Recurrent obstructive salivary disease after sialendoscopy. A narrative literature review
Over the last 20 years, interventional sialendoscopy has become the therapy of choice for the management of obstructive salivary disorders, favouring a significant reduction in the number of patients undergoing traditional sialadenectomy. The overall success rate of sialendoscopy is around 90% as reported by the largest case series published; recurrence is expected in about 10% of cases, and the patient should be informed about the possibility to undergo further conservative procedures to improve symptoms. Adequate pre-operative assessment, based on ultrasonography, cone beam 3D CT and MR-sialography, is mandatory to reduce the risk of unsuccessful procedures and, therefore, recurrence of obstructive sialadenitis; moreover, in case of recurrence, the surgeon should be experienced enough to manage these cases and be able to perform additional interventions, such as transoral/transfacial sialendoscopy-assisted procedures and imaging-assisted procedures in case of difficult anatomical situations. Botulinum toxin injection and traditional sialadenectomy would be considered as possible salvage treatments in case of failure of all conservative approaches.
Obstructive salivary gland disease is a relatively common event; it has been estimated, in England, that the incidence of symptomatic sialadenitis and sialolithiasis accounts for 27.5 and 31.5 per million population per annum respectively 1; stones are the main obstructive cause, especially in the submandibular gland (80%), followed by duct stenoses and anomalies 2, autoimmune inflammatory disorders such as Sjogren’s disease and immunoglobulin (Ig) G4-related chronic sclerotising sialadenitis 3, radio-iodine induced parotitis 4, foreign bodies 4, and juvenile recurrent parotitis (JRP) 5. Over the last 20 years, interventional sialendoscopy has become the therapy of choice for management of obstructive salivary disorders, favouring a significant reduction in the number of patients undergoing traditional sialadenectomy 4. The key role of sialendoscopy in the gland-preserving management of obstructive sialadenitis has been highlighted in the international literature, but only a few multicentre studies of large series of patients with a long-term follow-up have been published to date 1,3,4. An Italian multicentre study 4 studied 1152 patients (553 females; mean age 50 years) who, after clinical and radiological assessment, underwent a total of 1342 diagnostic and interventional sialendoscopies, 44.6% of which involved the parotid gland; in this series, 12% (n = 138) of patients underwent multiple treatments to pursue the goal of obtaining recovery of obstructive symptoms. Salivary stones were the main cause of obstruction (55%), followed by ductal stenosis and anomalies (16%), mucous plugs (14.5%) and sialodochitis (4.7%). While the procedure was successful in 1,309 cases, in 33 cases (2.4%) the procedure could not be concluded mainly because of complete salivary duct stenosis (21 cases). Complete therapeutic success was obtained in 92.5% of patients after one or more procedures and was ineffective in < 8% (86 patients). Moreover, in this case series, the therapeutic success was obtained with one treatment in 752 patients (65.3%), and in 11.3% of patients after multiple treatments. Finally, in 184 patients (15.9%), the therapeutic success was partial. Zenk et al. 6, in a study involving 1,154 patients treated for parotid and submandibular stones (5% and 22%, respectively), described a success rate of > 90% and 98%, although most patients underwent a combination of endoscopic and transoral procedures; the authors concluded that sialendoscopy is an important diagnostic and therapeutic tool in the management of sialolithiasis, but needs to be combined with additional techniques to ensure a high rate of stone clearance, symptom recovery, and gland preservation. These large case series demonstrate that sialendoscopy is an effective therapeutic option in experienced hands, but recurrence can be expected, and the patient is to be informed about the possibility to undergo further conservative procedures to improve symptoms. Adequate clinical and radiological pre-operative assessment is mandatory to reduce the risk of unsuccessful procedures and, therefore, recurrence of obstructive sialadenitis; moreover, in case of recurrence, the surgeon should be experienced enough to manage these cases and be able to perform additional endoscopic or surgical procedures in a patient, previously treated, with possible inflammatory or fibrotic sequelae. The aim of this paper is to review the published experience on management of recurrent obstructive salivary disease after sialendoscopy and briefly describe the additional therapeutic options available, including traditional sialadenectomy as a possible salvage surgery (Fig. 1).
