Head and neck adult-type soft tissues sarcomas: survival analysis and comparison between the last two editions of the TNM staging system.

PURPOSE: Head and neck soft tissues sarcomas (HNSTS) are a heterogeneous group of rare tumours. The 8th edition of the TNM staging system (8TNM) considered these lesions separately for the first time. The aim of this study is to assess its effectiveness and identify the most significant prognostic factors for HNSTS. METHODS: A retrospective survival analysis on 101 HNSTS operated between 1995 and 2015 at the National Cancer Institute of Milan was carried out. The variables considered were pathological stage (according to both the 7TNM and 8TNM), site, histotype, depth, grading, surgical radicality, (neo)adjuvant radiotherapy and/or chemotherapy. RESULTS: According to the 7TNM, the T category distribution was 35 T1a, 23 T1b, 11 T2a, and 32 T2b. Applying the 8TNM, the distribution changed to 19 T1, 18 T2, 35 T3, and 29 T4. Five-year overall and disease-specific survivals were 74.3 and 76.2%, respectively. Univariate analysis demonstrated an increased hazard ratio (HR) for deep lesions invading adjacent structures, high-grade, surgery with close/microscopically positive margins, and chemotherapy. Multivariate analysis confirmed an increased HR for deep location and size > 5 cm, G2-G3 tumours, and marginal surgery. No significant difference was found among T categories of the 8TNM. CONCLUSION: The present study underlines the negative prognostic impact of depth, size > 5 cm, high grade, and marginal treatment for HNSTS. Our results did not allow to validate the 8TNM staging system since, apparently, it was not associated with meaningful prognostic stratification. Further studies with wider multicentric cohorts should, however, be performed to obtain more powerful statistical data.

Fascio-cutaneous-free flaps as primary reconstruction in salvage total laryngectomy.

INTRODUCTION: Salvage total laryngectomy (STL) is the most common treatment for recurrent laryngeal cancer after (chemo)-radiotherapy [(C)RT]. In this scenario, a higher rate of local wound complications, such as pharyngo-cutaneous fistula (PCF) and pharyngo-esophageal stenosis (PES), is generally expected. The aim of the present study is to evaluate outcomes using a standardized reconstructive protocol. METHODS: Between 2009 and 2019, patients undergoing STL after (C)RT were collected at two referral hospitals with the objective of evaluating surgical outcomes using a standardized reconstructive policy based on the use of fascio-cutaneous free flaps as inlay patch grafts and a long-lasting salivary bypass stent. RESULTS: Fifty-five patients (mean age, 66 years; male-to-female ratio, 8:1) were included in the study. Previous treatments were RT in 22 (40%) patients, CRT in 21 (38.2%), and partial laryngeal surgery followed by adjuvant (C)RT in 12 (21.8%). Reconstruction was accomplished by radial forearm and anterolateral thigh free flaps in 16 (29.1%) and 39 (70.9%) patients, respectively. Flap success rate was 98.2%. Concerning postoperative complications, we encountered 3 PCFs (5.4%) and 1 PES (1.8%). CONCLUSION: The standardized reconstructive protocol analyzed herein granted significantly lower rates of PCF and PES after STL compared with data available in the literature.

Management of loco-regionally advanced squamous laryngeal cancer in elderly patients.

