From the clavicle to the windpipe: Tracheal window resections reconstructed with calcifying periosteum in thyroid cancer.

OBJECTIVES: We aimed to evaluate the outcomes of tracheal window resection and reconstruction using a vascularized periosteal flap (intended for calcification) harvested from the medial clavicle. This is one of several surgical techniques for tracheal resection and reconstruction used for patients with thyroid carcinoma invading the trachea. Importantly, in partial tracheal resection postoperative dynamic airway collapse must be prevented. Reconstruction of the tracheal defect with a vascularized periosteal flap is one method of achieving a stable airway. METHODS: Twelve patients with locally advanced thyroid carcinoma who underwent tracheal resection and reconstruction at Oslo University Hospital from 2004 to 2017 were studied retrospectively. The primary outcome was a stable airway not requiring airway stenting. The secondary outcomes were the time to decannulation, morbidity, and survival. RESULTS: Eleven of 12 patients did not require airway stenting postoperatively after a median of 111 days. Seven patients developed postoperative complications. The median observation time was 74.8 months (range 10.5-153.5) for all patients. The median disease-free survival was 40 months (range 0-147). By February 1, 2020, seven patients were alive, of whom five showed no evidence of disease. CONCLUSIONS: Tracheal reconstruction with a vascularized periosteal flap yielded good results in terms of establishing a stable airway. This procedure is a viable reconstructive option that allows for decannulation by preventing airway collapse, thereby potentially mitigating the need for end-to-end (ETE) anastomosis or sleeve resections. For selected patients, this procedure may prevent local fatal complications from thyroid cancer invading the trachea. LEVEL OF EVIDENCE: Level 4.

Impact of stage, management and recurrence on survival rates in laryngeal cancer.

A retrospective, longitudinal study of 1,616 patients with primary laryngeal squamous cell carcinoma (LSCC) at a single center in Norway during 1983-2010 was undertaken to investigate overall survival, disease specific survival, disease-free survival, prognostic factors for overall survival, and impact of recurrence among all-stage laryngeal cancer patients over 15 years' follow-up. The prognostic impact of gender, age, smoking/alcohol, subsite, tumour, node and metastasis staging, period and modality of treatment were evaluated using Kaplan-Meier and Cox proportional hazard analyses. The importance of recurrence on survival was assessed based on case fatality rates. Five-year overall survival was 56.8%, 64.0% and 38.8%, and disease-specific survival was 80.2%, 87% and 61.6%, respectively, for the entire cohort and for glottic and supraglottic LSCC. Old age, advanced-stage LSCC and supraglottic cancer were associated with lower overall survival. The risk of disease-specific death plateaued after five years and varied significantly by subsite. Multivariate analysis of glottic LSCC revealed that surgical treatment improved overall survival, whereas old age, alcohol, T3-T4 status, positive N-status and no treatment were associated with worse survival. In supraglottic LSCC, age, alcohol, and positive N-status had a significant impact on overall survival by multivariate analysis. Five-year overall survival and disease-specific survival among patients with recurrent disease were 34% and 52%, respectively. In conclusion, marked difference in overall survival between glottic and supraglottic LSCC underline the importance of subsite-specific survival analysis. T-status and primary surgical management is essential only for glottic LSCC, emphasizing the importance of correct disease classification. Inferior outcomes in supraglottic LSCC are associated with old age, positive N-status, and improved follow-up routines are necessary. Primary tumor control is essential since recurrence impairs survival considerably in all subsites. The potential benefit of a primary surgical approach towards T3 LSCC awaits further investigation.

Idiopathic subglottic stenosis: an epidemiological single-center study.

