Submandibular Glands Of Patients Research Articles

Localized or Diffuse Lesions of the Submandibular Glands in Immunoglobulin G4-Related Disease in Association With Differential Organ Involvement

Objectives The purpose of this study was to assess the relationship between the sonographic characteristics of the submandibular glands and organ involvement at the initial presentation in patients with immunoglobulin G4 (IgG4)-related disease. Methods We conducted a retrospective study that included 15 patients who had bilateral swollen submandibular glands and elevated serum IgG4 levels between January 2005 and December 2010. Results In all 15 patients, sonography revealed the involvement of both sides of the submandibular glands. The sonographic appearance of each gland was classified into two types: localized tumor-forming and diffuse focal types. On the basis of this typing, all 15 patients were classified into two groups: a group with the localized tumor-forming type observed on one or both sides of the glands (n = 10) and a group with the diffuse focal type present on both sides (n = 5). All 10 patients in the former group had lesions in local exocrine organs, such as the lacrimal and parotid glands, with regional lymphadenopathy. In contrast, all 5 patients in the latter group had lesions in abdominal organs, such as autoimmune pancreatitis and sclerosing cholangitis. Conclusions The sonographic patterns of the submandibular glands in patients with IgG4-related disease can be divided into two types: localized tumor-forming and diffuse focal. The distinctive patient groups defined by the sonographic patterns in both glands were associated with differential organ involvement and thus could be used as indicators of the disease extension and specific organ involvement.

Localized or Diffuse Lesions of the Submandibular Glands in Immunoglobulin G4-Related Disease in Association With Differential Organ Involvement

The purpose of this study was to assess the relationship between the sonographic characteristics of the submandibular glands and organ involvement at the initial presentation in patients with immunoglobulin G4 (IgG4)-related disease. We conducted a retrospective study that included 15 patients who had bilateral swollen submandibular glands and elevated serum IgG4 levels between January 2005 and December 2010. In all 15 patients, sonography revealed the involvement of both sides of the submandibular glands. The sonographic appearance of each gland was classified into two types: localized tumor-forming and diffuse focal types. On the basis of this typing, all 15 patients were classified into two groups: a group with the localized tumor-forming type observed on one or both sides of the glands (n = 10) and a group with the diffuse focal type present on both sides (n = 5). All 10 patients in the former group had lesions in local exocrine organs, such as the lacrimal and parotid glands, with regional lymphadenopathy. In contrast, all 5 patients in the latter group had lesions in abdominal organs, such as autoimmune pancreatitis and sclerosing cholangitis. The sonographic patterns of the submandibular glands in patients with IgG4-related disease can be divided into two types: localized tumor-forming and diffuse focal. The distinctive patient groups defined by the sonographic patterns in both glands were associated with differential organ involvement and thus could be used as indicators of the disease extension and specific organ involvement.

Sonographic appearance of submandibular glands in patients treated with external beam radiotherapy for nasopharyngeal carcinoma

The purpose of this study was to investigate the sonographic (US) appearances of submandibular glands in patients with nasopharyngeal carcinoma after external beam radiotherapy (RT) and compare them with those of healthy subjects. A total of 81 nasopharyngeal carcinoma patients treated with RT and 66 healthy subjects were recruited and underwent submandibular gland US. Bilateral submandibular glands were assessed for their size, echogenicity, echogenicity margin sharpness, and echotexture. The mean ± SD transverse dimension of submandibular glands in patients treated with RT (2.5 ± 0.4 cm) was significantly smaller than that of healthy subjects (3.3 ± 0.4 cm) (p < 0.05). Submandibular glands in patients treated with RT tended to be heterogeneous (72%) with hypoechoic areas (46%) and ill-defined margins (89%). However, there were no statistically significant differences in echogenicity and conspicuity of intraglandular ducts of submandibular glands between patients and healthy subjects. RT-induced changes of the submandibular glands were demonstrated on US.

