Experimental Animal Model Systems for Understanding Salivary Secretory Disorders.

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.

Role of the Accessory Parotid Gland in the Etiology of Parotitis: Statistical Analysis of Sialographic Features.

This retrospective study aimed to identify if the existence of the accessory parotid gland correlated with the etiology of parotitis. This may aid the development of better treatment strategies in the future. Sialographic features of cases with parotitis and healthy subjects were reviewed. The chi-square test was used to compare the incidence of accessory parotid gland between the groups. The Student's t test was used to compare the length of Stensen's duct, the length from the orifice to the confluence of the accessory duct, and the angle between the accessory duct and Stensen's duct between the groups. The incidence of accessory parotid gland in patients with parotitis was 71.8% (28/39), which was significantly higher than that in healthy subjects (P = 0.005). Patients with parotitis had a longer Stensen's duct than healthy subjects (P = 0.003). There was no significant difference in the length from the orifice to the confluence of the accessory duct or the angle between the accessory duct and Stensen's duct (P = 0.136 and 0.511, respectively) between the groups. The accessory parotid gland might play a role in the pathogenesis of parotitis. The existence of an accessory parotid gland is likely to interfere with salivary flow. Computational fluid dynamics analysis of salivary flow in the ductal system would be useful in future etiologic studies on parotitis.

Ultrasound and CT imaging features in a patient with salivary duct carcinoma of the parotid gland: a case report with literature review.

The aim of this paper was to present the ultrasound (US) and computed tomography (CT) appearance of a patient with salivary duct carcinoma of the parotid gland. US showed a voluminous mass of the parotid gland, with multiple calcifications. Furthermore, it revealed regional multiple lymph nodes with malignant characters. Sonoelastography of the lesion and lymph nodes detected increased rigidity. Contrast enhanced CT scan of the neck completed the data description regarding the mass expansion and invasion of surrounding tissues. US and CT imaging features played a key role in establishing the malignant character of the mass and lymph nodes.

Human adipose tissue­derived stem cells alleviate radiation­induced xerostomia.

Hyposalivation is an intractable side­effect of radiotherapy for head and neck cancer. It is caused by the irreversible loss of acinar cells and decreased saliva secretion. However, this situation severely compromises the quality of life of affected patients. Currently, there is no effective treatment for this condition. In the present study, we developed a novel approach to regenerate the function of the irradiation­damaged salivary glands using human adipose tissue­derived stem cell (hADSC) intraglandular transplantation. ZsGreen­labeled hADSCs were adoptively transferred into Sprague­Dawley (SD) rat submandibular glands immediately following exposure to 18 Gy irradiation. A higher salivary flow rate (SFR) was observed in the hADSC­treated group. Tissue improvement, including angiogenesis, anti­apoptosis and anti­fibrosis, was detected in the hADSC­treated glands as compared to the untreated glands. Quantitative reverse transcription PCR (RT-qPCR) revealed a significantly higher expression of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), cyclooxygenase­2 (COX­2) and matrix metalloproteinase­2 (MMP­2) in the hADSC­treated rats. Furthermore, immunohistochemical analysis indicated that the hADSCs had differentiated into acinar and ductal cells in the rat submandibular glands. Thus, our results suggest that hADSCs are able to regenerate irradiation­damaged salivary glands through glandular transplantation.

Obstructive sialadenitis of a transplanted submandibular gland: chronic inflammation secondary to ductal obstruction.

AIMS: To determine the pathological basis and clinical features of obstructive sialadenitis in transplanted submandibular glands (SMGs). METHODS: A total of 161 patients (174 eyes) with keratoconjunctivitis sicca underwent microvascular SMG transplantation. Patients were followed up at approximately 1 and 4 months and annually thereafter. Clinical data, including dry eye discomfort, symptoms of ductal obstruction, and Schirmer test, were recorded. Sialography was performed in six patients. In addition, SMG autotransplantation was performed in 22 rabbits. Salivary flow was recorded and the morphology of glands was examined at 6 months postoperatively by light microscopy. RESULTS: Among the patients, 16 out of 172 glands during the latent period (0-3 months) and 2 out of 154 glands with long-term follow-up (>1 year) showed obstructive sialadenitis. Typical manifestations were continuous small volumes of viscous secretions, recurrent gland swelling, decreased Schirmer test values, and irregular dilation of the main duct on sialography. The transplanted SMGs eventually showed no secretion in five cases. Of the 22 rabbit SMGs, 4 had obstructive sialadenitis. Morphological examination showed chronic inflammatory infiltration with salivary deposits. CONCLUSIONS: Obstructive sialadenitis of transplanted SMGs is a chronic inflammation secondary to ductal obstruction, which leads to insufficient ocular lubrication and potential treatment failure.