A retrospective epidemiological study of patients treated for idiopathic subglottic stenosis (ISS) during 2003-2013 at Oslo University Hospital, Rikshospitalet, was undertaken to assess its incidence, management and treatment outcomes. Out of a total of 123 patients with subglottic stenosis (84 female, 39 men), 38 patients were diagnosed with ISS, all of whom were female. Of these, 23 lived in the South-Eastern Norway Regional Health Authority, representing an incidence of 0.2 per 100,000 (95% CI 0.13-0.3) in this region of 2.9 million inhabitants. Mean age at diagnosis was 54 years (range 20-85 years), and the mean interval between symptom onset and diagnosis was 3.1 years. The 38 patients with ISS underwent a total of 132 operations between 2003 and 2013. All patients were managed endoscopically using laser surgery, with or without corticosteroids and Mitomycin C, with dilatation by balloon or bougie. Eight patients (21.1%) required only one procedure, while 30 patients (78.9%) had multiple operations. The median follow-up for all patients from the first operation was 5.3 years. The mean interval between procedures was 1 year for patients aged 20-48 years, 1.3 years for patients aged 49-61 years and 3.0 years for patients aged 62-85 years. No clinically significant complications were observed. In conclusion, the symptoms of ISS can be treated effectively with laser surgery and dilatation but the recurrence rate remains high and the time interval between operations does not increase with time, making ISS a continuing challenge.

Risk of Recurrence in Laryngeal Cancer.

A cohort study was undertaken to analyze the risk of recurrence among 1616 patients with primary squamous cell carcinoma of the larynx from 1983 to 2010 at a single, tertiary academic center in Oslo, Norway. The cohort was followed from the date of diagnosis to September 2011. Competing risk regression analysis assessed the association between various risk factors and the risk of recurrence, where death was considered a competing event. Recurrence was observed in 368 patients (23%) during the study period. The majority (71%) of recurrences involved the location of the primary tumor. The overall risk of recurrence during the first three years after initiating treatment was 20.5%. Increased risk of recurrence was observed in patients with supraglottic cancer, younger patients, those with T2-T3 tumors and in patients treated in the earlier part of the study period. Significant factors for recurrence in glottic carcinomas were age, treatment in the earlier part of the study and T-status, whereas age was a significant factor in supraglottic cancer. N-status appeared less significant. In conclusion, follow-up of laryngeal squamous cell carcinoma should place particular emphasis on the site of the primary tumor, younger patients, cases of supraglottic cancer and T2-T4 primary tumors, especially during the first three years after treatment. More studies are needed to assess the impact of surgical versus non-surgical treatment, and eventually the significance of recurrence, for disease-specific and overall survival in cases of advanced laryngeal squamous cell carcinoma.

Risk factors for aggressive recurrent respiratory papillomatosis in adults and juveniles.

In this cohort study we examined whether gender, age at onset, observation time or human papillomavirus (HPV) genotype are risk factors for an aggressive clinical course in Recurrent Respiratory Papillomatosis (RRP). Clinical data from patient records comprised gender, age at onset, date of first endolaryngeal procedure with biopsy, date of last follow-up, total number of endolaryngeal procedures, and complications during the observation period. Disease was defined as juvenile (JoRRP) or adult onset (AoRRP) according to whether the disease was acquired before or after the age of 18. Aggressive disease was defined as distal spread, tracheostomy, four surgical operations annually or >10 surgeries in total. DNA was extracted from formalin-fixed paraffin-embedded tissue. HPV genotyping was performed by quantitative PCR assay identifying 15 HPV genotypes. The study included 224 patients. The majority were males (141/174 in AoRRPs and 31/50 in JoRRPs; p = 0.005). The median follow-up from initial diagnosis was 12.0 years (IQR 3.7-32.9) for JoRRPs and 4.0 years (IQR 0.8-11.7) for AoRRPs. The disease was more aggressive in juveniles than adults (p<0.001), a difference that disappeared after 10 years' observation. JoRRPs with aggressive disease were younger at onset (mean difference 4.6 years, 95%CI [2.4, 6.8], p = 0.009). HPV6 or -11 was present in all HPV-positive papillomas. HPV11 was more prevalent in aggressive disease, and HPV6 in non-aggressive disease (p<0.001). Multiple logistic regression revealed that only age at onset (OR = 0.69, 95% CI [0.53, 0.88], p = 0.003) was associated with aggressive disease in juveniles, while HPV11 (OR = 3.74, 95% CI [1.40, 9.97], p = 0.008) and observation time >10 years (OR = 13.41, 95% CI [5.46, 32.99[, p<001) were risk factors in adults. In conclusion, the only significant risk factor for developing aggressive disease in JoRRPs was age at onset, but both HPV11 and observation time >10 years were risk factors for an aggressive disease course in AoRRPs.

