How can we identify subglottic stenosis in patients with suspected obstructive disease?

PURPOSE: Subglottic stenosis, a rare condition of the upper airway, is frequently misdiagnosed as obstructive lung disease. The aim of this study was to investigate whether subglottic stenosis could be identified and distinguished from asthma and chronic obstructive pulmonary disease (COPD) using spirometry or the dyspnea index (DI). METHODS: The study population included 43 patients with asthma, 31 patients with COPD and 50 patients with subglottic stenosis planned to undergo endoscopic intervention. All patients completed the DI and underwent dynamic spirometry registering both inspiratory and expiratory volumes and flows, including the expiratory disproportion index (EDI), the ratio of forced expiratory volume in 1 s to peak expiratory flow. One-way analysis of variance assessed the discrepancy of the variables among the study groups, and receiver operating curve (ROC) analysis determined the measurement with the best discriminatory power providing a cutoff value, maximizing both sensitivity and specificity. RESULTS: The only statistically significant variables differing between all three groups were the EDI and the DI. The EDI showed an excellent area under the ROC curve (0.99, p < 0.001) with a cutoff value of 0.39 (98% sensitivity, 96% specificity), followed by DI (0.87, p < 0.001) with a cutoff score of > 25 (83% sensitivity and 78% specificity). CONCLUSION: In patients with dyspnea of unknown cause, an increase in EDI should arouse a suspicion of extrathoracic airway obstruction, advocating for further evaluation with laryngotracheoscopy.

Balloon dilatation is superior to CO2 laser excision in the treatment of subglottic stenosis.

INTRODUCTION: Endoscopic treatment of subglottic stenosis (SGS) is regarded as a safe procedure with rare complications and less morbidity than open surgery yet related with a high risk of recurrence. The abundance of techniques and adjuvant therapies complicates a comparison of the different surgical approaches. The primary aim of this study was to investigate disease recurrence after CO2 laser excisions and balloon dilatation in patients with SGS and to identify potential confounding factors. MATERIALS AND METHODS: In a tertiary referral center, two cohorts of previously undiagnosed patients treated for SGS were retrospectively reviewed and followed for 3 years. The CO2 laser cohort (CLC) was recruited between 2006 and 2011, and the balloon dilatation cohort (BDC) between 2014 and 2019. Kaplan‒Meier and multivariable Cox regression analyzed time to repeated surgery and estimated hazard ratios (HRs) for different variables. RESULTS: Nineteen patients were included in the CLC, and 31 in the BDC. The 1-year cumulative recurrence risk was 63.2% for the CLC compared with 12.9% for the BDC (HR 33.0, 95% CI 6.57-166, p < 0.001), and the 3-year recurrence risk was 73.7% for the CLC compared with 51.6% for the BDC (HR 8.02, 95% CI 2.39-26.9, p < 0.001). Recurrence was independently associated with overweight (HR 3.45, 95% CI 1.16-10.19, p = 0.025), obesity (HR 7.11, 95% CI 2.19-23.04, p = 0.001), and younger age at diagnosis (HR 8.18, 95% CI 1.43-46.82, p = 0.018). CONCLUSION: CO2 laser treatment is associated with an elevated risk for recurrence of SGS compared with balloon dilatation. Other risk factors include overweight, obesity, and a younger age at diagnosis.

Dyspnea Index: An upper airway obstruction instrument; translation and validation in Swedish.

