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.

Analysis of Complications in (Crico-) Tracheal Resection Anastomosis in Adults: A Multicenter Study.

OBJECTIVES: The gold standard treatments for advanced laryngotracheal stenosis (LTS) are represented by partial crico-tracheal (PCTRA) or tracheal resection and anastomosis (TRA). These procedures are potentially burdened by high postoperative complication rates. We investigated the impact of the most common stenosis and patient-related characteristics on the onset of complications in a multicentric cohort. METHODS: We retrospectively analyzed patients who underwent PCTRA or TRA for LTS of different etiologies in three referral centers. We tested the effectiveness of these procedures, the impact of complications on the outcomes, and identified factors causing postoperative complications. RESULTS: A total of 267 patients were included in the study (130 females; mean age, 51.46 ± 17.64 years). The overall decannulation rate was 96.4%. Altogether, 102 (38.2%) patients presented at least one complication, whereas 12 (4.5%) had two or more. The only independent predictor of post-surgical complications was the presence of systemic comorbidities (p = 0.043). Patients experiencing complications needed additional surgery more frequently (70.1% vs. 29.9%, p < 0.001), and had a longer duration of hospitalization (20 ± 10.9 vs. 11.3 ± 4.1 days, p < 0.001). Six of 102 (5.9%) patients with complications had restenosis, although this event did not occur among patients without complications. CONCLUSION: PCTRA and TRA have an excellent success rate even when performed for high-grade LTS. However, a significant percentage of patients may experience complications associated with a longer duration of hospitalization or the need for additional surgeries. The presence of medical comorbidities was independently related to an increased risk of complications. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2910-2919, 2023.

Office-Based Treatment of Vocal Fold Polyps and Reinke's Edema: A Rational Comparison With Suspension Laryngoscopy.

OBJECTIVE: Benign laryngeal lesions have traditionally been treated through suspension laryngoscopy under general anesthesia (GA). Recently, the development of operative videoendoscopes coupled with photoangiolytic lasers has allowed clinicians to treat these conditions in the outpatient clinic. We report our experience in the office-based (OB) setting for the treatment of patients affected by vocal fold polyps (VFPs) and Reinke's edema (RE), comparing it to patients treated under GA. METHODS: A retrospective analysis was conducted on patients affected by VFP or RE. A 445 nm diode blue laser was used through the operative channel of a flexible video-endoscope for OB procedures, while GA surgeries were carried out with cold steel instrumentation. The Voice Handicap Index-10 (VHI-10) represented the primary outcome. Endoscopic outcomes, duration, and morbidity of the procedures were investigated as secondary outcomes. RESULTS: A total of 153 patients were retrospectively enrolled. 52 were treated in an OB setting, while 91 underwent GA. Regarding patients with RE, both the OB and GA cohorts showed a significant improvement in VHI-10 (from 12.7 to 2.6 and 19.5 to 5.1, respectively; p < 0.001), as did those with VFPs (from 11.8 to 2.3 and 15.9 to 2.9 respectively; p < 0.001). No differences were found when comparing VHI-10 in the OB and GA cohorts. The mean procedural time of OB treatment (4.9 min) was significantly shorter than GA (37.1 min). No adverse events were reported. CONCLUSION: Our data demonstrate the efficacy and safety of the OB setting. For selected patients, OB treatments offer comparable vocal outcomes, favorable morbidity, and reduced operation times, making them an appealing alternative to the traditional approach. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:2665-2672, 2023.

Functional outcomes after transoral CO2 laser treatment for posterior glottic stenosis: a bicentric case series.

PURPOSE: The aim of this study is to evaluate functional outcomes in terms of decannulation rate and quality of life of patients affected by PGS (Grades I-IV) treated only by transoral CO2 laser microsurgery (TOLMS) in two tertiary centers. METHODS: An observational retrospective study was carried out, enrolling 22 patients affected by PGS who were treated by a transoral approach at two tertiary referral centers. Surgical treatment included TOLMS with tailored laser resection of the scar tissue combined with posterior cordotomy, resurfacing of the raw area with mucosal microflap, or placement of a Montgomery T-tube or Keel stent. All patients were evaluated and staged preoperatively and postoperatively, at least 6 months after the surgery. Functional outcomes were objectively evaluated by the Airway-Dysphonia-Voice-Swallowing (ADVS) staging system, Voice Handicap Index-30 (VHI-30), and Eating Assessment Tool-10 (EAT-10) questionnaires. RESULTS: Quality of life significantly improved as measured by the VHI-30 questionnaire with a median variation of - 31.0 (p = 0.003), the EAT-10 with a median variation of - 4.0 (p = 0.042), and the ADVS with a median variation of - 3.5 (p < 0.001). No significant changes were observed in swallowing scores. We were able to decannulate 7 of 9 patients (almost 80%) with previous tracheotomy. CONCLUSION: In conclusion, even if there is still no general agreement on an exact therapeutic algorithm to treat PGS, our results confirm that transoral surgery, in terms of scar tissue removal, combined in selected patients with posterior cordotomy and pedicled local flaps and/or placement of stents, represents a safe and effective surgical approach even for more severe PGS.

