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.

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.

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.

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.

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.

Survival Outcomes in Oral Tongue Cancer: A Mono-Institutional Experience Focusing on Age.

OBJECTIVE: The prognostic role of age among patients affected by Oral Tongue Squamous Cell Carcinoma (OTSCC) is a topic of debate. Recent cohort studies have found that patients diagnosed at 40 years of age or younger have a better prognosis. The aim of this cohort study was to clarify whether age is an independent prognostic factor and discuss heterogeneity of outcomes by stage and treatments in different age groups. METHODS: We performed a study on 577 consecutive patients affected by primary tongue cancer and treated with surgery and adjuvant therapy according to stage, at European Institute of Oncology, IRCCS. Patients with age at diagnosis below 40 years totaled 109 (19%). Overall survival (OS), disease-free survival (DFS), tongue specific free survival (TSFS) and cause-specific survival (CSS) were compared by age groups. Multivariate Cox proportional hazards models were used to assess the independent role of age. RESULTS: The median follow-up time was 5.01 years (range 0-18.68) years with follow-up recorded up to February 2020. After adjustment for all the significant confounding and prognostic factors, age remained independently associated with OS and DSF (respectively, p = 0.002 and p = 0.02). In CSS and TSFS curves, the role of age seems less evident (respectively, p = 0.14 and p = 0.0.37). In the advanced stage sub-group (stages III-IV), age was significantly associated with OS and CSS with almost double increased risk of dying (OS) and dying from tongue cancer (CSS) in elderly compared to younger groups (OS: HR = 2.16 95%, CI: 1.33-3.51, p= 0.001; CSS: HR = 1.76 95%, CI: 1.03-3.01, p = 0.02, respectively). In our study, young patients were more likely to be treated with intensified therapies (glossectomies types III-V and adjuvant radio-chemotherapy). Age was found as a prognostic factor, independently of other significant factors and treatment. Also the T-N tract involved by disease and neutrophil-to-lymphocyte ratio ≥3 were independent prognostic factors. CONCLUSIONS: Young age at diagnosis is associated with a better overall survival. Fewer younger people than older people died from tongue cancer in advanced stages.

Ultrasound dye-assisted parathyroidectomy (USDAP): Experience of a tertiary center.

BACKGROUND: Primary hyperparathyroidism is primarily caused by parathyroid adenoma, followed by hyperplasia and parathyroid carcinoma. In the era of minimally invasive, targeted parathyroidectomy, the main challenge remains that of distinguishing intraoperatively pathological parathyroid from normal glands and peri-thyroid fat tissue. The aim of this study is to evaluate the surgical outcomes of a novel minimally invasive technique called ultrasound-guided dye-assisted parathyroidectomy (USDAP). METHODS: We perform a retrospective analysis of patients affected by parathyroid adenoma, treated with USDAP at our institution between 2014 and 2019. Data were collected on patient age and sex, tumor location and size, preoperative investigations, histopathology, perioperative complications and surgical outcomes. RESULTS: Between January 2014 and June 2019, 43 patients underwent parathyroidectomy in our Institute. Each case was discussed by the Institutional Multidisciplinary Board. All patients undergoing thyroidectomy together with USDAP or patients undergoing USDAP under endoscopic control were excluded from the present study. The final cohort, the largest to our knowledge, consisted of 29 patients. All patients were successfully treated with USDAP and remained disease-free during follow up. In all cases, pathological parathyroid was correctly identified and removed. There was no postoperative allergic reaction, nor were there neurotoxicity complications. USDAP permitted a shortening of operative and hospitalization time. CONCLUSIONS: USDAP is an effective and safe procedure both as first line treatment and as a re-operative procedure after previous surgical failures in selected cases.

Image-Guided Thermal Ablation as an Alternative to Surgery for Papillary Thyroid Microcarcinoma: Preliminary Results of an Italian Experience.

