In reply to the letter to the editor regarding "Clinical outcomes of teeth adjacent to the site of mandibulotomy or mandibulectomy in patients with head and neck cancer: results from a multidisciplinary mono-institutional head and neck tumor board".

This paper aims to reply to Somay et al., regarding their comment to a previous paper from our group, titled "Clinical outcomes of teeth adjacent to the site of mandibulotomy or mandibulectomy in patients with head and neck cancer: results from a multidisciplinary mono-institutional head and neck tumor board".The following concerns were addressed: 1) Within the limits of a case series, mandibulectomy might be considered a risk factor for the loss of tooth vitality as well as mandibulotomy. 2) Root canal therapy before surgery on the teeth adjacent to the surgical site could be an appropriate strategy, although in some cased it may involve teeth which are not destinate to have endodontic complications. 3) Dose-volume data of the included teeth were provided: the impact of radiotherapy (RT) as a confounding factor seems not to be as relevant as Somay et al. have pointed out.

Clinical outcomes of teeth adjacent to the site of mandibulotomy or mandibulectomy in patients with head and neck cancer: results from a multidisciplinary mono-institutional head and neck tumor board.

INTRODUCTION: The aim of this case series was to evaluate the necrosis of teeth adjacent to the site of mandibulotomy or mandibulectomy in a cohort of patients suffering from head and neck cancers. METHODS: Fourteen patients who underwent segmental mandibulectomy or paramedian mandibulotomy for oral, oropharynx or major salivary gland cancer and a total of 23 teeth were included in this case series. Twelve patients underwent adjuvant head and neck radiotherapy. Cold sensitivity pulp testing and/or electric pulp testing were performed on teeth at the margin of mandibulectomy and on teeth adjacent to mandibulotomy after surgery. A "positive" response was considered the healthy state, and "negative" was considered the diseased state of the tooth. RESULTS: The 10 patients who underwent mandibulotomy had 12 teeth with a negative response. The 4 patients treated by mandibulectomy had two positive and three negative responses to cold and electric pulp tests. Fifteen out of 23 teeth (65.2%) showed a negative response to sensitivity testing. CONCLUSIONS: Tooth necrosis seems to be a common event after mandibulectomy and mandibulotomy. CLINICAL RELEVANCE: To avoid post-surgery complications, performing root canal therapy before surgery on the teeth adjacent to the surgical site could be an appropriate strategy.

Parathyroid hormone-related peptide and parathyroid hormone-related peptide receptor type 1 in locally advanced laryngeal cancer as prognostic indicators of relapse and survival.

BACKGROUND: Parathyroid hormone-related peptide (PTHrP) overexpression and poor patient outcome have been reported for many human tumors, but no studies are available in laryngeal cancer. Therefore, we studied the expression of PTHrP and its receptor, parathyroid hormone-related peptide receptor type 1 (PTH1R), in primary locally advanced laryngeal squamous cell carcinomas (LALSCC) also in relation to the clinical outcome of patients. METHODS: We conducted a retrospective exploratory study, using immunohistochemistry, on PTHrP, PTH1R and HER1 expressions in LALSCC of 66 patients treated with bio-radiotherapy with cetuximab. RESULTS: The expressions of PTHrP and PTH1R in LALSCC were associated with the degree of tumor differentiation (p = 0.01 and 0.04, respectively). Poorly differentiated tumors, with worse prognosis, expressed PTHrP at nuclear level and were PTH1R negative. PTHrP and PTH1R were expressed at cytoplasmic level in normal larynx epithelium and more differentiated laryngeal cancer cells, suggesting an autocrine/paracrine role of PTHrP in squamous cell differentiation of well differentiated tumors with good prognosis. Eighty-one percent HER1 positive tumors expressed PTHrP (p < 0.0001), mainly at nuclear level, consistent with the known up-regulation of PTHrP gene by HER1 signaling. In multivariable analyses, patients with PTHrP positive tumors had a higher relative risk of relapse (HR = 5.49; CI 95% = 1.62-22.24; p = 0.006) and survival (HR = 8.21; CI 95% = 1.19-105.00; p = 0.031) while those with PTH1R positive tumors showed a lower relative risk of relapse (HR = 0.18; CI 95% = 0.04-0.62; p = 0.002) and survival (HR = 0.18; CI 95% = 0.04-0.91; p = 0.029). CONCLUSIONS: In LALSCC nuclear PTHrP and absence of PTH1R expressions could be useful in predicting response and/or resistance to cetuximab in combined therapies, contributing to an aggressive behavior of tumor cells downstream to HER1.