Recurrent respiratory papillomatosis: HPV genotypes and risk of high-grade laryngeal neoplasia.

Patients with recurrent respiratory papillomatosis (RRP) in Norway treated between 1987 and 2009 were recruited to this cohort study. They were followed from disease onset and data recorded until January 2012. Here, we describe the distribution of human papillomavirus (HPV) genotypes, the prevalence of multiple HPV infections, and the risk of high-grade laryngeal neoplasia and respiratory tract invasive carcinoma in a large cohort of patients with RRP. We also examined whether HPV genotype, gender, age or clinical course are risk factors for this development. Clinical records and histological specimens were reviewed. Using formalin-fixed paraffin-embedded biopsies, HPV genotyping were performed by quantitative polymerase chain reaction assays identifying 15 HPV types. HPV-negative specimens were analyzed by metagenomic sequencing. Paraffin blocks were available in 224/238 patients. The DNA quality was approved in 221/224 cases. HPV DNA was detected in 207/221 patients and all were HPV 6 or HPV 11 positive, comprising HPV 6 in 133/207, HPV 11 in 40/207 cases and HPV 6/11 in 15/207 cases. Co-infection with one or two high-risk HPV types together with HPV 6 or HPV 11 was present in 19/207 patients. Metagenomic sequencing of 14 HPV-negative specimens revealed HPV 8 in one case. In total, 39/221 patients developed high-grade laryngeal neoplasia. 8/221 patients developed carcinoma of the respiratory tract (six patients with laryngeal carcinoma and two patients with lung carcinoma). High-grade laryngeal neoplasias were found more frequently in HPV-negative versus HPV-positive patients, (RR = 2.35, 95% CI 1.1, 4.99), as well as respiratory tract carcinomas (RR = 48, 95% CI 10.72, 214.91). In summary, the majority of RRP were associated with HPV 6 and/or 11. HPV-negative RRP biopsies occurred more frequently in adult-onset patients, and were associated with an increased risk of laryngeal neoplasia and carcinoma in the respiratory tract.

Long-term trends in gender, T-stage, subsite and treatment for laryngeal cancer at a single center.

To investigate the changes in the epidemiology of laryngeal squamous cell carcinoma (LSCC) regarding gender, T-stage and subsite distribution, and to identify the potential effect of introducing new therapeutic alternatives for early and advanced stage LSCC. A prospective cohort study of LSCC patients diagnosed and treated at a single tertiary referral center in Norway. Retrospective analysis of prospectively recorded data from 1,616 patients treated for LSCC in all subsites of the larynx during 1983-2010. Females represented an increasing proportion of cases throughout the study (p < 0.01) and presented more often than men with supraglottic cancer (p < 0.01). Marked changes in the distribution of T-stages over time were observed in both early and advanced stage LSCC. T1a glottic tumors constituted 56 % of all early-stage LSCC and were predominantly treated by transoral endoscopic laser surgery. The introduction of chemoradiotherapy for advanced stage LSCC offers a distinct advantage for laryngeal preservation. The increasing proportion of females with LSCC may be explained by changes in smoking habits. The proportion of T1a glottic LSCC gradually increased over time, while T4 supraglottic LSCC became less frequent. Videostroboscopy should be considered mandatory in the diagnosis and follow-up of LSCC. Transoral laser microsurgery is the standard first-line treatment for T1a glottic tumors. Chemoradiotherapy has reduced the number of total laryngectomies and is now regarded as the primary treatment for advanced stage tumors.

