Previous randomized studies comparing the two commonly used palliative treatments for incurable esophageal cancer, i.e. stent insertion and intraluminal brachytherapy, have revealed the pros and cons of each therapy. While stent treatment offers a more prompt effect, brachytherapy results in more long-lasting relief of dysphagia and a better health-related quality of life (HRQL) in those living longer. This prospective pilot study aimed to explore the feasibility and safety of combining these two regimes and incorporating a single high dose of internal radiation. Patients with newly diagnosed, incurable cancer of the esophagus and dysphagia were eligible for inclusion, and stent insertion followed by a single dose (12 Gy) of brachytherapy was performed as a two-stage procedure. Clinical parameters including HRQL and adverse events were registered at inclusion, and 1, 2, 3, 6, and 12 months later. Twelve patients (nine males) with a median age of 73 years (range 54-85) were included. Stent insertion followed by a single dose of brachytherapy was successfully performed in all but one patient who was treated with stent only. Relief of dysphagia was achieved in the majority of cases (10/11, P < 0.05), but HRQL did not improve except for dysphagia-related items. Only minor adverse events, including chest pain, reflux, and restenosis, were reported. The median survival time after inclusion was 6.6 months. Our conclusion is that the combination of stent insertion and single high-dose brachytherapy seems to be a feasible and safe palliative regime in patients with advanced esophageal cancer. Randomized trials comparing the efficacy of this strategy to stent insertion or brachytherapy alone are warranted.

Background: Hypoglossal nerve stimulation has been demonstrated to relieve upper airway obstruction acutely, but its effect on obstructive sleep apnea is not known.Objective: To determine the response in obstructive sleep apnea to electrical stimulation of the hypoglossal nerve.Methods: Eight patients with obstructive sleep apnea were implanted with a device that stimulated the hypoglossal nerve unilaterally during inspiration. Sleep and breathing patterns were examined at baseline before implantation and after implantation at 1, 3, and 6 months and last follow-up.Results: Unilateral hypoglossal nerve stimulation decreased the severity of obstructive sleep apnea throughout the entire study period. Specifically, stimulation significantly reduced the mean apnea-hypopnea indices in non-rapid eye movement (mean +/- SD episodes per hour, 52.0 +/- 20.4 for baseline nights and 22.6 +/- 12.1 for stimulation nights; P<.001) and rapid eye movement (48.2 +/- 30.5 and 16.6 +/- 17.1, respectively; P<.001) sleep and reduced the severity of oxyhemoglobin desaturations. With improvement in sleep apnea, a trend toward deeper stages of non-rapid eye movement sleep was observed. Moreover, all patients tolerated long-term stimulation at night and did not experience any adverse effects from stimulation. Even after completing the study protocol, the 3 patients who remained free from stimulator malfunction continued to use this device as primary treatment.Conclusion: The findings demonstrate the feasibility and therapeutic potential for hypoglossal nerve stimulation in obstructive sleep apnea.

Cancer of the pharyngoesophageal junction (PEJ) is associated with late onset of symptoms, high morbidity, and a dismal prognosis. Radical surgery with pharyngolaryngectomy and reconstruction with a free vascularized jejunal transplant has been increasingly practiced in the treatment of these patients. This strategy is not devoid of challenges, and the present study is aimed at evaluating the long-term functional outcome among patients who have undergone such surgical treatment. Ten patients (mean age 59 years) with a mean follow-up time of 54 months were included. Clinical assessment, health-related quality of life (HRQL) questionnaires, and a standardized radiography examination were used for evaluation. The Karnofsky index ranged from 60 to 90 (mean 82). Global QL scores (EORTC QLQ-C30) had a mean value of 74, and the mean scores for dysphagia-related items of the EORTC QLQ OES-18 questionnaire were within the lower range. Radiographic signs of disturbed bolus transport through the jejunal transplant were found in all patients examined despite the grading of dysphagia from 0 to 1. The Watson dysphagia score varied between 0.5 and 45.0 (mean 16.2). No correlations were found between radiographic findings and the clinical evaluations or the outcomes assessed by the HRQL questionnaires. HRQL was found to be generally good after cancer of the PEJ and jejunal transplant insertion. Most patients reported mild dysphagia. Radiologic signs of disturbed bolus passage were common, but their clinical impact seemed questionable.