First introduced in clinical practice in the 1990s, interventional sialendoscopy (intSE), together with extracorporeal shock-wave lithotripsy (ESWL), intracorporeal laser (ILL) or pneumatic lithotripsy (IPL), and transoral duct surgery (TDS), has become part of a novel therapeutic work-up for obstructive sialolithiasis, and has contributed to reduce the rate of gland resection from 40%-50% to less than 5% 6,7. Prognostic factors influencing therapeutic success are size, location and mobility of the stone, in combination with the anatomy of the duct system and its variations 8. One international report published in 2009 summarised the results after treatment of around 4,700 cases in 5 salivary gland centers adopting minimally-invasive treatment procedures: 80.5% of patients were completely cured (stone-free and symptom-free), 16.7% were partially cured (symptom-free, but not stone-free), and 2.9% had to undergo gland resection 8. In this case series, a total of 1,522 patients were treated by intSE: stones were eradicated in 1,394 (91.6%); some stone fragments persisted, and partial success was obtained in 79 (5.2%) of cases and treatment was unsuccessful in 49 (3.2%). In all, 70 patients were subsequently treated with other techniques, and 52 refused further intervention or were lost to follow-up. After further treatment, the overall success rate was 1,460/1,522 (95.9%), and partial success was achieved in 57/1,522 (3.7%). In 5/1,522 patients (0.3%), the salivary gland was removed. Management of failure after sialendoscopy and therefore persistence or recurrence of obstructive sialolithiasis is mainly related to the location of the stone: a sialendoscopy-assisted transoral surgery is the best option technique for submandibular stones 9, while an intracorporeal lithotripsy during interventional sialendoscopy or a transfacial and/or transoral approach to the main duct and parenchyma of the parotid gland is usually proposed to the patient 10-13. This difference in the way of approaching salivary stones is often related to the need of balancing therapeutic efficacy with the desire of the patient to avoid facial nerve damage. The recent clinical experience with sialendoscopy-assisted laser and pneumatic intracorporeal lithotripsy (ISWL), has contributed to pursuing the minimal invasive therapeutic pathway 11.
A separate consideration is management of pure unpalpable parenchymal stones. In the past, ESWL was considered to be the best option, especially for parotid stones, but nowadays this technique has almost been abandoned and is available in very few centres in Europe (10). Interventional sialendoscopy with ESWL or ISWL can be useless if the stone is not reachable due to acute duct angles of the secondary branches of duct system and this is the case in 5%-15% of stones. A sialendoscopy-assisted transfacial approach with computed tomography (CT) navigation (Fig. 2) has been recently proposed for inaccessible and unpalpable parenchymal parotid stones 14,15. With regards to pure parenchymal submandibular stones, sialendoscopy-assisted transoral robotic salivary surgery (TORSS) has been recently described for unpalpable stones 16. Finally, botulinum toxin therapy finalised to functional silencing of the affected gland may be proposed to patients with recurrent obstructive disease after sialendoscopy before planning traditional invasive sialadenectomy.
Two main classification of duct strictures have been published to date. Koch et al. 17 divided these in three types:
- type I: marked inflammation, slight fibrotic remodelling of the wall, obstructive plaques;
- type II: fibrotic stenosis, short segment slight to moderate (< 50%) narrowing, “web-like” or megaduct;
- type III: marked fibrotic stenosis, high grade obstruction (> 50%), segmental or diffuse fibrotic reaction.
ESGS classification identified 5 different conditions: S0: no stenosis; S1: intraductal diaphragmatic stenosis; S2: unique main duct stenosis; S3: multiple or diffuse main duct stenosis; S4: generalised ductal stenosis 2.
