A multicenter protocol to assess the prognostic significance of the tumor microenvironment in patients with squamous cell carcinoma of the larynx.

BACKGROUND: The purpose of this multicenter study was to retrospectively investigate the prognostic significance of the tumor microenvironment, in relation to survival in a large cohort of patients with laryngeal squamous cell carcinoma (LSCC), using the method proposed by the International TILs Working Group in breast cancer. METHODS: All consecutive patients with biopsy-proven LSCC who underwent total laryngectomy (TL) between January 2014 and January 2023 were retrospectively included in the study. A retrospective review of medical records including surgical, pathological and follow-up reports was performed. The density of TILs was determined according to the recommendations of the International TILs Working Group. RESULTS: The study group included 186 patients with LSCC. High TILs were statistically correlated with reduced size and extension of primary tumor (pT stage) with a statistically significant value (S: p = 0.01; P: p = 0.0003) and without needs of salvage therapy (S: p = 0.03; P: p = 0.004). Low TILs were indicative of worse prognosis. CONCLUSIONS: Our study confirmed the protective value of TILs and the prognostic role of the tumor microenvironment in LSCC; furthermore, our results showed that the score proposed by the International TILs Working Group for breast cancer can be applied to LSCC.

Role of Tumor-Infiltrating Lymphocytes and the Tumor Microenvironment in the Survival of Malignant Parotid Gland Tumors: A Two-Centre Retrospective Analysis of 107 Patients.

Background: This study aims to retrospectively investigate the prognostic significance of the tumor microenvironment, with a focus on TILs (tumor-infiltrating lymphocytes), in relation to survival in a large cohort of patients with parotid gland cancer, and it uses the method proposed by the International TILs Working Group in breast cancer. Methods: We included a cohort of consecutive patients with biopsy-proven parotid cancer who underwent surgery between January 2010 and September 2023. A retrospective review of medical records, including surgical, pathological and follow-up reports, was performed. The density of TILs was determined according to the recommendations of the International TILs Working Group for breast cancer. Results: A weak negative correlation (p = 0.3) between TILs and time of survival and a weak positive correlation (p = 0.05) between TILs and months of survival (high TILs were correlated with longer survival in months) were identified. High TILs were weakly negatively, but not statistically significantly p (0.7), correlated with the grading of tumor; this means that high TILs were associated with low-grade tumors. Conclusions: Contrary to previous preliminary reports, this retrospective work found no statistically significant prognostic role of TILs in parotid gland malignancies. This case series represents the largest cohort ever reported in the literature and includes all malignant histological types. Future larger molecular studies may be useful in this regard.

Magnetic resonance imaging-based prediction models for tumor stage and cervical lymph node metastasis of tongue squamous cell carcinoma.

Purpose: To evaluate the ability of preoperative MRI-based measurements to predict the pathological T (pT) stage and cervical lymph node metastasis (CLNM) via machine learning (ML)-driven models trained in oral tongue squamous cell carcinoma (OTSCC). Materials and methods: 108 patients with a new diagnosis of OTSCC were enrolled. The preoperative MRI study included post-contrast high-resolution T1-weighted images acquired in all patients. MRI-based depth of invasion (DOI) and tumor dimension-together with shape-based and intensity-based features-were extracted from the lesion volume segmentation. The entire dataset was randomly divided into a training set and a validation set, and the performances of different types of ML algorithms were evaluated and compared. Results: MRI-based DOI and tumor dimension together with several shape-based and intensity-based signatures significantly discriminated the pT stage and LN status. The overall accuracy of the model for predicting the pT stage was 0.86 (95%CI, 0.78-0.92) and 0.81 (0.64-0.91) in the training and validation sets, respectively. There was no improvement in the model performance upon including shape-based and intensity-based features. The model for predicting CLNM based on DOI and tumor dimensions had a fair accuracy of 0.68 (0.57-0.78) and 0.69 (0.51-0.84) in the training and validation sets, respectively. The shape-based and intensity-based signatures have shown potential for improving the model sensitivity, with a comparable accuracy. Conclusion: MRI-based models driven by ML algorithms could stratify patients with OTSCC according to the pT stages. They had a moderate ability to predict cervical lymph node metastasis.

