We present a pedagogical derivation of the Hartree–Fock equations using the second-quantization atomic-orbital density-matrix formalism developed by Kjærgaard, Jørgensen, Olsen, Coriani, and Helgaker for AO-based response theory. The purpose is to introduce an alternative derivation of the Hartree–Fock equation, showing that the standard AO Hartree–Fock stationarity condition follows naturally from the exponential parametrization of the one-particle density matrix in a nonorthogonal AO basis. This route provides a compact bridge between elementary Hartree–Fock theory and the density-matrix machinery used in modern response theory and linear-scaling formulations.

INTRODUCTION:Endoscopic surgery of T1a glottic squamous cell carcinoma (SCC) is believed to have advantages compared to radiotherapy (RT), including short duration, cost-effectiveness, repeatability, and RT reserved for second tumors/failures. The equality of tumor control probability after treatments is unresolved. METHODS:In the DAHANCA 27 phase II study, selected Danish patients suspected of T1a glottic SCC between 2012 and 2016 were offered one-step diagnostic and curatively intended transoral laser microsurgery (TLM). The 5-year outcome was compared to a 2003-2012 national cohort of T1a glottic SCC patients treated with accelerated RT (accRT). RESULTS:The TLM (n = 94) treatment included cordectomy type I (n = 44), II (n = 38), and III (n = 12). Failure was observed in 10/94 TLM and 36/534 accRT patients, resulting in 1 and 23 laryngectomies, respectively. The 5-year laryngectomy-free disease-specific survival was TLM 97.9% and accRT 94.6%, HR: 0.37 (0.09, 1.54). CONCLUSIONS:Primary TLM for selected T1a glottic SCC patients is an organ preserving treatment with high disease control comparable to accRT.

PURPOSE:To examine patient-centred outcome following endoscopic treatment of central airway stenosis in terms of days alive and out of hospital (DAOH), need for re-intervention, and complications, with reference to aetiology of disease and applied treatment methodology. METHODS:Analyses were based on data from consecutive adult patients treated endoscopically for benign central airway obstruction at Aarhus University Hospital from 2012 to 2022, with a minimum follow-up of one year. DAOH was calculated for 30 and 365 days. Complications were graded based on the Clavien-Dindo classification. Univariate and multivariate analyses were performed to identify predictors for DAOH, re-intervention and complications. RESULTS:82 consecutive adult patients underwent endoscopic treatment during the period of inclusion, comprising a total of 175 dilatations, 42 benign tumour resections, and 67 stent insertions. Multiple interventions and short re-intervention intervals was more likely amongst patients reporting significant preoperative dyspnoea or requiring preoperative respiratory support, as well as patients treated with endoscopic insertion of silicone stents. The overall complication rate per procedure was 11.7%, and complications were more likely to occur in patients with high age, high BMI and comorbidity. Overall DAOH during the first year after intervention was 343 days, lowest amongst patients with tracheobronchomalacia or severe airway stenosis, and in those who underwent endoscopic stent insertion. CONCLUSION:Endoscopic treatment is a safe and viable intervention in the management of benign central airway obstruction in adults with few complications and a high overall outcome.