Nuclear HER3 expression improves the prognostic stratification of patients with HER1 positive advanced laryngeal squamous cell carcinoma.

BACKGROUND: Compared to the other members of human epidermal growth factor family receptors (HER), the role of HER3 has not been well defined in laryngeal cancer. The predictive and prognostic role of HER3 has been the focus of clinical attention but the research findings are contradictory, especially in laryngeal squamous cell carcinoma (LSCC). The variable localization of HER3 within cancer cells and the role of HER3 in primary and acquired resistance to HER1-targeted therapies remain unclear. METHODS: We performed a retrospective analysis of two cohorts of 66 homogeneous consecutive untreated primary advanced LSCC patients, in which co-expression of HER1, HER2 and HER3 receptors was investigated by semi-quantitative immunohistochemistry. The association of their pattern of expression with survival was evaluated by Kaplan-Meier and Cox's proportional hazard analyses. Multivariable Cox proportional hazards models were developed to predict median 2- and 3-year RFS and 2.5- and 5-year OS. The Akaike information criterion technique and backwards stepwise procedure were used for model selections. The performance of the final Cox models was assessed with respect to calibration and discrimination. RESULTS: Immunohistochemical labeling for HER1 and HER2 was localized both in the cell membrane and in the cytoplasm, while HER3 labeling was observed both in the cell cytoplasm and in the nucleus. HER3 expression was inversely correlated with HER1 positivity. The expression patterns of HERs were associated with tumor differentiation. In both cohorts of patients, HER1 expression was associated with reduced relapse-free (RFS) and overall survival (OS). In HER1 positive tumors, the co-expression with nuclear HER3 was associated with better RFS and OS, compared with HER3 negative tumors or tumors expressing HER3 at cytoplasmic level. HER3 expressing tumors had a higher Geminin/MCM7 ratio than HER3 negative ones, regardless of HER1 co-expression. Multivariable analyses identified age at diagnosis, tumor site, HER1, HER3 and age at diagnosis, tumor stage, HER1, HER3, as covariates significantly associated with RFS and OS, respectively. Bootstrapping verified the good fitness of these models for predicting survivals and the optimism-corrected C-indices were 0.76 and 0.77 for RFS and OS, respectively. CONCLUSIONS: Nuclear HER3 expression was strongly associated with favourable prognosis and allows to improve the prognostic stratification of patients with HER1 positive advanced LSCC carcinoma.

Impact of Tracheal Tube on Swallowing in Post-Operative Head and Neck Cancer Patients: Scintigraphic Analysis.

Dysphagia is common in tracheostomized patients who underwent head and neck surgery for cancer treatment. The objective of this study was to evaluate, by means of oropharyngoesophageal scintigraphy (OPES), the impact of an occluded tracheal tube (TT) on swallowing in patients treated for head and neck cancer before hospital discharge, to provide further information to the benefit of out-patient care management. From October 2018 to November 2019, we enrolled 19 tracheostomized patients (6 females and 13 males; mean age 61 years) who underwent primary surgical resection of head and neck tumor and swallowing rehabilitation during hospitalization. All subjects underwent a double-standard OPES, one with occluded tracheal tube and the other without TT, with their tracheal stoma being closed directly by a plaster. For each study, we assessed and compared the following quantitative parameters: oral transit time (OTTsec), pharyngeal transit time (PTTsec), esophageal transit time (ETTsec), oral retention index (ORI%), pharyngeal retention index (PRI%), esophageal retention index (ERI%), and aspiration percentage (AP%). The mean values of OTT, PTT, ORI%, PRI%, and ERI% were abnormal during OPES both with TT and without TT and did not statistically differ between the two tests (p > 0.05). Aspiration was detected in 4 cases out of 19 (21.05%) cases during OPES with TT and in 4/19 (21.05%) cases without TT who showed a mean AP% of 11.4% and 11.5% respectively (p > 0.05). Patients with abnormal AP% (> 0%) during OPES with TT showed aspiration signs without TT. Our study showed that the mere presence of a closed tracheal tube does not impact significantly the oropharyngeal transit of bolus during swallowing. This result suggests the possibility to maintain a small-diameter occluded tracheal tube in place for the postsurgical management of head and neck cancer patients.