Treatment of oropharyngeal squamous cell carcinoma: Is swallowing quality better after TORS or RT?

BACKGROUND AND PURPOSE: To answer an important question regarding the long-term morbidity of two oncological equivalent treatment for oropharyngeal squamous cell carcinoma (OPSCC), namely a comparison of swallowing function results between patients treated with trans-oral robotic surgery (TORS) versus patients treated with radiotherapy (RT). MATERIALS AND METHODS: Studies included patients with OPSCC treated with TORS or RT. Articles reporting complete data on MD Anderson Dysphagia Inventory (MDADI) and comparing the two treatments (TORS vs RT) were included in the meta-analysis. Swallowing assessed with MDADI was the primary outcome, the evaluation with instrumental methods was the secondary aim. RESULTS: Included studies provided a total of 196 OPSCC primarily treated with TORS vs 283 OPSCC primarily treated with RT. The mean difference in MDADI score at the longest follow-up was not significantly different between TORS and RT group (mean difference [MD] -0.52; 95% CI -4.53-3.48; p = 0.80). After treatment, mean composite MDADI scores demonstrated a slight impairment in both groups without reaching a statistical difference compared to the baseline status. DIGEST score and Yale score showed a significantly worse function in both treatment groups at 12-month follow-up compared to baseline status. CONCLUSION: The meta-analysis demonstrates that up-front TORS (+- adjuvant therapy) and up-front RT (+- CT) appear to be equivalent treatments in functional outcomes in T1-T2, N0-2 OPSCC, however, both treatments cause impaired swallowing ability. Clinicians should have a holistic approach and work with patients to develop an individualized nutrition plan and swallowing rehabilitation protocol from diagnosis to post-treatment surveillance.

Partial laryngectomy for naïve pT3N0 laryngeal cancer: Systematic review on oncological outcomes.

The first aim was to define the oncologic outcomes of open partial laryngectomy (OPL) in naïve pT3 laryngeal cancer. The second aim was to analyze the outcomes after OPL versus total laryngectomy (TL). A literature search was conducted in three databases (MEDLINE, EMBASE, and Cochrane Library) until January 2022. In 805 patients treated with OPL, 5-year OS, DSS, DFS and LFS were 80.5% (95% CI 70.6-87.6), 83.4% (95% CI 75.7-89), 77.4% (95% CI 66.3-85.7) and 77.9% (95% CI 68.7-85), respectively. Three articles compared TL versus OLP: 5-year OS, DSS and DFS risk difference were 0.100 (95% CI -0.092 to 0.291), 0.067 (95% CI -0.085 to 0.220) and 0.018 (95% CI -0.164 to 0.201) respectively. OPL for selected pT3 laryngeal cancer is able to guarantee a high percentage of oncological success. Accurate patient selection is of utmost importance to differentiate advanced disease amenable to conservative surgery.

Cell-Free Human Papillomavirus-DNA for Monitoring Treatment Response of Head and Neck Squamous Cell Carcinoma: Systematic Review and Meta-Analysis.

