Some kinds of chronic sialadenitis were recognized during the recent years. They have specific pathogenesis, clinical and histopathologic appearances, and require specific treatment. IgG4-related sialadenitis (IgG4-RS) is one of the immune-mediated diseases, characterized by tumefactive lesions. The incidence of IgG4-RS obviously increased during the past 30 years. The study on the potential relationship between occupational exposure to chemical substances and the incidence of IgG4-RS showed that subjects with occupational exposure to agents known to cause IgG4-RD had an increased risk for IgG4-RS. Surgical excision of involved SMG could not control the disease progression, which is not recommended for treatment of IgG4-RS. The combination of glucocorticoid and steroid-sparing agents is effective for treating IgG4-RS, and restores salivary gland function. Radioiodine induced sialadenitis (RAIS) is one of the common complications of postoperative adjuvant treatment of differentiated thyroid cancer by ¹³¹I. The incidence of the disease is related to radiation dosage. Clinically, the patients suffered from swelling and tenderness in the buccal or submandibular regions, especially during the mealtime. Imaging appearances are similar to those of chronic obstructive sialadenitis. Conservative managements, such as gland massage, sialagogues, are the mainstream methods in the treatment of RAIS. Sialendoscopy is feasible for RAIS, but not as effective as conventional obstructive sialadenitis (COS). Therefore the prevention of RAIS is crucial. Eosinophilic sialodochitis (ES) is a new type of chronic inflammatory disease of the salivary gland related to allergy. It has characteristics of swelling of multiple major salivary glands, strip-like gelatinous plugs discharged from the duct orifice of the gland, elevated level of serum IgE and eosinophils in peripheral blood, infiltration of eosinophils and IgE positive plasma cells in the tissues, allergic history, increased expression of allergy-related cytokines, such as IL-4, IL-5, IL-13, and eotaxin, which suggest allergic reactions as a potential pathogenesis of the disease. The clinical, laboratory, histological, and immunohistochemical characteristics of ES are significantly different from conventional obstructive sialadenitis (COS). Therefore, it is suitable to separate ES from COS. Conservative managements, such as self-maintenance therapy and anti- allergic modality are the choices of treatment for ES. Based on the results of our comprehensive studies a new classification of chronic sialadenitis is suggested.
Humans ; Immunoglobulin G ; Iodine Radioisotopes ; Salivary Glands ; Sialadenitis/etiology* ; Submandibular Gland

OBJECTIVE: To investigate the effect of acid stimulation on salivary flow rate and compositions of human parotid and submandibular glands, so as to provide basis for comprehensive evaluation of salivary gland function in both health and disease status. METHODS: In the study, 210 healthy participants' whole saliva samples were collected under passive drooling, and their parotid gland and submandibular gland secretions were collected by negative pressure suction. 2% citric acid was dropped on the tip of tongue every 1 min for acid stimulation for a total of 5 times to collect stimulated whole saliva, parotid and submandibular gland saliva. The collected saliva was weighed and saliva flow rate was calculated. The K⁺, Na⁺, Cl^-, Ca²⁺, total protein, total phosphorus and α-amylase in saliva samples were detected by biochemical analyzer, and the changing features of flow rate and compositions of different kinds of saliva were compared and analyzed. RESULTS: After acid stimulation, saliva flow rate significantly increased. The increase proportion of parotid gland saliva (10.7 folds) was much higher than that of submandibular gland saliva (2.9 folds). The concentrations of Na⁺, Cl^-, Ca²⁺, total protein and α-amylase in parotid gland saliva increased significantly (P < 0.05), but there was no significant difference in total phosphorus and K⁺ (P=0.89, P=0.34). The concentration of Na⁺ and Ca²⁺ in saliva of submandibular gland increased significantly(P < 0.05), the concentration of total phosphorus decreased significantly(P < 0.05), and the concentration of Cl^- increased, but the difference was not significant(P=0.068). There was no significant difference in total protein, K⁺ and α-amylase (P=0.85, P=0.07, P=0.95). The compound secretion rate of total phosphorus in saliva of submandibular gland remained unchanged(P=0.066), while the secretion rate of K⁺, Na⁺, Cl^-, Ca²⁺, total protein and α-amylase significantly increased(P < 0.01). The compound secretion rate of K⁺, Na⁺, Cl^-, Ca²⁺, total protein and total phosphorus and α-amylase in parotid gland saliva increased(P < 0.01). The concentrations of Na⁺, Cl^-, K⁺, total phosphorus, total protein and α-amylase in parotid were higher than those in submandibular gland (P < 0.01), and the concentration of Ca²⁺ in submandibular gland saliva was significantly higher than that in parotid (P < 0.001). CONCLUSION The response of parotid to acid stimulation is stronger, and the secretion of submandibular gland is more stable. Acid stimulation significantly influences the concentrations of electrolytes in saliva, and the composited secretion rate is an evaluation index to reflect both flow rate and composition concentration of saliva. The parotid gland plays an important role in the secretion of total protein, total phosphorus and α-amylase in saliva, and the submandibular gland is the main source of Ca²⁺ in saliva.
Humans ; Parotid Gland ; Saliva ; Secretory Rate ; Submandibular Gland ; Tongue

