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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.

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.

Salivary secretory disorders are life-disrupting pathologic conditions with a high prevalence, especially in the geriatric population. Both patients and clinicians frequently feel helpless and get frustrated by the currently available therapeutic strategies, which consist mainly of palliative managements. Accordingly, to unravel the underlying mechanisms and to develop effective and curative strategies, several animal models have been developed and introduced. Experimental findings from these models have contributed to answer biological and biomedical questions. This review aims to provide various methodological considerations used for the examination of pathological fundamentals in salivary disorders using animal models and to summarize the obtained findings. The information provided in this review could provide plausible solutions for overcoming salivary disorders and also suggest purpose-specific experimental animal systems.

Purpose This systematic review aimed to assess the updated literature for the prevention of salivary gland hypofunction and xerostomia induced by non-surgical cancer therapies. Methods Electronic databases of MEDLINE/PubMed, EMBASE, and Cochrane Library were searched for randomized controlled trials (RCT) that investigated interventions to prevent salivary gland hypofunction and/or xerostomia. Literature search began from the 2010 systematic review publications from the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) up to February 2024. Two independent reviewers extracted information regarding study design, study population, cancer treatment modality, interventions, outcome measures, methods, results, risk of bias (RoB version 2), and conclusions for each article. Results A total of 51 publications addressing preventive interventions were included. Eight RCTs on tissue-sparing radiation modalities were included showing significant lower prevalence of xerostomia, with unclear effect on salivary gland hypofunction. Three RCTs on preventive acupuncture showed reduced prevalence of xerostomia but not of salivary gland hypofunction. Two RCTs on muscarinic agonist stimulation with bethanechol suggested a preventive effect on saliva flow rate and xerostomia in patients undergoing head and neck radiation or radioactive iodine therapy. Two studies on submandibular gland transfer showed higher salivary flow rates compared to pilocarpine and lower prevalence of xerostomia compared to no active intervention. There is insufficient evidence on the effectiveness of vitamin E, amifostine, photobiomodulation, and miscellaneous preventive interventions. Conclusion This systematic review continues to support the potential of tissue-sparing tecniques and intensity-modulated radiation therapy (IMRT) to preserve salivary gland function in patients with head and neck cancer, with limited evidence on other preventive strategies, including acupuncture and bethanecol. Preventive focus should be on optimized and new approaches developed to further reduce radiation dose to the parotid, the submandibular, and minor salivary glands. As these glands are major contributors to moistening of the oral cavity, limiting the radiation dose to the salivary glands through various modalities has demonstrated reduction in prevalence and severity of salivary gland hypofunction and xerostomia. There remains no evidence on preventive approaches for checkpoint inhibitors and other biologicals due to the lack of RCTs.

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.

Objectives: The origin of strictures of Stensen's duct often remains unclear, but chronic recurrent parotitis may be one associated disease. Failure of conservative therapy leads to a recommendation of parotidectomy in a high percentage of cases. Nowadays, development of new, minimally invasive methods may lead to a fundamental change in the treatment regimen. Methods: We retrospectively evaluated 39 patients who presented with symptomatic strictures of Stensen's duct from 2002 to 2005. Sialoscopy was performed with semirigid endoscopes. Therapy consisted of irrigation and intraductal infusion of cortisone. If possible, interventional sialoscopy was carried out as the first-line procedure. If indicated, operative procedures of the duct were performed. Results: After irrigation and intraductal medication, 17.9% of the patients were free of symptoms. Interventional sialoscopy was carried out in 74.4%, with a success rate of 75.9%. Operative duct procedures (extended papillotomy or resection of papilla stricture with duct reinsertion) were carried out in 23% of cases. In 5.1% of the total cases, parotidectomy was unavoidable. Conclusions: Sialoscopy-based methods play a central role in gland-preserving treatment of strictures of Stensen's duct. Sialoscopy has proven to be a fast, useful, and relatively safe therapeutic tool with a high success rate. Parotidectomy is the last choice in symptomatic cases.

Salivary gland dysfunction is one of the common side effects of high-dose radioiodine therapy for thyroid cancer. The purpose of this study was to determine whether an early start of sucking lemon candy decreases salivary gland injury after radioiodine therapy. The incidence of the side effects of radioiodine therapy on the salivary glands was prospectively and longitudinally investigated in 2 groups of patients with postsurgical differentiated thyroid cancer with varying regimens for sucking lemon candy. From August 1999 to October 2000, 116 consecutive patients were asked to suck 1 or 2 lemon candies every 2-3 h in the daytime of the first 5 d after radioiodine therapy (group A). Lemon candy sucking was started within 1 h after radioiodine ingestion. From November 2000 to June 2002, 139 consecutive patients (group B) were asked to suck lemon candies in a manner similar to that of group A. In the group B, lemon candies were withheld until 24 h after the ingestion of radioiodine. Patients with salivary gland disorders, diabetes, collagen tissue diseases, or a previous history of radioiodine therapy or external irradiation to the neck were excluded. Thus, 105 patients in group A and 125 patients in group B were available for analysis. There were no statistical differences in the mean age (55.2 y vs. 58.5 y), average levels of serum free thyroxine (l-3,5,3',5'-tetraiodothyronine) (0.40 ng/dL vs. 0.47 ng/dL), and the mean dose of (131)I administered (3.96 GBq vs. 3.87 GBq) between the 2 groups. The onset of salivary side effects was monitored during hospital admission and regular follow-up on the basis of interviews with patients, a visual analog scale, and salivary gland scintigraphy using (99m)Tc-pertechnetate. When a patient showed a persistent (>4 mo) dry mouth associated with a nonfunctioning pattern on salivary gland scintigraphy, a diagnosis of xerostomia was established. The incidences of sialoadenitis, hypogeusia or taste loss, and dry mouth with or without repeated sialadenitis in group A versus group B were 63.8% versus 36.8% (P < 0.001), 39.0% versus 25.6% (P < 0.01), and 23.8% versus 11.2% (P < 0.005), respectively. Permanent xerostomia occurred in 15 patients in group A (14.3%) and 7 patients in group B (5.6%) (P < 0.05). In both groups, bilateral involvement of the parotid gland was the most frequently seen and was followed by bilateral involvement of the submandibular gland. An early start of sucking lemon candy may induce a significant increase in salivary gland damage. Lemon candy should not be given until 24 h after radioiodine therapy.

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. Copyright © 2024 American Academy of Family Physicians.)