The purpose of this study was to evaluate a single institution's outcome for patients with advanced laryngeal cancer treated with accelerated radiotherapy ( RT). Fifty- eight patients with advanced laryngeal cancer ( T3/ T4N0/ N -/- M0) were treated with curative intent with accelerated RT during the period 1990 - 1998. Patients received radiotherapy alone or with induction chemotherapy. The 5- year local control ( LC) and loco- regional control ( LRC) probabilities were both 49% for T3 and 75% for T4 tumors. The 5- year disease- free survival probability was 46% and 68% and overall survival probability was 30% and 39% for T3 and T4 tumors respectively. No significant statistical difference in outcome was found, either between T3 and T4 tumors, or between patients who received induction chemotherapy and those who did not. The treatment results for advanced laryngeal cancer at this institution were comparable to those reported in the literature. The results for T3 and T4 were similar. T4 classification alone should not be an exclusion criterion for larynx preservation. Overall survival was poor, partly because of a high incidence of deaths from intercurrent diseases.

SUMMARY:Esophageal cancer often presents as advanced stage disease with a dismal prognosis, with only 10-15% of patients surviving 5 years. Therefore, in a large proportion of patients, palliative treatment is the only option available. The aim of this study was to prospectively compare the palliative effect of self-expandable stent placement with that of endoluminal brachytherapy regarding the effect on quality of life and on specific symptoms. Sixty-five patients with advanced cancer of the esophagus or gastroesophageal junction were randomized to treatment with either an Ultraflex expandable stent or high-dose-rate endoluminal brachytherapy with 7 Gy x 3 given in 2-4 weeks. Clinical assessment and health-related quality of life (HRQL) were measured at inclusion and 1, 3, 6, 9 and 12 months later. The HRQL was measured with standardized questionnaires (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Oesophageal Module and Hospital Anxiety and Depression Scale). Twenty-eight patients completed the stent treatment and 24 patients the brachytherapy. The group of patients treated with stent reported significantly better HRQL scores for dysphagia (P < 0.05) at the 1-month follow-up, but most other HRQL scores, including functioning and symptom scales, deteriorated. Among brachytherapy-treated patients, improvement was found for the dysphagia-related scores at the 3-months follow-up, whereas other significant changes of scores were few. The median survival time was comparable in the two groups (around 120 days). In conclusion, insertion of self-expandable metal stents offered a more instant relief of dysphagia compared to endoluminal brachytherapy, but HRQL was more stable in the brachytherapy group.

Objective To relieve dysphagia is the main goal in palliative treatment of patients with incurable cancer of the oesophagus or the gastro-oesophageal junction. The aim of this prospective, randomized multicentre study was to compare stent placement and brachytherapy regarding health economy and clinical outcomes.Methods Patients with incurable cancer of the oesophagus or gastro-oesophageal junction were randomized to receive a self-expandable metallic stent or 3 x 7 Gy brachytherapy. At clinical follow-up visits, dysphagia was scored and health care consumptions were recorded. Costs were based on hospital debits. Total lifetime healthcare consumption costs and costs for the initial treatments were calculated and a sensitivity analysis was conducted.Results Thirty patients were randomized to each treatment group. There was no difference in survival or complication rates between the two treatment strategies. There was a significant difference in the change of dysphagia scores between the time of inclusion and the 1 month follow-up visit, in favour of the stented group (P=0.03). This difference had disappeared at 3 months. Median total lifetime costs were EURO7 690 for the stented group compared with EURO33 171 for the brachytherapy group (P=0.005). This difference was due to higher costs for the initial treatment (EURO4615 versus EURO23 857, P < 0.0001). Sensitivity analyses showed that the charges for a brachytherapy session had to be reduced from is an element of 6092 to EURO4222 (31%) to make this therapeutic concept costcompetitive.Conclusion Stenting is currently more cost-effective compared with fractionated 3 x 7 Gy brachytherapy for patients with incurable cancer of the oesophagus and gastro-oesophageal junction. Eur J Gastroenterol Hepatol 17:1369-1377 (c) 2005 Lippincott Williams & Wilkins.

Objectives/Hypothesis. Electrical stimulation of the posterior cricoarytenoid muscle, when paced with inspiration, offers a physiological approach to restore ventilation in bilateral laryngeal paralysis without any of the disadvantages associated with conventional treatment. Study Design: A prospective study of six patients. Methods. The patients were successfully implanted with an Itrel II stimulator (Medtronic, Inc). In postoperative sessions, stimulated vocal fold abduction, patient ventilation, and voice were assessed and compared with preoperative values. Results. The optimum stimulus paradigm was a 1- to 2-second train of 1-millisecond pulses delivered at a frequency of 30 to 40 Hz and amplitude of 2 to 7 V. Posterior cricoarytenoid stimulation produced a large dynamic abduction (3.5-7 mm) in three patients and moderate abduction (3 mm) in a fourth patient. The fifth patient showed a large but delayed response of 4 mm to stimulation with some lateralization of the vocal fold. In the sixth patient, stimulated abduction was noted on device implantation but was lost postoperatively. All five patients with stimulated abduction postoperatively met the ventilatory criteria for decannulation, and three patients subsequently had decannulation. Long-term stimulation of the posterior cricoarytenoid muscle had no appreciable effect on voice quality. Conclusions. Electrical stimulation of the posterior cricoarytenoid muscle shows potential as an improved therapy for bilateral vocal fold paralysis.

