Improving the TIR3B oncological stratification: try to bridge the gap through a comprehensive presurgical algorithm.

PURPOSE: Indeterminate cytology still puzzles clinicians, due to its wide range of oncological risks. According to the Italian SIAPEC-IAP classification, TIR3B cytology holds up to 30% of thyroid cancer, which justifies the surgical indication, even if more than half of cases do not result in a positive histology. The study aim is to identify potential clinical, ultrasound or cytological features able to improve the surgical indication. METHODS: Retrospective analysis. A consecutive series of TIR3B nodules referred to the Endocrine Unit of Careggi Hospital from 1st May 2014 to 31st December 2021 was considered for the exploratory analysis (Phase 1). Thereafter, a smaller confirmatory sample of consecutive TIR3B diagnosed and referred to surgery from 1st January 2022 to 31st June 2022 was considered to verify the algorithm (Phase 2). The main clinical, ultrasound and cytological features have been collected. A comprehensive stepwise logistic regression was applied to build a prediction algorithm. The histological results represented the final outcome. RESULTS: Of 599 TIR3B nodules referred to surgery, 451 cases were included in the exploratory analysis. A final score > 14.5 corresponded to an OR = 4.98 (95% CI 3.24-7.65, p < 0.0001) and showed a PPV and NPV of 57% and 79%, respectively. The Phase 2 analysis on a confirmatory sample of 58 TIR3B cytology confirmed that a threshold of 14.5 points has a comparable PPV and NPV of 53% and 80%, respectively. CONCLUSIONS: A predictive algorithm which considers the main clinical, US and cytological features can significantly improve the oncological stratification of TIR3B cytology.

Will a tumor pandemic come after the COVID-19 pandemic? Head and Neck cancer perspective.

The COVID-19 pandemic demands a reassessment of head and neck oncology treatment paradigms by posing several challenges for oncology services, with unprecedented pressure on the regional health care system. Since February 2020 this has severely disrupted health-care services, leading to accumulating clinic caseload and substantial delays for operations. The head and neck cancer services have been faced with the difficult task of managing the balance between infection risk to health-care providers and the risk of disease progression from prolonged waiting times. Herein, we share our experience in Firenze (Italy) and propose our action plan on the management of head and neck cancer services via multi-institution collaboration.

Impact of COVID-19 on otolaryngology in Italy: a commentary from the COVID-19 task force of the Young Otolaryngologists of the Italian Society of Otolaryngology.

OBJECTIVE: The ongoing pandemic of coronavirus disease 2019 is having a dramatic effect on most medical disciplines. Otolaryngology Head and Neck Surgery is one of the most engaged disciplines, and otolaryngology specialists are facing a radical change of their role and daily activities that will have severe impact on the return to the ordinary. In this paper, the COVID-19 Task Force of the Young Otolaryngologists of the Italian Society of Otolaryngology comment on the changes that occurred for otolaryngology in Italy during the pandemic. Changes include organizational rearrangement of Otolaryngology Units, with merges and closures that affected a significant portion of them; reallocation of otolaryngology personnel, mainly to COVID-19 wards; reduction of elective clinical and surgical activity, that was mainly limited to oncology and emergency procedures; and execution of screening procedures for SARS-CoV-2 among healthcare providers and patients in otolaryngology units in Italy.

How to avoid life-threatening complications following head and neck space infections: an algorithm-based approach to apply during times of emergency. When and why to hospitalise a neck infection patient.

BACKGROUND: Head and neck space infections present with a potential mortality rate of 40-50 per cent. This paper proposes an algorithm-based management of head and neck space infection to prevent life-threatening events. METHODS: A total of 225 patients with head and neck space infection were prospectively analysed at our institution. An experimental scoring system determined the level of clinical risk for the development of major complications. Accordingly, patients were classified into three risk groups: low-, intermediate- and high-risk. RESULTS: Only intermediate- and high-risk patients were hospitalised. Intermediate-risk patients received intravenous medical therapy with daily re-evaluation; 18 of them required delayed surgery. Of the high-risk patients, three required immediate surgical treatment and five received delayed surgery, while in five cases medical therapy was the only treatment received. Low-risk patients were treated in an out-patient setting. CONCLUSION: The algorithm-based management of head and neck space infection was successful in enabling the avoidance of lethal complications onset.

Potential use of acupuncture in the treatment of first bite syndrome.