The usefulness of the IMAP propeller flap for trachea and tracheostome reconstruction after resection of parastomal recurrence of squamous cell carcinoma following salvage total laryngectomy.

PURPOSE: Parastomal recurrence of squamous cell carcinoma (SCC) with tracheal involvement following salvage total laryngectomy after prior concurrent chemoradiotherapy is one of the most insidious challenges in head and neck surgery because a complex reconstruction is often required for covering a large area of skin loss, filling the dead space beneath, tracheal reconstruction and suspension, and tracheostome resurfacing. The aim is to describe our experience with the internal mammary artery perforator (IMAP) propeller flap for tracheal and tracheostome reconstruction and neck resurfacing after parastomal and cervical trachea resection, especially for suspension and anchoring the stump of the residual distal trachea to the island flap itself. METHODS: We describe IMAP flap reconstruction after resection of parastomal recurrence of SCC requiring cervical trachea resection in five patients between January 1, 2005 and August 30, 2019. RESULTS: IMAP propeller flap was successfully used for reconstruction after complex resection of parastomal recurrence of SCC with cervical trachea involvement in all cases. The mean length and width were, respectively, 16.8 cm (range 13-23) and 6.9 cm (range 5.5-8). We did not report complications of both the donor and the recipient site. Pharyngo-cutaneous or tracheoesophageal fistulas and wound dehiscence were not observed. CONCLUSIONS: to the best of our knowledge, this is the first report about the use of the IMAP propeller flap in this more complex clinical setting and we provide the message that this surgical procedure is worthy of consideration.

HPV and EBV Infections in Neck Metastases from Occult Primary Squamous Cell Carcinoma: Another Virus-Related Neoplastic Disease in the Head and Neck Region.

BACKGROUND: Approximately 1-9 % of all head and neck squamous cell carcinomas are neck metastases from clinically undetectable primary tumors. Human papillomavirus (HPV) and Epstein-Barr virus (EBV) are proven carcinogenic factors that are associated with oropharyngeal squamous cell carcinoma and nasopharyngeal carcinoma, respectively. In the present study, we evaluated the prevalence of these viruses in neck metastases from unknown primary squamous cell carcinoma. METHODS: We evaluated fresh samples from a consecutive series of 22 neck dissections for metastases from unknown primary squamous cell carcinoma obtained between 2010 and 2012 at a single institution. The samples were tested for the presence of HPV E6 and E7 mRNA and EBV DNA. RESULTS: Oncogenic viral infections were detected in 12 cases (54 % total; 2 HPV18, 5 HPV16, 2 EBV infection, and 3 EBV/HPV16 coinfections). The most frequent primarily involved neck level in our series was IIA (70 %), which had the highest prevalence of viral infection (66 %). We did not find any other significant correlations between virus detection and clinicopathologic parameters or prognosis. DISCUSSION: Neck metastasis from unknown primary squamous cell carcinoma could be another virus-related malignancy in the head and neck region, along with nasopharyngeal and oropharyngeal carcinoma. An evaluation of the impact of viral infection on patient prognosis and sensitivities to different treatment modalities could modify our prognostic assessments and treatment planning. Furthermore, virus detection would have a decisive impact on diagnostic/decisional algorithms, especially if detection methods are implemented on cytologic samples (e.g., thin prep).

Evaluation of swallowing function after supracricoid laryngectomy as a primary or salvage procedure.

The primary functional issues following conservative therapy for advanced laryngeal cancer concern swallowing. Here, we evaluated the recovery of swallowing after supracricoid partial laryngectomy (SCL) in patients with primary or recurrent laryngeal cancer. We evaluated the swallowing recovery in 27 SCL patients through oropharyngoesophageal scintigraphy, and we evaluated their quality of life using EORTC questionnaires. Four patients underwent total laryngectomy during follow-up. Patients who retained their larynges were able to feed without nutritional support and without tracheostoma. The only significantly different parameter between the primary and salvage cases was the time elapsed to the removal of nasogastric/PEG tubes, which was longer in salvage cases. SCL has been demonstrated as a valuable option for primary and recurrent laryngeal cancer patients. The present data demonstrate good functional results, particularly in terms of swallowing after previous treatments and in primary settings. The combination of oropharyngoesophageal scintigraphy and questionnaires appears to be an adequate, standardizable approach to assessing swallowing function after SCL.