Immunonutrition in major oncologic head and neck surgery: Analysis of complications, plasmatic equilibrium, and costs.

BACKGROUND: Malnutrition, in patients with solid tumors, is associated with a worse clinical outcome and about 40% of patients affected by head and neck cancers (HNC) are malnourished at the time of cancer diagnosis. We investigated the potential benefit of a standardized immunonutritional protocol (INP) to patients with HNC receiving major ablative surgery. METHODS: An observational study was conducted enrolling 199 patients: 50 treated with the INP and 149 with standard enteral nutrition. Complication rates, need for medications, and costs were considered as outcomes. RESULTS: INP played a protective role in development of major surgical complications (OR 0.23, p = 0.023), albumin administration (RR 0.38, p = 0.018), and antibiotic duration (p < 0.001) and is cost-effective in patients with moderate or severe malnutrition (-6083€ and -11 988€, p < 0.05). CONCLUSIONS: Our study supports the utility of INP, and accurate nutritional screening can help to identify malnourished patients who would receive the most benefits from this protocol.

On the Development of Nanocomposite Covalent Associative Networks Based on Polycaprolactone and Reduced Graphite Oxide.

In this work, the development of nanocomposite systems based on reduced graphite oxide (rGO) was combined with the development of crosslinked materials characterized by dynamic covalent bonds, i.e., a covalent associative network, starting from ad-hoc synthesized hydroxyl terminated polycaprolactone (PCL-OH). The crosslinking reaction was carried out using methylenediphenyl diisocyanate (MDI) to create systems capable of bond exchanges via transesterification and transcarbamoylation reactions, in the presence of stannous octoate as a catalyst. The above materials were prepared at two different temperatures (120 and 200 °C) and two PCL-OH:MDI ratios. FT-IR measurements proved the formation of urethane bonds in all the prepared samples. Crosslinking was demonstrated by contacting the samples with a solvent capable of dissolving the star-shaped PCL. These tests showed a significant increase in the crosslinked fraction with increasing the temperature and the PCL-OH:MDI ratio. In order to evidence the effect of crosslinking on rGO dispersion and the final properties of the material, a nanocomposite sample was also prepared using a linear commercial PCL, with the nanofiller mixed under the same conditions used to develop the crosslinked systems. The dispersion of rGO, which was investigated using FE-SEM measurements, was similar in the different systems prepared, indicating that the crosslinking process had a minor effect on the dispersibility of the nanofiller. As far as the thermal properties are concerned, the DSC measurements of the prepared samples showed that the crosslinking leads to a decrease in the crystallinity of the polymer, a phenomenon which was particularly evident in the sample prepared at 200 °C with a PCL-OH: MDI ratio of 1:1.33 and was related to the decrease in the polymer chain mobility. Moreover, rGO was found to act as a nucleating agent and increase the crystallization temperature of the nanocomposite sample based on linear commercial PCL, while the contribution of rGO in the crosslinked nanocomposite samples was minor. Rheological measurements confirmed the crosslinking of the PCL-OH system which generates a solid-like behavior depending on the PCL-OH:MDI ratio used. The presence of rGO during crosslinking generated a further huge increase in the viscosity of the melt with a remarkable solid-like behavior, confirming a strong interaction between rGO and crosslinked PCL. Finally, the prepared nanocomposites exhibited self-healing and recyclability properties, thus meeting the requirements for sustainable materials.

Post-COVID-19 airway stenosis treated by tracheal resection and anastomosis: a bicentric experience.