Laser diverticulotomy for Zenker's diverticulum--does it improve quality of life?

To determine quality of life (QoL) in individuals with dysphagia related to identified Zenker's diverticulum before (T1) and one year after undergoing endoscopic laser diverticulotomy surgery (T2). A total of 43 individuals (18 women and 25 men) were included at T1 and 37 of these responded at T2 (13 women and 24 men). Health-related QoL (HRQoL) was determined with the short form 36 (SF-36) and disease-specific QoL (DSQoL) was assessed with the MD Anderson Dysphagia Inventory (MDADI). In addition, two questions about specific symptoms related to Zenker's diverticulum were added and ordered as a fifth subscale of MDADI. Comparisons were made between patients and an age- and gender-adjusted normative sample from the Norwegian population. Significant differences were found in all subscales on MDADI, but none between T1 and T2 on SF-36. Compared to the normative sample, the component score MCS of SF-36 was significantly lower in the dysphagia patients at both T1 and T2. The attrition sample had significantly lower PCS than the completers. The results substantiate that disease severity is associated with poorer disease-related QoL, and that the disease-specific QoL is significantly improved one year after laser diverticulotomy.

Epidemiological aspects of recurrent respiratory papillomatosis: a population-based study.

OBJECTIVES/HYPOTHESIS: The incidence of genital infections, cervical cancer, and oropharyngeal cancer induced by human papillomaviruses (HPV) is increasing in Western countries. Primarily, this study was conducted to estimate the incidence rate of recurrent respiratory papillomatosis (RRP) in juveniles and adults in two Norwegian subpopulations for each year between 1987 and 2009. The secondary objective of the study was to investigate whether there are trends in the incidence rates of RRP in the study period similar to what we have seen for HPV-related cancer. STUDY DESIGN: Population-based study. METHODS: Two Norwegian subpopulations with 2.6 million and 1.1 million inhabitants were investigated for the juvenile and adult forms of RRP, respectively, between the years of 1987 and 2009. Patients treated for RRP were identified in all ear/nose/throat departments located in the two areas. RESULTS: The overall incidence rates of RRP in juveniles and adults were 0.17 (95% confidence interval [CI], 0.10-0.25) and 0.54 (95% CI, 0.44-0.65) per 100,000, respectively. We found a preponderance of males in both groups (P = .000 for adults and P = .038 for children). There was no significant change in the yearly incidence rate during the study period, for either adults or children, even when stratifying for gender in each group. The median age at onset was 4 years for children and 34 years for adults, with no significant difference between genders, nor significant changes during the study years. CONCLUSIONS: This study does not support our hypothesis of an increasing incidence of RRP, for either children or adults. The estimated incidence rates in the Norwegian subpopulations are consistent with former population-based studies. Male preponderance in children was an unexpected finding. Further studies are warranted.

Radiotherapy or CO(2) laser surgery as treatment of T(1a) glottic carcinoma?

Both radiotherapy and laser surgery give excellent results in the treatment of T(1a) glottic carcinoma. In this study, we compared the outcome of these treatment options. Demographic details and continuous follow-up with exact cause of death have been recorded prospectively for 351 patients with T(1a) glottic carcinoma at a tertiary referral centre in two consecutive decennia 1986-2005. Patients were treated with radiotherapy (163 patients) until 1996 when laser surgery was adopted as primary treatment (188 patients). The minimum follow-up time was 29 months. Neither the estimated 5-year disease-free survival, the disease-specific survival nor the crude survival differ between the two treatment options. The incidence of mainly local recurrences was equal during the first 3 years, followed by an increase in number of recurrences in the laser-operated patients. The odds ratio for a laryngectomy was 13.5 in patients treated with radiotherapy (P = 0.002), but mortality due to recurrence did not differ between the groups. The incidence of second primaries was equal (11%) but death due to second primaries differed significantly, favouring laser-treated patients (P = 0.003). In conclusion, the relative risk for a laryngectomy when a tumour recurs is 12.7 times higher in patients primarily treated with irradiation for T(1a) laryngeal carcinoma, compared with patients treated with laser surgery. Regarding the treatment costs, treatment impact on patients and organ preservation, we consider laser therapy to be the better treatment option for patients with T(1a) glottic cancer as no difference in survival could be observed.