PURPOSE: To describe the management and outcomes of loco-regionally advanced (stages III-IV) laryngeal cancer (LRALC) in elderly patients. METHODS: Clinical records of 88 LRALC patients treated at our Institution from 2002 to 2017 were retrospectively reviewed. Patients were divided in 2 subgroups: age > 65 years (elderly) and age ≤ 65 years (controls). Survivals were estimated with Kaplan-Meier method and compared with log-rank test, multivariate analysis were performed with Cox proportional hazard methods. RESULTS: Eighty-eight LRALC patients were included: 45 elderly and 43 controls. Median follow-up was 55.3 months. Median age was 66 years (range 41-84) in the overall population, 72 years (range 66-84) in the elderly cohort. The majority (98%) of elderly patients had at least one comorbidity (ACE27 1-3), while ACE27 was 0 in 37% of controls (p = 0.0001). ECOG PS was 0 in 42% of elderly vs 79% of controls (p = 0.0029). Clinical stage (TNM eighth edition) was III in 67%, IVA in 22% and IVB in 11%. Treatment consisted in total laryngectomy (TL) in 55%, chemo-radiation in 29%, exclusive radiotherapy in 9%, and conservative surgery in 7%. In elderly patients 2-year disease-free and overall survivals were 58% and 74%, respectively. Multivariate analysis performed on the overall group of 88 patients showed that age (HR 1.07, p = 0.0006) and TNM (for both 7th and 8th Editions HR 0.27 for stage III vs IV, p = 0.0005) maintained an independent statistical significant association with OS. CONCLUSIONS: In this monocentric cohort, age and TNM confirmed their independent prognostic role in LRALC patients. Organ-preservation is still an unmet need in a significant portion of elderly patients.

Matrix for Mucosal Regeneration in Transoral Glossectomy for Squamous Cell Carcinoma: Objective and Subjective Functional Evaluation.

BACKGROUND: Numerous options to manage local reconstruction following transoral partial glossectomy are possible. In this work, we present our experience using a matrix for mucosal regeneration, Integra®, after transoral resections of squamous cell carcinoma of the oral tongue. METHODS: A retrospective analysis of patients treated for tongue carcinoma and reconstruction with Integra®, from September 2017 to September 2022. Functional outcomes were evaluated by measuring swallowing and speech abilities, tongue motility, and subjective quality of life. RESULTS: The series accounts for 13 consecutive patients, staged from Tis to T3, no positive resection margins were found, average defect size was 17.8 cm2. The average histologically measured depth of invasion was 4.1 mm (range 2-12 mm), and no recurrences were observed during follow-up. All patients maintained excellent swallowing function, the average number of recognized words by an external listener during a phone call was 70.5 out of 75, the lingual motility test was good (a mean score of 4.5 out of 6 movements correctly executed) and subjective questionnaires results were optimal. Less satisfying functional results were recorded in elderly patients receiving a wider surgical resection. CONCLUSIONS: This reconstructive technique for allows obtaining optimal healing and functional outcomes in patients with tumors suitable for transoral glossectomy.

Radiation-Induced Oropharyngeal Squamous Cell Carcinoma: Case Report and Review of the Literature.

BACKGROUND: Radiation therapy (RT) is a mainstay for the treatment of head and neck (HN) cancers, with 80% of patients receiving such treatment. Radiation-induced malignancies represent a life-threatening long-term effect of RT, with an incidence of 0.5% to 15%. CASE DESCRIPTION: After 13 years, a 33-year-old woman treated with chemo-radiotherapy for nasopharyngeal carcinoma developed a locally advanced, radiation-induced, p16-negative oropharyngeal squamous cell carcinoma (SCC) at the base of the tongue. Chemo/immunotherapy was administered as a first-line treatment. Given the optimal response and the feasibility of surgery, after three cycles, the patient underwent a total glossectomy, bilateral neck dissection, and reconstruction with a thoraco-dorsal free flap. A histological examination found SCC with a residual cancer burden of 70% and free margins. DISCUSSION: The mechanisms responsible for carcinogenesis after RT are still not completely clear. Diagnosis may be challenging due to the previous treatment; growth patterns are unusual, and lymphotropism is lower. Prognosis is usually poor since surgical resectability is often not achievable. CONCLUSIONS: Radiation-induced malignancies are difficult to treat. Patient management should always be discussed at a multidisciplinary level. Future research is needed to assess whether the promising results of clinical studies with pre-operative immunotherapy in locally advanced HN SCC patients may be translated into radiation-induced cancers.

