Salivary Gland Disorders: Rapid Evidence Review.

The major salivary glands are the paired parotid, submandibular, and sublingual glands. Salivary gland disorders can affect the glandular tissue or its excretory system. The parotid glands are the largest and produce aqueous serous secretions that are less immunogenic. They are more susceptible to infections and neoplasms. The submandibular glands produce mucinous secretions that are high in calcium and phosphate salts through a long submandibular duct that flows against gravity. The submandibular glands are responsible for more than 80% of salivary stones. Sialadenitis can be acute or chronic and caused by bacterial, viral, and obstructive etiologies; the most common bacteria is Staphylococcus aureus. The most common viral etiologies in children are mumps (globally) and juvenile recurrent parotitis (in vaccinated populations). Sialadenosis is a chronic asymptomatic enlargement of the salivary glands due to systemic disease. Sialolithiasis causes up to 50% of salivary gland disorders. It is associated with salivary stasis and inflammation caused by dehydration, malnutrition, medications, or chronic illness. Obstruction is also caused by trauma, stenosis, and mucoceles. Neoplasms are rare and typically benign, but they warrant referral and imaging with ultrasonography, computed tomography, or magnetic resonance sialography. Most disorders are managed with conservative measures by treating the underlying etiology, optimizing predisposing factors, controlling pain, and increasing salivary flow with sialagogues, hydration, massage, warm compresses, oral hygiene, and medication adjustment. Sialendoscopy is a gland-sparing technique that can treat obstructive and nonobstructive disorders. (Am Fam Physician. 2024;109(6):550-559.

Aging-Related Metabolic Dysfunction in the Salivary Gland: A Review of the Literature.

Aging-related salivary dysfunction commonly induces the poor oral health, including decreased saliva flow and dental caries. Although the clinical significance of the salivary glands is well-known, the complex metabolic pathways contributing to the aging-dysfunction process are only beginning to be uncovered. Here, we provide a comprehensive overview of the metabolic changes in aging-mediated salivary gland dysfunction as a key aspect of oral physiology. Several metabolic neuropeptides or hormones are involved in causing or contributing to salivary gland dysfunction, including hyposalivation and age-related diseases. Thus, aging-related metabolism holds promise for early diagnosis, increased choice of therapy and the identification of new metabolic pathways that could potentially be targeted in salivary gland dysfunction.

Rare Diseases of the Salivary Glands and of Facial Nerve. / Seltene Erkrankungen der Speicheldrüsen und des Nervus Facialis.

Salivary gland diseases are rare. In the European Union (EU) a disease is considered to be rare if not more than 5 of 10,000 people are affected by it. According to estimates in Germany are about 4 million people with a rare disease. In the EU are about 30 million people with rare diseases [1]. In the present work most of the described diseases of salivary glands and of the facial nerve fall in this category. They form a very heterogeneous group whose treatment takes place mainly in specialized centers. Still, it is essential for the otolaryngologist to identify and to diagnose these diseases in order to initiate the right therapeutic steps. The work is a compilation of innate andacquired rare salivary gland disorders and of rare facial nerve disorders. The etiologies of inflammatory diseases, autoimmune disorders and tumors are taken into account. For the individual topics, the current literature, if available, was evaluated and turned into summarized facts. In this context the development of new processes, diagnostics, imaging and therapy are considered. Genetic backgrounds of salivary gland tumors and the trends in the treatment of tumorous lesions of the facial nerve are picked up. Furthermore, also rare diseases of the salivary glands in childhood are described. Some of them can occur in adults as well, but differ in frequency and symptoms. Due to the rarity of these diseases, it is recommended to tread these in centers with special expertise for it. Finally, the difficulties of initiation of studies and the problems of establishing disease registries concerning salivary gland disorders are discussed. This is very relevant because these pathologies are comparatively seldom.

Quality of Care for Salivary Gland Diseases. / Qualität der Therapie von Speicheldrüsenerkrankungen.