OBJECTIVES/HYPOTHESIS: The aim of this study was to assess the value of cell-free human papillomavirus-DNA (cfHPV-DNA) as a diagnostic test for the post-treatment surveillance of patients with HPV-positive head and neck squamous cell carcinoma (HNSCC) through a systematic review and meta-analysis. STUDY DESIGN: Systematic review and meta-analysis. METHODS: A literature search was conducted in three databases (MEDLINE, Embase, and Scopus) in January 2021. The population included patients with HPV-positive HNSCC. The intervention was the use of the repeated liquid biopsy with circulating HPV-DNA detection during follow-up. The outcome was to establish the value of cfHPV-DNA as a diagnostic test for the post-treatment surveillance of patients with HPV-positive HNSCC. RESULTS: Ten studies included in the meta-analysis provided a total of 457 patients with HPV-positive HNSCC. The meta-analytic study estimated the diagnostic performance of cfHPV-DNA as follows: pooled sensitivity and specificity of 0.65 (95% confidence interval [CI]: 0.40-0.84) and 0.99 (99% CI: 0.96-0.99), respectively; positive and negative likelihood ratios of 62.5 (99% CI: 22.9-170.2) and 0.05 (99% CI: 0.013-0.24), respectively; and pooled diagnostic odds ratio of 371.66 (99% CI: 60.4-2286.7). CONCLUSION: Currently, the follow-up protocol for HNSCC patients includes routine clinical evaluation and radiological imaging. Biomarkers to monitor this disease are not established. Considering its high specificity, cfHPV-DNA represents a potential confirmatory test in the case of positive positron emission tomography and computed tomography. In the near future, cfHPV-DNA could be used as a biomarker for monitoring the treatment response during the clinical trials of de-escalation therapy or immunotherapy. Larger sample sizes and the homologation of study protocols and methodology are needed to better establish its utility in the clinical practice. Laryngoscope, 132:560-568, 2022.

Anomaly of digastric muscle: an alarm bell for head and neck surgeon.

Objectives: Here follows the discussion of a case of hypoplasia of both bellies of digastric muscle and the difficult during neck dissection, because of his surgical importance like a pivotal landmark. METHODS: We reported a case report concerning digastric muscle abnormalities, accidentally discovered during neck dissection due to surgical excision of a glottic squamous cell carcinoma staged as cT3N0. A brief literature review was done to compare and research similar cases. RESULTS: Literature counts several reports of digastric muscle abnormalities, namely involving the anterior belly. Little has been written about hypoplasia of digastric muscle. CONCLUSION: Digastric muscle abnormalities are rare, which can be absent or, more frequently, duplicated. Albeit its anomalies are anecdotal, it is advisable to give due consideration to the hypoplasia of both bellies of the digastric muscle during the analysis of radiological imaging, in order to prevent the risk of operative complications. According to our knowledge, this is the first and singular case of digastric muscle's hypoplasia.

Antibody Persistence 6 Months Post-Vaccination with BNT162b2 among Health Care Workers.

BACKGROUND: We present immunogenicity data 6 months after the first dose of BNT162b2 in correlation with age, gender, BMI, comorbidities and previous SARS-CoV-2 infection. METHODS: An immunogenicity evaluation was carried out among health care workers (HCW) vaccinated at the Istituti Fisioterapici Ospitalieri (IFO). All HCW were asked to be vaccine by the national vaccine campaign at the beginning of 2021. Serum samples were collected on day 1 just prior to the first dose of the vaccine and on day 21 just prior to the second vaccination dose. Thereafter sera samples were collected 28, 49, 84 and 168 days after the first dose of BNT162b2. Quantitative measurement of IgG antibodies against S1/S2 antigens of SARS-CoV-2 was performed with a commercial chemiluminescent immunoassay. RESULTS: Two hundred seventy-four HWCs were analyzed, 175 women (63.9%) and 99 men (36.1%). The maximum antibody geometric mean concentration (AbGMC) was reached at T2 (299.89 AU/mL; 95% CI: 263.53-339.52) with a significant increase compared to baseline (p < 0.0001). Thereafter, a progressive decrease was observed. At T5, a median decrease of 59.6% in COVID-19 negative, and of 67.8% in COVID-19 positive individuals were identified with respect to the highest antibody response. At T1, age and previous COVID-19 were associated with differences in antibody response, while at T2 and T3 differences in immune response were associated with age, gender and previous COVID-19. At T4 and T5, only COVID-19 positive participants demonstrated a greater antibody response, whereas no other variables seemed to influence antibody levels. CONCLUSIONS: Overall our study clearly shows antibody persistence at 6 months, albeit with a certain decline. Thus, the use of this vaccine in addressing the COVID-19 pandemic is supported by our results that in turn open debate about the need for further boosts.

Application of a symptoms score questionnaire after conjunctivodacryocystorhinostomy: outcomes.

