottic Carcinoma: A Preoperative Imaging Approach for Prognostication.

OBJECTIVE: The prognostic value of depth of invasion (DOI) in oral squamous cell cancer carcinoma and cutaneous melanoma is well established, while there is a lack of reports investigating the role of DOI in laryngeal cancer. This study aims to explore the association of glottic cancer DOI with other established pathological risk factors and nodal metastasis and evaluate the feasibility of measuring DOI preoperatively using tomographic imaging. METHODS: The medical records of glottic cancer patients treated between 2015 and 2020 in a single tertiary referral center were screened retrospectively. Pathologically measured DOI (pDOI) value was also reviewed and registered. Preoperative computer tomography (CT) was used to obtain the radiological DOI (rDOI) measured by two dedicated radiologists. Their inter-rated agreement was assessed and the correlation between pDOI and rDOI was calculated. pDOI association with the main pathology report features was assessed with univariable analysis. Cox univariable and multivariable models were used to explore the role of pDOI on survival. RESULTS: Ninety-one patients had pDOI data available, of which 59 also had rDOI data. A strong concordance between the two radiologists was found (concordance correlation coefficient = 0.96); rDOI and pDOI were highly and significantly correlated (R = 0.85; p < 0.001). pDOI was significantly higher in patients with perineural invasion (PNI; p < 0.001), lymphovascular invasion (LVI; p < 0.001), and nodal metastasis (p < 0.001). pDOI was associated with disease-free survival at univariable analysis (p = 0.04) while it did not show a significant impact (p = 0.10) at multivariable analysis. CONCLUSION: Glottic carcinoma DOI correlates with PNI, LVI, and nodal metastasis and it can be reliably assessed in a preoperative setting using CT imaging. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Exploring the landscape of AI-assisted decision-making in head and neck cancer treatment: a comparative analysis of NCCN guidelines and ChatGPT responses.

PURPOSE: Recent breakthroughs in natural language processing and machine learning, exemplified by ChatGPT, have spurred a paradigm shift in healthcare. Released by OpenAI in November 2022, ChatGPT rapidly gained global attention. Trained on massive text datasets, this large language model holds immense potential to revolutionize healthcare. However, existing literature often overlooks the need for rigorous validation and real-world applicability. METHODS: This head-to-head comparative study assesses ChatGPT's capabilities in providing therapeutic recommendations for head and neck cancers. Simulating every NCCN Guidelines scenarios. ChatGPT is queried on primary treatments, adjuvant treatment, and follow-up, with responses compared to the NCCN Guidelines. Performance metrics, including sensitivity, specificity, and F1 score, are employed for assessment. RESULTS: The study includes 68 hypothetical cases and 204 clinical scenarios. ChatGPT exhibits promising capabilities in addressing NCCN-related queries, achieving high sensitivity and overall accuracy across primary treatment, adjuvant treatment, and follow-up. The study's metrics showcase robustness in providing relevant suggestions. However, a few inaccuracies are noted, especially in primary treatment scenarios. CONCLUSION: Our study highlights the proficiency of ChatGPT in providing treatment suggestions. The model's alignment with the NCCN Guidelines sets the stage for a nuanced exploration of AI's evolving role in oncological decision support. However, challenges related to the interpretability of AI in clinical decision-making and the importance of clinicians understanding the underlying principles of AI models remain unexplored. As AI continues to advance, collaborative efforts between models and medical experts are deemed essential for unlocking new frontiers in personalized cancer care.

Real-Time Laryngeal Cancer Boundaries Delineation on White Light and Narrow-Band Imaging Laryngoscopy with Deep Learning.

OBJECTIVE: To investigate the potential of deep learning for automatically delineating (segmenting) laryngeal cancer superficial extent on endoscopic images and videos. METHODS: A retrospective study was conducted extracting and annotating white light (WL) and Narrow-Band Imaging (NBI) frames to train a segmentation model (SegMENT-Plus). Two external datasets were used for validation. The model's performances were compared with those of two otolaryngology residents. In addition, the model was tested on real intraoperative laryngoscopy videos. RESULTS: A total of 3933 images of laryngeal cancer from 557 patients were used. The model achieved the following median values (interquartile range): Dice Similarity Coefficient (DSC) = 0.83 (0.70-0.90), Intersection over Union (IoU) = 0.83 (0.73-0.90), Accuracy = 0.97 (0.95-0.99), Inference Speed = 25.6 (25.1-26.1) frames per second. The external testing cohorts comprised 156 and 200 images. SegMENT-Plus performed similarly on all three datasets for DSC (p = 0.05) and IoU (p = 0.07). No significant differences were noticed when separately analyzing WL and NBI test images on DSC (p = 0.06) and IoU (p = 0.78) and when analyzing the model versus the two residents on DSC (p = 0.06) and IoU (Senior vs. SegMENT-Plus, p = 0.13; Junior vs. SegMENT-Plus, p = 1.00). The model was then tested on real intraoperative laryngoscopy videos. CONCLUSION: SegMENT-Plus can accurately delineate laryngeal cancer boundaries in endoscopic images, with performances equal to those of two otolaryngology residents. The results on the two external datasets demonstrate excellent generalization capabilities. The computation speed of the model allowed its application on videolaryngoscopies simulating real-time use. Clinical trials are needed to evaluate the role of this technology in surgical practice and resection margin improvement. LEVEL OF EVIDENCE: III Laryngoscope, 134:2826-2834, 2024.

