Unlocking tracheoesophageal speech from pharyngoesophageal spasm: preliminary results of a videofluoroscopic-guided botulinum toxin A injection technique.

PURPOSE: The tracheoesophageal puncture for the voice prosthesis (VP) placement is the recognized gold standard in post-laryngectomy voice rehabilitation. Despite the development of specific intraoperative techniques, a subset of patients will suffer from poor functional outcomes due to pharyngoesophageal spasms (PES). This paper evaluates the functional outcomes after transcutaneous botulinum toxin type A (BTX-A) infiltration for PES with a videofluoroscopy-guided technique. METHODS: Since 2022, eight consecutive patients with VP and affected by PES were treated with BTX-A injection by a standard videofluoroscopic guided technique at the European Institute of Oncology, IRCCS (IEO) in Milan. A lidocaine test was performed pre-operatively to evaluate the potential effect of chemical neurectomy. All patients with positive lidocaine tests were injected with 50 IU of BTX-A (Allergan, Irvine, CA) according to the sites marked during the videofluoroscopy. Reported symptoms (VHI, SECEL), perceptual (INFVo), aerodynamic (MPT) and manometric parameters were collected before and after treatment. RESULTS: In all cases, BTX-A was performed as an outpatient procedure without complications. For seven patients, only one BTX-A injection was needed, while one patient required a re-injection. Subjective and perceptive improvement after BTX-A was significant for VHI, SECEL and INFVo. MPT showed significant improvement after a chemical neurectomy. After a mean follow-up of 6 months, all patients maintained a good TES quality. CONCLUSION: The videofluoroscopic guided BTX-A injection of the pharyngoesophageal tract showed to be a feasible and reproducible technique in all cases. The pharyngoesophageal videofluoroscopy allows defining of patients' anatomical landmarks that help the surgeon to perform a homogeneous injection, empowered by post-injection massage.

Outcomes of mini-invasive transoral surgery without neck dissection in supraglottic laryngeal cancer: Real world data from a tertiary cancer center.

PURPOSE: The neck management in early-stage cN0 supraglottic cancer represents an argument of debate. The aim of our study is to evaluate the oncological and functional outcomes in patients with early-stage cN0 supraglottic carcinoma treated with a wait-and-see policy for the neck. MATERIALS AND METHODS: Retrospective monocentric cohort study in a referral cancer care center. We collected a consecutive sample of patients from 2000 to 2020 with Squamous Cell Carcinoma of the supraglottis without clinical evidence of nodal metastases (cN0), surgically treated with Transoral Surgery (Laser or Robotic) without neck dissection. From 316 supraglottic cancer we finally selected 66 eligible participants that met all inclusion criteria. RESULTS: Sixty-six patients (M 75.8 % vs F 24.2 %), median age 65.8 years (IQR 60.9, 70.5). The most common subsite was the epiglottis (62.1 %). Tumor stage distribution was as follows: 35 % cT1, 53 % cT2, 15.2 % cT3. Neither deaths nor major treatment-related complications were reported after surgery. The median follow-up was 62 months. For oncological outcomes, we evaluated 56 patients (10 excluded for adjuvant radiotherapy): 5-year overall survival rate 87 % (CI 95 %: 73.1-94), disease- specific survival rate 95.3 % (CI 95 %: 82-98.8) and neck recurrence-free survival rate 87 % (CI 95 %: 73.1-94). Six patients developed neck recurrence, with a median time of 13 months. CONCLUSIONS: Supraglottic carcinoma has been historically associated to a considerable risk of occult metastasis. However, in early-stage cases data are still inconclusive. Our results suggest that in such patients a wait-and-see policy does not impact negatively on survival outcomes, while granting the reduced morbidity associated to a minimally invasive surgical approach.

The Genetic and Immunologic Landscape Underlying the Risk of Malignant Progression in Laryngeal Dysplasia.