On the Dependency of the Electromechanical Response of Rotary MEMS/NEMS on Their Embedded Flexure Hinges' Geometry.

This paper investigates how the electromechanical response of MEMS/NEMS devices changes when the geometrical characteristics of their embedded flexural hinges are modified. The research is dedicated particularly to MEMS/NEMS devices which are actuated by means of rotary comb-drives. The electromechanical behavior of a chosen rotary device is assessed by studying the rotation of the end effector, the motion of the comb-drive mobile fingers, the actuator's maximum operating voltage, and the stress sustained by the flexure when the flexure's shape, length, and width change. The results are compared with the behavior of a standard revolute joint. Outcomes demonstrate that a linear flexible beam cannot perfectly replace the revolute joint as it induces a translation that strongly facilitates the pull-in phenomenon and significantly increases the risk of ruptures of the comb-drives. On the other hand, results show how curved beams provide a motion that better resembles the revolute motion, preserving the structural integrity of the device and avoiding the pull-in phenomenon. Finally, results also show that the end effector motion approaches most precisely the revolute motion when a fine tuning of the beam's length and width is performed.

Compartmental tongue surgery for intermediate-advanced squamous cell carcinoma: A multicentric study.

BACKGROUND: A multicentric study was conducted on technical reproducibility of compartmental tongue surgery (CTS) in advanced tongue cancers (OTSCC) and comparison to standard wide margin surgery (SWMS). METHODS: We studied 551 patients with OTSCC treated by CTS and 50 by SWMS. Oncological outcomes were analyzed. A propensity score was performed to compare survival endpoints for the two cohorts. RESULTS: In the CTS group, survival and prognosis were significantly associated with positive lymph-nodes, extranodal extension, depth of invasion and involvement of the soft tissue connecting the tongue primary tumor to neck lymph nodes (T-N tract), independently from the center performing the surgery. SWMS versus CTS showed a HR Cause-Specific Survival (CSS) of 3.24 (95% CI: 1.71-6.11; p < 0.001); HR Loco-Regional Recurrence Free Survival (LRRFS) of 2.54 (95% CI: 1.47-4.40; p < 0.001); HR Overall Survival (OS) of 0.11 (95% CI: 0.01-0.77; p = 0.03). CONCLUSION: Performing the CTS could provide better CSS and LRRFS than SWMS regardless of the center performing the surgery, in advanced OTSSC.

Oncological outcomes of compartmental surgery and wide local excision in oral tongue and floor of the mouth cancer.

OBJECTIVES: Oral tongue carcinomas represent more than half of the tumors arising in the oral cavity, a site with a high cancer specific mortality and impact on quality of life. Current guidelines are lacking for a standardized surgical approach of these tumors. The aim of this study is to compare two currently adopted surgical strategies, compartmental surgery (CTS) and wide local excision (WLE), with loco-regional control as the main oncological endpoint. MATERIALS AND METHODS: An observational retrospective multicentric study was carried out enrolling a cohort of patients affected by oral tongue or floor of the mouth squamous cell carcinoma and surgically treated in 4 international tertiary referral centers. Survival analysis was performed by propensity-score matching approach and multivariable Cox regression analysis. RESULTS: A cohort of 933 patients was enrolled. CTS was applied in 113 patients (12.1%) and WLE in 820 (87.9%). Analyzing a propensity-score matched cohort (98 CTS vs. 172 WLE) and applying a survival multivariable modeling strategy on the whole cohort, both confirmed that CTS and WLE are comparable and oncologically safe. Parameters such as number of positive lymph nodes, depth of invasion, and lymphovascular invasion still represent the key prognosticators. CONCLUSION: The main goals for surgical resection of oral cancer remain its three-dimensional circumferential clearance with adequate margins and en-bloc removal of the tumor-lymph node tract, independently of the technique adopted (CTS or WLE). Further prospective studies including quality of life evaluation are needed to better understand if one of these approaches can provide superior functional outcomes.