Paradoxical vocal cord movement in newborn and congenital idiopathic vocal cord paralysis: two of a kind?

The second most common cause of stridor reported in the newborn is bilateral vocal cord paralysis (BVCP) and one-third of the cases have been categorized as idiopathic. During the last year four children with stridor since birth were referred to our department for examination. Videotaped flexible laryngoscopy, carried out with the patient awake or under general anaesthesia with a spontanous respiration, revealed instead of abduction of the vocal cords during inspiration, rather an active adductory movement. Consequently instead of BVCP, we made the diagnosis paradoxical vocal cord movement (PVCM). One of the twins required a tracheostomy, the three other patients have been observed without the need of further treatment. No previous publications have described PVCM in newborn. However, our observations and video recordings clearly show that the stridor in our four patients is due to PVCM. This is possibly the same condition as earlier reported as congenital, idiopathic BVCP where incoordinated vocal cord movement or dyskinesia has been a part of the laryngoscopic findings. The mechanism behind PVCM in this age group or site of lesion is unclear.

Alcohol, smoking and human papillomavirus in laryngeal carcinoma: a Nordic prospective multicenter study.

PURPOSE: Human papillomavirus (HPV) has been linked to oropharyngeal carcinomas, but its role in laryngeal squamous cell carcinoma (LSCC) is not clear. A prospective multicenter study based on known tumor-cell percentage of fresh frozen carcinoma biopsies was established to determine the HPV prevalence. Moreover risk factors such as smoking, alcohol abuse, chronic laryngitis and gastroesophageal reflux disease (GERD) were evaluated METHODS: Fresh-frozen laryngeal cancer biopsies from 108 patients in Finland, Norway, and Sweden were investigated. Patients whose biopsy samples contained at least 20% tumor tissue (N = 69) entered the study. HPV DNA was determined with MY09/11 and GP5+/6+ nested PCR and SPF10 PCR hybridization assay. Patients were examined by an ENT specialist and an extensive questionnaire concerning risk factors was filled in. RESULTS: Only three patients (4.4%) harbored HPV DNA in their carcinoma sample. Heavy alcohol drinking was associated with an increased risk of death, advanced-stage disease, and younger age at diagnosis. Chronic laryngitis, GERD, and orogenital sex contacts were rare. Poor oral hygiene was not associated with survival, although it correlated with heavy drinking. CONCLUSION: In our series HPV was not important in LSCC. Heavy drinking led to major mortality in LSCC and promoted early carcinogenesis.

Laser resection of T1a glottic carcinomas: results and postoperative voice quality.

OBJECTIVES: To calculate recurrence, mortality and complication rates and evaluate postoperative voice quality after laser resection of T(1a) glottic carcinoma. MATERIAL AND METHODS: Since 1995 we have treated 118 patients with a T(1a) glottic carcinoma with laser surgery. In order to evaluate postoperative voice quality, patients who were alive and free of recurrence were sent the Voice Handicap Index (VHI) questionnaire containing 30 questions concerning how their voice affects their daily life physically, emotionally and socially. RESULTS: Twelve patients (10%) had a local recurrence and received further treatment, either a second laser treatment, radiotherapy or a total laryngectomy. One patient (0.84%) died due to the laryngeal cancer. Ninety-nine patients were sent the VHI questionnaire and 94 of the completed questionnaires were included in the study and analyzed. The mean total score was 13.2, with mean subscores of 6.5 (physical), 4.1 (functional) and 2.5 (emotional). CONCLUSIONS: The results indicate that these patients as a group do not consider that their voice has a negative impact on their daily life. Good surgical technique is essential to obtain a good functional result. The laser strength should be kept low and the surgical margins small in order to minimize scarring and vocal cord stiffness.