OBJECTIVES: First bite syndrome (FBS) is an early postoperative pain syndrome characterized by the sudden onset of pain in the parotid region at the first bite of each meal. The etiology is not certain, hence a standardized therapy does not exist. METHODS: A 50-year old woman referred to us complaining of a swelling in the right parotid region. Fine-needle aspiration biopsy (FNAB) was diagnostic for pleomorphus adenoma of the deep lobe of the parotid gland. A 50-year old man presented with a mass in the right side of the neck, FNAB was diagnostic for parapharyngeal space neurinoma. The first patient was submitted to total parotidectomy with facial nerve preservation, the second to extracapsular dissection of the tumor. A week after surgery both patients developed FBS. A qualitative/quantitative description of pain was obtained by means of a self-coded questionnaire. The score ranges from 8 to 44, corresponding to the lowest and the highest discomfort possible, respectively. Acupuncture was used to treat these 2 patients. The treatment protocol comprised 6 sessions, one per week, lasting 30 minutes each. RESULTS: Our questionnaire was administered before and after treatment and the score dropped from 33 to 25 in the female, from 30 to 15 in the male patient. CONCLUSION: FBS is a complication of upper cervical surgery with a high morbidity rate. We describe the first two cases of FBS that were successfully treated with acupuncture in our ENT department. We believe that this procedure may represent a valid therapeutic alternative in the future.

Detection of putative stem cell markers, CD44/CD133, in primary and lymph node metastases in head and neck squamous cell carcinomas. A preliminary immunohistochemical and in vitro study.

OBJECTIVES: Investigators hypothesized that cancer stem cells (CSCs) could play a role in determining cancer progression by metastasizing to cervical lymph node (N+) and then influencing prognosis of head and neck squamous cell carcinomas (HNSCCs) patients. DESIGN: To identify CSCs in HNSCCs and their clonogenic capacity. SETTING: In vitro study. PARTICIPANTS: Putative CSCs from 29 primary HNSCCs and 19 corresponding node metastases were analyzed. MAIN OUTCOME MEASURES: Immunohistochemical (IHC) was performed, and CSCs' clonogenic in vitro capacity was tested; ones epithelial nature of cancer cells forming colonies was confirmed by a second IHC, fluorescence-activated cell sorting (FACS) analysis helped in counting CD44/CD133-CSCs markers percentage expression in HNSCC tumour-derived cultures. RESULTS: Immunohistochemical showed CD44 (93.1%) and CD133 (10.34%) expression; FACS-analysis showed the enrichment of CD44/CD133 cancer cells, with the highest clonogenic capacity of CD44+-subpopulation; a higher CD44 rates were documented from N+ subcultures than from original tumours (P < 0.05). CONCLUSIONS: A putative cancer stem-like cell population is detectable in HNSCCs, and our findings show their in vitro clonogenic capacity by demonstrating that CD44+-cultured cells are the main population proliferating obtained by N+ HNSCC metastases, emphasizing their possible role in tumour progression.

Mesenchymal stem cells are enriched in head neck squamous cell carcinoma, correlates with tumour size and inhibit T-cell proliferation.

BACKGROUND: Cancer is a multifactorial disease not only restricted to transformed epithelium, but also involving cells of the immune system and cells of mesenchymal origin, particularly mesenchymal stem cells (MSCs). Mesenchymal stem cells contribute to blood- and lymph- neoangiogenesis, generate myofibroblasts, with pro-invasive activity and may suppress anti-tumour immunity. METHODS: In this paper, we evaluated the presence and features of MSCs isolated from human head neck squamous cell carcinoma (HNSCC). RESULTS: Fresh specimens of HNSCC showed higher proportions of CD90+ cells compared with normal tissue; these cells co-expressed CD29, CD105, and CD73, but not CD31, CD45, CD133, and human epithelial antigen similarly to bone marrow-derived MSCs (BM-MSCs). Adherent stromal cells isolated from tumour shared also differentiation potential with BM-MSCs, thus we named them as tumour-MSCs. Interestingly, tumour-MSCs showed a clear immunosuppressive activity on in vitro stimulated T lymphocytes, mainly mediated by indoelamine 2,3 dioxygenase activity, like BM-MSCs. To evaluate their possible role in tumour growth in vivo, we correlated tumour-MSC proportions with neoplasm size. Tumour-MSCs frequency directly correlated with tumour volume and inversely with the frequency of tumour-infiltrating leukocytes. CONCLUSIONS: These data support the concept that tumour-MSCs may favour tumour growth not only through their effect on stromal development, but also by inhibiting the anti-tumour immune response.

