Real-World Outcomes of Inoperable and Metastatic Cutaneous Head and Neck Melanoma Patients.

OBJECTIVE: This study aims to describe the overall survival (OS) and to identify associated prognostic factors in patients with inoperable and metastatic cutaneous melanoma of the head and neck (H&N) region, undergoing modern systemic treatments. METHODS: This is a retrospective single institutional study. Data on all consecutive H&N melanoma patients treated with systemic oncologic treatments between 2015 and 2022 were collected from electronic medical files. Kaplan-Meier curves were used to describe survival and Cox regression analysis was used to identify patient and tumor factors associated with prognosis. RESULTS: A total of 144 patients were included. Median OS was 45 months (95% confidence interval [CI] 28-65 m). On univariable analysis for OS, the primary disease site, specifically the nape and neck (hazard ratio [HR] 3.3, 95% CI 1.4-7.7, p = 0.007), high Eastern Cooperative Oncology Group Performance Status ([ECOG-PS], HR 2.5, 95% CI = 1.9-3.3, p < 0.001), high lactate dehydrogenase (LDH) levels (HR 2.8, 95% CI = 1.7-4.6, p < 0.001), and treatment with targeted therapy (TT) as compared with immunotherapy (HR 2.6, 95% CI = 1.06-6.3, p = 0.03) were all associated with shorter OS. High-grade adverse events (AEs) were associated with a longer OS (HR 0.41, 95% CI = 0.25-0.68, p = 0.001). On multivariable analysis for OS, the ECOG-PS, LDH levels, site of disease, and the development of moderate-severe AEs remained significant. CONCLUSIONS: In the era of modern oncologic treatments, the prognosis of inoperable and metastatic cutaneous H&N melanoma aligns with other cutaneous melanomas. Primary tumor site of the nape and neck region emerges as a significant prognostic factor. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:2762-2770, 2024.

Virtual reality-based training and pre-operative planning for head and neck sentinel lymph node biopsy.

OBJECTIVE: Sentinel lymph node biopsy (SLNB) is crucial for managing head and neck skin cancer. However, variable lymphatic drainage can complicate SLN detection when using Single-Photon Emission Computed Tomography (SPECT) or lymphoscintigraphy. Virtual Reality (VR) can contribute to pre-operative planning by simulating a realistic 3D model, which improves orientation. VR can also facilitate real-patient training outside the operating room. This study explored using a VR platform for pre-operative planning in head and neck skin cancer patients undergoing SLNBs and assessed its value for residential training. MATERIALS AND METHODS: In this prospective technology pilot study, attending surgeons and residents who performed 21 SLNB operations on patients with head and neck skin cancers (81% males, mean age 69.2 ± 11.3) used a VR simulation model based on each patient's pre-operative SPECT scan to examine patient-specific anatomy. After surgery, they completed a questionnaire on the efficiency of the VR simulation as a pre-operative planning tool and training device for residents. RESULTS: The attending surgeons rated the VR model's accuracy at 8.3 ± 1.6 out of 10. Three-quarters (76%) of residents reported increased confidence after using VR. The physicians rated the platform's contribution to residents' training at 7.4 ± 2.1 to 8.9 ± 1.3 out of 10. CONCLUSION: A VR SLNB simulation can accurately portray marked sentinel lymph nodes. It was rated high as a surgical planning and teaching tool among attending surgeons and residents alike and may play a role in pre-operative planning and resident training. Further studies are needed to explore its applications in practice.

Is There a Role for Molecular Testing for Low-Risk Differentiated Thyroid Cancer? A Cost-Effectiveness Analysis.

Molecular testing for thyroid nodules has been rapidly developed in recent years, aiming to predict the presence of malignancy and aggressive features. While commonly utilized to predict malignancy, its role in guiding the management approach is still developing. The high cost of genetic tests and long-term sequences of thyroid cancer is limiting to real-life studies. Objective: To evaluate the cost effectiveness of molecular testing for low-risk differentiated thyroid cancer (lrDTC). Methods: We developed a Markovian decision tree model of a simulated lrDTC cohort, comparing two management strategies: (I) Conducting genetic tests (GT)-patients are stratified into three risk groups for distant metastasis by the identified molecular markers: low-, intermediate- and high-risk molecular profile; followed by management accordingly: patients with low-risk will undergo hemithyroidectomy (HT), patients with intermediate-risk will undergo total thyroidectomy (TT), and high-risk patients will undergo TT with central neck dissection; (II) Without genetic tests (wGT)-all patients will undergo HT according to the ATA recommendations for lrDTC. Outcomes were measured as quality-adjusted life years (QALYs) and costs of each strategy. Results: GT was found as cost effective, leading to a gain of 1.7 QALYs with an additional cost of $327 per patient compared to wGT strategy. This yielded an incremental cost-effectiveness ratio of $190 per QALY. Sensitivity analysis demonstrated robust results across the variables' ranges. The most impactful variable was the benefit from performing TT rather than HT for intermediate to high-risk patients. Conclusions: Our model found that molecular testing for lrDTC is cost-effective, allowing tailored management according to the patient's personal risk level reflected in the genetic profile, hence improving outcomes.