Importance:Early-stage oropharyngeal squamous cell carcinoma (OPSCC) is challenging to diagnose using clinical examination and cross-sectional imaging. Ultrasonography performed transorally can provide high-resolution images of oropharyngeal structures; however, whether it improves diagnostic evaluation of patients with suspected OPSCC is unknown, and yet there is a need for improved early detection and T staging. Objectives:To compare the accuracy of clinical examination, ultrasonography, and magnetic resonance imaging (MRI) in detection of oropharyngeal tumors. Design, Setting, and Participants:This multicenter diagnostic clinical trial was conducted in the outpatient clinics of 3 tertiary cancer centers. Consecutive patients with suspected OPSCCs or neck metastases (without visible primary tumors) were screened from February 1, 2023, to June 30, 2024, and those eligible after a clinical examination by a head and neck surgeon were included. Exclusion criteria were a prior head and neck cancer diagnosis or a known histopathologically or imaging-verified oropharyngeal tumor present. Data were analyzed from August 1 to October 31, 2024. Intervention:Surgeon-performed transoral and transcervical ultrasonography of the oropharynx during initial clinical examination followed by cross-sectional imaging (MRI) that was evaluated blinded to results of ultrasonography and histopathologic testing. Main Outcome and Measure:Oropharyngeal tumor detection with reference to final histopathologic results (presence or absence of an oropharyngeal tumor). Results:The study included 162 participants (median [range] age, 63 [32-85] years; 58 female [35%] and 105 male [65%]), of whom 106 (65%) had an oropharyngeal tumor (OPSCC, 95 [59%]; lymphoma, 7 [4%]; other type, 4 [5%]). Ultrasonography had significantly higher overall accuracy (139 patients [86%]) in correctly diagnosing patients compared to clinical examination (110 [68%]; odds ratio [OR], 0.31; 95% CI, 0.18-0.52) and MRI (123 [76%]; OR, 0.48; 95% CI, 0.28-0.82). The sensitivity of the 3 diagnostic methods to detect oropharyngeal tumors was similar (ultrasonography, 95 patients [90%]; clinical examination, 87 [82%]; MRI, 97 [92%]); however, ultrasonography demonstrated nearly twice the level of specificity in the 56 patients without tumors (44 patients [79%] vs 23 [41%] and 26 [46%], respectively). Conclusions and Relevance:This diagnostic clinical trial found that surgeon-performed transoral and transcervical ultrasonography in patients with suspected OPSCC provided higher diagnostic accuracy than clinical examination alone or MRI. Ultrasonography improves the clinical evaluation of suspected oropharyngeal cancers by providing higher diagnostic certainty.

Chronic obstructive sleep apnoea (OSA) is a common disease in Denmark but is still grossly underdiagnosed. This is concerning, as OSA predisposes to serious conditions such as hypertension, type 2 diabetes, cardiovascular disease, and early death. Awareness of OSA and identification of patients suspected of OSA is of utmost importance in order to initiate relevant treatment and prevent long-term morbidity and mortality. Primary treatment of OSA in Denmark is continuous positive airway pressure (CPAP), while surgery and mandibular advancement devices are the first choice for selected patients and should always be considered for patients who fail CPAP treatment, as argued in this review.

The paradigm for management of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (HPV + OPC) has evolved significantly in recent years. Following the interim futility analysis of NRG HN005, which reaffirmed standard-dose cisplatin-based chemoradiation as the standard of care in the nonsurgical setting, this review examines whether surgical approaches now represent the most viable path to treatment deintensification for appropriate patients with HPV + OPC. In this narrative review, we summarize data from key surgical deintensification clinical trials, discuss surgeon credentialing considerations, and review emerging technologies that may further refine patient selection and treatment response assessment.

This study protocol for a prospective, multicenter, diagnostic, clinical trial describes the integration of transoral and transcervical ultrasonography (US) in the initial clinical work-up of patients referred to tertiary head and neck cancer centers with suspected oropharyngeal cancer. The study evaluates the blinded detection rate of oropharyngeal tumors and their US-estimated size and T-stage before histopathology and cross-sectional imaging are available. Magnetic resonance imaging (MRI) scans will be prospectively rated while blinded to T-site histopathology and US. The primary outcome measures of diagnostic accuracy, including sensitivity, specificity, positive and negative predictive values, and overall accuracy, will be reported for both US and MRI. A sub-analysis of prospectively rated 18F-Fluorodeoxyglucose (FDG) positron emission tomography/computerized tomography (PET/CT) scans in patients with clinically suspected unknown primary tumors will also be compared to US and MRI. Secondary outcome measures, including a comparison of tumor size estimation between US, MRI, and CT, will also be reported. This prospective multicenter study will provide clinically impactful information regarding the use of transoral and transcervical US for the diagnostic work-up of oropharyngeal cancer.

Background Operation with a 3D exoscope has recently been introduced in clinical practice. The exoscope consists of two cameras placed in front of the operative field. Images are shown on a large 3D screen with high resolution. The system can be used to enhance precise dissection and provides new possibilities for improved ergonomics, fluorescence, and other optical-guided modalities. Methods Initial experience with the ultra-high-definition (4K) 3D exoscope in thyroid and parathyroid operations. The exoscope (OrbEye TM ) was mounted on a holding system (Olympus). Results We used the exoscope in parathyroidectomy (N = 6) and thyroidectomy (N = 6). Immediate advantages and disadvantages were discussed and recorded. The learning curve for use of the exoscope may be shorter for surgeons with training in endoscopic or robotic procedures. There may be improved ergonomics compared with normal open-neck operations. Further, the optical guided operations can be used with fluorescence and have potential for different on-lay techniques in the future. The 4 K 3D image quality is state-of-art and is highly appreciated during fine surgical dissection and eliminates the need for loupes. Conclusion In several ways, using the ORBEYE™ in thyroid and parathyroid surgery provides the surgical team with a new and enhanced experience. This includes improved possibility for teaching, surgical ergonomics, and a 4K 3D camera with a powerful magnification system. However, it is not clear if utilization of these features would improve surgical outcomes. Furthermore, the ORBEYE™ lacks incorporation of parathyroid autofluorescence, and the current costs for the system do not facilitate general access to exoscope assisted operations.