Management of nasal vestibule carcinomas: recommendations by the Oncological Committee of the Italian Society of Otorhinolaryngology - Head and Neck Surgery.

Objective: Squamous cell carcinoma of the nasal vestibule (NV SCC) is a head and neck malignancy for which there is no established consensus on most aspects of clinical management. The purpose of this document is to give updated recommendations that incorporate recent evidence on its clinical characteristics and the high efficacy of brachytherapy as primary treatment modality. Methods: A working group consisting of the members of the Scientific Committee for Oncology and Reconstructive Surgery of the Italian Society of Otorhinolaryngology Head and Neck Surgery and radiation oncologists expert in brachytherapy was formed to achieve a consensus. Results: Consensus was reached on a set of recommendations, proposing a refined anatomical definition of the nasal vestibule, a novel T staging system of the NV SCC, and brachytherapy as standard of care, with a new method for catheter implantation. Conclusions: The Committee emphasises the critical role of an accurate classification in clinical practice and encourages further research to validate the novel staging system and further improve treatment strategies. Where appropriate, it is recommended that patients be referred to centres with specific experience in brachytherapy for NV SCC.

The observational clinical registry (cohort design) of the European Reference Network on Rare Adult Solid Cancers: The protocol for the rare head and neck cancers.

INTRODUCTION: Care for head and neck cancers is complex in particular for the rare ones. Knowledge is limited and histological heterogeneity adds complexity to the rarity. There is a wide consensus that to support clinical research on rare cancer, clinical registries should be developed within networks specializing in rare cancers. In the EU, a unique opportunity is provided by the European Reference Networks (ERN). The ERN EURACAN is dedicated to rare adults solid cancers, here we present the protocol of the EURACAN registry on rare head and neck cancers (ClinicalTrials.gov Identifier: NCT05483374). STUDY DESIGN: Registry-based cohort study including only people with rare head and neck cancers. OBJECTIVES: to help describe the natural history of rare head and neck cancers;to evaluate factors that influence prognosis;to assess treatment effectiveness;to measure indicators of quality of care. METHODS: Settings and participants It is an hospital based registry established in hospitals with expertise in head and neck cancers. Only adult patients with epithelial tumours of nasopharynx; nasal cavity and paranasal sinuses; salivary gland cancer in large and small salivary glands; and middle ear will be included in the registry. This registry won't select a sample of patients. Each patient in the facility who meets the above mentioned inclusion criteria will be followed prospectively and longitudinally with follow-up at cancer progression and / or cancer relapse or patient death. It is a secondary use of data which will be collected from the clinical records. The data collected for the registry will not entail further examinations or admissions to the facility and/or additional appointments to those normally provided for the patient follow-up. Variables Data will be collected on patient characteristics (eg. patient demographics, lifestyle, medical history, health status); exposure data (eg. disease, procedures, treatments of interest) and outcomes (e.g. survival, progression, progression-free survival, etc.). In addition, data on potential confounders (e.g. comorbidity; functional status etc.) will be also collected. Statistical methods The data analyses will include descriptive statistics showing patterns of patients' and cancers' variables and indicators describing the quality of care. Multivariable Cox's proportional hazards model and Hazard ratios (HR) for all-cause or cause specific mortality will be used to determine independent predictors of overall survival, recurrence etc. Variables to include in the multivariable regression model will be selected based on the results of univariable analysis. The role of confounding or effect modifiers will be evaluated using stratified analysis or sensitivity analysis. To assess treatment effectiveness, multivariable models with propensity score adjustment and progression-free survival will be performed. Adequate statistical (eg. marginal structural model) methods will be used if time-varying treatments/confounders and confounding by indication (selective prescribing) will be present. RESULTS: The registry initiated recruiting in May 2022. The estimated completion date is December 2030 upon agreement on the achievement of all the registry objectives. As of October 2022, the registry is recruiting. There will be a risk of limited representativeness due to the hospital-based nature of the registry and to the fact that hospital contributing to the registry are expert centres for these rare cancers. Clinical Follow-up could also be an issue but active search of the life status of the patients will be guaranteed.

Botulinum Neurotoxin A in the Treatment of Pharyngocutaneous Fistula after Salvage Surgery in Head and Neck Cancer Patients: Our Preliminary Results.