Is molecular testing in patients with low risk papillary thyroid carcinoma justified? A Markovian model.

BACKGROUND: Current guidelines consider all cases of papillary thyroid carcinoma (PTC) smaller than 4 cm and without extrathyroidal extension (ETE) and/or lymph node metastases as belonging to the same prognostic group, and therefore the recommendation is for uniform treatment. Xing draws our attention to a small subgroup with Duet Mutations (BRAF E600 and TERT 3636 genes) that are aggressive biologically and should be treated differently. Thus the aim of the present study is to test the validity of this recommendation. METHODS: A Markovian Model is used to evaluate the above hypothesis. RESULTS: A Monte Carlo sensitivity test shows a 5.6 year survival advantage for patients with low-grade PTC, who have the Duet Mutations, and were treated by total thyroidectomy rather than hemithyroidectomy. CONCLUSIONS: We conclude that there is a place for routine molecular tests in low-risk patients with PTC.

Comparison of lateral neck X-ray to neck CT in patients with suspicious bone impaction: "Old habits die hard".

OBJECTIVE: Bone impaction (BI) is a common cause for emergency room visits. Among foreign bodies, fish bone is considered the most common. The sensitivity of symptoms in predicting BI is relatively low, making imaging a central tool to aid diagnosis. Current imaging practices include both neck plain film radiography and none-contrast CT scans of the neck. We evaluated the accuracy of neck plain film radiography and CT scans of the neck for the diagnosis of BI. METHODS: Retrospective review of all patients who presented to the emergency room between 2009 and 2016 with a suspicious history of BI whom underwent plain film neck radiography or CT. All Images were reviewed by two neuro-radiologist blinded to the clinical symptoms and findings. Symptoms, clinical findings and images results were compared to the final diagnosis. RESULTS: 89 patients (30.7%), out of 290 patients who presented with complaints of BI, were diagnosed with BI. Mean age was 44.7 years old. Plain film neck radiography failed to predict BI (sen. 14.4%, spe 89.8% accuracy 63.2%), neck CT has an improved accuracy and sensitivity in locating BI (sen. 83.3%, spe. 94.1% accuracy 92.5%). Interobserver agreement between the two neuro-radiologists was moderate (0.46) and substantial (0.77) in neck radiography and CT images, respectively. Neck radiography missed 60 (out of 61) oropharyngeal BI's. CONCLUSION: Neck radiography has high inter-observer variability and low sensitivity for the diagnosis of BI. Neck CT should be the first imaging modality in patients with suspicious complaints for BI and negative physical exam.

Early vs. late tracheostomy in ventilated COVID-19 patients - A retrospective study.

BACKGROUND: Tracheostomy is one of the most common surgical procedures performed on ventilated COVID-19 patients, yet the appropriate timing for operating is controversial. OBJECTIVES: Assessing the effect of early tracheostomy on mortality and decannulation; elucidating changes in ventilation parameters, vasopressors and sedatives dosages immediately following the procedure. METHODS: A retrospective cohort of 38 ventilated COVID-19 patients, 19 of them (50%) underwent tracheostomy within 7 days of intubation (early tracheostomy group) and the rest underwent tracheostomy after 8 days or more (late tracheostomy group). RESULTS: Decannulation rates were significantly higher while mortality rates were non-significantly lower in the early tracheostomy group compared with the late tracheostomy group (58% vs 21% p < 0.05; 42% vs 74% p = 0.1, respectively). Tidal volume increased (446 ml vs 483 ml; p = 0.02) while PEEP (13 cmH20 vs 11.6 cmH2O, p = 0.04) decreased at the immediate time following the procedure. No staff member participating in the procedures was infected with SARS-CoV-2 virus. CONCLUSION: Early tracheostomy might offer improved outcomes with higher decannulation rates and lower mortality rates in ventilated COVID-19 patients, yet larger scale studies are needed. Most likely, early exposure to COVID-19 patients with appropriate personal protective equipment during open tracheostomy does not put the surgical team at risk.

Human Nasal and Lung Tissues Infected Ex Vivo with SARS-CoV-2 Provide Insights into Differential Tissue-Specific and Virus-Specific Innate Immune Responses in the Upper and Lower Respiratory Tract.