OBJECTIVE: Upper airway dyspnoea is a challenging condition in which assessing the discomfort experienced by the patient is essential. There are three patient-reported outcome (PRO) instruments developed particularly for this patient group, none of which is available in Swedish. The aim of this study was to translate the Dyspnea Index (DI) into Swedish and validate the instrument for use in the Swedish-speaking population by investigating its basic psychometric properties. DESIGN: A prospective instrument validation study. SETTING: Tertiary referral centre. PARTICIPANTS: Fifty-three (n = 53) patients with upper airway dyspnoea and 19 healthy controls. MAIN OUTCOME MEASURES: The questionnaire was translated into Swedish (swDI) with a forward-backward method. Reliability, repeatability, responsiveness and construct validity were assessed by asking the subjects to complete the swDI, a visual analog scale (VAS) at exertion and at rest and the Voice Handicap Index (VHI). RESULTS: The swDI showed excellent internal consistency (Cronbach's α: 0.85) and repeatability (interclass correlation coefficient: 0.87 and Pearson's r: .89) in the patient group. No ceiling effect was observed (maximum score achieved was 39; 85% of the patients scored ≤ 36). SwDI scores moderately correlated with VAS at exertion (r: .59) and at rest (r: .42), yet poorly with the VHI (r: .36). The effect size (ES) was 3.8. CONCLUSIONS: The swDI is a valid, robust and reliable questionnaire for self-assessment in Swedish-speaking patients with upper airway obstruction. A future anchor-based longitudinal study is needed to assess the smallest detectable change (SDC) and minimal important change (MIC) that were not estimated in our study.

Distribution of sentinel nodes from parotid tumors-A feasibility study.

BACKGROUND: Optimum management of the N0 neck is unresolved in parotid salivary gland cancer. Sentinel node biopsy (SNB) can reliably detect microscopic lymph node metastasis and its´ clinical use is increasing for head and neck tumors. The object of this study was to establish whether the technique is applicable to detect distribution of sentinel nodes for parotid tumors. MATERIALS AND METHODS: Prosepective observational study in 30 patients with benign or low-grade T1-T2N0 malignant tumors in the parotid gland planned for surgical treatment. Distribution of SN was detected with a preoperative ultrasound-guided peritumoral injection with a technetium-99 (Tc-99 m) laballed tracer followed by a SPECT-CT and intraoperative measurement in the neck and parotidal tissue. In patients with cytologically suspected malignant tumor or highly unclerar cytology, SNB was also performed. RESULTS: Sentinel nodes (SNs) were detected in 26/30 cases. Out of these, 7 presented with only one SN, whereas multiple sentinel nodes where detected in 19 cases. No SNs were found in neck level 1. SN was detected in level 5 independent of tumor location within the parotid gland. An intraparotidal distribution of SNs was more frequent in larger tumors. CONCLUSIONS: The use of SN-technique in the planning of surgical treatment of parotid tumors seems feasible. It may be of clinical value for patients with parotid cancer to enable a more accurate staging and to detect occult metastasis in the SNs within the parotid as well as in the neck, enabaling the possibility to surgically remove all positive SNs at primary surgery and with reduced surgical morbidity.

Brachytherapy and osteoradionecrosis in patients with base of tongue cancer.

BACKGROUND: Base of tongue cancer incidence and patient survival is increasing why treatment sequelae becomes exceedingly important. Osteoradionecrosis (ORN) is a late adverse effect of radiotherapy and brachytherapy (BT) could be a risk factor. Brachytherapy is used in three out of six health care regions in Sweden. AIMS: Investigate if patients treated in regions using BT show an increased risk for ORN and whether brachytherapy has any impact on overall survival. MATERIAL AND METHODS: We used data from the Swedish Head and Neck Cancer Register between 2008-2014. Due to the nonrandomized nature of the study and possible selection bias we compared the risk for ORN in brachy vs non-brachy regions. RESULTS: Fifty out of 505 patients (9.9%) developed ORN; eight of these were treated in nonbrachy regions (16%), while 42 (84%) were treated in brachy regions. Neither age, sex, TNM-classification/stage, p16, smoking, neck dissection, or chemotherapy differed between ORN and no-ORN patients. The risk for ORN was significantly higher for patients treated in brachy regions compared to non-brachy regions (HR = 2,63, p = .012), whereas overall survival did not differ (HR = 0.95, p = .782). CONCLUSIONS AND SIGNIFICANCE: Brachytherapy ought to be used cautiously for selected patients or within prospective randomized studies.

Monitoring Adult Subglottic Stenosis With Spirometry and Dyspnea Index: A Novel Approach.