Objective: To analyze the effect of intraparotid injection of botulinum neurotoxin A (BoNT-A) on salivary production and the course of pharyngocutaneous fistula (PCF) in post-radiation therapy salvage surgery. Methods: A total of 13 patients who had undergone total laryngectomy or pharyngolaryngectomy were treated with BoNT-A to both parotid glands, within three days from PCF onset. The salivary flow was evaluated using a subjective rating scale as the percentage of normal function from 0% (no saliva) to 100% (normal saliva flow), before injection, every day for 2 weeks, and once a week for three months. PCFs were monitored daily. Results: Spontaneous closure of PCF occurred in 7/13 (53.84%) cases 13.6 days (range: 7-18) after treatment; 6/13 (46.16%) patients needed revision surgery. Salivary flow significantly decreased in all patients seven days after injection (from 67.2% to 36.4%; p < 0.05). Patients who had undergone either conservative or surgical treatment did not differ in salivary flow before injection, whereas the mean percentages of salivary flow calculated at each time point after injection were different (p < 0.05). Conclusions: BoNT-A contributed to the closure of the fistula in most of our cases. The subjective perception of salivary flow predicted the closure of PCF. The mean time to closure may contribute to establishing the timing of PCF surgical treatment.

Oral Candida spp. Colonisation Is a Risk Factor for Severe Oral Mucositis in Patients Undergoing Radiotherapy for Head & Neck Cancer: Results from a Multidisciplinary Mono-Institutional Prospective Observational Study.

BACKGROUND: This study aims to find a correlation between Candida spp. oral colonisation prior to radiotherapy (RT) and (i) the development of severe oral mucositis (OM) (grade 3/4) and (ii) early development of severe OM (EOM). METHODS: The protocol was registered on ClinicalTrials.gov (ID: NCT04009161) and approved by the ethical committee of the 'Fondazione Policlinico Universitario Gemelli IRCCS' (22858/18). An oral swab was obtained before RT to assess the presence of Candida spp. Severe OM occurring before a dose of 40 Gy was defined as EOM. RESULTS: No patient developed G4 OM, and only 36/152 patients (23.7%) developed G3 OM. Tumour site and lymphocytopenia were risk factors for severe OM (OR for tumour site: 1.29, 95% CI: 1-1.67, p = 0.05; OR for lymphocytopenia: 8.2, 95% CI: 1.2-55.8, p = 0.03). We found a correlation between Candida spp. and EOM (OR: 5.13; 95% CI: 1.23-21.4 p = 0.04). Patients with oral colonisation of Candida spp. developed severe OM at a mean dose of 38.3 Gy (range: 28-58; SD: 7.6), while negative patients did so at a mean dose of 45.6 Gy (range: 30-66; SD: 11.1). CONCLUSIONS: Candida spp. in the oral cavity appears to be a predictive factor of EOM.

Elective Neck Dissection during Salvage Total Laryngectomy: Personal Experience.

The role of elective neck dissection during salvage surgery in patients with a clinically negative neck (cN0) is still discussed. The main objective of this work was to estimate the prevalence and predictive factors of occult neck nodes metastasis; we therefore aimed to evaluate the survival rate and the main oncologic outcomes of cN0 patients who underwent salvage total laryngectomy and elective bilateral neck dissection. In this retrospective observational study, we enrolled 80 cN0 patients affected by recurrent laryngeal cancer and who underwent salvage total laryngectomy and bilateral selective elective neck dissection. Several parameters were collected in order to find prognostic factors; finally, postoperative complications were reviewed and survival analysis was performed. Occult lymph node metastases were reported in 18 out of 80 patients (22.5%). Significant statistical correlation between lymphovascular invasion (p = 0.007), perineural invasion (p = 0.025) and occult nodal metastasis was found. Other variables (glottic subsite of recurrence, clinical T, pathological T, previous chemotherapy) were not significantly predictive of occult nodal metastasis. The 5-year OS, DSS, and RFS were 50.4%, 64.7%, and 63.4%, respectively. In conclusion, our single-institution data on a large cohort of patients, suggest performing routinely elective selective bilateral neck dissection during salvage total laryngectomy in cN0 patients due to the biological attitude of the tumor to spread to cervical nodes, considering an acceptable complications rate.

Bioradiotherapy with Cetuximab May Reduce the Risk of Neck Node Relapse in Locoregionally Advanced Laryngeal Glottic Carcinoma: May HER1-Profile Be Useful in the Bioselection of Patients?