Development of machine learning models for the prediction of long-term feeding tube dependence after oral and oropharyngeal cancer surgery.

PURPOSE: To predict the necessity of enteral nutrition at 28 days after surgery in patients undergoing major head and neck oncologic procedures for oral and oropharyngeal cancers. MATERIAL AND METHODS: Data from 193 patients with oral cavity and oropharyngeal squamous cell carcinoma were retrospectively collected at two tertiary referral centers to train (n = 135) and validate (n = 58) six supervised machine learning (ML) models for binary prediction employing 29 clinical variables available pre-operatively. RESULTS: The accuracy of the six ML models ranged between 0.74 and 0.88, while the measured area under the curve (AUC) between 0.75 and 0.87. The ML algorithms showed high specificity (range 0.87-0.96) and moderate sensitivity (range: 0.31-0.77) in detecting patients with ≥28 days feeding tube dependence. Negative predictive value was higher (range: 0.81-0.93) compared to positive predictive value (range: 0.40-0.71). Finally, the F1 score ranged between 0.35 and 0.74. CONCLUSIONS: Classification performance of the ML algorithms showed optimistic accuracy in the prediction of enteral nutrition at 28 days after surgery. Prospective studies are mandatory to define the clinical benefit of a ML-based pre-operative prediction of a personalized nutrition protocol.

Predicting the need for prophylactic gastrostomy in major head and neck cancer surgery: The PEG score.

BACKGROUND: To elaborate a preoperative score to predict the necessity of enteral nutrition at 28 days postoperatively in patients undergoing head and neck surgery. METHODS: A total of 424 patients with oral cavity, oropharyngeal, laryngeal, and hypopharyngeal carcinoma were retrospectively enrolled and analyzed to identify preoperative predictors of prolonged postsurgical enteral feeding which were used to create a prediction model with an easy-to-use nomogram. RESULTS: Five preoperative variables (body mass index, previous radiotherapy, preoperative dysphagia, type of surgery, flap reconstruction) were found to be independent predictive factors and were used to create a prediction model named PEG score together with the related nomogram. Accuracy, F1, and the area under the curve (AUC) were 0.74, 0.83, and 0.74. Different decision thresholds can be used to vary the sensitivity and specificity. CONCLUSIONS: The PEG score showed high prediction performances for modeling the need for enteral nutrition at 28 days postoperatively. Prospective studies are needed to define a personalized nutrition protocol.

Can High-Frequency Intraoral Ultrasound Predict Histological Risk Factors in Oral Squamous Cell Carcinoma? A Preliminary Experience.

Despite advancements in multidisciplinary care, oncologic outcomes of oral cavity squamous cell carcinoma (OSCC) have not substantially improved: still, one-third of patients affected by stage I and II can develop locoregional recurrences. Imaging plays a pivotal role in preoperative staging of OSCC, providing depth of invasion (DOI) measurements. However, locoregional recurrences have a strong association with adverse histopathological factors not included in the staging system, and any imaging features linked to them have been lacking. In this study, the possibility to predict histological risk factors in OSCC with high-frequency intraoral ultrasonography (IOUS) was evaluated. Thirty-four patients were enrolled. The agreement between ultrasonographic and pathological DOI was evaluated, and ultrasonographic margins' appearance was compared to the Brandwein-Gensler score and the worst pattern of invasion (WPOI). Excellent agreement between ultrasonographic and pathological DOI was found (mean difference: 0.2 mm). A significant relationship was found between ultrasonographic morphology of the front of infiltration and both Brandwein-Gensler score ≥ 3 (p < 0.0001) and WPOI ≥4 (p = 0.0001). Sensitivity, specificity, positive predictive value, and negative predictive value for the IOUS to predict a Brandwein-Gensler score ≥3 were 93.33%, 89.47%, 87.50%, and 94.44%, respectively. The present study demonstrated the promising role of IOUS in aiding risk stratification for OSCC patients.