(1) Background: The development of laryngeal cancer is a multistep process involving structural alterations of the epithelial mucosa, from dysplasia (LDy) to invasive carcinoma. In this study, we define new biomarkers, prognostic for malignant transformation, in patients affected by LDy. (2) Methods: We used targeted next-generation sequencing and immunohistochemical analysis to define the mutational and immunological landscape of 15 laryngeal dysplasia progressing to invasive cancer (progressing dysplasia), as well as 31 cases of laryngeal dysplasia that did not progress to carcinoma (non-progressing dysplasia). Two pathologists independently analyzed the presence of tumor-infiltrating lymphocytes in LDy pre-embedded paraffin-fixed specimens. The RNA-based next-generation sequencing panel OIRRA was used to evaluate the expression of 395 genes related to immune system activation. (3) Results: High TILs are significantly correlated with a higher risk of malignant transformation. The non-brisk pattern was significantly associated with an 86% reduced risk of malignant progression (OR = 0.16, 95% CI: 0.03-0.5, p = 0.008). TILs showed a highly positive correlation with CCR6, CD83, HLA-DPB1, MX1 and SNAI1, and they were inversely correlated with CD48, CIITA, CXCR4, FCER1G, IL1B, LST1 and TLR8. (4) Conclusions: TILs have a great potential to identify high-risk progression dysplasia and thus to define surveillance protocols and prevention programs.

Small tongue squamous cell carcinoma with neck metastasis at diagnosis: operative insights and surgical technique.

BACKGROUND: The treatment of tongue tumors includes different surgical procedures ranging from a simple mucosal resection to complex combined resection depending on the tumor stage and size. In 2019 we reported an international glossectomy classification with the purpose of standardizing all the different types of surgical procedures adopted for tongue cancer. METHODS: The present communication aims at providing further insight into the glossectomy classification. More specifically, it is intended to better specify the indications to glossectomy type IIIA and B in selected tongue cancers, with positive cervical lymph nodes at the diagnosis. RESULTS AND CONCLUSIONS: Type IIIA glossectomy permits a high function sparing surgery in selected cases, with better postoperative functional outcomes. From an oncological perspective, it permits a radical surgery, avoiding postoperative radiation in the absence of extracapsular spread, multiple nodal metastases or T-N tract involvement.

Upfront transoral robotic surgery (TORS) versus intensity-modulated radiation therapy (IMRT) in HPV-positive oropharyngeal cancer: real-world data from a tertiary comprehensive cancer centre.

Objective: This study aims to provide real-world data on oncologic and functional outcomes of the most modern surgical and non-surgical treatments of locally advanced HPV-positive oropharyngeal cancer. Methods: We reviewed data on patients treated for stage III and IV HPV-positive oropharyngeal squamous cell carcinoma with either endoscopic surgery (Transoral Robotic Surgery, TORS; Transoral Laser Microsurgery, TLM - group A) or intensity-modulated radiotherapy (IMRT - group B). The minimum follow-up required was 6 months. Survival outcomes and toxicities of treatments were evaluated. Results: 30 patients in group A and 66 in group B were eligible for the analysis. 28% of patients in group A underwent a unimodal treatment, while 42% needed trimodal treatment. 90% of patients in group B underwent concurrent chemoradiation. We found no statistically significant difference in survival outcomes (group A: overall survival 97%, progression-free survival 83%; group B: OS 98%, PFS 86%) or toxicities between groups. Conclusions: Both transoral surgery and IMRT provide excellent outcomes in HPV-positive oropharyngeal cancer. Because of the good prognosis, treatments need to be refined to reduce toxicities while preserving oncologic soundness.

Oral tongue carcinoma: prognostic changes according to the updated 2020 version of the AJCC/UICC TNM staging system.