The treatment of salivary gland diseases represents an important segment of otorhinolaryngology. The individual otorhinolaryngologist might, however, see only a few cases per year from a large variety of salivary gland diseases. Surgical and endoscopic minimal-invasive therapy concepts play a key role. Therefore, gain of knowledge cannot only be provided by prospective clinical trials but also by meta-analyses and potentially also by registry data. Many reliable indicators are established to measure the function of a diseased salivary gland or the improvement of its function after therapy. In contrast, patient-reported outcome measures (PROMs) are not sufficiently developed. It has to be demanded that these indicators are consequently used in clinical trials. Perspectively, the same indicators could also be used for quality control for the outpatient and inpatient sector in clinical routine. The framework conditions for high-quality acquisition of knowledge are given by the otorhinolaryngology specialist medical training, the obligation of life-long continuous medical education, and certified salivary gland courses. Nevertheless, the specifications of quality standards for the treatment of patients with salivary gland diseases are not well formulated. In contrast to other disciplines also addressing salivary gland diseases, otorhinolaryngology ought to develop standards with high requirements of quality of care for salivary gland diseases.

World Workshop on Oral Medicine VII: Immunobiologics for salivary gland disease in Sjögren's syndrome: A systematic review.

OBJECTIVE: This systematic review evaluated the efficacy of immunobiologics for the management of oral disease in Sjögren's syndrome (SS). MATERIALS AND METHODS: MEDLINE® , Embase, Scopus, and the Cochrane Library were searched for evidence on the use of immunobiologics for management of glandular disease in SS. Primary outcomes were xerostomia and salivary gland dysfunction, assessed via visual analogue scales, disease-specific scales for SS, measurement of salivary flow, ultrasound data, and quality of life measures. RESULTS: Seventeen studies (11 randomized controlled trials and 6 observational studies) met inclusion criteria. Rituximab showed efficacy in improving salivary gland function but not xerostomia. Abatacept showed promise in improving both xerostomia and salivary flow. Belimumab exhibited long-term improvement of salivary flow and subjective measures. The novel agent CFZ533 improved both disease activity and patient-reported indexes. CONCLUSIONS: There is strong evidence pointing to the efficacy of rituximab in the management of oral disease in SS. Future controlled trials may elucidate the efficacy of belimumab and abatacept. The new drug CFZ533 is a promising alternative for the management of SS and its salivary gland involvement. In considering these agents, the promise of efficacy must be balanced against the harmful effects associated with biologic agents.

Percutaneous treatment of ranulas: ultrasound-guided drainage with salivary gland chemical ablation.

BACKGROUND: Ranulas are salivary pseudocysts in the floor of the mouth adjacent to damaged salivary glands. Current surgical management is drainage of the ranula with removal of the offending gland. An analogous percutaneous procedure could potentially offer similar treatment efficacy in a more minimally invasive way. OBJECTIVE: To evaluate the outcomes of a cohort of patients with ranulas treated with percutaneous ranula aspiration and chemical ablation of the source salivary gland to see whether this technique could be proposed as a minimally invasive treatment alternative. MATERIALS AND METHODS: This retrospective single-center study evaluated 24 patients treated percutaneously for ranulas between January 2004 and December 2014. All patients were treated with percutaneous ranula aspiration and chemical ablation of the offending salivary gland. Treatment success and any complications were recorded. RESULTS: Complete ranula eradication was successfully accomplished in 87.5% of the patients with no complications. CONCLUSION: Initial results suggest that our technique of percutaneous aspiration of ranulas and chemical ablation of the source salivary gland is safe and effective.

Radioactive iodine: An unappreciated threat to salivary gland function.

Thyroid cancer is an endocrine malignancy whose prevalence is increasing in the United States. Nearly 57,000 new cases of thyroid cancer are estimated to be diagnosed in 2017. The standard of care for differentiated thyroid cancer is thyroidectomy followed by ablation of thyroid remnants with high-dose radioactive iodine (131 I). Apart from thyroid glands, 131 I accumulates in cells of salivary glands and compromises its function. Xerostomia is, therefore, a frequent and often persistent complaint of patients. Despite adoption of standard preventive measures, parenchymal damage and chronic salivary dysfunction are observed in a substantial number of patients. Saliva is important for oral homeostasis, and its reduction increases the risk of oral morbidity. As differentiated thyroid cancer patients have an excellent survival rate, preservation of salivary gland function carries added significance. A focus on treatments that preserve or restore long-term salivary flow can significantly improve the quality of life of thyroid cancer survivors.

Sialendoscopy in treating pediatric salivary gland disorders: a systematic review.