Recurrent laryngeal papillomatosis: multimodal therapeutic strategies. Literature review and multicentre retrospective study.

Objectives: Recurrent respiratory papillomatosis (RRP) is a benign, rare disease caused by Human Papilloma Virus (HPV) that can be divided into juvenile and adult forms. The course of the disease is variable, but is usually more aggressive in the juvenile form. The standard surgical treatment is represented by CO2 laser resection, although photoangiolytic lasers represent a valid alternative. Adjuvant therapies have been proposed for disease control in case of frequent surgical resections or spreading into the lower airways. In recent years, the development of immunotherapy led to the use of bevacizumab either intratumorally or intravenously, but the most promising therapeutic development is represented by HPV vaccination. This paper aims to present a narrative review of the literature and the experience of three different University Centres in the treatment of RRP. Methods: A retrospective analysis of the clinical charts of all patients affected by laryngeal papillomatosis and treated in three different University Centres between 2002 and 2022 was performed. The following parameters were collected: sex, age at first evaluation, sites of larynx involved, HPV type, type of first surgical treatment, presence and number of recurrences, surgical treatment of recurrences, adjuvant therapies, side effects and status at last follow-up. Results: Seventy-eight patients were available for evaluation. Of these, 88% had adult onset RRP (Ao-RRP) and 12% juvenile onset RRP (Jo-RRP). The glottis was the most frequently involved subsite; all patients were submitted to surgical resection with CO2 laser under general anaesthesia. Recurrences appeared in 79% of the patients, the patients who did not recur were all adults. The mean number of recurrences was 9 (range 1-110). Recurrences were more frequent in children (M = 20; range 2-110) than adults (M = 5; range 1-21). Thirty-two (52%) of the 62 patients who recurred were re-treated with CO2 laser under general anaesthesia, while office-based treatment with a photoangiolytic laser was preferred in the remaining 30 (48%) patients. Adjuvant treatments were applied in 26 patients. The analysis of the course of the disease showed that in the 9 patients with Jo-RRP, 6 (67%) were free of lesions at the last follow-up, while the other 3 (33%) had papillomas. Of the 69 patients with Ao-RRP, 53 (77%) were alive and free of disease at the last visit, 14 (21%) were alive with disease, 1 (1%) was lost at follow-up and 1 (1%) died for other disease. Severe side effects were not observed except for 2 patients, who developed posterior glottic stenosis. Conclusions: Our results confirmed the literature review. RRP is a potentially aggressive disease, especially in juvenile onset. Surgical resection is still first-line treatment, but in case of multiple recurrences the use of adjuvant therapies must be taken into consideration.

High-resolution US of the facial vessels with new facial vein landmarks for reconstructive surgery and dermal injection.

BACKGROUND: Accurate knowledge of vessel anatomy is essential in facial reconstructive surgery. The technological advances of ultrasound (US) equipment with the introduction of new high-resolution probes improved the evaluation of facial anatomical structures. Our study had these objectives: the primary objective was to identify new surgical landmarks for the facial vein and to verify their precision with US, the secondary objective was to evaluate the potential of high-resolution US examination in the study of both the facial artery and vein. METHODS: Two radiologists examined a prospective series of adult volunteers with a 22-8 MHz hockey-stick probe. Two predictive lines of the facial artery and vein with respective measurement points were defined. The distance between the facial vein and its predictive line (named mandibular-orbital line) was determined at each measurement point. The distance from the skin and the area of the two vessels were assessed at every established measurement point. RESULTS: Forty-one volunteers were examined. The median distance of the facial vein from its predictive line did not exceed 2 mm. The facial vein was visible at every measurement point in all volunteers on the right side, and in 40 volunteers on the left. The facial artery was visible at every measurement point in all volunteers on the right and in 37 volunteers on the left. CONCLUSIONS: The facial vein demonstrated a constant course concerning the mandibular-orbital line, which seems a promising clinical and imaging-based method for its identification. High-resolution US is valuable in studying the facial artery and vein. RELEVANCE STATEMENT: High-resolution US is valuable for examining facial vessels and can be a useful tool for pre-operative assessment, especially when combined with the mandibular-orbital line, a new promising imaging and clinical technique to identify the facial vein. KEY POINTS: • High-resolution US is valuable in studying the facial artery and vein. • The facial vein demonstrated a constant course concerning its predictive mandibular-orbital line. • The clinical application of the mandibular-orbital line could help reduce facial surgical and cosmetic procedure complications.