Quantitative MRI analysis of salivary glands in sickle cell disease

The purpose of this prospective study was to characterize the MR relaxometric features of the major salivary glands in patients with sickle cell disease (SCD). 15 patients with SCD (aged 19.8-43.6 years) and 12 controls were imaged with the mixed turbo-spin echo pulse sequence. The major salivary glands were manually segmented and T1, T2 and secular T2 relaxometry histograms were modelled with Gaussian functions. Shortened T1 relaxation times were seen solely in the submandibular glands of patients with SCD (747.5±54.8 ms vs 807.1±38.3 ms, p<0.001). Slight T2 and secular T2 shortening were seen in the parotid gland; however, this difference was not significant (p=0.07). The sublingual gland showed no changes under MR relaxometry. There was no difference in glandular volumes, and no correlation was demonstrated between history of blood transfusion and salivary gland relaxometry. Patients with SCD exhibited changes in quantitative MRI T1 relaxometry histograms of the submandibular glands.

Sonographic Appearance of the Submandibular Glands in Patients With Immunoglobulin G4-Related Disease

Swelling of the salivary glands is often an initial sign of immunoglobulin G4 (IgG4)-related disease or IgG4-related sclerosing/autoimmune disease. We encountered 2 patients with IgG4-related disease who showed swollen submandibular glands with a unique characteristic sonographic pattern. Bilateral submandibular glands of both patients were enlarged with a smooth contour. The internal echo texture indicated multiple hypoechoic foci scattered against a heterogeneous background, which characteristically appeared with a mottled or irregular netlike appearance. A histopathologic examination of a resected section showed multiple foci of dense infiltrated lymphoplasmacytic cells and lymph follicles encircled by fibrous bands. A mottled appearance in the sonographic findings of the submandibular glands suggests the characteristic of IgG4-related disease and can be helpful in the differential diagnosis at the initial manifestation.

Proteomic analysis of secretion from human transplanted submandibular gland replacing lacrimal gland with severe keratoconjunctivitis sicca

Purpose: Proteomic analysis of secretions from transplanted or non-transplanted submandibular glands in patients with severe keratoconjunctivitis sicca and tears from normal eyes. Experimental design: Secretions from submandibular glands transplanted to replace lacrimal glands and non-transplanted submandibular glands were collected at 1year from 5 patients with severe keratoconjunctivitis sicca undergoing transplantation, and tears were collected from 3 normal subjects. 2-D electrophoresis (2-DE), then mass spectrometry was used to identify proteins. Western blot analysis was used to confirm protein expression. Results: We identified 34 and 11 distinct proteins in the saliva from transplanted submandibular glands and tears, respectively. The saliva from transplanted submandibular glands contained almost all the proteins abundant in tear fluid. The functions of identified proteins in the saliva from transplanted submandibular gland were mainly immune response and anti-bacterial. In total, 7 proteins showed differential expression between the saliva of transplanted and non-transplanted submandibular glands. The upregulation of short palate, lung and nasal epithelium carcinoma-associated protein 2 and carbonic anhydrase VI was confirmed by Western blot analysis. Conclusions: Identified proteins in saliva from transplanted submandibular glands may protect ocular structures. These findings can help in understanding the functional status of transplanted submandibular glands.

Changes of parotid and submandibular glands caused by radiotherapy—an ultrasound evaluation

Radiotherapy may alter the normal morphology of salivary glands located in the radiation field. These changes could be evaluated safely by sonography; however, there have been few studies in this regard. This study is aimed at evaluating the sonographic changes of the parotid and submandibular glands in patients undergoing radiotherapy for head and neck malignancies. 20 patients (16 males and 4 females) with head and neck malignancies who had been referred for radiotherapy to the Qaem Hospital in Mashhad, Iran, entered the study. Length, height, depth, echotexture, echogenicity and margins of parotid and submandibular glands were evaluated in three stages (I, before radiotherapy; II, 2 weeks after radiotherapy; and III, 6-7 weeks after radiotherapy) using sonography. Peak systolic velocity (PSV), end diastolic velocity (EDV) and resistive index (RI) were also evaluated by Doppler sonography. Significant differences in length, height and depth (p = 0.000, p = 0.000, and p = 0.39, respectively) and also echotexture, echogenicity and gland margins (p = 0.000) were observed before and after radiotherapy. Doppler sonography results showed no significant differences regarding PSV, EDV and RI between sonographic stages. Echotexture and echogenicity were the only independent parameters that showed significant differences in sonographic stages I and II (p = 0.000). Length in stage I and II (p = 0.000) and echogenicity in stage III (p = 0.038) were the only parameters that showed significant differences between the two glands. Radiotherapy may change the echotexture, echogenicity and margins of the salivary glands from homogenic to heterogenic, hyperechoic to hypoechoic and regular to irregular, respectively, and may reduce their size.

