Intraoperative visualisation and treatment of salivary glands in Sjögren’s syndrome by contrast-enhanced ultrasound sialendoscopy (CEUSS): protocol for a phase I single-centre, single-arm, exploratory study

Abstract

IntroductionWe established a promising sialendoscopic treatment for in vivo enhancement of salivation in salivary glands affected by Sjögren’s syndrome (SS). In this technique, the ducts of the salivary glands are irrigated with saline and steroids. This allows for dilatation of ductal strictures and removal of debris. Unfortunately, it is not possible to assess the delivery and penetration of saline or medications in the ductal system and parenchyma. To address this problem, we will conduct contrast-enhanced ultrasound sialendoscopy (CEUSS) using sulphur hexafluoride microbubbles. To the best of our knowledge, microbubbles have never been used for the treatment of salivary glands in SS. It is, therefore, imperative to test this application for its safety and feasibility.Methods and analysisA single-arm phase I study will be performed in 10 SS patients. Under local anaesthesia, ultrasound (US) guided infusion of the parotid and submandibular glands with microbubbles will be performed. Continuous US imaging will be used to visualise the glands, including the location of strictures and occlusions. Main outcomes will be the evaluation of safety and technical feasibility of the experimental treatment. Secondary outcomes will consist of determinations of unstimulated whole mouth saliva flow, stimulated whole mouth saliva flow, stimulated parotid saliva flow, clinical oral dryness, reported pain, xerostomia, disease activity, salivary cytokine profiles and clinical SS symptoms. Finally, salivary gland topographical alterations will be evaluated by US.Ethics and disseminationEthical approval for this study was obtained from the Medical Ethics Committee of the Amsterdam University Medical Centre, Amsterdam, The Netherlands (NL68283.029.19). data will be presented at national and international conferences and published in a peer-reviewed journal. The study will be implemented and reported in line with the Standard Protocol Items: Recommendations for Interventional Trials’ statement.Trial registration numbersThe Netherlands Trial Register: NL7731, MREC Trial Register: NL68283.029.19; Pre-results.

A randomized controlled trial to verify the irrigation of salivary glands in relieving xerostomia in patients with Sjögren’s syndrome

“…In our study, the presence or absence of stenosis of the main duct based on the presence or absence of obstruction symptoms after eating can be roughly determined. Moreover, sialography, MR or ultrasound can be used to determine whether there is stenosis in the main duct for some SS patients with food-induced obstructive symptoms that could not be caused by severe hyposalivation ( 16 , 17 , 33 ). Thus sialendoscopy-assisted treatment may be suggested for patients with definite stenosis of the main duct ( 33 ).…”

“…Moreover, sialography, MR or ultrasound can be used to determine whether there is stenosis in the main duct for some SS patients with food-induced obstructive symptoms that could not be caused by severe hyposalivation ( 16 , 17 , 33 ). Thus sialendoscopy-assisted treatment may be suggested for patients with definite stenosis of the main duct ( 33 ). While for SS patients without significant stenosis in the main ducts, the application of sialendoscopy is not recommended owing to the risk of complications caused by sialendoscopy procedures ( 18 ).…”

Intraoperative Visualization and Treatment of Salivary Gland Dysfunction in Sjögren’s Syndrome Patients Using Contrast-Enhanced Ultrasound Sialendoscopy (CEUSS)

“…It is not possible to enter and explore all ducts with the sialendoscope because of decreasing ductal diameters from the main duct to terminal glandular tissue. In addition, it is difficult to intraoperatively monitor the delivery and degree of penetration of the irrigation fluids or medications into the ductal system and parenchyma, as well as to evaluate therapeutic efficacy (i.e., removal of obstructions and restoration of flow rate) [ 20 ].…”

“…To address these limitations of sialendoscopy and improve our therapy, we postulated that contrast-enhanced ultrasound sialendoscopy (CEUSS), using commercially available sulfur hexafluoride microbubbles (SonoVue; Bracco Imaging SpA, Milan, Italy), might be useful [ 20 ]. These microbubbles, consisting of 5–10 µm gas-filled particles, are currently used in the cardiology field to image and dissolve arterial occlusions (sonothrombolysis) [ 21 , 22 , 23 , 24 ].…”

“…Our study aimed to assess the safety, practical applicability, and initial efficacy of CEUSS in the salivary glands of patients with SS. The protocol of this study was published in 2020 [ 20 ].…”