Functional outcomes of soft palate reconstruction after oncologic surgery: a systematic review and meta-analysis.

OBJECTIVE: The aim of this study is to analyze functional outcomes of soft palate reconstruction after oncologic surgery. METHODS: This study was conducted in conformity with the PRISMA statement. A single arm meta-analysis was performed for feeding tube dependence (FTD) (primary outcome), velopharyngeal insufficiency (VPI) and hypernasality (HN) (secondary outcomes) incidences. RESULTS: A total of 510 patients (males: 77.75%, n = 353/454) with a median age of 58 years (n = 480/510; 95% CI 57.0-61.0) who underwent soft palate surgical resection with primary reconstruction were included. Overall, the cumulative FTD rate was 1.55% (n = 28/510; 95% CI 0.24-3.96%), the VPI rate was 22.18% (n = 119/379; 95% CI 12.99-33.02%), and the HN rate was 33.01% (n = 88/234; 95% CI 19.03-46.61%). CONCLUSIONS: Soft palate reconstruction results in a low incidence of FTD, and most patients resume a full oral diet. Both obturators, primary closure, local and free flaps seem good reconstructive options. Nevertheless, more specific postoperative functional deficiencies like VPI and HN owns higher incidences, potentially affecting the quality of the swallowing and speaking function and the patient's quality of life.

Surviving cancer following total laryngectomy: a phenomenological study.

PURPOSE: Total laryngectomy followed by radiotherapy is a life-preserving treatment for patients with locally advanced laryngeal cancer. This study explored how persons who had undergone total laryngectomy perceived themselves as cancer survivors in the follow-up phase. METHODS: A descriptive phenomenological approach was adopted. We employed a purposive sampling strategy to collect data through interviews at the otorhinolaryngology outpatient clinics of two research hospitals in northern Italy. The interviews were transcribed verbatim and analysed, following the seven analytical steps of Colaizzi's descriptive analysis. RESULTS: The final sample included 19 patients. The following main themes were identified: (i) accepting a life with the "without" to survive; (ii) feeling unpleasant emotions; (iii) getting the hang of communication again; and (iv) reclaiming one's role. Together, they highlight the lived experiences of laryngectomised patients during the follow-up phase and how they perceived themselves as cancer survivors. CONCLUSION: Laryngectomised patients are a uniquely vulnerable population. This study provides insights into how surgical procedures change and affect their lives over time to improve care models, patient education, and support systems. Survivors must be adequately prepared to transition from treatment and return to the community. This preparation should begin before treatment is started. Functional education, accurate information, and psychological support must be arranged and provided before surgery. Regarding the post-treatment phase, it is essential to support voice rehabilitation and peer support, and improve the family network, to ensure these patients' reintegration into society and social recognition.

Electric Bioimpedance Sensing for the Detection of Head and Neck Squamous Cell Carcinoma.

The early detection of head and neck squamous cell carcinoma (HNSCC) is essential to improve patient prognosis and enable organ and function preservation treatments. The objective of this study is to assess the feasibility of using electrical bioimpedance (EBI) sensing technology to detect HNSCC tissue. A prospective study was carried out analyzing tissue from 46 patients undergoing surgery for HNSCC. The goal was the correct identification of pathologic tissue using a novel needle-based EBI sensing device and AI-based classifiers. Considering the data from the overall patient cohort, the system achieved accuracies between 0.67 and 0.93 when tested on tissues from the mucosa, skin, muscle, lymph node, and cartilage. Furthermore, when considering a patient-specific setting, the accuracy range increased to values between 0.82 and 0.95. This indicates that more reliable results may be achieved when considering a tissue-specific and patient-specific tissue assessment approach. Overall, this study shows that EBI sensing may be a reliable technology to distinguish pathologic from healthy tissue in the head and neck region. This observation supports the continuation of this research on the clinical use of EBI-based devices for early detection and margin assessment of HNSCC.

Instance segmentation of upper aerodigestive tract cancer: site-specific outcomes.