Is it oncologically safe to leave the ipsilateral submandibular gland during neck dissection for head and neck squamous cell carcinoma?

To investigate the incidence of metastasis to the submandibular gland in patients with head and neck squamous cell carcinoma. We retrospectively evaluated histological reports of neck dissections for upper respiratory tract carcinoma (performed 2002-2009), recording: primary tumour site, tumour-node-metastasis stage, level Ib involvement, previous radiotherapy, perineural invasion, lymphovascular invasion, extracapsular spread, and the presence of malignant disease in the submandibular gland. We evaluated 107 cases. The most common primary site was the oral cavity (49 per cent) followed by the supraglottis (21 per cent), glottis (14 per cent), oropharynx (9 per cent) and hypopharynx (6 per cent). Forty-eight per cent of patients had advanced local disease, with 21 per cent at tumour stage 3 and 27 per cent at tumour stage 4. Fifty-six per cent had cervical lymph node metastasis, and 8 per cent received pre-operative radiotherapy. Forty-eight per cent had perineural invasion, 46 per cent lymphovascular spread, 27 per cent extracapsular spread and 8 per cent level Ib metastasis. Only one patient had submandibular gland involvement, due to direct spread (a case with prior radiotherapy and macroscopic submandibular gland involvement evident peri-operatively). Submandibular gland metastasis from head and neck primary squamous cell carcinoma is extremely rare. Preservation of the ipsilateral submandibular gland during neck dissection is oncologically safe, except in patients with prior surgery or radiotherapy, or a primary tumour in close relation to the gland.

Proteomic Analysis of Human Transplanted Submandibular Gland in Patients with Epiphora after Transplantation

Submandibular gland autotransplantation is effective for treating severe dry eye syndrome. However, more than 40% of patients show epiphora within 3-6 months after treatment. The mechanism underlying the hypersecretion in epiphora remains to be elucidated for developing novel interventions. Since salivary gland secretion is dependent on a variety of proteins, we analyzed the changes in protein expression in transplanted glands of epiphora patients with 2-D gel electrophoresis and electrospray ionization quadrupole/time-of-flight mass spectrometry and evaluated their possible roles in epiphora. There were 23 proteins that showed altered expression in the glands of epiphora patients, 15 being up-expressed and 8 being down-expressed. The expression of secretory proteins was decreased in these glands, including alpha-amylase, cystatin S, SA, and SN. In contrast, cytoskeletal proteins were all up-regulated, including actin and vimentin. Immunofluorescence revealed that the intensity ratio of F-actin in apical and lateral cytoplasm to total F-actin in acini was decreased in the glands of epiphora patients. Carbachol stimulation induced a similar redistribution of F-actin in the control glands. Phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) was increased in both carbachol-stimulated and epiphora glands. Preincubation of submandibular glands with ERK1/2 inhibitors PD98059 or U0126 inhibited carbachol-induced F-actin redistribution. These results indicated that differentially expressed proteins participated in the hypersecretion of transplanted submandibular glands and the redistribution of F-actin might be involved in this hypersecretion in an ERK1/2-dependent manner.

Plexiform neurofibroma of the submandibular gland in patient with von Recklinghausen's disease

Plexiform neurofibroma of the submandibular gland is an extremely rare tumor. Herein, we report a case of plexiform neurofibroma in a patient with a von Recklinghausen's disease (NF-1) who presented with a submandibular mass mimicking a submandibular gland tumor. Complete surgical excision provides the best treatment and final diagnosis. A neurofibroma should be considered in the differential diagnosis for submandibular mass.