Background: This study aimed to evaluate the performance of the 2017 8th TNM edition and the latest update in 2020 compared to the 7th in a large cohort of patients affected by oral tongue squamous cell carcinoma (OTSCC), considering all stages. Materials and methods: The cohort involved 300 patients affected by OTSCC treated with surgery. All cases were classified according to the 7th, 8th (2017), and the latest updated TNM edition (October 2020),. Patients were grouped based on the shift in tumour (T) category, lymph nodal (N) category and final pathological stage. Overall survival (OS) and disease-free survival (DFS) were calculated with the Kaplan-Meier method. Univariate and multivariate analyses were carried out. Results: According to the 7th edition, multivariate analysis OS revealed that stage IV patients had an almost 4-fold risk of death compared to stage I (HR = 3.81 95% CI: 2.32-6.25; p < 0.001). Regarding DFS, stage IV patients had a 2-fold greater risk of relapses, or second primary, than patients in stage I (HR = 2.51 95% CI: 1.68-3.74; p < 0.001). According to 2017 8th edition for OS, stage IV patients presented a 5-fold higher risk of death compared to patients in stage I (HR = 5.18 95% CI: 2.96-9.08; p < 0.001) and almost 4-old greater risk of relapses or second primary compared to patients in stage I considering DFS (HR = 3.61 95% CI: 2.28-5.71; p < 0.001). Regarding the recent edition of 8th TNM (2020), stage IV patients had an almost 5-fold greater risk of death compared to patients in stage I considering OS (HR = 4.84 95% CI: 2.74-8.55; p < 0.001), while for DFS they had 3-fold greater risk of relapse or second primary compared to patients in stage I (HR = 3.13 95% CI: 1.99-4.91; p < 0.001). Conclusions: This study confirmed that the recent update of the 8th edition of the TNM (2020) improves stratification and identification of advanced tumours, reducing the number of T3 compared to the 2017 edition and increasing the number of patients with pT4. This improvement made by the updated edition may reduce the risk of skipping adjuvant therapy.

Tongue cancer treatment and oncological outcomes: The role of glossectomy classification.

BACKGROUND: Nowadays surgery remains the gold standard of treatment for tongue cancer. Via a more clear and precise terminology, the glossectomy classification by Ansarin et al. facilitates shared communication between surgeons, allowing comparison between published research and improving surgical practice and patient care. To establish the association of glossectomies, according to their classification by Ansarin et al. with overall survival (OS), disease-free survival (DSF), and cause-specific survival (CSS) in tongue cancer, we conducted a systemic retrospective study on 300 consecutive patients affected by primary oral tongue cancer and treated with surgery at the European Institute of Oncology, IRCCS (IEO). METHODS: Three hundred patients with tongue squamous cell carcinoma and treated at the Division of Otorhinolaryngology and Head and Neck Surgery of the European Institute of Oncology, IRCCS were cataloged according to the glossectomy classification. OS, DFS, and CSS were compared by surgical treatments. RESULTS: OS-5yrs was 80% for the type I glossectomy group, 75% for type II, 65% for type III, and 35% for type IV-V. DFS-5yrs was 74%, 60%, 55%, and 27%, respectively for I, II, III, and IV-V glossectomy group; CSS-5yrs was 82%, 80%, 72%, and 48%, respectively for I, II, III, and IV-V glossectomy group (p < 0.01). CONCLUSIONS: This study confirmed that the application of the glossectomy classification was statistically correlated with patients' oncological outcomes.

Modified transcervical lipofilling of the base of the tongue under local anaesthesia: Case series.

Laryngeal carcinoma represents one-third of all head and neck cancers and is burdened by significant morbidity and mortality for advanced-stage disease. Surgical treatments, including Open Partial Horizontal Laryngectomy (OPHL), are often followed by long-lasting swallowing rehabilitation and more rarely, persistent dysphagia. Some authors reported single cases, successfully treated with fat injection of the base of tongue, but nowadays, a standardized technique has never been described so far. We provide a step-by-step technique description of the trans-cervical lipofilling of the base of the tongue (BOT) under local anaesthesia in a case series of three patients. The functional results have been evaluated with a videofluoroscopic study of deglutition and Penetration-Aspiration Score. The procedure was well tolerated; all patients were discharged after 24 hours without any majorcomplications. After six months, all patients had a steady improvement in swallowing. During follow-up, the videofluoroscopic study of deglutition confirmed a sensitive amelioration of the Penetration-Aspiration Score and an empowered base of tongue retropulsion. Finally, the lipofilling of the BOT under local anaesthesia showed to be a feasible, and reproducible procedure, for dysphagia after OPHLs.

Outcomes of head and neck cancer management from two cancer centres in Southern and Northern Europe during the first wave of COVID-19.