Objective: To achieve instance segmentation of upper aerodigestive tract (UADT) neoplasms using a deep learning (DL) algorithm, and to identify differences in its diagnostic performance in three different sites: larynx/hypopharynx, oral cavity and oropharynx. Methods: A total of 1034 endoscopic images from 323 patients were examined under narrow band imaging (NBI). The Mask R-CNN algorithm was used for the analysis. The dataset split was: 935 training, 48 validation and 51 testing images. Dice Similarity Coefficient (Dsc) was the main outcome measure. Results: Instance segmentation was effective in 76.5% of images. The mean Dsc was 0.90 ± 0.05. The algorithm correctly predicted 77.8%, 86.7% and 55.5% of lesions in the larynx/hypopharynx, oral cavity, and oropharynx, respectively. The mean Dsc was 0.90 ± 0.05 for the larynx/hypopharynx, 0.60 ± 0.26 for the oral cavity, and 0.81 ± 0.30 for the oropharynx. The analysis showed inferior diagnostic results in the oral cavity compared with the larynx/hypopharynx (p < 0.001). Conclusions: The study confirms the feasibility of instance segmentation of UADT using DL algorithms and shows inferior diagnostic results in the oral cavity compared with other anatomic areas.

Impact of lymph node ratio and number of lymph node metastases on survival and recurrence in laryngeal squamous cell carcinoma.

INTRODUCTION: The aim of this study is to assess the impact of lymph node ratio (LNR) and number of positive lymph nodes (NPLN) on mortality and recurrence rates in patients with laryngeal squamous cell carcinoma. MATERIALS AND METHODS: We conducted a retrospective multicenter international study involving 24 Otorhinolaryngology-Head and Neck Surgery divisions. Disease-specific survival (DSS) and disease-free survival (DFS) were evaluated as the main outcomes. The curves for DSS and DFS according to NPLN and LNR were analyzed to identify significant variations and establish specific cut-off values. RESULTS: 2507 patients met the inclusion criteria. DSS and DFS were significantly different in the groups of patients stratified according to LNR and NPLN. The 5-year DSS and DFS based on LNR and NPLN demonstrated an improved ability to stratify patients when compared to pN staging. CONCLUSION: Our data demonstrate the potential prognostic value of NPLN and LNR in laryngeal squamous cell carcinoma.

The prometastatic relevance of tumor-infiltrating B lymphocytes in laryngeal squamous cell carcinoma.

Objectives: Laryngeal squamous cell carcinomas (LSCCs) typically have an excellent prognosis for stage I tumors but a significant risk of locoregional and distant recurrence for intermediate to advanced disease. This study will investigate the clinical relevance of the tumor microenvironment in a large cohort of treatment-naïve patients affected by stage II-IV LSCC. Methods: Whole slide-based digital pathology analysis was applied to measure six immune cell populations identified by immunohistochemistry (IHC) staining for CD3, CD8, CD20, CD66b, CD163 and CD38. Survival analysis was performed by Cox proportional hazards models and unsupervised hierarchical clustering using the k-means method. Double IHC staining and in-situ hybridisation by RNAscope allowed further analysis of a protumoral B cell population. Results: A cohort of 98 patients was enrolled and analysed. The cluster of immune-infiltrated LSCCs demonstrated a significantly worse disease-specific survival rate. We also discovered a new association between high CD20+ B cells and a greater risk of distant recurrence. The phenotypic analysis of infiltrating CD20+ B cells showed a naïve (BCL6-CD27-Mum1-) regulatory phenotype, producing TGFß but not IL10, according to an active TGFß pathway, as proved by positive pSMAD2 staining. Conclusion: The identification of regulatory B cells in the context of LSCC, along with the activation of the TGFß pathway, could provide the basis for new trials investigating the efficacy of already available molecules targeting the TGFß pathway in the treatment of LSCC.

Bilateral selective laryngeal reinnervation in patients with bilateral vocal cord palsy.

Objective: Bilateral selective reinnervation of the larynx aims to restore both vocal cord tone and abductor movements in patients with bilateral vocal cord palsy. Methods: Four females and one male treated by bilateral selective reinnervation of the larynx were included in the present study. In all cases, both posterior cricoarytenoid muscles were reinnervated using the C3 right phrenic nerve root through the great auricular nerve graft, while adductor muscle tone was bilaterally restored using the thyrohyoid branches of the hypoglossal nerve through transverse cervical nerve grafts. Results: After a minimum follow-up of 48 months, all patients were successfully tracheostomy free and had recovered normal swallowing. At laryngoscopy, the first patient recovered a left unilateral partial abductor movement, the second had complete bilateral abductor movements, the third did not show improvements of abductor movements, but symptomatology was improved, the fourth recovered partial bilateral abductor movements and the fifth case did not show improvements and needed posterior cordotomy. Conclusions: Bilateral selective laryngeal reinnervation, although a complex surgical procedure, offers a more physiologic recovery in the treatment of bilateral vocal fold paralysis. Selection criteria still needs to be precisely defined to avoid unexpected failures.