Pneumoparotitis: a case report.

BACKGROUND: Pneumoparotid is a rare cause of parotid enlargement. Pneumatic enlargement of the gland is caused by retrograde insufflation via Stensen's duct. Most reported cases have been managed conservatively, thus running a short course. METHODS AND RESULTS: We report on a case of a 48-year-old man with a chronic painful right facial swelling and symptoms of repeated infection. Clinical examination found a parotid swelling with surgical emphysema and a dilated Stensen's duct. Pneumoparotitis with cystic changes and dilated intraparotid ducts was confirmed by CT. The patient proceeded to undergo excision of the gland, with subsequent resolution of symptoms. CONCLUSION: Repeated retrograde movement of air and contaminated saliva leads to chronic infection and sialectasis. Management is aimed at preventing these sequelae by identifying and addressing the insult early; however, repeated pneumoparotid leads to chronic pneumoparotitis, the management of which is excision of the gland.

Computational fluid dynamics for investigation of saliva pressure in parotid obstruction.

UNLABELLED: OBJECTIVES/HYOTHESIS: Parotid obstruction is one of the most common problems affecting the parotid gland. We aimed to investigate the blockage ratio (BR) and the intraductal pressure change of Stensen's duct using computational fluid dynamics. STUDY DESIGN: Retrospective review of 16 patients who had undergone interventional sialendoscopy for parotid obstruction from 2009 to 2011. METHODS: The three-dimensional configurations of Stensen's duct were reconstructed from computed tomography (CT) sialographic images. Finite volume modeling in fluid dynamics of parotid obstruction was used to analyze the pressure distribution under conditions of rest and stimulation. RESULTS: Intraductal pressure increased with increasing distance from the orifice. The upstream pressure was higher than that of downstream pressure in the same BR (P < .05). The upstream pressure increased as the BR increased. Statistically, the pressure turning point was indicated when BR = 60%. Only when the BR was much greater than 90% did the pressure reach 811.64 Pa, at which point patients could feel the painful swelling under the rest condition. Under the stimulated condition, the upstream pressure increased from 1.3- to 2.9-fold of that of the no blocking state when the BR increased from 80% to 90%, which may aggravate the obstructive symptoms. There was no significant difference observed for downstream pressure under the same condition (P > .05). CONCLUSIONS: CT sialography was effectively used for analysis of the intraductal pressure distribution in patients with parotid obstruction. Analysis of salivary fluid dynamics in Stensen's duct may provide a further pathophysiological mechanism for obstructive diseases.

Comparison of oral mucosal pH values in bulimia nervosa, GERD, BMS patients and healthy population.

OBJECTIVES: The aim of this study was to compare the oral mucosal pH in healthy individuals to patients with gastroesophageal reflux disease (GERD), Bulimia nervosa (BN) and burning mouth syndrome (BMS). SUBJECTS AND METHODS: Using a flat pH meter sensor, pH levels were established in eight mucosal sites in 26 healthy individuals, 26 GERD patients, 22 BN patients and 29 BMS patients. RESULTS: A significantly lower pH was found in the BN and GERD groups (6.38 ± 00.45, 6.51 ± 0.32 respectively, P < 0.05) and a higher, but non-significant, pH level in the BMS group (7.01 ± 0.34, P > 0.05) compared with the control (C) group (6.82 ± 0.33). CONCLUSIONS: BMS patients showed no pH differences from C group. The mucosa of BN and GERD patients was significantly acidic relative with controls; thus this simple technique may serve as a diagnostic tool for identifying gastro-esophageal conditions.

Acute salivary gland hypofunction in the duct ligation model in the absence of inflammation.