Endoscopy ; Humans ; Neoplasms/surgery* ; Submandibular Gland/surgery* ; Thyroidectomy

Diagnosis, Differential ; Head ; Humans ; Immunoglobulin G ; Mikulicz' Disease/diagnosis* ; Submandibular Gland

The saliva secreted from submandibular gland (SMG) accounts for 60%-65%. It plays an important role in maintaining the human function of swallow, digestion, testing, speech, protection of oral mucosa, and prevention from dental carries. The SMG is frequently resected during the treatment for various kinds of oral and maxillofacial diseases, resulting in xerostomia and decreased quality of life. During the past 15 years, Research Center of Salivary Gland Diseases in Peking University School and Hospital of Stomatology conducted a series of studies on new techniques for preservation of SMG and achieved remarkable results. The clinicopathologic and imaging characteristics of IgG4-related sialadenitis (IgG4-RS) were clarified based on systematic studies. The results of studies on the pathogenesis of IgG4-RS showed that unbalance of inflammatory factors mediated the abnormality of secretion of SMG. IL-4 participates in occurring and development of glandular fibrosis of SMG. Regulation of tumor necrosis factor α (TNF-α) and cleaning of senescent cells might be taken as the targets for treatment of IgG4-RS. The combination of glucocorticoid and steroid-sparing agents showed effective results for treating IgG4-RS, clinical remission was achieved in all the patients, serum IgG4 levels decreased, and salivary gland secretion significantly increased. Sialoendoscopy-assisted sialolithectomy was applied in the treatment of about 1 000 cases with submandibular hilar calculi with a success rate of more than 90%. Transfer of SMG was used for prevention from radiation-induced xerostomia in the patients with head and neck carcinoma. SMG was transferred to the submental region before radiotherapy and was kept away from the ra-diation field. The results of prospective clinical controlled study showed this technique could effectively preserve the function of SMG and prevent from xerostomia. Based on the micro-anatomical study on the blood vessels and ducts of SMG, partial sialoadenectomy was applied for treatment of benign tumors in the SMG. A clinical controlled study confirmed its safety for control of the tumors and its advantage of preservation of SMG function. The studies on the involvement of SMG in oral squamous cell carcinoma (OSCC) provided the anatomical and histopathological basis for preservation of SMG during neck dissection for early cases with OSCC. A innovated surgical modality "four preservations including SMG" was used during the neck dissection for the early cases with OSCC. A prospective randomized clinical controlled study confirmed its safety, feasibility, effectiveness for control of the carcinoma, and advantages of preservation of SMG function.
Humans ; Carcinoma, Squamous Cell/pathology* ; Glucocorticoids ; Immunoglobulin G ; Interleukin-4 ; Mouth Neoplasms/pathology* ; Prospective Studies ; Quality of Life ; Sialadenitis/surgery* ; Submandibular Gland/surgery* ; Tumor Necrosis Factor-alpha ; Xerostomia/prevention & control* ; Randomized Controlled Trials as Topic