The development of minimally-invasive treatment options for salivary duct stenosis, including sialendoscopy-assisted procedures, has led to a significant reduction in the failure rate after conservative treatment and therefore in the rate of gland resection 4, which now accounts for less than 10% of cases. According to Koch et al. 17, sialendoscopy-guided therapy fails in 10.7% and 5.2% of patients, respectively, for the parotid and submandibular glands. Failures may be secondary to inadequate pre-operative diagnostic work-up, which is essential to obtain a precise characterisation of stenoses and choose the ideal treatment. From a diagnostic point of view, traditional sialography has been progressively replaced by dynamic ultrasonography (US) and magnetic resonance (MR) sialography; in particular, dynamic MR sialography (stimulation with citric acid) does not require contrast media 4 since saliva is used as a natural contrast due to specific sequences and this permits to outline and depict the normal and pathologic anatomical course of the salivary duct system. MR-sialography may be not sufficient to identify duct anomalies, and in particular type I inflammatory stenoses that can be better visualised by diagnostic sialendoscopy 17. According to Koch et al. 17,18, parotid sialendoscopy is useful for type I inflammatory limited circumferential stenosis, while for type II (severe stenosis with megaduct) and III stenoses (severe diffused stenosis), the best approach is use of combined procedures: in such cases, a transoral 19 (Fig. 3) or transfacial sialendoscopy-assisted approach 13,14 can be useful to restore salivary duct patency and resolve the stenosis. Moreover, in case of a difficult anatomical situation secondary to recurrent infection and/or previous surgery with complete scarring of the duct and anatomical distortion, increasing the risk of failure or intra-operative facial nerve injury, an imaging-assisted approach 14,15 with CT and/or MRI guidance (Fig. 4) can be useful to achieve therapeutic success. Intraparenchymal injection of botulinum toxin 20 under US-guidance to silence the gland and/or parotidectomy can be considered as alternative options in case of recurrence of parotid duct stenosis, since ligature of the parotid duct is effective in only 50% of patients 17.
Submandibular duct stenosis can be adequately managed after failure of sialendoscopy by a sialendoscopy-assisted transoral approach with positioning of a salivary stent to guarantee the long-term patency of salivary duct lumen 8; adequate pre-operative imaging work-up with US and MR-sialography is mandatory to define the exact location and type of stenosis. Submandibular sialadenectomy is advocated only in the case of hilar or intraparenchymal stenosis.
Autoimmune obstructive sialadenitis
Autoimmune diseases of major salivary glands essentially include Sjögren’s syndrome and a complex of disorders classified as IgG4 related diseases. Sjögren’s syndrome (SJS) is a systemic autoimmune disease that affects 0.2%-0.4% of the general population. It is characterised by an immuno-mediated destruction of exocrine glands (mainly salivary and lacrimal glands) and often by B lymphocyte activation and proliferation with production of auto-antibodies, such as rheumatoid factor (RF), anti-SS-A/Ro and anti-SS-B/La 21,22. The precise aetiology of SJS is unknown, but is probably triggered by both genetic and environmental factors. Patients with SS are usually enrolled according to the 2002 American-European Consensus Group (AECG) criteria 23; almost recently a joint venture between SJS recognised experts from the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) have produced a new set of criteria for SJS that has been recently published 24. An international steering committee of the European League Against Rheumatism (EULAR) SJS Task Force has also developed two disease activity indices: the EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI), which measures the symptoms of patients with primary SJS in 3 domains (dryness, pain, fatigue) using 0-10 numerical scales 25-27 and the EULAR SJS Disease Activity Index (ESSDAI) 26-28 that provides a standardised instrument for homogeneous evaluation of systemic activity in clinical trials and daily practice 23,29. This latter scoring system is composed by a number of domains for different organs and systems. The glandular domain allows grading the swelling