OBJECTIVE: The commonly associated aetiology of salivary gland inflammation and salivary hypofunction has led to the widely held belief that inflammation causes salivary gland hypofunction. Indeed, our own recent study seemed to support this contention. Here, we tested the hypothesis that, in an acute duct ligation model, eliminating inflammation the submandibular gland would recover normal function. MATERIALS AND METHODS: Ligation of the rat submandibular gland excretory duct for 24 h was used to induce inflammation and salivary gland hypofunction. A group of duct ligated rats was compared with a second group given dexamethasone, on the day of duct ligation. Twenty-four hours later salivary gland function was assessed and salivary glands were collected. RESULTS: Histology and myeloperoxidase activity assay revealed a profound decrease in inflammatory cell infiltration of ligated glands from rats given dexamethasone, compared with ligated glands in the absence of dexamethasone. Salivary flow rate evoked by methacholine was decreased (P < 0.01) by approximately 56% (ligated vs control, 79 +/- 9 microl min(-1) g(-1)vs 177 +/- 11 microl min(-1) g(-1)) and salivary flow from ligated dexamethasone-treated and ligated glands was similar. CONCLUSION: Despite eliminating the inflammatory reaction in the ligated gland, salivary hypofunction was not reversed, suggesting that other mechanisms must be at work in the ligation-induced salivary hypofunction.

Dynamic magnetic resonance sialography as a new diagnostic technique for patients with Sjögren's syndrome.

OBJECTIVE: To evaluate the clinical utility of dynamic magnetic resonance (MR) sialographic images as a diagnostic tool for patients with Sjögren's syndrome. METHODS: The morphological findings and various kinds of functional parameters in volunteers on dynamic MR sialographic images were compared with those in five patients with definite Sjögren's syndrome. RESULTS: On the MR sialographs of all five patients with Sjögren's syndrome, the so-called 'apple-tree appearance' was seen. The difference in two functional parameters using the dynamic MR sialographic data was elucidated between the two groups. The maximum area of the detectable ducts in the group of patients was significantly smaller (P < 0.001) than that in the group of volunteers. The ratio of change in the detectable ducts in the group of patients was significantly lower (P = 0.011) than that in the group of volunteers. CONCLUSIONS: Our study suggests that dynamic MR sialographic data in addition to MR sialographic images might be useful for the diagnosis of Sjögren's syndrome.

Sjögren's syndrome: a condition with features of chronic graft-versus-host disease: does duct cell adhesion or permeability play a role in pathogenesis?

Primary and Secondary Sjögren's syndrome are disease complexes characterized by periductal inflammatory cell infiltration of the salivary and lacrimal glands and manifest as dry mouth and dry eyes. Secondary Sjögren's syndrome may be associated with a connective tissue disorder. Additional extraglandular features in Sjögren's syndrome include a generalized inflammatory exocrinopathy that might be associated with abnormalities of both humoral and cellular mediated immunity. Similar inflammatory changes and extraglandular features, including an altered immune response, have been reported in patients developing graft-versus-host disease after bone-marrow transplantation and in patients with primary biliary cirrhosis. The periductal nature of the inflammatory response involving minor salivary and other glands raises the possibility of altered duct cell adhesion or permeability in playing a role in the aetiopathogenesis of Sjögren's syndrome. The paper pulls together evidence that could be interpreted in this light. Evidence for bacterial or viral factor(s) altering the antigenicity of the histocompartibility (HC) complex on ductal cells in Sjögren's syndrome patients is also described. A hypothesis is proposed for Sjögren's syndrome in which the principal feature is an alteration in salivary gland duct cell adhesion or permeability. A re-evaluation of current knowledge of these two conditions from a clinical and experimental context are interpreted in this light.

An unusual cause of obstructive sialadenitis.

A case of bilateral recurrent submandibular sialadenitis is presented in a patient with decreased salivary flow. The condition was caused by trapping of the submandibular papillae between the lingual flange of the denture and the enlarged genial tubercles. Removal of these causes led to resolution of her symptoms. The value of plain radiography, sialography and scintigraphy is discussed.

Acceleration of rat salivary gland tissue repair by basic fibroblast growth factor.