OBJECTIVE: The primary aim of this study is to conduct a systematic review in order to evaluate the use of sialendoscopy in treating pediatric salivary gland disorders. METHODS: Eligible articles were identified through a comprehensive search of electronic databases. Using predefined inclusion criteria, published articles on sialendoscopy in children were selected and reviewed. RESULTS: 17 articles including 323 pediatric patients and 424 salivary glands managed by sialendoscopy were identified. The most common salivary gland disorder affected was the parotid (83% of cases), followed by the submandibular gland (16.5% of cases). Juvenile recurrent parotitis (68.9%) was the most frequent diagnosis followed by sialolithiasis (14.7%). The most common complication was ductal perforation. During a pooled mean follow-up time of 18.3 months, recurrences were reported in 14.5% of patients mostly in patients diagnosed with juvenile recurrent parotitis. CONCLUSION: Sialendoscopy is a minimally invasive diagnostic and therapeutic tool for inflammatory salivary gland disorders in pediatric patients. Based on the current review, sialendoscopy can be successfully implemented in cases of pediatric salivary gland disorders.

The Application of Absolute Ethanol in the Treatment of Mucocele of the Glands of Blandin-Nuhn.

Mucocele of the anterior lingual salivary glands is a more common cystic lesion, especially in patients aged less than 20 years. The study is aimed to observe the effect of treatment by injection of absolute ethanol instead of surgery. Fourteen outpatients diagnosed as mucocele of the glands of Blandin-Nuhn were selected. These patients, after blood investigation, were treated by injection of absolute ethanol into a mucous cavity of lesion under superficial anesthesia with 2% lidocaine once a week and followed up from 3 months to 2 years. Mucocele of the glands of Blandin-Nuhn was extirpated in all patients after 1 to 3 injections. There were no other complications except slight distending pain occurred on the same day when the patients were treated. The recurrence was not observed during the follow-up period. In conclusion, the study suggests that injection of absolute ethanol may be an alternative means for treating mucocele of the glands of Blandin-Nuhn, because it is mininvasive, safe, effective, economic, and simply manipulated compared with surgical treatment.

Delayed treatment of parotid sialocele: a functional approach and review.

The present report focused on 2 cases treated successfully with a delayed minimally invasive surgical approach and reviewed the available studies in which this method was used and their outcomes. The current data available suggest that the diversion of salivary flow into the oral cavity by cannulation of the distal portion of the parotid gland duct from the sialocele into the mouth, through the ostium or using a new controlled internal fistula creation, is a reliable, relatively simple, and effective procedure. It is available to the clinician when delayed treatment is needed, with low complication potential and great tolerability. The procedure allows a definite solution to the problem, avoiding undesirable outcomes, and preserves parotid gland functionality throughout the process of healing.

Early responses to adenoviral-mediated transfer of the aquaporin-1 cDNA for radiation-induced salivary hypofunction.

No conventional therapy exists for salivary hypofunction in surviving head and neck cancer patients with Radiation Therapy Oncology Group late grade 2-3 toxicity. We conducted a phase I clinical trial to test the safety and biologic efficacy of serotype 5, adenoviral-mediated aquaporin-1 cDNA transfer to a single previously irradiated parotid gland in 11 subjects using an open label, single-dose, dose-escalation design (AdhAQP1 vector; four dose tiers from 4.8 × 10(7) to 5.8 × 10(9) vector particles per gland). Treated subjects were followed at scheduled intervals. Multiple safety parameters were measured and biologic efficacy was evaluated with measurements of parotid salivary flow rate. Symptoms were assessed with a visual analog scale. All subjects tolerated vector delivery and study procedures well over the 42-d study period reported. No deaths, serious adverse events, or dose-limiting toxicities occurred. Generally, few adverse events occurred, and all were considered mild or moderate. No consistent changes were found in any clinical chemistry and hematology parameters measured. Objective responses were seen in six subjects, all at doses <5.8 × 10(9) vector particles per gland. Five of these six subjects also experienced subjective improvement in xerostomia. AdhAQP1 vector delivery to a single parotid gland was safe and transfer of the hAQP1 cDNA increased parotid flow and relieved symptoms in a subset of subjects.

World Workshop on Oral Medicine VI: a systematic review of medication-induced salivary gland dysfunction: prevalence, diagnosis, and treatment.