Comparison of Different Staging Systems Applied to a Cohort of Patients With Oral Tongue and Floor of the Mouth Cancer.

Purpose: The present work compares the effects produced by the application of the 7th edition of the tumor node metastasis (TNM) staging system (TNM7), 8th Edition (TNM8) with its two subsequent revisions, and pN-N+ classification on a cohort of patients with oral tongue and floor of the mouth cancer. Methods: A monocentric cohort of 148 patients was retrospectively analyzed. Patients were staged according to the TNM7, TNM8 and revisions, and pN-N+ classification. Stage migration was assessed and overall survival (OS) analyzed with the Kaplan-Meier method. The pT, pN, and stage stratification was evaluated with univariate and multivariate Cox regression and comparing adjacent categories with the log-rank method. Results: pT3-T4a categories showed significant differences in comparison to pT1-T2 for each staging metric employed in both uni- and multivariate analysis. When comparing adjacent pT categories, OS was significantly different only between pT2 and pT3 categories of the TNM8. Disproportionate patient distribution among pN categories was observed in the TNM8, and stratification was scarce. Conversely, in the pN-N+ classification the difference between pN2 and pN3a categories was significant. Only stage IVa reached statistical significance in TNM7, whereas stage III and above were significant in TNM8 and revisions in both uni- and multivariate analysis. However, no significant difference was noted comparing adjacent stages. Conclusion: The TNM8 pT classification differentiated low- from high-risk diseases. Nonetheless, it failed to separate pT1 from pT2 and pT3 from pT4a categories. Conversely, although TNM8 nodal staging was inaccurate, the number of metastatic lymph nodes was more valuable.

COVID-19 screening protocols for preoperative assessment of head and neck cancer patients candidate for elective surgery in the midst of the pandemic: A narrative review with comparison between two Italian institutions.

BACKGROUND: Preoperative screening had a key role in planning elective surgical activity for head and neck cancer (HNC) during the COVID-19 pandemic. METHODS: All patients undergoing surgery for HNC at two Italian referral hospitals (University of Padua and National Cancer Institute [NCI]) during the peak of the COVID-19 epidemic in Italy were included. Accuracy of screening protocols was assessed. RESULTS: In the Padua protocol, 41 patients were screened by pharyngeal swab. The entire sample (100%) was admitted to surgery, diagnostic accuracy was 100%. In the NCI protocol, 23 patients underwent a telephone interview, blood test, and chest CT. Twenty patients (87%) were negative and were directly admitted to surgery. In the remaining 3 (13%), pharyngeal swab was performed. The screening was repeated until a negative chest CT was found. Diagnostic accuracy was 85%. CONCLUSIONS: Dedicated screening protocols for COVID-19 allow to safely perform elective HNC surgery.

Herding or wisdom of the crowd? Controlling efficiency in a partially rational financial market.

Herding has often been blamed as one of the possible causes of market instabilities, ultimately yielding to bubbles and crushes. On the other hand, researchers hypothesized that financial systems may benefit from the so-called wisdom of the crowd. To solve this apparent dichotomy, we leverage a novel financial market model, where the agents form their expectations by combining their individual return estimation with the expectations of their neighbors. By establishing a link between herding, sociality, and market instabilities, we point out that the emergence of collective decisions in the market is not necessarily detrimental. Indeed, when all the agents tend to conform their expectations to those of one or few leaders, herding might dramatically reduce market efficiency. However, when each agent accounts for a plurality of opinions, thus following the wisdom of the crowd, market dynamics become efficient. Following these observations, we propose two alternative control strategies to reduce market instability and enhance its efficiency.

From head and neck lipoma to liposarcoma: a wide spectrum of differential diagnoses and their therapeutic implications.

