Combined stent insertion and single high-dose brachytherapy in patients with advanced esophageal cancer--results of a prospective safety study.

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.

Left ventricular hypertrophy independent of hypertension in patients with obstructive sleep apnoea.

To evaluate cardiac structure and function as well as blood pressure in the obstructive sleep apnoea syndrome (OSAS), we investigated 61 male patients and 61 male controls with M-mode and two-dimensional echocardiography. All patients had a history of habitual snoring and a diagnosed light to severe OSAS by previous investigations of nocturnal oxygen saturation status. No subject in the control group had a history of OSAS or hypertension. Body weight was higher in the OSAS patients than in the controls (P less than 0.001). Fifty per cent (31 out of 61) of the OSAS patients had systemic hypertension; 17 of these 31 were on pharmacological antihypertensive treatment. Neither the systolic nor the diastolic blood pressures were found to correlate to the severity of the OSAS (desaturation index). The heart rate was higher at rest in the OSAS patients with or without systemic hypertension compared to the controls with or without a blood pressure level above 165/95 mmHg (P less than 0.05 and P less than 0.01, respectively). Left ventricular (LV) internal dimensions as assessed by echocardiography did not differ between the two groups, while the interventricular septum and the LV posterior wall were thicker in the OSAS group. Thus, the LV mass and the LV mass index were significantly higher among the OSAS patients (P less than 0.001 and P less than 0.001). The LV mass index was approximately 15% higher among the 30 normotensive OSAS patients with no history of cardiac disease compared with the normotensive controls (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

A double-blind, randomized trial of sabeluzole--a putative glutamate antagonist--in obstructive sleep apnea.

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.

Effect of serotonin uptake inhibition on breathing during sleep and daytime symptoms in obstructive sleep apnea.

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.

Augmented resting sympathetic activity in awake patients with obstructive sleep apnea.

Muscle nerve sympathetic activity (MSA) was recorded during wakefulness in 11 patients with obstructive sleep apnea (OSA) and in 9 sex- and age-matched healthy control subjects. Plasma levels of norepinephrine (NE) and neuropeptide Y were analyzed. Five patients had established hypertension (resting supine systolic BP/diastolic BP > or = 160/95 mm Hg). The investigation was performed after a minimum of 3 weeks' washout period of antihypertensive medication. Muscle sympathetic activity during supine rest was higher in patients compared with controls (p < 0.01) with no difference between normotensive and hypertensive patients. However, systolic, but not diastolic, BP was positively related to resting MSA (n = 20, p < 0.01). There was no significant correlation between body mass index and MSA. Resting MSA was unrelated to disease severity expressed as apnea frequency or minimum SaO2 during the overnight recording. Both the arterial and venous plasma norepinephrine was higher in patients compared with controls (p < 0.05). Plasma levels of NE correlated to resting MSA (p < 0.01) in the whole study group (patients and controls) but not within the respective subgroups. No significant correlation, however, was found between plasma NE (arterial and venous) and BP. Plasma neuropeptide Y-like immunoreactivity was similar in patients and controls. However, one patient with hypertension had approximately twice this level in repeated samples. It is concluded that neurogenic sympathetic activity as well as circulating plasma NE is increased in patients with OSA. This increased sympathetic activity during awake supine rest may reflect a pathophysiologic adaptation to hypoxia and hemodynamic changes occurring at repetitive apneas during sleep. The correlation between MSA and systolic BP implies that this mechanism may be directly or indirectly involved in the development of cardiovascular complications in OSA.

Long-term results with a simple surgical treatment of bilateral vocal cord paralysis.

Since 1979, we have treated patients suffering from bilateral vocal cord paralysis with laterofixation of one vocal cord, a simple and comparatively atraumatic method. To evaluate the long-term results of this method of laterofixation, 11 consecutive patients were examined at least 5 years postoperatively regarding breathing capacity, voice function, and swallowing ability. Breathing capacity was assessed by determination of orolaryngeal (upper) airway resistance and spirometry. Voice function was judged by two listening panels. Swallowing ability was studied by barium contrast radiography. Postoperative improvement of breathing capacity was, in most cases, found to be long lasting. Furthermore, there was no deterioration of voice function, nor were there aspiration problems during the postoperative follow-up period. We suggest this method of laterofixation as the treatment of choice in patients suffering from breathing difficulties due to bilateral vocal cord paralysis.