Objective: The COVID-19 pandemic was an extraordinary challenge for the global healthcare system not only for the number of patients affected by pulmonary disease, but also for the incidence of long-term sequalae. In this regard, laryngo-tracheal stenosis (LTS) represents one of the most common complications of invasive ventilation. Methods: A case series of patients who underwent tracheal resection and anastomosis (TRA) for post-COVID-19 LTS was collected from June 2020 to September 2021. Results: Among 14 patients included, 50% had diabetes and 64.3% were obese. During intensive care unit stay, mean duration of orotracheal intubation (OTI) was 15.2 days and 10 patients (71.4%) underwent tracheostomy, which was maintained in 7 for an average of 31 days. According to the European Laryngological Society classification, 13 patients (92.9%) had a grade IIIa LTS and one a grade IIIa+. All patients underwent Type A TRA, according to the authors' classification. No major perioperative complications were reported and at the last follow-up all patients were asymptomatic. Conclusions: With the appropriate indications, TRA represents an effective treatment in post-COVID-19 LTS patients. Short OTI times and careful tracheostomy are required in order to reduce the incidence of airway injury.

Deep Learning Applied to White Light and Narrow Band Imaging Videolaryngoscopy: Toward Real-Time Laryngeal Cancer Detection.

OBJECTIVES: To assess a new application of artificial intelligence for real-time detection of laryngeal squamous cell carcinoma (LSCC) in both white light (WL) and narrow-band imaging (NBI) videolaryngoscopies based on the You-Only-Look-Once (YOLO) deep learning convolutional neural network (CNN). STUDY DESIGN: Experimental study with retrospective data. METHODS: Recorded videos of LSCC were retrospectively collected from in-office transnasal videoendoscopies and intraoperative rigid endoscopies. LSCC videoframes were extracted for training, validation, and testing of various YOLO models. Different techniques were used to enhance the image analysis: contrast limited adaptive histogram equalization, data augmentation techniques, and test time augmentation (TTA). The best-performing model was used to assess the automatic detection of LSCC in six videolaryngoscopies. RESULTS: Two hundred and nineteen patients were retrospectively enrolled. A total of 624 LSCC videoframes were extracted. The YOLO models were trained after random distribution of images into a training set (82.6%), validation set (8.2%), and testing set (9.2%). Among the various models, the ensemble algorithm (YOLOv5s with YOLOv5m-TTA) achieved the best LSCC detection results, with performance metrics in par with the results reported by other state-of-the-art detection models: 0.66 Precision (positive predicted value), 0.62 Recall (sensitivity), and 0.63 mean Average Precision at 0.5 intersection over union. Tests on the six videolaryngoscopies demonstrated an average computation time per videoframe of 0.026 seconds. Three demonstration videos are provided. CONCLUSION: This study identified a suitable CNN model for LSCC detection in WL and NBI videolaryngoscopies. Detection performances are highly promising. The limited complexity and quick computational times for LSCC detection make this model ideal for real-time processing. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:1798-1806, 2022.

Quality of life after transoral CO2 laser posterior cordotomy with or without partial arytenoidectomy for bilateral adductor vocal cord paralysis.

OBJECTIVES: Bilateral adductor vocal cord paralysis (BAVCP) is a rare and challenging condition whose main consequence is reduction of airway patency at the glottic level, often causing respiratory distress, while vocal function tends to remain almost normal. We investigated the effect of transoral glottal widening on quality of life and decannulation rates in patients affected by BAVCP. METHODS: We retrospectively evaluated patients affected by BAVCP and treated by transoral CO2 posterior cordotomy with or without medial partial arytenoidectomy (PC ± MPA) at two referral centers. The primary outcome was change in quality of life, evaluated pre- and post-operatively by the ADVS, VHI-30, and EAT-10 questionnaires. Secondary outcomes were the need for retreatments and, for patients with tracheotomy, the time to decannulation. RESULTS: Thirty-three patients met selection criteria. The etiology was post-surgical in 27 cases (81.8%), idiopathic in 4 (12.1%), a trauma-related in 1 (6.0%), and to other causes in 1 (3.0%). In 22 cases (66.7%), PC was combined with MPA. A significant improvement in responses for the ADVS (p < .0001) and EAT-10 (p < .0001) was observed, whereas the VHI-30 score did not change significantly post-operatively. All nine patients with a tracheostomy were successfully decannulated within 18 months after the surgical procedure. CONCLUSIONS: For patients affected by BAVCP, PC ± MPA by transoral CO2 laser microsurgery is a safe, customizable and minimally invasive treatment that can guarantee an affordable balance between quality of life in terms of phonation and swallowing and acceptable airway patency.