PURPOSE OF REVIEW: To overview the array of differential diagnoses among lipomatous tumours of the head and neck with special focus on their evaluation, three-dimensional assessment, and their available treatments. RECENT FINDINGS: The head and neck is an infrequent localization for lipomatous tumours, even though they represent the most common mesenchymal lesions. Lipoma, spindle cell/pleomorphic lipoma (SC/PL), atypical lipomatous tumour/well differentiated liposarcoma (ALT/WDLPS), de-differentiated liposarcoma (DDLPS), myxoid liposarcoma (MLPS), and pleomorphic liposarcoma (PLPS) are the most distinctive histotypes. Lipoma and SC/PL present alterations of chromosomes 12 and 13, ALT/WDLPS and DDLPS both show the Mouse Double Minute 2 amplification, whereas MLPS presents a CHOP gene fusion. Diagnosis of PLPS is purely morphological as there is no pathognomonic genetic alteration identified to date. Radiological assessment can be challenging for the presence of nonadipose components within the lesion. Surgery is the mainstay of treatment, even though achieving true radicality in terms of a large cuff of healthy tissue surrounding the tumour is not always realistic in the head and neck. Adjuvant radiation, eventually in combination with systemic chemotherapy, has been shown to improve overall survival in patients with positive margins, high-grade, deep, and more than 5 cm lesions. Further studies should be aimed at the evaluation of the role of hadron therapy, as well as targeted drugs against overexpressed proteins. SUMMARY: Adequate differential diagnosis of the histotypes collected under the umbrella term of head and neck lipomatous tumours plays a fundamental role in treatment and follow-up of these lesions and requires specific expertise with referral to high-volume centres.

The transmanubrial osteomuscular-sparing approach: a valuable adjunct to the head and neck surgical armamentarium.

PURPOSE OF REVIEW: To describe and popularize the transmanubrial osteomuscular-sparing approach (TOSA) outside its original thoracic surgical field of application, based on the consideration that it could be of interest for the management of a number of head and neck cases in both elective and emergent scenarios. RECENT FINDINGS: The main advantages of TOSA compared with transclavicular techniques are its superb exposure of anatomic structures located at the level of the cervicothoracic junction, and superior postoperative aesthetic and functional outcomes. Recently, a number of studies have described the association of TOSA with other minimally invasive approaches, such as video-assisted thoracoscopic surgery and robotic hybrid approaches, with the aim of avoiding association of the transmanubrial route with anterior/posterior thoracotomies, or more extended surgeries, such as the trapdoor or hemiclamshell procedures. SUMMARY: TOSA, even though originally conceived to reduce the morbidity ensuing from classic transclavicular approaches for management of Pancoast tumors, may well play an important role in a number of head and neck surgical conditions, including those related to mediastinal goiter and thyroid cancer, management of stenosis and lesions of the thoracic trachea and esophagus, treatment of the junction between innominate, internal jugular, and subclavian veins, epiaortic arteries, thoracic duct, brachial plexus, and low sympathetic chain. Whenever comprehensive control of vascular and nonvascular structures of the upper mediastinal inlet is required, TOSA should be planned and performed by combining the expertise of cooperating professionals.

Unknown primary of the head and neck: a new entry in the TNM staging system with old dilemmas for everyday practice.

PURPOSE OF REVIEW: To summarize the most recent nuances in diagnosis, management, and prognostic stratification of carcinoma of unknown primary of the head and neck (CUPHN), in light of its recent re-assessment in the eighth edition of the TNM Classification Manual. RECENT FINDINGS: At least in Western Countries, most CUPHN are expected to be Human Papilloma Virus (HPV)-positive with an oropharyngeal origin. Their appropriate diagnosis starts with fine needle aspiration cytology and/or core biopsy of pathologic lymph node(s) with staining for p16 by immunohistochemistry and subsequent HPV detection by PCR. If these exams are negative (especially in Eastern Countries), in-situ hybridization for Epstein-Barr virus detection should be added. Thorough clinical examination should encompass white light videoendoscopy with the adjunction of bioendoscopic techniques (such as narrow band imaging). Radiologic workup (by CT, MR and/or PET) should be limited to cases that are persistently negative after comprehensive endoscopic evaluation. Invasive diagnostic procedures, such as unilateral or bilateral palatine tonsillectomy and base of tongue mucosectomy, may play a staging as well as a therapeutic role in CUPHN management. SUMMARY: Every effort should be made to identify and remove the primary site of a CUPHN: in doing so, possible subsequent de-intensification protocols by irradiation of the neck alone (with or without previous neck dissection according to the cN category, patient's risk profile, and general status) can be taken into consideration on a case-by-case basis.