Purpose: To report the results of our preliminary experience in treating patients with papillary thyroid microcarcinoma (PTMC) with image-guided thermal ablation, in particular estimating the feasibility, safety and short-term efficacy. Materials and Methods: From 2018 patients with cytologically proven PTMC < 10 mm were discussed in a multidisciplinary team and evaluated for feasibility of image-guided thermal ablation. In case of technical feasibility, the three possible alternatives (i.e., image-guided thermal ablation, surgery, and active surveillance) were discussed with patients. Patients who agreed to be treated with image guided thermal ablation underwent radiofrequency (RFA) or laser ablation under local anesthesia and conscious sedation. Treatment feasibility, technical success, technique efficacy, change in thyroid function tests, side effects, minor and major complications, patients satisfaction and pain/discomfort perception during and after treatment, and disease recurrence during follow-up were recorded. Results: A total of 13 patients were evaluated, and 11/13 (84.6%) patients (9 female, 2 male, mean age 49.3 ± 8.7 years) resulted suitable for image-guided thermal ablation. All 11 patients agreed to be treated with image-guided thermal ablation. In addition, 3/11 (27.3%) were treated with laser ablation and 8/11 (72.7%) with RFA. All procedures were completed as preoperatively planned (technical success 100%). Technique efficacy was achieved in all 11/11 (100%) cases. Ablated volume significantly reduced from 0.87 ± 0.67 ml at first follow-up to 0.17 ± 0.36 at last follow-up (p = 0.003). No change in thyroid function tests occurred. No minor or major complications occurred. All patients graded 10 the satisfaction for the treatment, and mean pain after the procedure was reported as 1.4 ± 1.7, and mean pain after the procedure as 1.2 ± 1.1 At a median follow-up of 10.2 months (range 1.5-12 months), no local recurrence or distant metastases were found. Conclusions: Image guided thermal ablations appear to be feasible and safe in the treatment of PTMC. These techniques hold the potential to offer patients a minimally invasive curative alternative to surgical resection or active surveillance. These techniques appear to be largely preferred by patients.

The role of the T-N tract in advanced stage tongue cancer.

BACKGROUND: We investigated the role of the soft tissue tract between the primary tumor and the neck lymph nodes, the "T-N tract," in patients with tongue squamous cell carcinoma at an advanced stage. METHODS: We performed a compartmental tongue surgery in 233 patients. Cumulative incidence of relapses and overall survival curves were compared by T-N tract involvement. Multivariate Cox proportional hazards models were used to assess the independent role of T-N tract. RESULTS: At 4 years of follow-up, patients with disease in the T-N tract experienced a significantly more distant recurrence (40%) than did patients without T-N tract involvement (22%; P = .02). Multivariate Cox models indicate a significant almost triple risk of distant metastases (hazard ratio [HR], 2.70; 95% CI, 1.01-7.19; P = .05) and double risk of death (HR, 2.09; 95%CI, 1.13-3.85; P = .02) in patients with "T-N tract involvement." CONCLUSIONS: Our data show that the T-N tract plays an important role in prognosis and survival in patients with tongue cancer.

Minimally-invasive treatments for benign thyroid nodules: a Delphi-based consensus statement from the Italian minimally-invasive treatments of the thyroid (MITT) group.

Benign thyroid nodules are a common clinical occurrence and usually do not require treatment unless symptomatic. During the last years, ultrasound-guided minimally invasive treatments (MIT) gained an increasing role in the management of nodules causing local symptoms. In February 2018, the Italian MIT Thyroid Group was founded to create a permanent cooperation between Italian and international physicians dedicated to clinical research and assistance on MIT for thyroid nodules. The group drafted this list of statements based on literature review and consensus opinion of interdisciplinary experts to facilitate the diffusion and the appropriate use of MIT of thyroid nodules in clinical practice. (#1) Predominantly cystic/cystic symptomatic nodules should first undergo US-guided aspiration; ethanol injection should be performed if relapsing (level of evidence [LoE]: ethanol is superior to simple aspiration = 2); (#2) In symptomatic cystic nodules, thermal ablation is an option when symptoms persist after ethanol ablation (LoE = 4); (#3) Double cytological benignity confirmation is needed before thermal ablation (LoE = 2); (#4) Single cytological sample is adequate in ultrasound low risk (EU-TIRADS ≤3) and in autonomously functioning nodules (LoE = 2); (#5) Thermal ablation may be proposed as first-line treatment for solid, symptomatic, nonfunctioning, benign nodules (LoE = 2); (#6) Thermal ablation may be used for dominant lesions in nonfunctioning multinodular goiter in patients refusing/not eligible for surgery (LoE = 5); (#7) Clinical and ultrasound follow-up is appropriate after thermal ablation (LoE = 2); (#8) Nodule re-treatment can be considered when symptoms relapse or partially resolve (LoE = 2); (#9) In case of nodule regrowth, a new cytological assessment is suggested before second ablation (LoE = 5); (#10) Thermal ablation is an option for autonomously functioning nodules in patients refusing/not eligible for radioiodine or surgery (LoE = 2); (#11) Small autonomously functioning nodules can be treated with thermal ablation when thyroid tissue sparing is a priority and ≥80% nodule volume ablation is expected (LoE = 3).