Purpose To examine the role of the silicone stent in palliation of malignant central airway obstruction and identify potential preprocedural predictors for postprocedural outcome. Methods Patients treated with endoscopic insertion of tracheobronchial silicone stents for malignant central airway obstruction at Aarhus University Hospital from 2012 to 2022 were identified from electronic medical records. Statistical analyses were carried out to identify factors affecting Days Alive and Out of Hospital, complications and overall survival. Results 81 patients underwent a total of 90 tracheobronchial stent insertions. Days Alive and Out of Hospital (DAOH) for the first 30 days were affected negatively by urgent intervention, p < 0.001, preprocedural non-invasive respiratory support, p < 0.001, and preprocedural intubation, p = 0.02. Post-procedural oncological treatment was associated with a significant improved DAOH, p = 0.04. Symptomatology and lesion characteristics were not significantly associated with any impact on DAOH. Overall survival was poor (mean survival was 158 days), and only significantly affected by severe degree of dyspnea, p = 0.02, and postprocedural oncological treatment, p < 0.001. Complication where registered in 25.6% of cases within the first 30 days was observed. Procedure-related mortality was 3.7%. Based on chart annotations by an ENT-surgeon, 95% of the patients experienced relief of symptoms following stent insertion. Conclusions Palliative tracheobronchial airway stenting with silicone stents is found to have a beneficial impact, more research is required for identification of predictors for postprocedural outcome based on preprocedural classifications.

Introduction Squamous cell carcinoma of unknown primary in the head and neck (HNSCCUP) remains a diagnostic challenge. Tongue base mucosectomy by transoral robotic surgery (TORS-TBM) can increase the diagnostic yield and de-intensify treatment. However, the added value of TORS-TBM as an adjunct to work-up programs for HNSCCUP is unclear. Furthermore, the optimal extent of the procedure and selection criteria remain to be established. Aim The primary aim of the present study was to assess the diagnostic yield of TORS-TBM as a supplement to a standardized work-up program, using the Danish national guidelines as an example. Secondary aims include predictive values of HPV-testing and PET/CT. Methods This was a national multicenter observational cohort study including all patients diagnosed with HNSCCUP from January 2013 to December 2019, who subsequently underwent TORS-TBM. In most cases HPV status was based on dual testing (p16 and HPV-DNA). Predictive values of PET/CT and HPV status were calculated. Results A total of 100 consecutive patients underwent TORS-TBM; 93 total TBMs and 7 unilateral TBMs. The primary tumor was detected in 49 % (49/100) of patients. The detection rate was 58 % (47/81) in patients with HPV-associated disease (PPV of HPV status) and 11 % (2/19) in patients with HPV-independent disease. The NPV of HPV status was 89 %. The PPV and NPV of PET/CT was 53 % and 52 %, respectively. Conclusion Adding total TORS-TBM to the current Danish guideline-based work-up program on HNCCCUP patients with HPV-associated disease significantly improved the diagnostic yield.

ObjectiveDetermine participants' satisfaction with rehabilitation following total laryngectomy (TL) and investigate associations between dysphagia, voice problems, and possible explanatory variables.Methods172 Danish and Swedish participants having received a TL 1.6-18.1 years ago for laryngeal/hypopharyngeal cancer answered a questionnaire regarding satisfaction with rehabilitation following TL and the V-RQOL, MDADI, and HADS questionnaires.Results85% and 75% were satisfied with the help received from their local hospital and municipality, respectively. 22%, 78%, and 65% indicated having not received any vocal, swallow, or olfactory rehabilitation, respectively. MDADI mean score was 77.5, V-RQOL was 62.8 and the HADS questionnaire indicated that possible depression or anxiety was present in 16% and 20% of participants, respectively. Multivariate analysis found the following variables to be associated with dysphagia; more voice problems, higher depression score, higher anxiety score, and being treated and rehabilitated in Denmark vs. in Sweden. Furthermore, multivariate analysis found the following variables to be associated with voice problems; more problems with dysphagia and higher depression score.ConclusionWe found that the majority of participants were satisfied with the received rehabilitation but that a large proportion reported having no dysphagia or olfactory rehabilitation. We found that voice problems, dysphagia, and depression after TL are tightly linked, and therefore suggest that medical personnel in contact with TL patients should be aware of possible psychological late effects. We found that being treated and rehabilitated in Sweden, vs. in Denmark, was associated with a better swallow outcome and we suggest additional centralization of rehabilitation in especially Denmark.