Radiation-Induced Sarcoma of the Head and Neck: A Review of the Literature.

In the last decades, radiotherapy (RT) has become one of the cornerstones in the treatment of head and neck (HN) malignancies and has paralleled an increase in long-term patient survival. This lead to a concomitant increase in the incidence of radiation-induced sarcomas (RIS) of the irradiated field, with an annual rate up to 0.17%. The new techniques of irradiation do not seem to influence the risk of RIS of the HN (RISHN), which mainly develop within the middle-dose field. The median latency of RISHN after RT is 10-12 years and osteosarcoma is the most represented histotype, even though there is a high variability in time of occurrence and histological features observed. There is no clear evidence of predisposing factors for RISHN, and genetic findings so far have not revealed any common mutation. Early clinical diagnosis of RISHN is challenging, since it usually occurs within fibrotic and hardened tissues, while radiological findings are not pathognomonic and able to differentiate them from other neoplastic entities. Given the highly aggressive behavior of RISHN and its poor sensitivity to chemotherapy, radical surgery is the most important prognostic factor and the only curative option at present. Nevertheless, the anatomy of the HN district and the infiltrative nature of RIS do not always allow radical intervention. Therefore, a wise integration with systemic therapy and, when feasible, re-irradiation should be performed. Future findings in the genomic features of RISHN will be crucial to identify a possible sensitivity to specific drugs in order to optimize a multimodal treatment that will be ideally complementary to surgery and re-irradiation.

Endoscopic endonasal repair with polyethylene implants in medial orbital wall fractures: A prospective study on 25 cases.

The aim of the study was to assess the mid-term effectiveness and safety of an original technique consisting of reconstructing fractures of the medial wall of the orbit with porous polyethylene implants with an exclusive transnasal approach. Twenty-five patients were treated. Each patient underwent a pre-operative ophthalmologic evaluation and a CT scan. The surgery started with an anteroposterior ethmoidectomy of the fractured side; all the fractured bone fragments were removed and all usual landmarks of healthy bony margins were identified. A Medpor sheet was placed endoscopically to reconstruct the fractured wall. Each patient received an immediate postoperative CT scan, and was evaluated at day 1, 7, 30 and 6 months after surgery clinically and with an endoscopic examination. In all patients, preoperative enophthalmos and/or diplopia were corrected. The CT scans showed excellent reconstruction of the fractured bony walls. The immediate postoperative period was characterized by a very high degree of subjective comfort. No perioperative complications were detected. At the 6 months follow up, all meshes appeared covered by epithelialized mucosa at the endoscopic inspection, and clinical results were stable. Scars or lid complications are always prevented. The technique described has become the standard to treat medial wall fractures in our department.

Trismus, the first symptom in a challenging diagnosis of Tetanus.

Tetanus is a severe, life-threatening infectious disease present worldwide. The incidence of this disease is very low in developed countries, and practitioners are unfamiliar with its symptoms and signs, resulting in late diagnosis and low recovery rate. Furthermore, main symptoms, such as trismus, are often associated with several confounding factors: these may lead the physician to send patients towards an incorrect diagnostic management and the calling on of wrong specialists. This case focuses on the importance of considering tetanus in the differential diagnosis of trismus associated with systemic symptoms, and discusses the clinical implications of an initial wrong diagnostic pathway.