OBJECTIVE: To describe the approach and outcomes from two cancer centres in Southern and Northern Europe during the first wave of coronavirus disease 2019 (COVID-19) of patients with head and neck cancer (HNC). METHODS: Data collection was performed on a retrospective cohort of patients surgically treated for primary HNC between March and May 2020, using data from two tertiary hospitals: the European Institute of Oncology (Milan) and Guy's & St Thomas' NHS Foundation Trust (London). RESULTS: We included 77 patients with HNC. More patients with COVID-19 were taking angiotensin-converting enzyme (ACE) inhibitors and had Clavien-Dindo Classification grade I compared to negative patients, respectively (60% vs 22% [p = 0.058] and 40% vs 8% [p = 0.025]). Multivariate logistic regression analyses confirmed our data (p = 0.05 and 0.03, respectively). Sex and age were statistically significantly different (p = 0.05 and <0.001 respectively), showing more male patients (75% vs 53.66%, respectively) and more elderly patients in Italy than in the United Kingdom (patients aged >63 years: 69.44% vs 29.27%). CONCLUSIONS: This study presents a large cohort of patients with HNC with nasopharyngeal swab during the first peak of the COVID-19 pandemic in Europe. Patients with HNC with COVID-19 appeared more likely to develop postsurgical complications and to be taking ACE inhibitors. The preventive measures adopted guaranteed the continuation of therapeutic surgical intervention.

Upfront surgical organ-preservation strategy in advanced-stage laryngeal cancer.

PURPOSE: Advanced-stage laryngeal cancer is a challenging disease that needs multimodal treatment. Medical and surgical organ-preservation strategies have been developing in the last decades to spare these functions while granting cancer cure. The current work presents the experience of a tertiary-care center in conservative surgery for advanced-stage laryngeal cancer. MATERIALS AND METHODS: We collected clinical data of patients submitted to open partial horizontal laryngectomies (OPHLs) and any possible adjuvant treatment from 2005 to 2018. Outcomes were also compared to the most recent studies reporting on both medical and surgical organ-preservation strategies. RESULTS: One hundred ten patients were included in the analysis. Adjuvant therapy was employed in 51% of cases. The local control rate was 96.4%, while overall survival (OS) was 67%, and laryngo-esophageal dysfunction free survival (LEDFS) was 66%. Stage IV and vascular invasion were associated with a statistically-significant worse survival. CONCLUSIONS: OPHLs are valid as upfront treatment in fit patients affected by advanced-stage laryngeal cancer. Disease control and function preservation are granted in a significant percentage of cases, even when followed by adjuvant therapy.

Prevalence of Central Compartment Lymph Node Metastases in Papillary Thyroid Micro-Carcinoma: A Retrospective Evaluation of Predictive Preoperative Features.

Papillary thyroid micro-carcinomas are considered relatively indolent carcinomas, often occult and incidental, with good prognosis and favorable outcomes. Despite these findings, central lymph node metastases are common, and are related to a poor prognosis for the patient. We performed a retrospective analysis on patients treated with surgery for stage pT1a papillary thyroid micro-carcinomas. One hundred ninety-five patients were included in the analyses. The presence of central lymph node metastases was identified and studied. A multivariate analysis employing binary logistic regression was used to calculate adjusted odds ratios with 95% confidence intervals of possible central lymph node metastases risk factors. In the performed multivariate analysis, male gender, younger age, and histopathological characteristics, such as a tumor sub-capsular localization, were significantly associated with central lymph node metastases in pT1a patients. Central compartment lymph node metastases are present in a non-negligible number of cases in patients with papillary thyroid micro-carcinoma undergoing surgical resection. Studying these factors could be an effective tool for predicting patients' central lymph node metastases in papillary thyroid micro-carcinomas, defining a tailored surgical treatment in the future.

Leukoplakia in the Oral Cavity and Oral Microbiota: A Comprehensive Review.

We reviewed the current published literature on the impact of oral microbiota on oral cavity leukoplakia (OLK), aiming at clarifying its role in disease transformation. The analysis unveiled that bacterial richness and diversity in the oral cavity tend to be decreased in OLK compared to healthy controls, with a reduction in the prevalent commensals, such as Streptococci, and elevation of anaerobes. Moreover, Fusobacterium nucleatum, Porphyromonas gingivalis and Prevotella intermedia are recurrent findings, and they already have been linked to periodontal disease. These microbial community changes may also represent a marker for the transition from OLK to oral squamous cell carcinoma. Unfortunately, the reviewed studies present several limitations, making an objective comparison difficult. To overcome these biases, longitudinal studies are necessary.