Obstructive sleep apnea syndrome (OSAS) is characterized by snoring and apnea during sleep leading to decreased oxygen saturation and disturbed sleep, excessive daytime sleepiness and neuropsychological disturbances. This study investigates cognitive neuropsychological abilities in a group of 53 OSAS patients before and after treatment with uvulopalatopharyngoplasty. General intellectual ability, verbal learning and memory as well as executive functioning were measured at baseline and 6 months postoperatively. After surgery there were significant improvements in verbal learning and memory (mean change - 39, SD 57.3, p <0.001), recall (mean change - 24.3, SD 39.3, p <0.001) and executive functioning (as assessed by percentage of errors on the Wisconsin Card Sorting Test; mean change-9.1, SD 15.7, p <0.001). These improvements were in accordance with improvements in the degree of sleep apnea, the oxygen desaturation index (mean change -9.7, SD 15.9, p <0.001) and arterial minimum oxygen saturation (mean change 4.5%, SD 10.2%, p <0.01). Surgical treatment seems to improve verbal learning, memory and recall and executive functions in parallel with better oxygenation in OSAS.

OBJECTIVES:The aim was to study the relationship between perceptual evaluation of speech variables related to velopharyngeal function and the pattern of nasal airflow during the velopharyngeal closing phase in speech in children with and without cleft palate.PARTICIPANTS:Fourteen children with cleft lip and palate or cleft palate only and 15 controls aged 7 and 10 years. All were native Swedish speakers.METHOD:Three experienced listeners performed a blinded perceptual speech evaluation. Nasal airflow was transduced with a pneumotachograph attached to a nasal mask. The duration from peak to 5% nasal airflow, maximum flow declination rate, and nasal airflow at selected points in time during the transition from nasal to stop consonants in bilabial and velar articulatory positions in sentences were estimated. The analysis was focused on the perceptual ratings of "velopharyngeal function" and "hypernasality."RESULTS:A strong association was found between ratings of "velopharyngeal function" and "hypernasality" and the pattern of nasal airflow during the bilabial nasal-to-stop combination /mp/. Both the sensitivity and specificity were 1.00 for the bilabial temporal airflow measure in relation to ratings of "velopharyngeal function." The nasal airflow rate during /p/ in /mp/ had a sensitivity of 1.00 and specificity of 0.92 to 0.96 in relation to ratings of "hypernasality."CONCLUSION:Assessment of the nasal airflow dynamics during the velopharyngeal closing phase in speech presents quantitative, objective data that appear to distinguish between perceptually normal and deviant velopharyngeal function with high sensitivity and specificity.

Objectives: (1) To study the nasal airflow patterns during the velopharyngeal closing phase in speech produced by children with and without cleft palate. (2) To compare the nasal airflow patterns in bilabial, dental, and velar articulation in these children. Design: Prospective, cross-sectional study of a consecutive series of children with cleft palate referred for routine speech evaluation and controls. Setting: Sahlgrenska University Hospital, Göteborg, Sweden. Participants: Seventeen children with cleft lip and palate or cleft palate only and 22 controls aged 7 and 10 years. Method: Nasal airflow was transduced with a pneumotachograph attached to a nose mask and registered together with the acoustic speech signal. Sentences containing nasal-to-stop combinations in bilabial, dental, and velar articulatory positions were used. Main Outcomes Measures: The duration from peak to 5% nasal airflow, the maximum flow declination rate, and the nasal airflow at selected points in time during the transition from nasal-to-stop consonants. Results: In the cleft palate group, duration from peak to 5% nasal airflow was clearly longer than among the controls (p , .0001). The declination of airflow was slower (p , .006) and the rate of nasal airflow at the release of the stop consonant was higher (p , .004) in the cleft palate group. Differences between bilabial versus dental and velar articulation were found in the control group. Conclusion: Studies of the temporal and dynamic characteristics of the nasal airflow variations during speech appear potentially useful for the assessment of velopharyngeal function.