The aim of the study was to evaluate survival in patients with advanced glottic laryngeal squamous cell carcinoma treated by bioradiotherapy (BioRT) with cetuximab and eventual salvage surgery (group A, n = 66) or upfront surgery (total laryngectomy or near-total laryngectomy) with or without postoperative radiotherapy (PORT) (group B, n = 66). The predictive role of HER1 expression in the bioselection of tumors was evaluated. Relapse-free (RFS), metastasis-free (MFS), overall (OS) survivals, salvageability, and rates of larynx preservation were analyzed. The two groups were balanced by propensity score method on their baseline characteristics. No significant differences in RFS and OS were found, while MFS results were significantly higher in group A (p = 0.04). Group A showed a 22% reduction in the probability of nodal metastasis (p = 0.0023), mostly in tumors with higher HER1 expression. The salvageability with TL at 3 years was 54% after prior BioRT and 18% after prior upfront NTL (p < 0.05). BioRT with cetuximab showed a reduction in the risk of lymph node relapse, particularly in the case of HER1 positive tumors, and it allowed to achieve a higher rate of functional larynx preservation and a higher salvageability compared with upfront surgery. HER1 analysis could be clinically useful in the bioselection of tumors that may benefit from BioRT with cetuximab, particularly in those with neck node metastatic propensity.

The Pruitt-Inahara carotid shunt as an assisting tool to anastomose the arterial free flap pedicle to the internal carotid artery in the vessel-depleted neck.

Microvascular free tissue transfer in head and neck reconstruction requires suitable recipient vessels which are frequently compromised by prior surgery or radiotherapy to the neck. This article details a new technique of arterial free flap pedicle anastomosis to the internal carotid artery in a vessel-depleted neck. A 63-year-old female was referred because of recurrence of squamous cell carcinoma of the tongue, which involved the left-sided tongue base and pharynx with circumferential involvement of the homolateral external carotid artery. This artery and its branches were excluded as potential recipients. To close the defect after tumor excision, a free vertical rectus abdominis muscle arterial flap pedicle was anastomosed to the homolateral internal carotid artery with the help of a Pruitt-Inahara outlying carotid shunt. The venous anastomosis was performed to the internal jugular vein. The VRAM flap survived without complications. This procedure is to be considered an alternative rescue technique for salvage reconstruction in vessel depleted necks.

Regenerative Strategy for Persistent Periprosthetic Leakage around Tracheoesophageal Puncture: Is It an Effective Long-Term Solution?

Autologous tissue-assisted regenerative procedures have been considered effective to close different types of fistula, including the leakage around tracheoesophageal puncture. The aim of this study was to retrospectively review 10 years of lipotransfer for persistent periprosthetic leakage in laryngectomized patients with voice prosthesis. Clinical records of patients who experienced periprosthetic leakage from December 2009 to December 2019 were reviewed. Patients receiving fat grafting were included. The leakage around the prosthesis was assessed with a methylene blue test. Twenty patients experiencing tracheoesophageal fistula enlargement were treated with fat grafting. At the one-month follow-up, all patients were considered improved with no leakage observed. At six months, a single injection was sufficient to solve 75% of cases (n 15), whereas 25% (n 5) required a second procedure. The overall success rate was 80% (n 16). Results remained stable for a follow-up of 5.54 ± 3.97 years. Fat grafting performed around the voice prosthesis, thanks to its volumetric and regenerative properties, is a valid and lasting option to solve persistent periprosthetic leakage.

Not only gustatory sweating and flushing: Signs and symptoms associated to the Frey syndrome and the role of botulinum toxin A therapy.

BACKGROUND: The classic symptoms of Frey syndrome are gustatory sweating and flushing. Aims of the study were to describe prevalenceand severity of typical and atypical presentations of the disorder and to assess the effects of botulinum neurotoxin A (BoNT-A) therapy in patients with Frey syndrome after parotidectomy. METHODS: In this prospective, observational study on 18 patients, we assessed symptom severity before therapy, after 15 days, 1, 3 and 6 months' follow-up with the sweating-flushing-itch-paresthesia-pain (SFIPP) Frey scale specifically designed by the authors themselves for this study. RESULTS: Before BoNT-A injection, all patients (100%) complained gustatory sweating, 80% paresthesia, 77% gustatory flushing, 60% pain and 60% gustatory itch. The SFIPP-Frey overall score and the symptom-specific ones decreased significantly at each post-therapy control. CONCLUSIONS: The prevalence of "unusual" manifestations is not negligible. BoNT-A improves symptoms severity. The SFIPP-Frey scale may be useful to assess symptoms and to monitor post-therapy outcomes.