Coping With Oral Tongue Cancer and COVID-19 Infection.

To date, April 19, 2021, the coronavirus disease 2019 (COVID-19) caused about 140,886,773 confirmed cases and more than 3,000,000 deaths worldwide since the beginning of the pandemic. Oncology patients are usually frail due to the fear of prognosis, recurrence, and outcomes of treatments. Thus, coping with cancer is a complicated process that is necessary to overcome oncological challenge, even more in case of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) disease. This is a brief case report on a middle-aged man affected by advanced oral tongue cancer and COVID-19, describing his experience of cancer diagnosis, surgical treatment, and rehabilitation during the hospital quarantine for COVID-19. Besides the traumatic experience due to the functional alteration in breathing, eating, and speaking caused by major surgery and the concurrent facial disfigurement, our patient had to face a COVID-19 diagnosis, which implied hospital and social isolation. The aim of this perspective work is to focus on the role of the psychological support in the management of hospital distress related to COVID-19 psychophysical loneliness or alienation. In our experience, such support should anticipate patients' oncological surgery or treatment and should be implemented through telemedicine in case of isolation or after hospital discharge.

Oral cancer: changing the aim of the biopsy in the age of precision medicine. A review.

Oral cancer is a heterogeneous disease that develops through a complex, multi-step process. Precision medicine should help to better understand its molecular basis, integrate traditional classifications and have a positive impact on cancer management. To apply this information in clinical practice, we need to define its histology and identify biomarkers expressed by the tumour that provide useful information for planning tailored treatment. The most reliable information currently derives from evaluation of biomarkers on post-operative samples. To plan personalised treatment, oncologists need to assess these markers on biopsy samples. We reviewed the recent literature and identified 6 of 184 publications that compared markers measured on biopsy and post-operative samples or assessed their predictivity for the development of lymph node metastases. Data from these studies suggest that markers measured on biopsy samples can provide useful indications for tailoring treatments. However, due to their heterogeneity and low level of evidence, these results need to be confirmed by clinical studies on a large population to standardise and validate biomarkers in biopsies and to assess their reliability in other diagnostic mini-invasive procedures such as radiomics and liquid biopsy.^ieng

Il cancro orale è una malattia eterogenea che origina ed evolve con un processo complesso e multifasico. La medicina di precisione permette di pianificare un trattamento personalizzato sulla base delle caratteristiche biologiche e molecolari delle singole neoplasie. Le informazioni oggi più affidabili sono fornite dalla valutazione post-operatoria dei biomarcatori, ma per pianificare un trattamento personalizzato è necessario valutare questi marcatori sulla biopsia. Per questo abbiamo rivisto la letteratura dell'ultimo quinquennio ed abbiamo identificato 6/184 articoli che valutano i marcatori sulla biopsia confrontandone i valori con quelli misurati sul pezzo operatorio di ciascun paziente o valutandone la predittività per lo sviluppo di metastasi linfonodali. I dati che emergono da questi studi suggeriscono che la valutazione dei marcatori sul campione bioptico potrebbe fornire indicazioni utili per programmare trattamenti personalizzati. Tuttavia, a causa della eterogeneità e del basso livello di evidenza dei lavori considerati, questi risultati devono essere confermati da studi clinici su un'ampia popolazione per standardizzare e validare i biomarcatori e la loro affidabilità in altre procedure mini-invasive, ad esempio radiomica e biopsia liquida.

An innovative tool for mandibular reconstruction in oral malignancies: A pictorial essay.

Mandibular reconstruction is challenging for most head and neck surgeons. Technological advances have led to the development of a new innovative procedure based on the concepts of computer-assisted design (CAD) and virtual surgical planning (VSP). The main disadvantage of this technique is the lack of flexibility, especially in oncology. A possible solution is the development of a semi-standardized mandible and fibula resection cutting guide: the L1® mandible ReconGuide. We provided a step-by-step description of the operative technique for mandibular reconstruction with the L1® mandible ReconGuide. The L1® mandible ReconGuide is a guiding force toward mandibular reconstruction. Moreover, the tool has been designed to suit the needs of the patients, particularly those with oral cancer, thereby permitting intraoperative planning and increasing time and cost effectiveness. In this pictorial essay, we have presented the operative techniques of using the L1® mandible ReconGuide for reconstruction.