Is elective neck dissection necessary in cases of laryngeal recurrence after previous radiotherapy for early glottic cancer?

OBJECTIVES: To assess the clinical utility of elective neck dissection in node-negative recurrent laryngeal carcinoma after curative radiotherapy for initial early glottic cancer. METHODS: A retrospective review was undertaken of 110 consecutive early glottic cancer patients who developed laryngeal recurrence after radiotherapy (34 recurrent T1, 36 recurrent T2, 29 recurrent T3 and 11 recurrent T4a) and received salvage laryngeal surgery between 1995 and 2005. RESULTS: Six patients presented with laryngeal and neck recurrence and underwent salvage laryngectomy with therapeutic neck dissection, 97 patients with recurrent node-negative tumours underwent salvage laryngeal surgery without neck dissection and only 7 underwent elective neck dissection. No occult positive lymph nodes were documented in neck dissection specimens. During follow up, only three patients with neck failure were recorded, all in the group without neck dissection. There was no significant association between the irradiation field (larynx plus neck vs larynx) and the development of regional failure. A higher rate of post-operative pharyngocutaneous fistula development occurred in the neck dissection group than in the group without neck dissection (57.2 per cent vs. 13.4 per cent, p = 0.01). Multivariate logistic regression analysis showed that early (recurrent tumour-positive, node-positive) or delayed (recurrent tumour-positive, node-negative) neck relapse was not significantly related to the stage of the initial tumour or the recurrent tumour. An age of less than 60 years was significantly associated with early neck failure (recurrent tumour-positive, node-positive). CONCLUSION: Owing to the low occult neck disease rate and high post-operative fistula rate, elective neck dissection is not recommended for recurrent node-negative laryngeal tumours after radiation therapy if the initial tumour was an early glottic cancer.

Salvage surgery after unsuccessful radiotherapy in early glottic cancer.

Surgery is the main therapeutic option to control recurrent laryngeal cancer after radiotherapy (RT) relapse. Most RT-recurred cancer is treated aggressively; although, conservative laryngeal surgery was attempted in selected cases. Here, we report our experiences with salvage laryngeal surgery for early glottic cancers that did not respond to RT. We analyzed files from 1980 to 2006 and selected 173 patients surgically treated for a RT-failed early glottic carcinoma (stage I-II according to 2010 TNM: 114 T1N0, 59 T2N0). Among them, 47 patients (27%) underwent a salvage partial laryngectomy (SPL) and 126 (73%) had a salvage total laryngectomy (STL). When compared with initial T staging, we found 61% of lesions were up-staged, 31% had the same staged lesion, and only 8% were down-staged (according to rTNM). No statistically significant differences were found in terms of disease-free survival and overall survival when SPL and STL patients were compared. Univariate analysis showed that T, rT, and rTNM were prognostic factors for overall survival (p = 0.045, p = 0.028, and p = 0.037, respectively); yet, these significances were lost in multivariate analysis. Our results suggest that salvage surgery is feasible in most cases of RT-recurred early glottic cancer; although, a conservative approach achieves good oncological and functional results only in select RT-recurred patients.

Effectiveness and pitfalls of elective neck dissection in N0 laryngeal cancer.

The aim of the study was to evaluate the efficacy and potential pitfalls of selective neck dissection of levels II-IV in controlling occult neck disease in clinically negative neck (cN0) of patients with laryngeal squamous cell carcinoma. Charts of 96 consecutive cN0 laryngeal cancer patients undergoing 122 neck dissections at the University of Florence from January 2000 to December 2004 were reviewed. N0 neck was defined with contrast enhanced computed tomography scan. Occult neck disease rate was 12.5%, involvement per level was: 47.6% at level II, 38.1% at level III, 9.5% at level IV. Six patients developed neck recurrence (6.25%) after selective neck dissection of levels II-IV within the first two years after treatment. In conclusion, selective neck dissection of levels II-IV is effective in N0 laryngeal squamous cell carcinoma; posterior limits of surgical resection are missing therefore if post-operative radiation is required, the field should be extended beyond the dissected levels. The low incidence of occult neck disease indicates the need to refine treatment strategy, restricting elective neck dissection only to supraglottic T2 with epilaryngeal involvement, supraglottic T3-4 and glottic T4 tumours, and considering a "wait and see" protocol implemented with imaging techniques and cytological assessments for other lesions.