of submandibular and parotid glands by a semiquantitative method. The management of SJS patients is still debated because there is no effective treatment for the disease as a whole 29 and low-dose systemic steroid therapy is often ineffective for the management of recurrent sialadenitis 30. Interventional sialendoscopy has been described as an alternative means of controlling the number of episodes of sialadenitis 31-34. A recent randomised controlled trial showed that sialendoscopy resulted in an increased salivary flow during follow-up over 60 weeks and reduced xerostomia 35. Furthermore, irrigating the duct system with saline and/or steroid solution can also alleviate complaints in patients with inflammatory disease (Fig. 5). A recent systematic literature review provided support for the use of sialendoscopy in the treatment of SJS sialadenitis with an expected, at least temporary, improvement of symptoms in 90% to 99% of cases 36. Furthermore, we have recently shown that interventional sialendoscopy with steroid duct irrigation significantly reduces the number of painful episodes of sialadenitis and improves the subjective sensation of oral dryness and other disease symptoms in patients with SJS; in terms of recurrence, the beneficial effects of interventional sialendoscopy is reduced if only interventional sialendoscopy is performed without a cycle of outpatient steroid duct irrigations, and increases when it is combined with a cycle of outpatient steroid ductal irrigations, with an objective clinical improvement of 75 and 87%, respectively 37. With regard to IgG4-related disease, both Mikuliz’s disease and Kuttner’s disease have recently been considered as variations of IgG4-related sialadenitis that most frequently involves the submandibular gland. Biopsy of the affected gland is necessary to formulate a diagnosis of IgG4-related sialadenitis, although lip biopsy has been proposed as an alternative technique; serum IgG4 concentration > 135 mg/dl has been defined as a threshold value for diagnosis. Traditional management of this salivary disorder was based on sialadenectomy. Long-term systemic steroid therapy is nowadays considered first-line treatment and prednisone represents the most widely used drug. Our initial evidence in treating patients with IgG4-related sialadenitis by interventional sialendoscopy and irrigations with steroids is that this therapy has a transitory beneficial effect but is ineffective overall, thus favouring recurrence of sialadenitis if not associated with long-term systemic steroid therapy.
Interventional sialendoscopy has been recognised as an efficient therapeutic option for radioiodine-induced sialadenitis if standard medical treatments (hydration, sialagogues, anti-inflammatory drugs) fail 38. The parotid gland is most frequently affected due to a better ability to intake iodine in comparison with the submandibular gland 39. The subsequent salivary gland obstruction, secondary to parenchymal injuries due to an increased permeability of the gland vascular endothelium with leakage of proteins and electrolytes, is responsible of the fibrotic and stenotic feature of the main Stensen’s duct and its branches; interventional sialendoscopy, mainly based on ductal hydraulic dilation with saline solution plus steroids, and in case of stenosis on ductal balloon dilation, is effective in 89.3% of cases, as reported by a recent review of the literature including 122 patients and 264 sialendoscopic procedures 40. In this series, complete therapeutic success was achieved in 33.1% of patients, and partial success in 56.2% of patients, with 5.9% of patients requiring multiple procedures. The rate of unsuccessful treatment, and thus the rate of sialadenitis recurrence, was 10.7% (13 patients); one patient (0.8%) underwent parotidectomy for severe obstructive disease. The rate of recurrences is similar to that of stones and stenosis, with about 10% of patients having persisting symptoms and recurrent inflammation. In such cases, a cycle of outpatient duct irrigation with steroids can further contribute to silence the inflammatory reaction of the duct system 40; moreover, the use of oral steroids may help in controlling the severity of symptoms. To date, none of the patients treated with interventional sialendoscopy plus outpatient steroid duct irrigations had to undergo transcervical sialadenectomy in our long-term clinical experience 4.