OBJECTIVE: The aim was to examine the correlations among the anatomic Cotton-Myer classification, pulmonary function tests (PFTs), and patient-perceived dyspnea or dysphonia in patients with subglottic stenosis and identify measurements accurately reflecting treatment effects. STUDY DESIGN: Prospective cohort study. SETTING: Tertiary referral center. METHOD: Fifty-two adults receiving endoscopic treatment for isolated subglottic stenosis were consecutively included. Correlations were calculated among the preoperative Cotton-Myer scale, PFTs, the Dyspnea Index (DI), and the Voice Handicap Index. Receiver operating characteristic curves were determined for PFT, DI, and Voice Handicap Index pre- and postoperative measurements. RESULTS: The Cotton-Myer classification correlated weakly with peak expiratory flow (r = -0.35, P = .012), expiratory disproportion index (r = 0.32, P = .022), peak inspiratory flow (r = -0.32, P = .022), and total peak flow (r = -0.36, P = .01). The DI showed an excellent area under the curve (0.99, P < .001), and among PFTs, the expiratory disproportion index demonstrated the best area under the curve (0.89, P < .001), followed by total peak flow (0.88, P < .001), peak expiratory flow (0.87, P < .001), and peak inspiratory flow (0.84, P < .001). Patients treated endoscopically with balloon dilatation showed a 53% decrease in expiratory disproportion index (95% CI, 41%-66%; P < .001) and a 37% improvement in peak expiratory flow (95% CI, 31%-43%; P < .001). CONCLUSION: Expiratory disproportion index or peak expiratory flow combined with DI was a feasible measurement for the monitoring of adult subglottic stenosis. The percentage deterioration of peak expiratory flow and increase in expiratory disproportion index correlated significantly with a proportional percentage increase in DI.

Prevalence of cystic metastases in a consecutive cohort of surgically removed branchial cleft cysts.

BACKGROUND: Solitary cystic lesion of the neck may often be the only initial presenting symptom for branchial cleft cysts and cystic metastases. AIMS/OBJECTIVES: To analyse the malignancy rate detected in patients undergoing surgical treatment for lateral branchial cleft cyst. MATERIAL AND METHODS: The records of all patients with surgical procedure code ENB40 (Excision of lateral branchial cleft cyst- or fistula) between 2003 and 2019 were reviewed. After excluding 150 patients, 436 patients were included for final analysis. Re-evaluation of the cytology including HPV-analysis was performed in those who had a malignant cyst. RESULTS: Cystic metastases were demonstrated histologically after surgical excision in 13 patients (3%). In patients over 18 years of age, the prevalence of cystic metastasis regardless of the primary tumour type was 3.3%. CONCLUSION AND SIGNIFICANCE: When the investigation protocol for solitary cystic lesions of the neck is followed, the negative predictive value for malignancy is 97%. All adult patients with a cytologic verified diagnosis of branchial cyst should be examined with HPV-analysis of the cystic sample before excision of the cyst. Failure of predicting a malignancy is often associated with cytology of poor cellularity which may be improved by more frequent use of ultrasound guided fine-needle aspiration cytology (FNAC).

Ultrasound accurately assesses depth of invasion in T1-T2 oral tongue cancer.

Background: Depth of invasion (DOI) is important for the T-classification of squamous cell carcinoma of the oral tongue (SCCOT) and incorporated in the TNM 8 classification of oral cavity cancer. To determine DOI clinical palpation is performed, but the preferred radiological modality remains controversial. The aim of this study was to investigate the assessment of DOI using ultrasound (US-DOI). Methods: The DOI was assessed in 40 patients with T1-T3 SCCOT by ultrasound, palpation, computed tomography and magnetic resonance imaging (MRI). Histopathological DOI (H-DOI) was gold standard. Bland-Altman analysis was used to compare mean difference and 95% limits of agreement (LOA). Results: The mean difference of US-DOI was -0.5 mm (95% LOA -4.9-4.0) compared to H-DOI and the mean difference for MRI was 3.9 mm (95% LOA -2.3-10.2). In the subgroup analysis of cT1-T2 the US-DOI mean difference was 0.1 mm and the 95% LOA limits -2.5-2.7. Conclusions: Ultrasound seems to be the most accurate method to assess DOI in T1-T2 SCCOT. MRI overestimates DOI and cannot assess a substantial proportion of the tumors. Level of Evidence: 2c.