Classification of GLOSSECTOMIES: Proposal for tongue cancer resections.

BACKGROUND: Surgery of tongue tumors includes different procedures ranging from mucosal resection to complex combined resection. Numerous terms have been used to describe such procedures, but there is no consensus between the terminology and the extent of resection. METHODS AND RESULTS: We searched the medical literature and found a lack of published information. We undertook to describe a new classification of surgical procedures for tongue tumor resection. We based it upon the surgical anatomy of the tongue and the spread of the cancer. We posited that there were five major types of glossectomy embracing all the methods of tongue cancer resection. This classification was reviewed and endorsed by an international team of experts. CONCLUSION: We propose a more precise classification than that currently in practice, thereby bringing clarity and consistency to the terminology, facilitating shared communication between surgeons, comparison between published research, and ultimately improving surgical practice and patient care.

From transmandibular to transoral robotic approach for parapharyngeal space tumors.

PURPOSE: Parapharyngeal space (PPS) tumors are rare, accounting for 0.5% of all head-and-neck masses. Surgery remains the standard treatment for most cases, including different approaches (cervical approach, parotidectomy, mandibulotomy, transoral/robotic). We report our experience in the management of PPS tumors, aiming to create a surgical algorithm on the base of tumor's radiological and clinical characteristics. MATERIALS AND METHODS: Critical retrospective analysis of patients with PPS neoplasms who underwent surgery at our Institute. Data were collected on patient age and sex, tumor location and size, preoperative investigations, surgical approaches, histopathology, complications and outcomes. RESULTS: Between January 2000 and July 2015, 53 patients were treated at our Institute. Salivary gland tumors were the most common neoplasms followed by neurogenic tumors. CT scan/MRI were the most used preoperative imaging studies. The cervical approach with or without parotidectomy is the most used, providing the best compromise between the need for radicality and low risk of damage to the neurovascular structures. Mandibulotomy is used whenever the mass extends to the cranial base, assuming a higher morbidity, a slower functional recovery and the need for tracheotomy. Recently, TORS has been used for tumors of the PPS with promising outcomes. CONCLUSIONS: PPS surgery includes a wide spectrum of approaches but it is still a matter of debate which one guarantees better functional and oncological outcomes. We report a surgical algorithm based on surgical invasiveness and tumor characteristics to standardize PPS tumors management. We also highlight the upcoming role of TORS in this field.

Role of EGFR as prognostic factor in head and neck cancer patients treated with surgery and postoperative radiotherapy: proposal of a new approach behind the EGFR overexpression.