On the Development of an Effective Method to Produce Conductive PCL Film.

The aim of this work was to develop an effective approach to improve the graphite dispersion and, consequently, the electrical conductivity of nanocomposites based on polycaprolactone (PCL) and graphite nanoplates (GNP). With this aim, a polymeric additive was designed to be compatible with the polymer matrix and capable of interacting with the graphite layers. Indeed, the compound consists of a low molecular mass PCL ending with a pyrene group (Pyr-PCL). The exploitation of such a molecule is expected to promote from one side specific interactions of the pyrene terminal group with the surface of graphite layers and from the other to guarantee the compatibility with PCL, having a chain with the same nature as the matrix. The features of the nanocomposites prepared by directly blending PCL with GNP were compared with those of the same systems also containing the additive. Moreover, a neat mixture, based on PCL and PCL-Pyr, was prepared and characterized. The specific interactions between the ad hoc synthesized compound and graphite were verified by UV measurements, while SEM characterization demonstrated a finer dispersion of GNP in the samples containing Pyr-PCL. GNP nucleating effect, proved by the increase in the crystallization temperature, was observed in all the samples containing the nanofiller. Moreover, a significant improvement of the electrical conductivity was found in the systems based on the pyrenyl terminated PCL. This peculiar and interesting phenomenon was related to the optimized nanofiller dispersion and to the ameliorated compatibility with the polymer matrix.

Office-based procedures in laryngology.

OBJECTIVE: Development of transnasal fiberoptic laryngoscopy, integration of an operative channel (OC), the advent of high-definition television imaging, with improvements in laser technology, cleared the way for office-based laryngology. Three treatment categories can be identified: bioendoscopy-guided biopsy; laryngeal injection; laser-assisted surgery. METHODS: 26 patients underwent OBPs at the Otolaryngology Clinic of IRCCS Policlinico San Martino, Genoa, Italy. Sixty-eight procedures were performed: 60 for recurrent respiratory papillomatosis (RRP), 5 for unilateral vocal fold paralysis (UVFP) and 3 for glottic leukoplakias. Neoblucaine 5% was administrated through the operative channel, for local anaesthesia. All procedures were carried out with the physician standing behind the patient. Narrow band imaging (NBI - Olympus Medical) or i-scan (Pentax Medical) were used to enhance the accuracy of the biopsy thanks to identification of atypical vascular patterns. Laryngeal injections were made using a 25G flexible needle. Opera Evo (Quanta system IEC/EN 60825-1:2007) is a hybrid fibre laser that is used for "blanching" and vaporisation of RRP lesions and to treat selected leukoplakias that were previously biopsied. CONCLUSIONS: No major complications occurred during the procedures.

Phonosurgical Resection Using Submucosal Infusion Technique for Early Glottic Lesions: Diagnostic and Therapeutic Procedure?

OBJECTIVES:: The aim of this study was to assess the feasibility of the submucosal infusion combined with microflap dissection via laser CO2 as both a diagnostic and therapeutic procedure for superficial glottic lesions. To define a safe surgical procedure in terms of local control, a morphometric study of surgical margins was performed. METHODS:: From January 2011 to January 2016, we treated 122 patients with early glottic lesions with phonomicrosurgery. Patients with effective hydrodissection underwent a microflap and type I-II diagnostic cordectomy. In the others, a biopsy was carried out, and in the case of a malignant lesion, a type III to VI cordectomy was performed. Disease-free survival (DFS) for all the lesions was also determined according to comparative assessments of surgical margins. The Voice Handicap Index was used to evaluate functional outcomes. RESULTS:: In 27 cases (32%), hydrodissection was effective; specifically, 24 (88.8%) were premalignant lesions, and 3 (11.2%) had a carcinoma. In 56 patients (68%), hydrodissection was not adequate, and a biopsy was performed: 9 (16%) were premalignant and 47 (84%) malignant lesions. The DFS analysis suggests that margins >0.7 mm resulted in a cutoff that can guarantee a safe procedure in the case of effective hydrodissection ( P < .05). CONCLUSION:: Phonomicrosurgery may be both a diagnostic and therapeutic option with oncological efficacy for superficial glottic lesions of undetermined nature when surgical margins exceed 0.7 mm. In case of inadequate hydrodissection, the hypothesis of an infiltrative carcinoma warrants a wider cordectomy.