Ultrasound-assisted resection of oral tongue cancer.

BACKGROUND: In surgical resection of squamous cell carcinoma of the oral tongue (SCCOT), achieving clear margins is important for prognosis. Insufficient histopathological margins are common, particularly deep margins. AIMS/OBJECTIVES: The aim of the present study was to determine whether ultrasound (US)-assisted resection could decrease the proportion of insufficient histopathological deep margins in SCCOT. MATERIAL AND METHODS: 34 patients with SCCOT undergoing US-assisted resection (study group) were compared to 76 whose resections were performed without US (conventional group). Outcome measures were insufficient deep histopathological resection margins and mean difference in deep margins. RESULTS: Insufficient deep resection margins (<5.0 mm) were seen in 8 of 34 (23.5%) in the study group, compared to 31 of 76 (40.8%) in the conventional group, unadjusted RR 0.58 [95% CI 0.30-1.12; p = .11], adjusted RR 0.82 [95% CI 0.35-1.92; p = .64]. Unadjusted mean difference was 1.4 mm (95% CI 0.1-2.7, p = .04), adjusted mean difference 1.1 mm (95% CI -2.7 to 0.5, p = .19). CONCLUSIONS: Intraoperative US can visualize the deep resection margins in T1/T2 SCCOT. US-assisted resection seems to decrease the number of insufficient histopathological deep margins, though the results are not statistically significant. Comparatively good results in the conventional group is one explanation for the lack of significance. CLINICALTRIALS.GOV ID: NCT04059861.

Feasibility of an inexperienced examiner using trans-cervical ultrasound in the diagnosis of peritonsillar abscesses.

BACKGROUND: A peritonsillar abscess (PTA) is a common complication to acute tonsillitis. Needle aspiration (NA) is the gold standard for diagnosis of PTA. NA is usually painful and not risk-free. Ultrasound (US) is a noninvasive, portable radiological modality that could potentially be used in the diagnosis of PTA and selection of patients for NA. The reliability of US is dependent on the experience of the examiner which limits is usefulness. AIM: To evaluate the reliability of US in the diagnosis of PTA by an inexperienced examiner. METHODS: Thirty patients with suspected PTA were included. They were first examined with trans-cervical US by a medical student then clinically examined by a physician that performed a NA if clinically motivated. They were then followed for at least two days. RESULTS: Three patients were excluded from analysis because no NA was performed. In these patients, US correctly classified them as negative for PTA. In the remaining 27 patients, the sensitivity and negative predictive value was 100%. The specificity was 64.3% and the positive-predictive value was 72.2%. CONCLUSION: US can be very useful in the diagnosis of PTA and the selection for NA even with an inexperienced examiner. SIGNIFICANCE: The results highlight the usefulness of ultrasound in otolaryngology.

Swedish National Multicenter Study on Head and Neck Cancer of Unknown Primary: Prognostic Factors and Impact of Treatment on Survival.

Introduction Head and neck cancer of unknown primary (HNCUP) is a rare condition whose prognostic factors that are significant for survival vary between studies. No randomized treatment study has been performed thus far, and the optimal treatment is not established. Objective The present study aimed to explore various prognostic factors and compare the two main treatments for HNCUP: neck dissection and (chemo) radiation vs primary (chemo) radiation. Methods A national multicenter study was performed with data from the Swedish Head and Neck Cancer Register (SweHNCR) and from the patients' medical records from 2008 to 2012. Results Two-hundred and sixty HNCUP patients were included. The tumors were HPV-positive in 80%. The overall 5-year survival rate of patients treated with curative intent was 71%. Age ( p < 0.001), performance status ( p = 0.036), and N stage ( p = 0.046) were significant factors for overall survival according to the multivariable analysis. Treatment with neck dissection and (chemo) radiation (122 patients) gave an overall 5-year survival of 73%, and treatment with primary (chemo) radiation (87 patients) gave an overall 5-year survival of 71%, with no significant difference in overall or disease-free survival between the 2 groups. Conclusions Age, performance status, and N stage were significant prognostic factors. Treatment with neck dissection and (chemo) radiation and primary (chemo) radiation gave similar survival outcomes. A randomized treatment study that includes quality of life is needed to establish the optimal treatment.

