Nebulised hypertonic saline in moderate-to-severe bronchiolitis: a randomised clinical trial.

OBJECTIVES: To investigate whether nebulised hypertonic saline (HS) treatment would decrease length of hospital stay (LOS) among infants with moderate-to severe-bronchiolitis compared with standard supportive care (SC). METHODS: We conducted an open, multicentre, randomised clinical trial from 1 April 2013 to 31 March 2016, in Swiss children's hospitals. Patients aged 6 weeks to 24 months with a primary diagnosis of moderate or severe bronchiolitis were included. Children with previous episodes of wheezing, cardiac disease, chronic respiratory disease, immunodeficiency, prematurity (gestational age <34 weeks), corticotherapy in the preceding 2 weeks or inhaled bronchodilators within 24 hours before presentation were excluded. Patients were randomised to receive standard SC with nebulisation of 4 mL of 3% sodium chloride every 6 hours versus SSC. Main outcomes and measures were LOS duration of oxygen therapy, transfer to intensive care unit (ICU), readmission within 7 days following discharge and adverse events. RESULTS: 121 children were randomised. No statistically significant differences were found between treatment groups at baseline (age, Wang Score, atopic history, smoking exposure). Children in the HS group had a non-significant difference in length of stay -2.8 hours (-10; 16) compared with the SC group. There were no differences in oxygen therapy duration, transfer to ICU, readmission rate or adverse events. The intervention was discontinued at the parents' request in 16% of the cases. CONCLUSION: Our study does not support the use of HS nebulisation in children with moderate to severe bronchiolitis. TRIAL REGISTRATION NUMBER: NCT01812525.

Extensive (8 to 12 cm2) noncircumferential endoscopic mucosal resection for early esophageal cancer.

BACKGROUND: Endoscopic mucosal resection (EMR) is an appealing method for treating intramucosal esophageal cancer but must comply with the following stringent requirements: proper preoperative staging, complete resection of the lesion, obtaining a resected specimen for histologic analysis of safety margins, and squamous reepithelialization without stricture formation. METHODS: A rigid esophagoscope was created to resect up to 12 cm(2) of esophageal mucosa in a single specimen and at a constant depth through the submucosa. Under visual control, the esophageal mucosa is sucked into a transparent window and resected with a thin diathermy wire loop in 10 seconds. After extensive preclinical studies in a sheep model, this article reports our early experience in humans. RESULTS: Twenty-one hemi-circumferential EMRs were performed for 11 dysplastic Barrett's esophagi and 10 early squamous cell carcinomas with no perforation, one hemorrhage controlled by embolization of the left gastric artery, and one incomplete resection. Deep safety margins were clear in 19 of 21 resected specimens (2 patients, unfit for operations, had submucosal invasion of squamous cell carcinoma and adenocarcinoma, respectively). Lateral margins were not clear by definition in 7 circumferential Barrett's esophagi, but were clear in 4 incomplete Barrett's esophagi and 10 early squamous cell carcinomas. CONCLUSIONS: Large EMRs of 12 cm(2) can safely be performed at the submucosal level in the esophagus. Although feasible in one session, circumferential EMR in humans is not yet advisable because of the risk of stricture formation during the healing phase. The rate of complications of this series of 21 EMRs in humans is acceptable.

Assessment of a sheep animal model to optimise photodynamic therapy in the oesophagus.

BACKGROUND AND OBJECTIVES: Precursor lesions of oesophagus adenocarcinoma constitute a clinical dilemma. Photodynamic therapy (PDT) is an effective treatment for this indication, but it is difficult to optimise without an appropriate animal model. For this reason, we assessed the sheep model for PDT in the oesophagus with the photosensitiser meta-(tetra-hydroxyphenyl) chlorin (mTHPC). MATERIALS AND METHODS: Twelve sheep underwent intravenous mTHPC injection, blood sampling and fluorescence measurements. mTHPC's pharmacokinetics was measured in vivo and in plasma by fluorescence spectroscopy. Biopsies of sheep oesophagus were compared to corresponding human tissue, and the mTHPC's biodistribution was studied under fluorescence microscopy. Finally, the sheep oesophageal mucosa was irradiated, 4 days after mTHPC's injection. RESULTS: Histologically, the sheep and human oesophagus were closely comparable, with the exception of additional fatty tissue in the sheep oesophagus. mTHPC's pharmacokinetics in sheep and human plasmas were similar, with a maximum of concentration in the sheep 10 hours after i.v. injection. mTHPC's pharmacokinetics in vivo reached its maximum after 30-50 hours, then decreased to background levels, as in humans under similar conditions. Two days after injection, mTHPC was mainly distributed in the lamina propria, followed by a penetration into the epithelium. The sheep and human tissue sensitivity to mTHPC PDT was similar. CONCLUSION: In conclusion, this model showed many similarities with humans as to mTHPC's plasma and tissue pharmacokinetics, and for tissue PDT response, making it suitable to optimise oesophagus PDT.

Extended endoscopic mucosal resection in the esophagus and hypopharynx: a new rigid device.