Purpose: To examine the outcome of palliative endoscopic treatment of malignant central airway obstruction (CAO) and identify predictors for Days Alive and Out of Hospital (DAOH), overall survival and treatment related complications. Methods: Consecutive adult patients treated endoscopically for malignant CAO at Aarhus University Hospital from 2012 to 2022 were included in the study. Statistical analyses were carried out to identify predictors for DAOH, survival and complications. Results: 127 consecutive patients met the inclusion criteria. The majority of patients were categorised with stage IV lung cancer, the majority being males, with a median age of 67 years. The endoscopic interventions were mainly tumour debulking combined with airway stent insertion or tumour debulking alone. The complication rate was 21.0 % and the mortality rate was 3.9 %. In total, 89.8 % of the patients experienced symptom relief following surgery, and the majority (92.1 %) were discharged from hospital within two days after intervention. Mean survival time following intervention was 144 days, mean DAOH30 was 20.8 and mean DAOH365 was 157. Survival was associated with comorbidity, type of intervention, preoperative respiratory support and postoperative oncologic treatment. A high preoperative ASA-score, preoperative respiratory support, urgency of intervention, female gender and insertion of airway stent were predictors for a poorer DAOH-outcome. Conclusion: Endoscopic palliative treatment of malignant CAO is generally feasible and safe, offering symptom relief in most cases. The method is considered an effective measure for short to median term palliation of respiratory distress.

Voice problems, also called hoarseness or dysphonia, can cause significant morbidity with communication difficulties and social isolation. This review summarises the causes and treatment of voice problems. Common causes of voice problems are related to inflammation, non-physiological usage of the voice, benign lesions of the vocal cords and damage to the nerves innervating the larynx. Nonetheless, it is important to keep malignancy in mind as a differential diagnosis. Referral to an otorhinolaryngologist is recommended for voice problems in adults with a duration of more than two weeks.

Background: Pain is prevalent after most TransOral Robotic Surgery (TORS) procedures and may limit function i.e. swallowing. Currently, there is limited knowledge regarding optimal pain treatment in TORS. Aims/objectives: This clinical trial randomized patients to either a high-dose dexamethasone or low-dose dexamethasone treatment in addition to a multimodal basic analgesic protocol. The aim of the trial was to investigate the pain intensity during rest and swallowing using the Visual Analogue Scale (VAS) after TORS lingual tonsillectomy. Secondary outcomes were acceptable food consistency, nausea, vomiting, opioid rescue usage, length of hospitalization, feeding tube placements, readmissions, blood glucose levels and postoperative complications. Methods: The trial was conducted between August 2020 and October 2022. Eligible patients were patients scheduled for TORS-L treatment of obstructive sleep apnea syndrome or as part of the diagnostic work-up of head and neck carcinoma of unknown primary. Results: Eighteen patients were and randomized 1:1. There were overall no significant differences between groups in the reported VAS scores during rest or swallowing (p >= .05). Overall, there were no differences in the secondary outcomes. Conclusion: There were no differences in the pain intensity in the two treatment groups allocated to a basic multimodal analgesic package and either high-dose dexamethasone or low-dose dexamethasone treatment. The trial is the first RCT to include pain measurement during a procedure-relevant activity, thus creating a platform for future recovery studies.

Background: The reported hospital length of stay (LOS) following transoral robotic surgery lingual tonsillectomy ( TORS-L) is variable, with limited understanding of the factors requiring hospitalization and no evidence-based criteria for discharge. Aims/objectives: This observational cohort study investigated factors hindering discharge following TORS-L in a well-defined postoperative care program. Methods: Patients were included between August 2020 and October 2022. A discharge scheme was filled out twice daily, specifying the factor(s) for hospitalization among patients undergoing TORS-L. This trial was a sub-investigation of a national multicentre randomized clinical trial (RCT) testing the efficiency of high-dose dexamethasone on postoperative pain control. Participation in the RCT demanded admission to the fourth postoperative day as dexamethasone/placebo was given intravenously in repeated dosages till day 4 postoperatively. Results: Eighteen patients were included in the analysis. The main factor for hospitalization was nutritional difficulties, while pain was a limiting factor for discharge only on the first postoperative 1-3 days. More than half of the patients could have potentially been discharged on postoperative day 2 when omitting the RCT treatment plan in the analysis. Conclusion: The study estimates that the majority of patients may be discharged on postoperative day 2 following TORS-L.