A simple operation for bilateral vocal cord paralysis.

To reduce the laryngeal obstruction in bilateral vocal cord paralysis, a new method of laterofixation was developed. The method is technically simple and less traumatic than previously published methods. No peroperative tracheostomy is needed. During surgery two needles are inserted through the thyroid cartilage. A nylon thread is passed through the needles and the needles are then withdrawn. The thread thus forms a permanent loop around the vocal cord. The effects of the laterofixation on breathing and on the voice are documented by assessment of upper airway resistance and by two listening panels respectively. Thirteen patients have been operated upon so far. In most cases the breathing was improved and the influence on the voice was moderate and adjustable. If needed the possibility to perform a more extensive surgical procedure still remains. We suggest our method of laterofixation to be the first treatment of choice in patients suffering from bilateral vocal cord paralysis.

The effects of nasal dilation on snoring and obstructive sleep apnea.

The effects of nasal valve dilation on snoring and obstructed breathing were studied in 11 patients with habitual snoring and/or obstructive sleep apnea. The anterior part of the nose, the valve region, was dilated by means of a plastic device. Ten patients underwent polysomnographic investigation including pulse oximetry and measurement of snoring noise with and without the nasal dilator in a randomized manner. Snoring, nocturnal arousals, and daytime hypersomnolence were rated by the patient and partner on a questionnaire before and after a 10-day treatment period with the dilator. The nasal airflow, as assessed by rhinomanometry when awake in the sitting position, increased by 18% (range, 5.5% to 45%) when the nasal dilator was used. The frequency and severity of obstructed breathing decreased significantly with the nasal dilator. The apnea index with and without the nasal dilator was 6.4 (range, 1.3 to 15) and 18 (range, 1.8 to 60), respectively. The mean decrease of the apnea index was 47%. The overnight minimum arterial oxygen saturation (with and without the nasal dilator was 84% (range, 76% to 88%) and 78% (range, 68% to 89%), respectively. There was a substantial decrease in snoring noise (number of epochs with Leq values, equal energy level, above 55 or 60 dB) with the dilator in all patients who presented with snoring noise above these levels during the control night. No subjective effects on arousal frequency or daytime hypersomnolence were reported. Four of 11 patients were positive to continue using the nasal dilator.

Therapeutic electrical stimulation of the hypoglossal nerve in obstructive sleep apnea.

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.

New mobilization and laterofixation procedure for cricoarytenoid joint ankylosis in rheumatoid arthritis.

Ankylosis of the cricoarytenoid joints due to rheumatoid arthritis can cause severe laryngeal obstruction. With a mobilization and laterofixation procedure, five of six patients were successfully operated upon. Documented improvement of breathing was achieved and the voice function was acceptable after decannulation.

Tracheotomy--a satisfactory method in the treatment of acute epiglottitis. A clinical and functional follow-up study.

A follow-up study, including clinical examination, X-ray and function tests, of 27 children with acute epiglottitis treated with tracheotomy at the ENT-Department, Mölndal Hospital during 1971-1975 has been performed. The function tests were an important part of the investigation and included measurement with the He-dilution technique, flow--volume curves and the forced oscillation technique. No child had any detectable tracheal stenosis or any other serious per- or postoperative complication. The only complication at all was one ugly scar on the neck. The tracheotomized patient needs very little sedation and the time spent at the intensive care unit can be shorter than for those patients treated with nasotracheal intubation.

Staging of oesophageal carcinoma with high resolution endoluminal ultrasonography.

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.

Obstructive sleep apnea in patients with pharyngeal tumours.