We present a new device allowing for the diagnosis and treatment of extended superficial lesions of the esophagus and hypopharynx such as early squamous cell carcinoma, intestinal metaplasia with high grade intraepithelial neoplasia or early adenocarcinoma arising in Barrett's esophagus. A new modified rigid esophagoscope (Karl Storz GmbH, Germany) has been designed. A large mucosal area is sucked against a transparent and perforated hemi-cylindrical window. Mucosal resection is performed by an electrical wire loop at a constant depth of 1 +/- 0.1 mm. The resected surface varies from 4 to 12 cm(2). Circumferential resection consists of two opposite individual hemi-circumferential resections. We performed three series of animal trials: hemicircumferential mucosectomies; circumferential resections of variable (2 to 6 cm) length and long-segment mucosectomies with follow-up. Hemi- and circumferential resections could be done in one or two specimens only which allowed precise histological studies. This facilitated easy orientation and analysis of the surgical margins. The deep resection margin was precisely located at the submucosal level, a prerequisite for a safe resection of superficial cancers of the esophagus and hypopharynx.

Extensive circumferential endoscopic mucosal resection with a new rigid esophagoscope: an animal study.

OBJECTIVE: Current endoscopic mucosal resection techniques are suboptimal for large circumferential mucosal resections intended to treat Barrett mucosa with multicentric foci of high-grade intraepithelial neoplasia or early adenocarcinomas. A rigid modified endoscope was developed for extended endoscopic mucosal resection in the esophagus. This pilot animal study investigated the feasibility of circumferential endoscopic mucosal resections of different lengths in the sheep esophagus. METHODS: Circumferential esophageal endoscopic mucosal resections of 2.2 cm (n = 6), 3.3 cm (n = 6), 4.4 cm (n = 7), and 5.5 cm (n = 5) were performed in 24 sheep. Circumferential resections consisted of two opposite hemicircumferential mucosectomies. Animals were followed up with endoscopic examinations at 1 week and then monthly to 6 months, or until complete re-epithelialization without stenosis eventually ensued. Strictures were treated with a single or repeated dilatations with Savary bougies. RESULTS: Circumferential resections 2.2 to 5.5 cm in length were successfully performed in 23 of 24 of the animals. One perforation occurred directly after mucosectomy. Accurate depth of resection through the submucosa was obtained in 85% of the specimens. Cicatricial stenosis was controlled in 95% by bougienage. CONCLUSION: Endoscopic mucosal resection performed with the rigid esophagoscope allowed extensive circumferential resections in a single session. There is thus potential to eradicate complete Barrett esophagus with high-grade intraepithelial neoplasia or early adenocarcinomas.

Partial cricotracheal resection for pediatric subglottic stenosis: long-term outcome in 57 patients.

OBJECTIVE: We sought to assess the long-term outcome of 57 pediatric patients who underwent partial cricotracheal resection for subglottic stenosis. METHODS: Eighty-one pediatric partial cricotracheal resections were performed in our tertiary care institution between 1978 and 2004. Fifty-seven patients had a minimal follow-up time of 1 year and were included in this study. Evaluation was based on the last laryngotracheal endoscopy, the responses to a questionnaire, and a retrospective review of the patient's data. The following parameters were analyzed: decannulation rates, breathing, voice quality, and deglutition. RESULTS: A single-stage partial cricotracheal resection was performed in 38 patients, and a double-stage procedure was performed in 19 patients. Sixteen patients underwent an extended partial cricotracheal resection (ie, partial cricotracheal resection combined with another open procedure). At a median follow-up time of 5.1 years, the decannulation rates after a single- or double-stage procedure were 97.4% and 95%, respectively. Two patients remained tracheotomy dependent. One patient had moderate exertional dyspnea, and all other patients had no exertional dyspnea. Voice quality was found to improve after surgical intervention for 1 +/- 1.34 grade dysphonia (P < .0001) according to the adapted GRBAS grading system (Grade, Roughness, Breathiness, Asthenia, and Strain). CONCLUSIONS: Partial cricotracheal resection provides good results for grades III and IV subglottic stenosis as primary or salvage operations. The procedure has no deleterious effects on laryngeal growth and function. The quality of voice significantly improves after surgical intervention but largely depends on the preoperative condition.

Prefabrication of composite grafts for long-segment tracheal reconstruction.

OBJECTIVE: To investigate the prefabrication of vascularized mucosa-lined composite grafts intended to replace circumferential tracheal defects. DESIGN: Plane grafts composed of ear cartilage and full-thickness oral mucosa were revascularized by the laterothoracic fascia. The use of meshed vs nonmeshed mucosa to improve the epithelial coverage was examined. We also investigated the creation of a vascular bed over the cartilage and the subsequent application of meshed mucosa. Macroscopic aspects, viability, and degree of mucosal lining were analyzed. SUBJECTS: Twenty male New Zealand white rabbits. INTERVENTIONS: Ten animals underwent placement of auricular cartilage under the laterothoracic fascia. Intact (group 1) or meshed mucosa (group 2) was applied over the fascia and protected by a silicone sheet. After 3 weeks, prefabricated grafts were removed for comparison. In 10 other animals, a sheet of perforated cartilage was placed under the laterothoracic fascia. Two weeks later, 5 grafts (group 3) were harvested. The remaining 5 grafts were reopened for mucosal application over the cartilage and revascularized for 3 additional weeks (group 4). RESULTS: Vascularized plane grafts were obtained in all groups. Mucosal lining increased significantly with meshed mucosa (14%-68%; mean, 40%) compared with nonmeshed mucosa (3%-15%; mean, 10%) (P = .008). Induction of a vascular bed over perforated cartilage was achieved, but survival of secondary implanted mucosa was variable. CONCLUSIONS: A reliable technique to prefabricate composite grafts with cartilaginous support and mucosal lining is presented. The use of meshed mucosa significantly improves epithelial coverage.