OBJECTIVE: To evaluate medium/long term outcomes and patient satisfaction through relief of symptoms and improved quality of life (QoL) after Jones tube conjunctivodacryocystorhinostomy (JT-CDCR) using the Naso Lacrimal Duct Obstruction symptom-score (NLDO-SS). METHODS: We conducted a retrospective, non-comparative, multicentric study including patients with complete obstruction of the superior and inferior proximal lacrimal drainage system. All patients underwent JT-CDCR, and the patency of the tube was evaluated with saline irrigation and endoscopic examination. We assessed patient satisfaction and quality of life administering the NLDO-SS. RESULTS: We enrolled 16 patients, for a total of 21 eyes operated. The success rate for procedures was 81%. The success rate for single parameters was globally 95.9%; if considered separately, ocular symptoms and nasal symptoms were respectively 94.3% and 100%. CONCLUSIONS: JT-CDCR was a reliable procedure, able to solve symptoms in a majority of patients and guaranteed a good quality of life over a long period of time.

Early Onset of SARS-COV-2 Antibodies after First Dose of BNT162b2: Correlation with Age, Gender and BMI.

BACKGROUND: The first goal of the study was to analyse the antibody titre 21 days after the first dose of the BNT162b2 vaccine in a group of 252 healthcare workers (HCW). The second goal was to analyse how the antibody titre changes in correlation with age, gender and body mass index (BMI). METHODS: Participants had a nasopharyngeal swab for SARS-CoV-2 and were assessed for the presence of SARS-CoV-2 antibodies at baseline and 21 days after the BNT162b2 priming dose. RESULTS: First dose of BNT162b2 activated immune responses in 98% of the participants. Five HWC had no increase in antibody titre 21 days after the first dose. Antibody titre was greater in young (<38 years) vs. older participants (<38 vs. 47-56 p = 0.002; <38 vs. >56 p = 0.001). Higher antibody levels were detected in underweight vs. pre-obesity group (p = 0.026) and in normal-weight vs. pre-obesity group (p = 0.007). This association was confirmed after adjusting for age (p = 0.0001) and gender (p = 0.00001). CONCLUSIONS: Our study demonstrates that a single dose of BNT162b2 activates the immune response, and being young and normal-weight correlate positively with this response. Larger specifically designed clinical trials are needed to validate these results.

Initial observations on age, gender, BMI and hypertension in antibody responses to SARS-CoV-2 BNT162b2 vaccine.

BACKGROUND: Literature data suggests that age, gender and body mass index (BMI) could be associated with difference in immune responses to vaccines. The first goal of the study was to analyze the antibody titre seven days after the second dose of BNT162b2 vaccine in a group of 248 healthcare workers (HCWs). The second goal was to analyze how antibody titre changes in correlation with age, gender, BMI and hypertension. METHODS: An immunogenicity evaluation was carried out among HCWs vaccinated at the Istituti Fisioterapici Ospitalieri (IFO), Rome, Italy. All HCWs were asked to be vaccinated by the Italian national vaccine campaign at the beginning of 2021. 260 vaccinated HCWs were enrolled in the study. All eligible participants were assigned to receive the priming dose in two weeks' time and the booster dose exactly 21 days thereafter. Blood and nasopharyngeal swabs were collected at baseline and 7 days after second dose of vaccine. Quantitative measurements of IgG antibodies against S1/S2 antigens of SARS-CoV-2 were performed with a commercial chemiluminescent immunoassay. Presence of SARS-Cov-2 in nasopharyngeal swab was determined by commercial RT-PCR testing. FINDINGS: 248 HWCs were analyzed, 158 women (63.7%) and 90 men (36.3%). After the second dose of BNT162b2 vaccine, 99.5% of participants developed a humoral immune response. The geometric mean concentration of antibodies among the vaccinated subjects after booster dose (285.9 AU/mL 95% CI: 249.5-327.7) was higher than that of human convalescent sera (39.4 AU/mL, 95% CI: 33.1-46.9), with p<0.0001. Multivariate linear regression analysis of AU/mL by age, gender and BMI multivariate was performed by the inclusion of covariates. This analysis demonstrated that age (p<0.0001) and gender (p = 0.038) are statistically associated with differences in antibody response after vaccination, whereas BMI and hypertension have no statistically significant association (p = 0.078 and p = 0.52 respectively). INTERPRETATION: 99.5% of HCW developed a humoral immune response and female and young participants seem to have an increased capacity to mount humoral immune responses. BMI and hypertension seem not associated with difference in immune response to the vaccine. FUNDING: None.