OBJECTIVES: Medication-induced salivary gland dysfunction (MISGD) causes significant morbidity resulting in decreased quality of life. This systematic review assessed the literature on the prevalence, diagnosis, treatment, and prevention of MISGD. MATERIALS AND METHODS: Electronic databases were searched for articles related to MISGD through June 2013. Four independent reviewers extracted information regarding study design, study population, interventions, outcomes, and conclusions for each article. Only papers with acceptable degree of relevance, quality of methodology, and strength of evidence were retained for further analysis. RESULTS: There were limited data on the epidemiology of MISGD. Furthermore, various methods were used to assess salivary flow rate or xerostomia. Preventive and therapeutic strategies included substitution of medications, oral, or systemic therapy with sialogogues, use of saliva substitutes or of electro-stimulating devices. Although there are promising approaches to improve salivary gland function, most studies are characterized by small numbers and heterogeneous methods. CONCLUSIONS: Physicians and dentists should identify the medications associated with xerostomia and salivary gland dysfunction through a thorough medical history. Preferably, health care providers should measure the unstimulated and stimulated whole salivary flow rates of all their patients so that these values can be used as a baseline to rate the complaints of patients who subsequently claim to experience xerostomia or salivary gland dysfunction as well as the possibilities of effectively treating this condition. CLINICAL RELEVANCE: MISGD remains a major burden for the population. This systematic review provides a contemporary in-depth description of the diagnosis and treatment of MISGD.

Functional salivary gland regeneration as the next generation of organ replacement regenerative therapy.

Oral health is maintained by the coordinated function of many organs including the teeth and salivary glands. Dysfunction of these organs causes many problems, such as dental caries, swallowing dysfunction and periodontal disease. Regenerative therapy for salivary gland tissue repair and whole-salivary gland replacement is currently considered a novel therapeutic concept that may have potential for the full recovery of salivary gland function. Salivary gland tissue stem cells are thought to be candidate cell sources for salivary gland tissue repair therapies. In addition, whole-salivary gland replacement therapy may become a novel next-generation organ regenerative therapy. Almost all organs arise from reciprocal epithelial and mesenchymal interactions of the germ layers. We developed a novel bioengineering method, an organ germ method that can reproduce organogenesis through the epithelial-mesenchymal interaction. A bioengineered salivary gland germ can regenerate a structurally correct salivary gland in vitro, and bioengineered salivary glands successfully secrete saliva into the oral cavity from ducts in the recipient through the reestablishment of the afferent-efferent neural network. The bioengineered salivary gland can also improve the symptoms of xerostomia, such as bacterial infection and swallowing dysfunction. In this review, we describe recent findings and technological developments of salivary gland regenerative therapy.

Treatment for salivary gland hypofunction at both initial and advanced stages of Sjögren-like disease: a comparative study of bone marrow therapy versus spleen cell therapy with a 1-year monitoring period.

BACKGROUND AIMS: Non-obese diabetic mice (NOD) exhibit autoimmune Sjögren-like disease (SS-like). We reported previously that a combined-therapy consisting of immuno- and cell-based therapy rescued NOD from SS-like. However, therapies tested to date on NOD mice were aimed at the initial phase of SS-like. It is unknown whether therapies are effective in restoring salivary function when given at an advanced phase of SS-like. METHODS: The efficacy of two therapies (bone marrow versus spleen cells) was compared head-to-head for halting/reversing salivary hypofunction at two critical time points of SS-like (7-week-old NOD with normal saliva output and 20-week-old NOD with minimal saliva). NOD mice were divided into four groups: (i) control, (ii) complete Freund's adjuvant (CFA), (iii) bone marrow transplants with CFA or (iv) spleen cell transplants with CFA. Mice were monitored 8-12 months after therapy. RESULTS: Both cell therapies were effective during the initial phase of SS-like; salivary flow rates were maintained between 80-100% of pre-symptomatic levels. Spleen cell therapy was better than bone marrow when administered in the initial phase of SS-like. When cell therapies were given at an advanced phase of SS-like (20 weeks and older), salivary flow rates improved but were at best 50% of pre-symptomatic levels. Both cell therapies decreased tumor necrosis factor-α, transforming growth factor-ß1 levels and T and B cells while increasing epidermal growth factor and regulatory T cells. Elevated serum epidermal growth factor levels were measured in spleen-treated mice. CONCLUSIONS: A therapeutic effect in advanced phase disease, albeit in mice, holds promise for humans in which Sjögren syndrome is generally not diagnosed until a late stage.