Radiation‐induced volume changes in parotid and submandibular glands in patients with head and neck cancer receiving postoperative radiotherapy: A longitudinal study

To investigate changes in parotid and submandibular gland volumes of patients with head and neck cancer treated with postoperative intensity-modulated radiotherapy (IMRT) or conventional radiotherapy (CRT), and to relate the volume changes to different mean radiation therapy (RT) doses to the parotid and submandibular glands. Between May 2007 and May 2008, 82 head and neck cancer patients (oral cavity cancer, 71; oropharynx cancer, 11) were treated with surgery and postoperative RT (IMRT, 40; CRT, 42) at our institution. Every patient underwent four computed tomography (CT) scans: one before RT, one after 3 weeks or at the 15th fraction of RT, one upon completing RT, and one at 2 months after RT; 39 of 82 patients had an additional CT scan at 6 months after RT. A dose-volume histogram was used to evaluate the mean volumes of patients' parotid and submandibular glands and mean RT doses to the glands on every CT scan. Altogether, 241 salivary glands (parotid, 162; submandibular, 79) were analyzed. The volume changes of the glands were evaluated against three levels of mean gland doses: <30 Gy, 30 to 50 Gy, and >50 Gy. The mean RT doses to spared parotid glands, spared submandibular glands, and irradiated submandibular glands in patients treated with IMRT were 22.21 Gy, 18.26 Gy, and 52.19 Gy, respectively. The mean doses to parotid and submandibular glands in patients treated with CRT were 50.22 Gy and 62.09 Gy, respectively. The average volume loss rates in parotid glands after 3 weeks of RT, at the end of RT, and 2 months after RT versus before RT were 20.01%, 26.93%, and 27.21%, respectively. The average volume loss rates in submandibular glands after 3 weeks of RT, at the end of RT, and 2 months after RT versus before RT was 11.49%, 16.76%, and 16.29%, respectively. Parotid and submandibular glands did not continue to shrink after completing RT. We observed more volume loss during RT in the parotid glands than in the submandibular glands. The average rates of volume loss during the first 3 weeks of RT (20.01% and 11.49%, respectively) were larger than in the last 3 weeks of RT (8.57% and 6.0%, respectively). No significant differences were observed in the mean volumes of both parotid and submandibular glands between the end of RT, 2 months post-RT, and 6 months post-RT (P > .05). Volume loss at higher doses (>30 Gy) to the glands was significantly larger than at low doses (<30 Gy; P < .001). The parotid and submandibular glands shrunk during RT, but the parotid glands shrunk more than the submandibular glands. These gland volume reductions correlated significantly with the mean dose to the irradiated glands; the spared glands showed few changes.

Ultrasonography of salivary glands: an evolving approach for the diagnosis of Sjögren's syndrome

Sjögren's syndrome (SS) is a chronic autoimmune rheumatic disease, which primarily affects the exocrine glands. The diagnosis of SS is based on American-European diagnostic criteria that include, as independent diagnostic items, imaging techniques such as sialography and scintigraphy. In recent years, new imaging techniques--including MRI, magnetic resonance sialography and ultrasonography of the salivary glands--have been used to diagnose SS. Ultrasonography is a noninvasive method that provides information about the changes to major salivary glands during inflammation. In a recently published report by Wernicke and colleagues, ultrasonography revealed decreased echogenicity and volume of submandibular glands in patients with SS but not in normal individuals, with a specificity of more than 90% and sensitivity close to 60%. Nevertheless, this technique should be carefully validated, using disease-control patients with dry mouth and comparison with other diagnostic items. The clarification of these matters will enable the use of ultrasonography for diagnostic purposes in SS.

Submandibular glands in the metabolic syndrome

In addition to their stimulatory action on neuronal differentiation and survival, a variety of neurotrophic factors, such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and ciliary neurotrophic factor, exert metabotrophic effects, including improvement of glucose, lipid and energy homeostasis. It was recently reported that plasma levels of both NGF and BDNF are reduced in patients with advanced metabolic syndrome and with acute coronary syndromes, and that NGF tissue content is decreased in human atherosclerotic coronary arteries. Since NGF and BDNF are synthesized, stored, and released by submandibular salivary glands, we investigated the structure and function of these glands. Here we present our scintigraphic and echographic results of submandibular glands of patients with advanced stage of metabolic syndrome: (i) scintigraphic analysis using the radiotracer (99m)Tc-pertechnetate showed an inhibition of salivary gland excretory activity, and (ii) echographic evaluation revealed a parenchymal destruction and a prominent fibrosis of the glands. Both suggestive for the involvement of submandibular glands in decreased secretion of NGF and BDNF as implicated in the pathogenesis of metabolic syndrome. Biomedical Reviews 2007; 18: 65-67.