Closed for business: The mortality impact of business closures during the Covid-19 pandemic.

We investigate the effectiveness of business shutdowns to contain the Covid-19 disease. In March 2020, Italy shut down operations in selected sectors of its economy. Using a difference-in-differences approach, we find that municipalities with higher exposure to closed sectors experienced subsequently lower mortality rates. The implied life savings exceed 9,400 people over a period of less than a month. We also find that business closures exhibited rapidly diminishing returns and had large effects outside the closed businesses themselves, including spillovers to other municipalities. Overall, the results suggest business shutdowns are effective, but should be selectively implemented and centrally coordinated.

Validation of the European Laryngological Society classification of glottic vascular changes as seen by narrow band imaging in the optical biopsy setting.

PURPOSE: In 2016, the European Laryngological Society (ELS) proposed a classification for vascular changes occurring in glottic lesions as visible by narrow band imaging (NBI), based on the dichotomic distinction between longitudinal vessels (not suspicious) and perpendicular ones (suspicious). The aim of our study was to validate this classification assessing the interobserver agreement and diagnostic test performance in detecting the final histopathology. METHODS: A retrospective study was carried out by reviewing clinical charts, preoperative videos, and final pathologic diagnosis of patients submitted to transoral microsurgery for laryngeal lesions in two Italian referral centers. In each institution, two physicians, independently re-assessed each case applying the ELS classification. RESULTS: The cohort was composed of 707 patients. The pathologic report showed benign lesions in 208 (29.5%) cases, papillomatosis in 34 (4.8%), squamous intraepithelial neoplasia (SIN) up to carcinoma in situ in 200 (28.2%), and squamous cell carcinoma (SCC) in 265 (37.5%). The interobserver agreement was extremely high in both institutions (k = 0.954, p < 0.001 and k = 0.880, p < 0.001). Considering the diagnostic performance for identification of at least SIN or SCC, the sensitivity was 0.804 and 0.902, the specificity 0.793 and 0.581, the positive predictive value 0.882 and 0.564, and the negative predictive value 0.678 and 0.908, respectively. CONCLUSION: The ELS classification for NBI vascular changes of glottic lesions is a highly reliable tool whose systematic use allows a better diagnostic evaluation of suspicious laryngeal lesions, reliably distinguishing benign ones from those with a diagnosis of papillomatosis, SIN or SCC, thus paving the way towards confirmation of the optical biopsy concept.

The impact of nodal status in major salivary gland carcinoma: A multicenter experience and proposal of a novel N-classification.

OBJECTIVES: Despite differences in oncological behavior, the 8th edition of AJCC TNM staging currently proposes the same N-classification for major salivary glands (MSG) carcinoma and squamous cell carcinoma of the upper aerodigestive tract. The present study aims to investigate a more reliable definition of N-categories for MSG carcinoma. MATERIALS AND METHODS: A retrospective multicenter study was performed, including 307 patients treated for primary MSG carcinoma from 1995 to 2019. Outcome measures included overall survival (OS), disease specific survival, and local, regional, and distant recurrence. Survival analysis was performed using log-rank test and Cox proportional-hazards model. Overall number (ON) and largest diameter (LD) of nodal metastases, including intra-parotid metastases, were considered to develop three novel proposals of N-classification; their performance were compared with the current TNM staging using Akaike information criterion (AIC), Bayesian information criterion (BIC), and Nagelkerke pseudo-R2. RESULTS: Intra-parotid nodes, ON and LD of nodal metastases emerged as major prognosticators for OS, while extra-nodal extension did not impact on any survival. The current N-classification did not show a satisfactory OS stratification. Three novel N-classifications were developed according to number of metastatic nodes (0 vs 1-3 vs ≥ 4) and/or their maximum diameter (<20 mm vs ≥ 20 mm). They all showed better accuracy in OS stratification, and achieved better AIC, BIC and Nagelkerke pseudo-R2 indices when compared to current N-classification. CONCLUSION: All the proposed N-classifications improved OS stratification and could help in defining a specific N-classification for MSG carcinoma. Their validation and assessment in an external cohort is needed.