A systematic review and meta-analysis of the prognostic role of age in oral tongue cancer.

While evidence suggests an increasing incidence of tongue cancer in young adults, published findings regarding the prognostic role of age at diagnosis are inconsistent. We performed a meta-analysis of the literature to highlight key points that might help in understanding the association between age of oral tongue cancer patients at diagnosis and their prognosis. According to age at diagnosis, a systematic literature review of all published cohort studies assessing the recurrence risks and mortality associated with tongue cancer was conducted. We compared the risk estimates between patients aged >45 years and those aged <45 years at diagnosis. Random-effects models were used to calculate summary relative risk estimates (SRRs) according to different clinical outcomes and sources of between-study heterogeneity (I2 ) and bias. We included 31 independent cohort studies published between 1989 and 2019; these studies included a total of 28,288 patients. When risk estimations were not adjusted for confounders, no significant association was found between age at diagnosis and overall survival (OS). Conversely, after adjustment for confounders, older age at diagnosis was associated with a significantly increased risk of mortality. The difference between SRRs for adjusted and unadjusted estimates was significant (p < 0.01). Younger patients had a significantly higher risk of local recurrence. Younger patients with oral tongue cancer have better OS but a greater risk of recurrence than older patients. These findings should be validated in a large prospective cohort study which considers all confounders and prognostic factors.

Laryngeal dysplasia: Oncological outcomes in a large cohort of patients treated in a tertiary comprehensive cancer centre.

PURPOSE: Laryngeal dysplasia represents a series of precancerous lesions, observed as laryngeal leukoplakia. General agreement has been lacking for their management and treatment ranging from simple biopsy to complete excision with cold blade/laser. In this work, we aim at providing the oncological outcomes of patients affected by laryngeal dysplasia, treated with a single modality, and at identifying clinical parameters predictive of malignant transformation. MATERIALS AND METHODS: We performed a retrospective analysis of patients treated with transoral laser microsurgery between January 2005 and December 2015 in a tertiary comprehensive cancer centre. Data were collected about smoke and alcohol habits, site of the laryngeal lesion, surgical outcomes and progression to invasive squamous cell carcinoma. RESULTS: The grade of dysplasia, margins' status and smoke habit were not associated with a significantly worse DFS and a higher risk of invasive SCC. We identified three parameters (supraglottic involvement, multifocality and history of more than one recurrence of dysplasia) that have a significant prognostic value. CONCLUSIONS: On the base of these clinical parameters, a more intensive follow-up might be warranted for high-risk patients.

Role of Human Papillomavirus Infection in Head and Neck Cancer in Italy: The HPV-AHEAD Study.

Literature on the role of human papillomavirus (HPV) in head and neck cancer (HNC) in Italy is limited, especially for non-oropharyngeal tumours. Within the context of the HPV-AHEAD study, we aimed to assess the prognostic value of different tests or test algorithms judging HPV carcinogenicity in HNC and factors related to HPV positivity at the European Institute of Oncology. We conducted a retrospective cohort study (2000-2010) on a total of 696 primary HNC patients. Formalin-fixed, paraffin-embedded cancer tissues were studied. All HPV-DNA-positive and a random sample of HPV-DNA-negative cases were subjected to HPV-E6*I mRNA detection and p16INK4a staining. Multivariate models were used to assess for factors associated with HPV positivity and proportional hazards for survival and recurrence. The percentage of HPV-driven cases (considering HPV-E6*I mRNA positivity) was 1.8, 2.2, and 40.4% for oral cavity (OC), laryngeal (LC), and oropharyngeal (OPC) cases, respectively. The estimates were similar for HPV-DNA/p16INK4a double positivity. Being a non-smoker or former smoker or diagnosed at more recent calendar periods were associated with HPV-E6*I mRNA positivity only in OPC. Being younger was associated with HPV-E6*I mRNA positivity in LC. HPV-driven OPC, but not HPV-driven OC and LC, showed better 5 year overall and disease-free survival. Our data show that HPV prevalence in OPC was much higher than in OC and LC and observed to increase in most recent years. Moreover, HPV positivity conferred better prognosis only in OPC. Novel insights on the role of HPV in HNC in Italy are provided, with possible implications in the clinical management of these patients.