The nasal mucosa constitutes the primary entry site for respiratory viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While the imbalanced innate immune response of end-stage coronavirus disease 2019 (COVID-19) has been extensively studied, the earliest stages of SARS-CoV-2 infection at the mucosal entry site have remained unexplored. Here, we employed SARS-CoV-2 and influenza virus infection in native multi-cell-type human nasal turbinate and lung tissues ex vivo, coupled with genome-wide transcriptional analysis, to investigate viral susceptibility and early patterns of local mucosal innate immune response in the authentic milieu of the human respiratory tract. SARS-CoV-2 productively infected the nasal turbinate tissues, predominantly targeting respiratory epithelial cells, with a rapid increase in tissue-associated viral subgenomic mRNA and secretion of infectious viral progeny. Importantly, SARS-CoV-2 infection triggered robust antiviral and inflammatory innate immune responses in the nasal mucosa. The upregulation of interferon-stimulated genes, cytokines, and chemokines, related to interferon signaling and immune-cell activation pathways, was broader than that triggered by influenza virus infection. Conversely, lung tissues exhibited a restricted innate immune response to SARS-CoV-2, with a conspicuous lack of type I and III interferon upregulation, contrasting with their vigorous innate immune response to influenza virus. Our findings reveal differential tissue-specific innate immune responses in the upper and lower respiratory tracts that are specific to SARS-CoV-2. The studies shed light on the role of the nasal mucosa in active viral transmission and immune defense, implying a window of opportunity for early interventions, whereas the restricted innate immune response in early-SARS-CoV-2-infected lung tissues could underlie the unique uncontrolled late-phase lung damage of advanced COVID-19. IMPORTANCE In order to reduce the late-phase morbidity and mortality of COVID-19, there is a need to better understand and target the earliest stages of SARS-CoV-2 infection in the human respiratory tract. Here, we have studied the initial steps of SARS-CoV-2 infection and the consequent innate immune responses within the natural multicellular complexity of human nasal mucosal and lung tissues. Comparing the global innate response patterns of nasal and lung tissues infected in parallel with SARS-CoV-2 and influenza virus, we found distinct virus-host interactions in the upper and lower respiratory tract, which could determine the outcome and unique pathogenesis of SARS-CoV-2 infection. Studies in the nasal mucosal infection model can be employed to assess the impact of viral evolutionary changes and evaluate new therapeutic and preventive measures against SARS-CoV-2 and other human respiratory pathogens.

Is parotidectomy justified in elderly patients with pleomorphic adenoma? A decision analysis model.

PURPOSE: The value of parotidectomy in older patients is unclear. This study presents a decision model to help resolve this question. MATERIALS & METHODS: A Markov model with Monte Carlo simulation was used to compare outcomes in patients of different ages with pleomorphic adenoma of the parotid gland treated by surgery or surveillance. RESULTS: In 30-year-old patients, surgery conferred a 3.5-year gain in life expectancy whereas in 75-year-olds, it was only 0.74 months. The expected rate of malignant transformation at age 30 years was 6.5% after surgery and 26.5% after surveillance; at age 65, corresponding rates were 0.8% and 10.7%. Sensitivity analysis showed that age was the only parameter that significantly contributed to life expectancy. The benefit of surgery was restricted in older patients. CONCLUSION: Our Markov decision-analysis model suggests that patients older than 65 years with pleomorphic adenoma have a limited survival advantage with surgery compared to surveillance.

Trans-canal endoscopic ear surgery and canal wall-up tympano-mastoidectomy for pediatric middle ear cholesteatoma.

PURPOSE: To evaluate clinical parameters, outcomes and complications of transcanal endoscopic ear surgeries (EES) and canal wall-up tympano-mastoidectomy (CWU) for middle ear cholesteatoma in children and to compare between the two surgical approaches. METHODS: A retrospective chart review of all children (< 16 years) who underwent surgery for cholesteatoma involving the middle ear only with a minimal follow-up period of 12 months. Demographic features, site and extent of disease, outcome and complications were reviewed and compared between the groups. RESULTS: Thirty EES and 19 CWU were included. The overall disease relapse rates in the EES and CWU groups were 20% (n = 6, residual rate = 10%, recurrence rate = 10%) and 47% (n = 9, residual rate = 11%, recurrence rate = 37%), respectively (p = 0.04), with mean duration of follow-up of 32.6 and 37.2 months, respectively. In the EES and CWU groups, the most common site of residual disease was the mastoid cavity/antrum (n = 2, 66% and n = 2, 100%, respectively). Most recurrences involved the epitympanum and extended into the tympanic cavity (n = 2, 66%) in the EES group and into the tympanic cavity, posterior mesotympanum and mastoid cavity/antrum (n = 3, 43%, each) in the CWU group. The overall complication rates in the EES and CWU groups were 10% (n = 3) and 11% (n = 2), respectively (p = 0.61). CONCLUSIONS: Endoscopic ear surgeries in children were found to be an acceptable and safe technique for the treatment of cholesteatoma limited to the middle ear cavity. A better overall success rate and a similar complication rate were found in the EES group when compared to CWU.