Background:Prolonged healing of tracheostomy after decannulation has a negative impact on respiration, hygiene, cosmetics, and social life. Even so, evidence-based observations of tracheostoma healing time are lacking. Therefore, the aim of this study was to determine tracheostomy wound healing time after decannulation.Methods:In this prospective observational cohort study, we included 30 subjects undergoing decannulation following prolonged mechanical ventilation via tracheostomy. Our primary endpoint was tracheostomy healing time defined as time from decannulation to airtight healing. To identify any factors related to healing time, we included information about patient demographics, comorbidities, tracheostomy method, tube size, and intubation time. All subjects were observed daily until their tracheostomy wound had healed.Results:The median tracheostomy healing time was 6.5 (1-22) days. The duration of tracheal cannulation was the only factor significantly correlated with prolonged healing (p=0.03). Four patients were subjected to recannulation shortly after decannulation due to hypercapnia, respiratory failure, secretion accumulation, or self-decannulation. All wounds achieved complete spontaneous airtight closure.Conclusions:Duration of spontaneous tracheostomy closure after decannulation was 1-22 days, and closure time correlated with duration of cannulation.

OBJECTIVES/HYPOTHESIS:The aims were to determine health-related quality of life (HRQoL), including voice problems, dysphagia, depression, and anxiety after total laryngectomy (TL), and investigate the associations between HRQoL and the late effects.STUDY DESIGN:Cross-sectional study.METHODS:172 participants having received a TL 1.6 to 18.1 years ago for laryngeal/hypopharyngeal cancer filled in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire, Core and Head and Neck module (EORTC QLQ-C30, EORTC QLQ-H&N35), Voice-Related Quality of Life questionnaire (V-RQOL), M.D. Anderson Dysphagia Inventory (MDADI), and Hospital Anxiety and Depression Scale (HADS) questionnaires.RESULTS:Participants scored worse than normative reference populations on all scales/items of the EORTC questionnaires, except one, and almost half of the scales/items showed a clinically relevant difference. Moderate/severe dysphagia was present in 46%, moderate/severe voice problems in 57%, depression in 16%, and anxiety in 20%. Decreasing age, increasing numbers of comorbidities, increasing voice problems, increasing dysphagia, and increasing depression symptoms, were associated with a lowered EORTC QLQ-C30 summary score.CONCLUSION:A substantial proportion of participants experienced clinically significant late effects and increasing levels of these were associated with a lowered HRQoL.LEVEL OF EVIDENCE:3 Laryngoscope, 132:980-988, 2022.

Combined use of contact endoscopy (CE) and Narrow Band Imaging (NBI, Olympus®) is suggested for the visualization of specific vascular changes indicative of glottic neoplasia. We investigated the interrater reliability and agreement in 3 recognized classification systems of vascular changes applied to images from CE + NBI in patients suspected for glottic neoplasia. Six experienced head and neck surgeons familiar with NBI rated 120 images obtained by CE + NBI by 3 classification systems of vascular changes as suggested by Ni et al. (N-C), Puxeddu et al. (P-C), and the European Laryngological Society (ELS-C). Three raters were experienced in CE, and three raters had only limited experience with CE. Crude agreement and Fleiss’ kappa with 95% confidence interval were estimated for all 6 raters, and for the 2 levels of expertise for each original classification system and for dichotomized versions of the N-C and the P-C based on suggested neoplastic potential. The interrater crude agreement and the corresponding kappa values for the ELS-C were good and significantly higher than those for the N-C and P-C for all raters, irrespective of the level of experience with CE (p < 0.0001). There were no significant differences between the N-C and the P-C (p = 0.16). Kappa was considerably improved for both the N-C and the P-C to a level not different from the ELS-C (p = 0.21–0.71) when their 5 original categories were pooled into dichotomized classifications. Difficulties in reliably classifying vascular changes in CE + NBI are evident. Two-tier classification systems are the most reliable.