Prior small and retrospective studies have indicated that obstructive sleep apnea (OSA) disease-related psychiatric morbidity might be reversed by correcting the sleep-related breathing disorder.To evaluate the effect of surgical intervention (uvulopalatopharyngoplasty, UPPP) on associated psychiatric morbidity we prospectively evaluated a large cohort (n = 53) of OSA patients before and after UPPP.Surgical intervention resulted in a significant reduction of depressive disorder (p < .001) in parallel with improvement of the sleep disorder. Our results show that sleep disturbance and reduced daytime alertness may be at least one of the factors behind depressive symptoms in OSA.

We conducted sleep studies in a consecutive series of 21 children with craniofacial malformations and suspected obstructive sleep apnoea. Thirteen had sleep apnoea, and one patient with a tracheostomy could not be tested. Twelve children were admitted for initiation of treatment with nasal continuous positive airway pressure (nCPAP). Ten patients accepted nCPAP, two did not. Seven children use home treatment successfully. Obstructive sleep apnoea in most children is completely eliminated with nCPAP. The treatment is safe, effective, and leads to a reduction in the number of operations done for children with craniofacial malformations. Aesthetic operations can be delayed until facial growth is complete.

Pharmacologic enhancement of serotonergic transmission by serotonin uptake inhibition has been suggested as one approach to improve upper-airway patency and thus nocturnal breathing in patients with obstructive sleep apnea (OSA). To test this hypothesis, we performed a double-blind, randomized, placebo-controlled crossover study testing the effect of paroxetine (20 mg od) on polysomnographic and psychopathologic outcomes in 20 male OSA patients (mean age 52.1 years, mean BMI 28.7 kg/m2, mean oxygen desaturation index on a previous screening 25.4/hour). The two treatment periods of 6 weeks and the separating washout period of 4 weeks were completed by 17 patients. Paroxetine reduced the apnea index during NREM sleep (-35%, p = 0.003), but not during REM sleep. No significant effect on hypopnea indices was found. With the exception of a previously described REM-postponing effect (p = 0.05), sleep architecture was not significantly influenced by paroxetine. Similarly, the effect of paroxetine on apnea was not associated with a significant overall alleviation of psychopathologic symptoms as rated on the Comprehensive Psychopathological Rating Scale or OSA-related daytime complaints assessed by visual analog scales. We conclude that enhanced serotonergic transmission improves breathing during NREM sleep in OSA. This effect is poorly related to effects on sleep architecture or daytime symptoms.

Oesophageal carcinoma is a disease with poor prognosis despite improved treatment and diagnostic methods. The most important prognostic features are the degree of wall invasion and the presence of lymph node metastasis. Endoscopic ultrasonography (EUS) in the region of 7.5-12 MHz has improved the accuracy of tumour staging. In the course of 1 year, 21 patients with oesophageal carcinoma were examined with 20 MHz high resolution intraluminal ultrasonography (HRES). In 11 (52%) patients, both ultrasound catheter and fiber gastroscope could pass the tumour, in 5 (23%) only the ultrasound catheter could pass. In the remaining patients the ultrasound catheter could only partially pass without prior dilatation. One patient was classified as having a stage T2 tumour, 14 (67%) had T3 and 4 (19%) had T4. In 2 patients the tumour could not be fully classified but was at least T3. When comparing our results with findings at computed tomography (CT), the T stage coincided in 9 patients (42%), in 9 patients (42%) CT could not differentiate between T2 and T3 and in 3 investigations HRES showed a higher T stage than CT. In 3 patients (14%) ultrasonography found N1 stage where CT staged N0. In one patient, CT found lymph nodes not seen with HRES. Further studies comparing EUS, HRES and surgical findings are planned to assess our view that HRES is a useful method in preoperative staging of oesophageal carcinoma.

Plexiform neurofibroma of the larynx is a rare disease. Three cases in children with airway obstruction are presented. After tumour reduction via a lateral pharyngotomy their tracheostomies could be closed. The surgical treatment of plexiform neurofibroma of the superior laryngeal nerve is discussed and conservative, subtotal resection is recommended.

The effect of sabeluzole (SAB), an agent with anti-excitatory amino acid activity, on sleep, breathing and daytime symptoms was investigated in 13 patients with obstructive sleep apnea (OSA). There was marked interindividual variation in both the effect on sleep and breathing and the plasma concentration of SAB. However, individual plasma drug concentration was highly correlated (r = 0.82, p = 0.02) with a reduction of the oxygen desaturation index during sleep (ODI) after treatment with SAB. Further investigation of this and agents of this type are warranted in patients with OSA.