In an era of personalized treatment, there is a great interest in identifying factors which might predict patient response to radiotherapy (RT). The role of epidermal growth factor receptor (EGFR) in head and neck squamous cell carcinoma (HNSCC) remains still controversial. We performed a retrospective analysis on the prognostic value of EGFR in HNSCC patients treated with surgery and postoperative RT through a semiquantitative immunohistochemical analysis of EGFR membrane expression. We retrospectively analyzed 65 HNSCC patients treated in our Institute from 1997 to 2003 who underwent adjuvant RT after surgery. Median follow-up was 43.5 months (range 0.2-173 months). None of these patients were treated with postoperative concomitant chemotherapy. Tumor samples were obtained from surgical specimens. Membrane features (intensity, extension) of EGFR expression were evaluated, and a statistical analysis (univariate and multivariate) was conducted to correlate these parameters with overall survival (OS) and disease-free survival (DFS). Patients with an intense and complete labeling of EGFR presented worse OS and DFS compared with groups obtained by all other possible combination, and the difference was borderline statistically significant (P = 0.08 for OS and P = 0.006 for DFS). Moreover, a stratification of patients was performed considering EGFR expression on the tumor tissue and classifying its distribution as "homogeneous" or "heterogeneous." We found that patients showing an "heterogeneous" EGFR expression distribution had worse OS and DFS compared to the "homogeneous" group of patients. Based on our results, EGFR expression, especially referring to membrane features (semiquantitative analysis), might have a prognostic value for OS and DFS in locally advanced HNSCC treated with surgery and adjuvant RT. Prospective trials could be useful to confirm the prognostic role of EGFR expression and also to assess a predictive role to select that might benefit from more aggressive treatments.

Algorithm to predict postoperative complications in oropharyngeal and oral cavity carcinoma.

BACKGROUND: Preoperative data in patients with oral cavity/oropharyngeal cancer may predict postoperative complications that may modify therapeutic choices and improve patient care. METHOD: We reviewed 320 consecutive patients with oral cavity/oropharyngeal cancer, operated on 2003 through 2006 at the European Institute of Oncology. By multivariate analysis of preoperative patient and tumor characteristics, we developed an algorithm to predict postoperative complications. We tested the algorithm on a new series of 307 patients operated on 2007 through 2010. RESULTS: The final algorithm used to produce a nomogram was comprised of: alcohol consumption (p = .01), site of primary (p = .03), interaction of clinical T classification to sex (p = .007), and type of neck dissection (p < .0001). The algorithm had good ability to predict complications (concordance index [c-index] 0.74) in the new series. CONCLUSION: The nomogram accurately predicts presurgical risk of postoperative local/systemic complications in patients with oral cavity/oropharyngeal cancer and can be used to adapt therapy to patient characteristics, optimize ward admissions, and improve care.

Hypercalcitoninemia and thyroid nodules: when cytology (still) matters.

Medullary thyroid carcinoma (MTC) can assume various cytomorphological and architectural forms, mimicking other thyroid and extra-thyroid tumors and rendering the cytological and histological diagnosis challenging. Consequently, measurement of calcitonin (CT) levels is generally considered to be more accurate than cytology in diagnosing MTC. Here, we report on a patient with a multinodular goiter and significantly elevated basal CT levels; based on cytology examination and CT immunocytostains, neither MTC nor C-cell hyperplasia was detected upon final histopathological examination. CT testing has a high false-positive rate and low positive predictive value for detecting clinically relevant MTC. Judicious integration of cytological examination with immunocytochemical stains (when needed) may be useful for selecting the most appropriate therapy and avoiding overtreatment (i.e., central neck lymph node dissection in the present case). This case demonstrates that cytological examination with ancillary techniques is still valuable in patients with thyroid nodules and suspicious MTC.

Transoral robotic surgery vs transoral laser microsurgery for resection of supraglottic cancer: a pilot surgery.

BACKGROUND: Transoral laser microsurgery (TLM) is a mature approach to supraglottic cancer, while transoral robotic surgery (TORS) is emerging. The present study compared these approaches. METHODS: The first 10 patients (2002-2005) given TLM were compared with the first 10 (2007-2011) given TORS for cT1-3 cN0-cN2c supraglottic cancer. RESULTS: A feeding tube was used in four TLM and seven TORS patients. Margins were more often positive, but operating times shorter, in TORS. All 10 TORS patients are without evidence of disease, but only six TLM patients remain disease-free after much longer follow-up. TORS was considerably less uncomfortable and fatiguing for the surgeon. CONCLUSIONS: TORS seems as safe and effective as TLM. Shorter TORS operating times are probably attributable to prior experience with TLM. For laryngeal exposure, length of tube placement and margin evaluability, TLM was superior; however, this may change as TORS develops and transoral robotic instruments are optimized.