Application of 99mTc-Pertechnetate Scintigraphy to Microvascular Autologous Transplantation of the Submandibular Gland in Patients with Severe Keratoconjunctivitis Sicca

Our objective was to evaluate the role of (99m)Tc-pertechnetate scintigraphy on microvascular autologous transplantation of the submandibular gland in patients with severe keratoconjunctivitis sicca (KCS). (99m)Tc-Pertechnetate scintigraphy was performed on 106 patients with severe KCS. The patients were examined before surgery and at 1 wk and 3 mo afterward using a standardized protocol that included static scintigrams, time-activity curves, and delayed scintigrams to check the function and secretion of the major salivary glands. The scintigraphic findings were assessed visually. When possible, the scintigraphic findings were compared with the clinical appearance of the transplanted gland. The function of all 4 major salivary glands was almost completely lost in 10 patients, indicating that these patients were not suitable for transplantation. The other 96 patients were treated by autologous transplantation of the submandibular gland. In 14 patients, the function of the major salivary glands was below normal. One patient's scintigram, obtained on the second day after surgery, showed no uptake of (99m)Tc-pertechnetate in the transplanted gland. Surgical exploration showed embolism of the artery of the transplanted gland. Scintigraphy was performed 1 wk after surgery in 90 patients. There was no uptake of (99m)Tc-pertechnetate in the temporal region in 8 patients, indicating that the glands were not revascularized. Scintigraphy showed obvious uptake of (99m)Tc-pertechnetate in the temporal region of the other 82 patients, indicating that the transplanted glands were viable. At more than 3 mo after surgery, scintigraphy was again performed on 30 patients. Scintigraphy after a 120-min delay showed that (99m)Tc-pertechnetate drained into the orbit through the duct of the transplanted gland in 26 patients. However, no secretion into the orbit was found in 4 patients, indicating obstruction of the duct. Scintigraphy plays an important role in microvascular autologous transplantation of the submandibular gland in patients with severe KCS. Scintigraphy can be used to select patients and donor glands, to evaluate the viability of the graft, and to check the patency of Wharton's duct of the transplanted gland.

Minute pleomorphic adenoma of the submandibular gland in patients with oral malignancy: a report of two cases with histological and immunohistochemical examination

Minute pleomorphic adenoma of the submandibular gland in patients with oral malignancy: a report of two cases with histological and immunohistochemical examination

Lymphocyte subsets in irradiation‐induced sialadenitis of the submandibular gland

Irradiation-induced sialadenitis is a significant cause of morbidity in head and neck cancer patients receiving radiotherapy. Neither the exact aetiopathology of chronic irradiation-induced sialadenitis nor the mechanisms leading to atrophy of the glandular cells associated with an increase in extracellular matrix are understood. The aim of our study was to determine the phenotype of the inflammatory infiltrate and to study its distribution in the affected submandibular glands. Paraffin-embedded submandibular glands from a homogeneous group of 19 patients with advanced oropharyngeal cancer who received conventional radiotherapy to the primary site and upper neck were analysed. In all patients the radiation dose and field were approximately equal. The submandibular glands were obtained during neck dissection. To characterize the lymphoid infiltrate, all tissue sections were immunostained for T cells (CD3, CD4, CD8), cytotoxic T cells (granzyme B), B cells (CD20), and macrophages (Ki-M1p). A histopathological classification into four grades was established based on the degree of glandular atrophy, fibrosis and lymphocytic infiltration. Phenotypic analysis of submandibular gland sections revealed that the great majority of lymphocytic infiltrates were cytotoxic T cells associated with acinar cell destruction. The significantly elevated frequencies of cytotoxic cells in the submandibular glands of patients with irradiation-induced sialadenitis suggest that cell-mediated immune mechanisms may play a part in the pathogenesis of this disease.