OBJECTIVE: To investigate the effects of topical administration of cyclosporine A (CsA) on salivary secretion and inflammation of the submandibular glands in non-obese diabetic (NOD) mice. METHODS: Female NOD mice, 21 aged 14 weeks and 18 aged 21 weeks were selected and randomly divided into low-dose group, high-dose group and control group on average. CsA was injected into submandibular glands. One week later the saliva stimulated by pilocarpine was collected and measured. The submandibular glands were collected to make paraffin sections. The lymphocyte infiltration in submandi-bular gland was observed by microscope after hematoxylin-eosin (HE) staining. The number of lymphocyte infiltration foci was counted to calculate the focus sore and the ratio of lymphocyte infiltration area to total gland area was figured up by Leica image analysis system. The expressions of inflammatory cytokines tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-4 (IL-4), IL-13, IL-17F, IL22 and IL-23a in the submandibular glands of the NOD mice were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell apoptosis in the submandibular gland was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). The levels of serum creatinine (Scr), blood urea nitrogen (BUN), uric acid (UA), alanine aminotransferase (ALT), aspertate aminotransferase (AST), alkaline phosphatase (ALP), albumin (ALB) and γ-glutamyl transferase (GGT) were measured by automatic biochemical analyzer to evaluate liver and kidney functions. RESULTS: After topical injection of CsA in the submandibular gland, the stimulated salivary flow rate of the 14- and 21-week-old NOD mice significantly increased compared with the control group (P < 0.01 or P < 0.05), and the number and area of lymphocyte infiltration foci in the 14-week-old NOD mice low-dose group significantly decreased compared with the control group (P < 0.01). Low and high dose of CsA had similar effects on reducing inflammation and improving salivary secretion. The overall level of inflammatory cytokines in the submandibular gland did not decrease significantly. The number of cell apoptosis of submandibular gland in the NOD mice treated with CsA decreased compared with the control group, but there was no statistically significant difference. Topical injection of CsA had no adverse effect on liver and kidney function in the NOD mice. CONCLUSION Topical injection of CsA can reduce lymphocyte infiltration in submandibular gland of NOD mice and improve salivary secretion.
Animals ; Cyclosporine ; Diabetes Mellitus, Experimental/drug therapy* ; Disease Models, Animal ; Female ; Inflammation ; Mice ; Mice, Inbred NOD ; Saliva ; Sjogren's Syndrome ; Submandibular Gland

OBJECTIVES: This study aims to investigate the effects of ionizing radiation on the secretion of the paracellular pathway in rat submandibular glands (SMGs) and reveal the changes in the tight junction (TJ) protein claudin-4. METHODS: A total of 24 Wistar rats were randomly divided into control and irradiation groups. The irradiation groups were further divided into 1, 4, and 12 weeks groups after irradiation. One-time 20 Gy irradiation was given to the SMG area on the experimental side of the irradiation group. At 1, 4, and 12 weeks after irradiation, the secretion of SMGs was measured using the Schirmer's test. The pathological changes in the gland tissues were observed under light microscopy after hematoxylin⁃eosin (HE) staining. The changes in the TJ ultrastructure were observed under transmission electron microscopy. The immunofluorescence staining and Western blot were used to detect the expression levels of muscarinic acetylcholine M3 receptor, aquaporin 5 (AQP5), and claudin-4 protein. RESULTS: At 1, 4, and 12 weeks after irradiation, the secretion of SMGs in the irradiation group was significantly decreased and lower than that in the control group ( CONCLUSIONS The changes in the TJ structure, the upregulation of the claudin-4 expression, and the damage in the paracellular pathway were involved in the hyposecretion of SMGs after irradiation.
Animals ; Microscopy, Electron, Transmission ; Radiation, Ionizing ; Rats ; Rats, Wistar ; Submandibular Gland ; Tight Junctions