Six consecutive patients with pharyngeal tumours were investigated regarding disordered breathing during sleep. In addition to pulse oximetry, the investigations involved oral and nasal airflow as well as thoracic respiratory movements in four of the patients in whom the oxygen desaturation index (ODI, number of desaturations per hour of estimated sleep) was on average 24 (range 10-58). An almost total predominance of obstructive apnea was found in evaluated cases. In the 2 cases in whom only pulse oximetry was performed, numerous desaturations were found throughout the night (ODI 19 and 88, respectively). The overnight minimum oxygen saturation before treatment varied but was below 80% in 5 of the 6 patients (range less than 50-89%). On reinvestigation (n = 5) 3-4 months after treatment (radical surgery or, in one case, nasal continuous positive airway pressure (CPAP)), desaturations were totally or almost totally abolished in all patients. It is concluded that the obstructive sleep apnea syndrome may be a common finding in patients with tumours in the pharyngeal region. Radical surgery and/or nasal CPAP may result in complete disappearance of the disordered breathing during sleep in these patients.

Laryngeal obstruction after Teflon injection.

Respiratory effects of injection of teflon were studied in twelve patients with unilateral vocal cord paralysis by determination of the orolaryngeal airway resistance (Rol). Ordinary spirometry and flow volume loops were also performed but were found to be less adequate than determination of Rol. Within the first week postoperatively, Rol increased by on average about 75%. Only one patient had clinical symptoms of laryngeal obstruction. One month after the injection of teflon, Rol was in all patients the same as preoperatively. It is concluded that teflon injection should be used with caution in patients with severe respiratory impairment but could be used without fear of induced future respiratory effects in patients with progressive pulmonary disease.

Laryngeal involvement in rheumatoid arthritis.

Twenty-nine female patients with definite or classical rheumatoid arthritis (RA) and 30 controls were studied in order to assess the prevalence of laryngeal involvement in patients with RA and the occurrence of extrathoracic airway obstruction. Laryngeal involvement was assessed by physical examination including direct fiberoptic laryngoscopy, respiratory function tests and low-voltage radiography. Physical examination revealed laryngeal involvement in 17 RA patients (59%), extrathoracic airway obstruction was indicated by spirometry in 4 (14%) and radiography revealed pathological findings in 3 patients (10%). One or more signs of laryngeal involvement were found in 20 patients (69%). Symptoms of breathing difficulties were common (75%) among patients with laryngeal involvement. The erythrocyte sedimentation rate and class-specific rheumatoid factors were not correlated to laryngeal involvement.

Laryngeal obstruction assessed by computed tomography.

The aim of this study was to find out if laryngeal obstruction could be assessed by measuring the glottic area using computed tomography (CT). Results from model studies were compared with those from twelve patients with laryngeal diseases. Determination of the orolaryngeal airway resistance (Rol) was used as a reference method. The correlation between airway resistance and area in both the model and among the patients was consistent, with a curvilinear relationship. The results indicate that it is possible to measure the area of a short obstruction by CT and that this area determines the degree of obstruction.

Swallowing problems in rheumatoid arthritis.

Twenty-nine female patients with definite or classical rheumatoid arthritis (RA) and 30 controls were investigated in order to evaluate oral symptoms, particularly xerostomia, and swallowing difficulties in RA by means of a questionnaire, physical examination, stimulated saliva secretion, labial salivary gland biopsy, esophageal manometry and laboratory blood tests. Xerostomia was reported by 6 patients (21%), compared with no-one in the control group. Four of these 6 patients had decreased stimulated saliva secretion, compared with 2 of the remaining 23 patients. Dysphagia was experienced by 8 patients (28%), compared with one control subject. Dysphagia was associated with disease severity. Esophageal manometry revealed a decrease of the amplitude of the peristaltic pressure complex in the proximal part of esophagus in the RA group, indicating dysfunction of the striated muscles. No correlation was found between dysphagia and esophageal manometry results.

Airway obstruction in children due to plexiform neurofibroma of the larynx.

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.

Treatment of sleep apnoea with continuous positive airway pressure in children with craniofacial malformations.

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.

Is high and fluctuating muscle nerve sympathetic activity in the sleep apnoea syndrome of pathogenetic importance for the development of hypertension?

Muscle nerve sympathetic activity was recorded in six patients with the sleep apnoea syndrome (SAS). Compared with age- and sex-matched control patients, an increased activity during wakefulness was found. Sleep apnoic events were associated with sequencies of progressively increasing sympathetic activity followed by a sudden reduction of activity. The high sympathetic activity associated with SAS may be important in the development of the systemic hypertension commonly seen in these patients.