Long-term follow-up in patients treated with electrochemotherapy for non-melanoma skin cancer in the head and neck area.

BACKGROUND: Electrochemotherapy (ECT) is a cancer treatment modality where the intracellular accumulation of chemotherapeutic agents is enhanced by an applied electrical field. AIMS/OBJECTIVES: To evaluate the long-term efficacy, safety and functional outcome after ECT treatment in high-risk non-melanoma skin cancer (NMSC) with curative intent. MATERIALS AND METHODS: Seven patients with SCC or BCC in the head and neck area were treated with ECT with intratumoral bleomycin administration. RESULTS: Five patients were cured by ECT as a mono-modality treatment after a median 10-year follow-up period. Two patients had recurrences and/or persisting tumors after treatment that required salvage surgery and radiotherapy. In two patients, the eye was spared with no visual impairment. In another patient, full facial nerve function was spared. CONCLUSIONS: ECT can be a curative as well as an organ and function-sparing mono modality treatment in high-risk NMSC. SIGNIFICANCE: Today ECT is mostly used as a palliative treatment. Its curative potential should be further investigated. Randomized studies comparing ECT with standard treatment is needed. Hopefully, this small study can encourage such studies.

Transoral Robotic Surgery in the Nordic Countries: Current Status and Perspectives.

Background: The five Nordic countries with a population of 27 M people form a rather homogenous region in terms of health care. The management of head and neck cancer is centralized to the 21 university hospitals in these countries. Our aim was to gain an overview of the volume and role of transoral robotic surgery (TORS) and to evaluate the need to centralize it in this area as the field is rapidly developing. Materials and Methods: A structured questionnaire was sent to all 10 Departments of Otorhinolaryngology-Head and Neck Surgery in the Nordic countries having an active programme for TORS in December 2017. Results: The total cumulative number of performed robotic surgeries at these 10 Nordic centers was 528 and varied between 5 and 240 per center. The median annual number of robotic surgeries was 38 (range, 5-60). The observed number of annually operated cases remained fairly low (<25) at most of the centers. Conclusions: The present results showing a limited volume of performed surgeries call for considerations to further centralize TORS in the Nordic countries.

Swedish National Multicenter Study on Head and Neck Cancer of Unknown Primary: Prognostic Factors and Impact of Treatment on Survival

Abstract Introduction Head and neck cancer of unknown primary (HNCUP) is a rare condition whose prognostic factors that are significant for survival vary between studies. No randomized treatment study has been performed thus far, and the optimal treatment is not established. Objective The present study aimed to explore various prognostic factors and compare the two main treatments for HNCUP: neck dissection and (chemo) radiation vs primary (chemo) radiation. Methods A national multicenter study was performed with data from the Swedish Head and Neck Cancer Register (SweHNCR) and from the patients' medical records from 2008 to 2012. Results Two-hundred and sixty HNCUP patients were included. The tumors were HPV-positive in 80%. The overall 5-year survival rate of patients treated with curative intent was 71%. Age (p< 0.001), performance status (p= 0.036), and N stage (p= 0.046) were significant factors for overall survival according to the multivariable analysis. Treatment with neck dissection and (chemo) radiation (122 patients) gave an overall 5-year survival of 73%, and treatment with primary (chemo) radiation (87 patients) gave an overall 5-year survival of 71%, with no significant difference in overall or disease-free survival between the 2 groups. Conclusions Age, performance status, and N stage were significant prognostic factors. Treatment with neck dissection and (chemo) radiation and primary (chemo) radiation gave similar survival outcomes. A randomized treatment study that includes quality of life is needed to establish the optimal treatment.