Sclerotherapy for the mucoceles of the anterior lingual salivary glands with pingyangmycin.

Recurrence is very common if the mucoceles of the anterior lingual salivary glands (ALSGs) are treated by surgery due to its anatomic characteristics. Therefore, more effective and less invasive treatment methods are urgently required to be applied instead of surgery. In this study, 40 patients with the mucocele of the ALSGs received the intralesional injections of pingyangmycin, and the median number of injections per patient was 2.075 (range, 1-3). All cases completely recovered with no recurrence after follow-up of more than 16 months. The complications included the local swelling, pain, and ulceration following injection, and all these symptoms resolved 7-10 days after the injection. Taken together, sclerotherapy with pingyangmycin is an effective and safe treatment method for the mucocele of the ALSGs and may be the primary treatment modality.

Salivary gland disorders.

Salivary gland disorders include inflammatory, bacterial, viral, and neoplastic etiologies. The presentation can be acute, recurrent, or chronic. Acute suppurative sialadenitis presents as rapid-onset pain and swelling and is treated with antibiotics, salivary massage, hydration, and sialagogues such as lemon drops or vitamin C lozenges. Viral etiologies include mumps and human immunodeficiency virus, and treatment is directed at the underlying disease. Recurrent or chronic sialadenitis is more likely to be inflammatory than infectious; examples include recurrent parotitis of childhood and sialolithiasis. Inflammation is commonly caused by an obstruction such as a stone or duct stricture. Management is directed at relieving the obstruction. Benign and malignant tumors can occur in the salivary glands and usually present as a painless solitary neck mass. Diagnosis is made by imaging (e.g., ultrasonography, computed tomography, magnetic resonance imaging) and biopsy (initially with fine-needle aspiration). Overall, most salivary gland tumors are benign and can be treated with surgical excision.

[Pathogenesis of Sjögren's syndrome]. / Patogeneza zespolu Sjögrena.

Sjögren's syndrome (SS--Sjögren's Syndrom) is an autoimmune systemic disease of connective tissue. The aim of this study was to present the contemporary literature on the basis of the pathophysiology of the Sjögren's syndrome, with particular reference to the pathogenesis of the damage to the salivary glands. It also discusses the criteria for classification, aetiology and pathogenesis of the SS, as well as the clinical symptoms of the disease in the oral cavity and its influence on the composition of the saliva. The knowledge of the Sjbgren's syndrome is important for the diagnosis and treatment of this disease.

Pediatric Salivary Gland Pathology.

Benign and malignant salivary gland disorders are uncommon in the pediatric population; however, these can be frequently seen in pediatric otolaryngology or oral and maxillofacial surgery practices. The astute clinician should be aware of the clinical presentation, diagnosis, and management options for common inflammatory, infectious, benign, and malignant disorders of salivary glands.

Gene therapy in dentistry: a review.

Gene therapy is an emerging field of biomedicine that has commanded considerable scientific and popular attention. Genes are specific sequences of bases that encode instructions to make proteins. When genes are altered so that encoded proteins are unable to carry out their normal functions, genetic disorders can result. Gene therapy essentially consists of introducing specific genetic material into target cells to compensate for abnormal genes or to make a beneficial protein without producing toxic effects on surrounding tissue. Transferred genes can be used for either reparative or pharmacological purposes. Applications of gene therapy to dental and oral problems illustrate the potential impact of this technology on dentistry. This review provides an update on transfer techniques and clinical implications of gene therapy in dentistry.

[Sialendoscopy: endoscopic approach to obstructive salivary gland disease]. / Sialendoscopie: endoscopische benadering van obstructive speekselklieraandoeningen.

Sialendoscopy: endoscopic approach to obstructive salivary gland defects Obstructive defects of the parotid and the submandibular gland often present themselves clinically by mealtime-related swelling of the affected salivary gland, the so-called 'mealtime syndrome'. Salivary ductal obstruction of the parotid and submandibular gland is predominantly caused by the presence of a salivary stone, a mucous plug, or by ductal stenosis. Until recently, diagnostic and treatment options for these obstructive salivary gland defects were restricted. Surgical removal of the affected salivary gland was often the treatment of choice. By applying sialendoscopy, a minimally invasive, semi rigid optical technique, it is possible to diagnose and treat obstructions which are found in the salivary ductal system. In many cases, therefore, the surgical removal of the salivary gland becomes unnecessary.