Twelve patients with severe obstructive sleep apnoea were included in an open, long-term, prospective, follow-up study addressing the effects of nasal continuous positive airway pressure (CPAP) on sympathetic activity, cardiac structure and blood pressure. Plasma norepinephrine (P-NE) (daytime at rest), daytime and night-time urinary excretion of NE (U-NE), vanylmandelic acid and metanephrines, together with 24 h noninvasive blood pressure (BP) recording and Doppler-echocardiography, were assessed before and after a mean of 20.5 (range 14-26) months of CPAP. Average self-reported use of CPAP was 89% (range 65-100%) of time spent in bed. Resting daytime P-NE ranged 0.35-0.83 ng.ml-1, which is elevated compared to healthy controls. Only night-time U-NE, mean daytime BP and average 24 h BP were related to severity of OSA. Night-time metanephrine was related to daytime and night-time diastolic, as well as night-time systolic, BP. Left ventricular mass index (LVMI) at baseline was correlated to daytime systolic BP and P-NE. Long-term CPAP treatment reduced biochemical markers of sympathetic activity. P-NE decreased by approximately 50%, and daytime and night-time vanylmandelic acid and metanephrine by 32-54%. In contrast, there were no overall reductions in BP or LVMI. It is concluded that obstructive sleep apnoea is associated with high sympathetic activity both during sleep and waking periods. Urinary metanephrine excretion seemed to reflect blood pressure, but neither daytime nor night-time catecholamine excretion was directly related to disease severity in patients with severe obstructive sleep apnoea.(ABSTRACT TRUNCATED AT 250 WORDS)

The modulating effects of propoiol versus methohexital on the cardiovascular response to microlaryngoscopy were studied in 35 patients divided into four equal groups (one patient participated twice). Heart rate (HR), mean arterial blood pressure (MAP), cardiac output (CO; impedance cardiography), leg blood flow (LBF; occlusion plethysmography) and concentrations of arterial catecholamines were measured. After administration of atropine and fentanyl (2 μg·kg ‐1 ), anesthesia was induced by either an injection of propofol (2.0 mg·kg ‐1 ) followed by a low (6 mg·kg ‐1 ·h ‐1 ; n=91 or a high (12 mg·kg ‐1 ·h ‐1 ; n = 9) dose propofol infusion or an injection of methohexital (1.5 mg·kg ‐1 ) followed by a low (5 mg·kg ‐1 ·h ‐1 ; n=9) or a high (10 mg·kg ‐1 ·h ‐1 ; n—9) dose methohexital infusion. The low methohexital infusion dose was insufficient to control MAP, which increased 41% during microlaryngoscopy compared to the awake state. The HR increased in all groups but the increase was most prominent in the low dose methohexital group. There were no statistically significant changes in CO in any group, whereas LBF increased consistently in all groups except in patients anesthetized with the low dose of methohexital. The increases of LBF in the propofol groups were intermediate and not dose dependent. The methohexital low dose group showed increases in norepinephrine levels compared to awake values and in epinephrine levels compared to the other groups. Propofol seems to differ from methohexital in modulation of peripheral vascular tone. The insufficient control of the cardiovascular response to microlaryngoscopy by the low methohexital dose in addition to longer recovery after the high methohexital dose favors the use of propofol.

We wanted to assess whether benzodiazepines worsen sleep apnoea, since their use in such patients has been controversial. Fourteen male patients with mild to moderate obstructive sleep apnoea were investigated in a placebo-controlled, double-blind study evaluating the influence of nitrazepam (NIT) on apnoea frequency and severity. Each patient was given oral nitrazepam 5 or 10 mg, or corresponding placebo, in a randomized order on three separate nights. Wash-out time was one week. A complete sleep study was undertaken at each study night. Eleven patients completed the study. Although there were individuals with marked variability in apnoea index between the three study nights, there was no significant change in apnoea index or minimum arterial oxygen saturation with any of the two nitrazepam dosages studied. Only 3 out of 11 patients had a higher apnoea index after both nitrazepam doses compared to placebo, and in these patients the increase in sleep-disordered breathing was of marginal clinical significance. Nitrazepam caused a modest increase in total sleep time and a decrease in rapid eye movement (REM) sleep. These results demonstrate that nitrazepam does not worsen sleep apnoea in patients with mild to moderate sleep apnoea. The previously reported sleep apnoea promoting effects of benzodiazepines may be restricted to a small subgroup of patients with sleep-disordered breathing.