Electrochemotherapy - Evidence for Cell-type Selectivity In Vitro.

AIM: Electrochemotherapy (ECT) is a new cancer treatment modality that uses electroporation to potentiate chemotherapeutic agents, especially bleomycin. ECT causes both a direct toxic effect and an anti-vascular effect. The aim of the present study was to investigate a possible selective effect of ECT on the survival of fibroblasts, endothelial cells (HUVEC) and two squamous cell carcinoma cell lines (CAL-27 and SCC-4). MATERIALS AND METHODS: Cells were electroporated using two bleomycin concentrations. The survival rate was assessed 1, 2, 3 and 4 days after treatment, by two different assays. RESULTS: The survival rate of the fibroblasts was statistically significantly higher than the other cell lines at day 4. The HUVEC survival rate was statistically significantly lower than the other cell types at day 1 after electroporation-alone. CONCLUSION: A selective survival effect after ECT was observed in vitro, supporting the anti-vascular effect seen in vivo.

Outcome of primary treatment of early laryngeal malignancies using photodynamic therapy.

CONCLUSION: Photodynamic therapy (PDT) is a viable and safe option for early laryngeal cancer that would be less suitably treated with radiation or trans-oral laser surgery (TLS). The cure rates with PDT appear to be comparable to those of conventional therapy, and the voice outcomes are also comparable. In the case of many sarcomas, PDT appears to be an organ- and function-sparing therapy, although it is more costly than other treatments. OBJECTIVES: The aim of this study was to show the results of PDT when it is used as a primary treatment of early laryngeal cancer. METHODS: We studied the results of PDT when used as a primary treatment. We looked at survival, effect on tumor, side effects, voice, and costs. RESULTS: The follow-up period was a median of 59 months. Nine of 10 patients were cured of their laryngeal cancer. PDT alone cured seven patients. All four of the sarcomas were cured using temoporfin. Two of three tumors that involved the anterior commissure were cured using only interstitial illumination with PDT. No serious side effects were noted. The patient's voices were improved after treatment in 5 of 10 cases, and none had a worsened voice.

Pulsed dose rate brachytherapy as the boost in combination with external beam irradiation in base of tongue cancer. Long-term results from a uniform clinical series.

PURPOSE: To evaluate long time outcome with regard to local tumour control, side effects and quality of life of combined pulsed dose rate (PDR) boost and hyperfractionated accelerated external beam radiotherapy (EBRT) for primary base of tongue (BOT) cancers. MATERIAL AND METHODS: Between 1994 and 2007, the number of 83 patients were treated with primary T1-T4 BOT cancers. Seven patients (8%) were T1-2N0 (AJCC stage I-II) and 76 (92%) patients were T1-2N+ or T3-4N0-2 (AJCC stage III-IV). The mean estimated primary tumour volume was 15.4 (1-75) cm3. EBRT was given with 1.7 Gy bid to 40.8 Gy to primary tumour and bilateral neck lymph nodes in 2.5 weeks. PDR boost of 35 Gy and a neck dissection in clinical node positive case was performed 2-3 weeks later. The patients were followed for a median of 54 (2-168) months. RESULTS: The 2-, 5- and 10-years rates of actuarial local control were 91%, 89% and 85%, overall survival 85%, 65% and 44%, disease free survival 86%, 80% and 76%, respectively. The regional control rate was 95%. Six patients (7%) developed distant metastases. A dosimetric analysis showed a mean of 100% isodose volume of 58.2 (16.7-134) cm3. In a review of late complications 11 cases of minor (13%) and 5 of major soft tissue necroses (6%), as well as 6 cases of osteoradionecroses (7%) were found. The patients median subjective SOMA/LENT scoring at last follow up was as follow: grade 0 for pain and trismus, grade 1 for dysphagia and taste alteration, and grade 2 for xerostomia. Global visual-analogue-scale (VAS) scoring of quality of life was 8. CONCLUSION: Local and regional tumour control rate was excellent in this treatment protocol. The data shows the PDR boost as at least as effective as published continuous low dose rate (CLDR) results.