Intraoral ultrasonography in the assessment of DOI in oral cavity squamous cell carcinoma: a comparison with magnetic resonance and histopathology.

OBJECTIVE: The first-line therapeutic approach for oral cavity squamous cell carcinoma (OCSCC) is complete surgical resection. Preoperative assessment of depth of invasion (cDOI) is crucial to plan the surgery. Magnetic resonance (MR) and intraoral ultrasonography (IOUS) have been shown to be useful tools for assessment of DOI. The present analysis investigates the accuracy of MR and IOUS in evaluating DOI in OCSCC compared to histological evaluation (pDOI). MATERIALS AND METHODS: Forty-nine previously untreated patients with cT1-T3 OCSCC were reviewed. Nine patients were staged with MR alone, 10 with IOUS alone, and 30 with both MR and IOUS. RESULTS: Mean difference between cDOIMR and pDOI values of 0.2 mm (95% CI - 1.0-1.3 mm) and between cDOIIOUS and pDOI of 0.3 mm (95% CI - 1.0-1.6 mm). Spearman R between cDOIMR and pDOI was R = 0.83 and between cDOIIOUS and pDOI was R = 0.76. Both radiological techniques showed high performance for the correct identification, with the optimum cut-off of 5 mm, of patients with a pDOI ≥ 4 mm and amenable to a neck dissection, with an AUC of 0.92 and 0.82 for MR and IOUS, respectively. CONCLUSION: Both examinations were valid approaches for preoperative determination of DOI in OCSCC, although with different cost-effectiveness profiles and indications.

Surgeons reaching satisfying outcomes without surgery: nasal dorsum skin cancer recurrence treated with electrochemotherapy.

Cutaneous squamous cell carcinoma of the head and neck district are generally treated with surgery. Surgery is the standard treatment in early stages and local advanced tumors, followed by adjuvant therapy, radiation or concurrent chemoradiation therapy. Local recurrence treatment depends on previous therapies, though radical surgery is often the first choice at the expense of anatomy preservation. We present the case of a patient with cutaneous squamous cell carcinoma of the nasal dorsum which relapsed after surgery and radiation therapy. The patient refused radical surgery and electrochemotherapy under general anesthesia was administered. After 6 months from treatment, the patient showed a complete clinical response. Electrochemotherapy could be considered as an alternative to surgery in small lesion when other approaches are refused.

Literature in the time of COVID-19: The "phase two".

The sudden onset of the COVID-19 pandemic has put a strain on the whole scientific world. We assisted to a tremendous effort by researchers with the final goal of achieving a better management of COVID-19 patients. The world of otorhinolaryngology, likewise, has not been exempt from this commitment to research. In this commentary we perform a bibliometric review of the available academic literature about COVID-19 in the top 20-ranked ENT journal, with the goal of providing an overview of what has been published to date and encouraging a shift towards quantitative research.

COVID-19: Nasal and oropharyngeal swab.

Performing a proper nasal and oropharyngeal swab procedure is essential in the screening of COVID-19 infection. The video illustration of nasal and oropharyngeal swab is presented (Video S1). To correctly perform the nasopharyngeal swab, the patient must be seated comfortably with the back of their head against the headrest. The swab is inserted in the nose horizontally, along an imaginary line between the nostril and the ear. Oropharyngeal sampling is easier to perform. The swab is directed toward the rear wall of the oropharynx and it is rotated a few times before removal. After taking the sample, it is necessary to insert both swabs in the same tube, breaking the rod with one swift and controlled movement. Finally, carefully reset the cap. It appears to be extremely important to properly collect nasopharyngeal and oropharyngeal swabs in order to minimize the false negative rate among COVID-19 positive patients.