Juvenile Recurrent Parotitis (JRP)
Sialendoscopy is a valid and safe diagnostic and therapeutic tool for management of JRP; the procedure is usually performed under general anaesthesia, but local anaesthesia and deep sedation have been recently described 5. Typical endoscopic features of JRP are whitish appearance of the duct wall, mucous plugs, duct kinking and fibrotic strictures; interventional sialendoscopy is essentially performed by hydraulic dilation of the duct system up to the tertiary ductal branches thanks to continuous irrigation with saline solution and final irrigation with steroids (usually dexamethasone) 39. Recent published case series report complete therapeutic success after one sialendoscopy in about 75% of cases, and a higher success rate after multiple procedures 5,41,42: in a series of 32 consecutive patients, Capaccio et al. 41 reported complete therapeutic success in 25 patients, while in three cases a second endoscopic procedure was useful for relief of symptoms; one of the four remaining patients was treated with medical therapy (steroid and non-steroid anti-inflammatory drugs, sialogogues); Ezer et al. 42 reported that over 75% of patients treated with interventional sialendoscopy had no JRP recurrences after multiple procedures (usually three sialendoscopies). The main reason for recurrence of the disease could be intrinsic in the nature of this condition: some studies have suggested that the pathophysiology of JRP is immune-mediated, as shown by colour Doppler US findings of reactive lymphatic tissue in the affected glands 41, and by the histopathologic evidence of lymphocyte infiltrates near the salivary ducts 41,42 in children undergoing parotidectomy. Indeed, most of our patients with JRP show high grade of adeno-tonsillar hypertrophy or had previously undergone tonsillectomy and/or adenoidectomy 5 thus confirming the exuberant lymphatic reactivity of these patients for whom irrigation with saline solution and steroids may be not sufficient to completely extinguish the immunological burning state; moreover, it has been previously reported that controlling general concomitant comorbidities such as atopy, associated with JRP in severe cases, may help in controlling symptoms and the pathology 42. In reality, the management of recurrences, especially when multiple sialendoscopies have been performed with any or partial success, is still based on medical therapy, as previously described.
In the last 30 years, the development and the diffusion of minimally-invasive and conservative procedures such as extracorporeal and intracorporeal lithotripsy, interventional sialendoscopy, sialendoscopy-assisted transoral and transfacial surgical approaches for management of obstructive salivary disease has dramatically reduced the indication for traditional invasive parotidectomy or submandibular sialadenectomy; in favour of those who supported the choice of gland removal, there was previous evidence of association of chronic inflammatory condition of the affected gland in 65% of patients with sialolithiasis and a recurrence rate of about 50% in patients undergoing a cycle of extracorporeal shock-wave lithotripsy 43. On the other hand, the long-term experience acquired in dedicated international centres demonstrated, in particular for salivary stones, that multimodal therapy i.e., the combination of multiple therapeutic procedures such as extracorporeal or intracorporeal lithotripsy and interventional sialendoscopy, is more effective in terms of recurrence than each therapeutic modality used individually. Clear indications are now available in the literature based on different classification criteria, but with the common evidence that by exactly following those indications the risk of recurrence after sialendoscopy is extremely low. This is true for both stones and stenoses, where knowing the location and size of the stone and the location and type of stenoses reduces the risk of recurrence to less than 10%. Adequate pre-operative diagnostic assessment is therefore mandatory and is based on ultrasonography, cone beam three dimensional (3D) CT and MR-sialography. A separate consideration has to be made for management of salivary disorders such as autoimmune diseases, radioiodine-induced parotitis and JRP, where success and risk of recurrence depend not only on the quality of the procedure but also on the severity and grade of the underlying inflammatory and immune condition. To sum up, when performed under proper indications, interventional sialendoscopy is effective for all mobile stones and all stones < 4 mm. The combination of interventional sialendoscopy with laser or pneumatic lithotripsy is effective for intermediate stones (between 3 and 7 mm); a sialendoscopy-assisted transoral and transfacial approach is effective for palpable larger stones. Interventional sialendoscopy alone is effective for type I inflammatory stenoses, while sialendoscopy-assisted transoral and transfacial duct rehabilitation for type II or type III stenoses are associated a higher risk of recurrence and therefore of multiple salivary procedures. Interventional sialendoscopy is effective for all inflammatory and immune salivary disorders, although an additional sialendoscopic procedure is necessary in some patients to obtain complete inflammatory silencing of the affected gland, especially particular in radioiodine-induced sialadenitis and JRP. The role of interventional sialendoscopy in patients with IgG4-related sialadenitis is still debated, since very few patients have been treated with uncertain results.
Conflict of interest statement
The authors declare no conflict of interest.
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
PC, MG: study conception, acquisition and analysis of data, manuscript draft; PC, MG, PC, LP: critical revision of the manuscript. All authors: review of the final draft of the manuscript, approval of the manuscript’s submission.
Ethics approval was not required for this study because it was based on published studies.
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