OBJECTIVE: To measure the weight and volume of normal submandibular gland by in vitro detection of glandular body, to compare with the measurement values of CT volume rendering to evaluate the consistency of the two methods, and to explore the related factors affecting the weight and volume of the submandibular gland. METHODS: The patients who underwent neck dissection due to oral cancer and were confirmed with normal submandibular gland by postoperative histopathology in Peking University School and Hospital of Stomatology from May 2019 to January 2020 were collected in this study and divi-ded into 4 groups according to the age standards raised by the Society of Geriatrics Chinese Medical Association and WHO (2000) age standards. The submandibular gland was carefully dissected along with the capsule immediately after neck dissection. The weight and volume of submandibular gland were accurately measured by an integrated aseptic measuring device. The volume of submandibular gland was measured by CT volume rendering before operation and the consistency of the two methods was evaluated. The 95% confidence interval of the weight and volume of submandibular gland in the different groups of Chinese people, which were divided by gender and age, were calculated, and the correlation with age, gender, height, weight, body mass index (BMI) and other factors was analyzed. RESULTS: The weight and vo-lume of submandibular gland were measured in 220 subjects. The average weight and volume of submandibular gland were (11.69±2.45) g and (11.55±2.41) cm³ respectively. The volume of submandibular gland measured by CT volume rendering ranged from 70% to 82% of that measured by in vitro detection of glandular body, and the correlation coefficient between the two methods was 0.976 (P < 0.05). The gender difference of weight and volume of submandibular gland existed in the groups of youth, middle-aged, young elderly and elderly groups, the values of males were obviously higher than those of females (P < 0.05). There was no gender difference of weight and volume of submandibular gland in the adolescent group (P > 0.05). The weight and volume of submandibular gland had a strong positive correlation with body height (P < 0.05), a weak positive correlation with body weight (P < 0.05), and no correlation with BMI (P > 0.05). The female's weight and volume of submandibular gland in the young elderly and elderly groups were significantly lower than those in the other three groups (P < 0.05). CONCLUSION The normal reference range of the weight and volume of submandibular gland in vitro were established in different age and gender groups of Chinese people. The volume of submandibular gland mea-sured by CT volume rendering was 70%-82% of that measured by in vitro detection of glandular body. The results of the two methods had a high degree of consistency. The weight and volume of submandibular gland were related to age, gender, body height and body weight.
Adolescent ; Adult ; Aged ; Body Mass Index ; Body Weight ; Female ; Humans ; Male ; Middle Aged ; Mouth Neoplasms ; Neck Dissection ; Submandibular Gland/diagnostic imaging*

Corticosteroids are used in the treatment of many diseases; however, they also induce various side effects. Dexamethasone is one of the most potent corticosteroids, and it has been reported to induce the side effect of impaired salivary gland function. This study aimed to evaluate the effects of dexamethasone on mouse submandibular gland function to gain insight into the mechanism of dexamethasone-induced salivary hypofunction. The muscarinic agonist carbachol (CCh) induced salivary secretion and was not affected by short-term dexamethasone treatment but was decreased following long-term dexamethasone administration. The expression levels of the membrane proteins Na-K-2Cl cotransporter, transmembrane member 16A, and aquaporin 5 were comparable between the control and long-term dexamethasone treatment groups. The CCh-induced increase in calcium concentration was significantly lower in the presence of extracellular Ca in the long-term dexamethasone treatment group compared to that in the control group. Furthermore, CCh-induced salivation in the absence of extracellular Ca and Ca ionophore A23187-induced salivation was comparable between the control and long-term dexamethasone treatment groups. Moreover, salivation induced by the Ca-ATPase inhibitor thapsigargin was diminished in the long-term dexamethasone treatment group. In summary, these results demonstrate that short-term dexamethasone treatment did not impair salivary gland function, whereas long-term dexamethasone treatment diminished store-operated Ca entry, resulting in hyposalivation in mouse submandibular glands.
Acinar Cells ; drug effects ; metabolism ; Animals ; Calcium ; metabolism ; Calcium Signaling ; drug effects ; Carbachol ; pharmacology ; Dexamethasone ; therapeutic use ; Mice ; Muscarinic Agonists ; pharmacology ; Saliva ; metabolism ; Salivation ; drug effects ; Submandibular Gland ; drug effects ; metabolism

OBJECTIVE: To study the clinical features and treatments of congenital submandibular duct dilatation. METHODS: Seven children with congenital submandibular duct dilatation from January 2008 to March 2018 were included in this study, whose average age was 5 months and 22 days. The clinical manifestations are unilateral swelling of the mouth floor. All seven children underwent sublingual gland resection, submandibular gland dilatation catheter resection, and catheter reroute under general anesthesia. Intraoperatively, the orifice of the submandibular gland was constricted and part of the catheter was dilated. RESULTS: All seven patients had good healing without swelling or cyst formation. CONCLUSIONS Congenital submandibular duct dilatation occurs at a young age. Early diagnosis and treatment can help prevent further expansion of the catheter and avoid gland atrophy, feeding difficulty, and breathing obstruction. Simultaneous excision of the sublingual gland can avoid the formation of postoperative sublingual cyst.
Child ; Dilatation ; Humans ; Infant ; Ranula ; Salivary Ducts ; Sublingual Gland ; Submandibular Gland