Transplantation of the autologous submandibular gland for most severe cases of keratoconjunctivitis sicca

This study aimed to examine the long-term qualitative and quantitative function of the secretion of transplanted autologous submandibular glands in patients with most severe keratoconjunctivitis sicca. The study design was clinical. The authors performed 26 operation in 22 patients. A complete ophthalmologic examination was performed in 16 eyes of 13 patients 1 week and 3 months and in 8 eyes of 8 patients 1 year after surgery. The submandibular gland was moved from its natural site into the temporal fossa. The glands supplying vessels were connected to the temporal artery and vein, and its secretory duct was implanted into the conjunctival fornix. Scintigraphy with Tc 99m Pertechnetate was used to document the graft vitality. Subjective symptoms and application frequency of artificial tears were recorded. Baseline as well as stimulated secretion and breakup time were measured and rose bengal staining and ocular ferning test were performed. In selected cases, the secretory product could be sampled for the detection of electrolytes, amylase, and secretory immunoglobulin A (SIgA). Scintigraphy showed vital gland tissue in 14 of 16 grafts at 3 months and 6 of 8 grafts at 1 year after surgery. Two of the 16 transplants were lost completely during the first 3 postoperative months, 1 because of an underlying autoimmunopolyendokrinopathy and the other because of an insufficient vascular anastomoses. In eyes with a vital transplant, baseline secretion and breakup time were increased significantly at 3 months and 1 year after surgery. Patients with a vital transplant reported a strong relief of symptoms and were able to stop taking artificial tear substitution at 1 year. Electrolytes showed a fluctuating concentration. A year after transplantation, the SIgA and amylase concentrations were more than ten times increased compared to normal tear values. Microvascular transferral of an autologous, paralytic submandibular gland results in a significant relief of subjective symptoms, a reduction of artificial tear applications, and an increase of baseline secretion over the first postoperative year. The composition and volume of the secretory product fluctuate, but high values of SIgA and amylase show an actively secreting graft. Although the authors' long-term experience still is limited, they believe that the procedure is a promising alternative approach for desperate dry eye conditions.

Analysis of carbohydrate composition and sialidase activity in oral secretions of patients with tumors in the upper aerodigestive tract.

Total saliva and secretions from parotid and submandibular glands of patients with carcinomas in the oral cavity, oropharynx or larynx and a control group of healthy individuals were analyzed for concentrations of glycosidically bound sugars and free N-acetylneuraminic acid as well as for sialidase activity. When compared to the data obtained for normal donors, the relative amounts of the individual monosaccharides fucose, galactose, mannose, N-acetylgalactosamine, and N-acetylglucosamine as components of glycoconjugates showed variable differences to the group of tumor patients depending on the type of secretion and the location of the tumor. The percentage of glycosidically linked N-acetylneuraminic acid, however, was always higher for the healthy donors. A significant difference was found in the amount of free sialic acid, with the exception of submandibular gland secretion from a patient with an oropharyngeal carcinoma, and sialidase activity which were increased for tumor patients, independent of the type of secretion and the location of the tumor. From these results it is concluded that free sialic acid and sialidase activity may be considered as markers for carcinomas in the upper aerodigestive tract.

Sialadenosis and Sialadenitis: Pathophysiologic and Diagnostic Aspects,

The series<i>Advances in Oto-Rhino-Laryngology</i>, printed by S Karger in Basel, Switzerland, has provided our specialty with many excellent monographs on a variety of interesting topics. Those of us interested in salivary gland disorders and physiology welcome the newest edition,<i>Sialadenosis and Sialadenitis</i>. The contributors are members of the faculty at the University of Göttingen in Germany. There are four sections to this monograph. The first, by R. Chilla, discusses the physiology and pathophysiology of parotid secretion in patients with sialadenosis, and in rats treated with a variety of sympathetic stimulants and blockers.<i>Sialadenosis</i>refers to recurrent, painless bilateral swelling of the salivary glands, most often the parotid. This term is used frequently on the continent and less often in the United States. Here we talk about endocrine and metabolic disorders. Most of us are familiar with salivary "hypertrophy" in diabetic patients and enlargement of the submandibular glands in patients