Immunohistochemical detection of "ex novo" HLA-DR in tumor cells determines clinical outcome in laryngeal cancer patients.

There are controversial results about the role of "ex novo" HLA-DR expression by tumor cells and its correlation with the oncological outcomes. Unfortunately, little is known about HLA-DR expression in laryngeal cancer tumor cells. The main purpose of this retrospective study is to strengthen the usefulness of studying "ex novo" HLA-DR expression on tumor cells from primary laryngeal squamous cell carcinoma (LSCC) patients and investigate its correlation with clinical outcome. We analyzed HLA-DR expression by immunohistochemical analysis in 56 patients with LSCC. The "ex novo" HLA-DR expression on laryngeal cancer tumor cells, assessing non-neoplastic LSCC - adjacent tissue, and the association of HLA-DR expression (HLA-DR+) with clinical outcomes were investigated. HLA-DR+ tumor cells were detected in 18/56 LSCC patients (32.1%). All specimens of non-neoplastic laryngeal carcinoma-adjacent tissue resulted HLA-DR negative (HLA-DR-). A statistically significant association was observed between HLA-DR + and well differentiated tumors (G1) (p<0.001). The Kaplan-Meier method showed how HLA-DR+ is significantly associated with both a better disease specific survival (HLA-DR+=100% vs. HLA-DR-=77.4%; p=0.047) and a better relapse free survival (HLA-DR+=100% vs. HLA-DR-=72.3%; p=0.021). Cox regression univariate analysis for death of disease confirmed a higher HR for HLA-DR absence on the surface of epithelial tumor cell [HR:37.489; 95% CI:0.750-18730.776; p=0.253] and for high-grade (G3) tumors [HR:18.601; 95% CI:3.613-95.764; p<0.0001]. Our results confirm that MHC class II HLA-DR expression is activated in a sub-set of LSCC patients. Evaluation of HLA-DR expression in LSCC could be useful for prognosis and future approaches towards personalized therapy.

Stapler Use in Salvage Total Laryngectomy: A Useful Tool?

OBJECTIVES/HYPOTHESIS: To analyze stapler benefits in salvage total laryngectomy in terms of surgical time, hospitalization length, oral feeding time, and occurrence of pharyngocutaneous fistula, and to evaluate risk factors for its onset. STUDY DESIGN: Retrospective analysis. METHODS: One hundred fourteen patients affected by endolaryngeal squamous cell carcinoma who underwent salvage total laryngectomy following primary treatment failure were reviewed. We divided patients into two groups based on type of pharyngeal suture performed: mechanical suture with stapler (group A) and manual suture (group B). These two groups were compared for surgical time, start of oral feeding, hospitalization length, surgical margins and pharyngocutaneous fistula incidence considering its relationship with diabetes mellitus, nutritional status, primary treatment, and neck dissection. RESULTS: In group A and group B, oral feeding restarting time was 15 ± 9.33 versus 20.03 ± 13.81 days, hospitalization was 17.63 ± 10.08 versus 23.72 ± 14.29 days, and surgery lasted 268.39 ± 76.93 versus 294.26 ± 140.58 minutes, respectively (P < .05). Surgical margins resulted infiltrated in two patients (4.3%) in group A and 12 patients in group B (17.6%) (P = .03). Twenty-one patients (18.4%) presented with pharyngocutanoeus fistula. In group A and group B the incidence of fistula was 15.2% and 20.6%, respectively (P = .468). Fistula occurred in 7 of 18 diabetic patients (38.9%) and 14 of 96 (14.6%) nondiabetic patients (P = .015). Nineteen fistulas (90.5%) occurred in patients who had undergone previous radiation treatment (P = .013). CONCLUSIONS: Using a stapler shortened operative time and hospitalization, while also providing a faster restart of oral feeding. Moreover, mechanical pharyngeal suture seems to decrease fistula rate even though its prevention role in salvage laryngectomy should be confirmed by further studies. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E473-E478, 2021.

Erratum to "Prognostic Role of Serum Amino Acids in Head and Neck Cancer".

[This corrects the article DOI: 10.1155/2020/2291759.].