A model of atrophic rat submandibular gland was used to examine the ability of basic fibroblast growth factor (bFGF) to accelerate tissue repair. The gland duct was separated carefully from associated blood vessels and nerve, and ligated with a 8-0 suture under a surgical microscope. Two weeks after ligation, the glandular tissue showed severe atrophy and weight loss (to 26% of that in a sham-operated group). Thereafter, the ligature was removed and various amounts of bFGF, isoproterenol or saline were instilled retrogradely through the duct. Both isoproterenol and bFGF increased cell proliferation significantly. bFGF accelerated the proliferation of various cell types, including both acinar and ductal. The proliferative effects of bFGF peaked at a dose of 1 ng/gland. When bFGF (1 ng/gland) was administered to the atrophic gland, its weight increased to 125% of the glands in saline-treated control animals after 2 weeks. The effects of bFGF were also examined in normal submandibular glands: bFGF stimulated cell proliferation, but the effective concentration was at least 50 times higher than that required in the atrophic gland. The results from immunohistochemical tests against anti-FGF receptor-type 1 antibody demonstrated increased immunoreactivity in the damaged gland, which might be involved in the difference in the response to bFGF between damaged and normal glands. Overall, the results indicate that bFGF can accelerate tissue repair in salivary gland.

Buccinator window anomaly.

Four patients, three women and one man, with a mean age of 32 years, presented with a history of recurrent parotid swelling. In the women the swelling was unilateral. All had previously undergone sialography using a hand injection technique and no structural abnormality was demonstrated. Sialography was repeated using a continuous-infusion pressure-monitored system. In all cases an initial very high filling pressure (>200 mmHg) was recorded followed by a rapid reduction in pressure and a more normal filling pressure pattern. The duct system and glands all appeared morphologically normal. Treatment with acrylic appliance therapy and an intraductal catheter was attempted with some success.

Sialoendoscopy: three years' experience as a diagnostic and treatment modality.

PURPOSE: This article describes the use of endoscopy for treating sialolithiasis and compares this diagnostic method with other diagnostic methods. PATIENTS AND METHODS: Forty-six major salivary glands suspected for obstructive pathology (26 males and 20 females aged 12 to 65 years) were treated using a rigid mini endoscope. The indications for sialoendoscopy were 1) screening the ductal system for any residual calculi after sialolith removal, and 3) determining the status of the major duct lumens. RESULTS: Of the 46 endoscopies attempted, 5 were immediate failures as a result of technical problems. Of the remaining 41 patients, 32 had salivary stones, and nine had sialadenitis without evidence of sialolith formation. Within the former group (22 submandibular and 10 parotid), there were four patients in whom sialolithotomy was unsuccessful (three submandibular and one parotid). Of the 22 patients with submandibular sialolithiasis, seven (32%) were undetected by imaging methods (conventional radiography, sialography, and ultrasound). In the 10 parotid ducts, seven (70%) sialoliths were undetected. In the 28 patients who underwent successful calculus removal, no major post-operative complications were noted. Interesting findings noted during endoscopy were a sphincter-like mechanism in the ductal system, evidence of ductal wall changes associated with the presence of salivary stones, peculiar connection between calculi and the ductal wall, a salivary stone forming around a hair inclusion, and the presence of polyps projecting into the duct lumen. CONCLUSIONS: Endoscopy is a minimally invasive technique for removal of calculi from the salivary glands as well as an excellent diagnostic procedure.

Diversion of salivary flow to treat drooling in patients with cerebral palsy.

The authors performed six sialodochoplasties between 1991 and 1994 to treat drooling in six children who suffered from cerebral palsy. There were three boys and three girls, aged 13 to 22 years (mean, 16 years). All patients underwent parotid duct rerouting. The first four patients (group I) also underwent associated excision of submandibular ducts, and the last two patients (group II) benefited from rerouting of the submandibular ducts. In group I, results were considered good in two cases, fair in one case, and poor in one case. A fistula of the new Stenon duct appeared in one patient, which required excision and ligation followed by progressive involution of the parotid gland. Both group II patients had excellent and rapid results. The requirements leading to surgical decision are determined. The importance of physiotherapy is emphasized. Surgical techniques are described and discussed, as are objective criteria for the assessment of surgical results, namely salivary radioisotopic scanning.