Sublingual gland excision for the surgical management of plunging ranula.

OBJECTIVE: A plunging ranula is a pseudocystic collection of mucin extravasated from the sublingual gland into the floor of mouth and through the mylohyoid muscle into the neck. While the lining of a ranula is non-secreting and resection of the sublingual gland is adequate for simple sublingual mucoceles, many surgeons attempt to address plunging ranulas with extensive transoral and transcervical dissections. We review our experience managing plunging ranulas with intraoral sublingual gland excision and ranula drainage alone. METHODS: This is a case series of patients with plunging ranulas who underwent transoral sublingual gland excision and ranula drainage in the past 10 years at the Massachusetts Eye and Ear. All ranulas were confirmed by radiographic imaging. Data were gathered from the medical record and telephone surveys. RESULTS: Twenty-one patients with 22 distinct ranulas underwent this surgical approach. Average ranula size on imaging was 4.3 cm (SD = 1.3). Thirteen patients with 14 ranulas were followed up for greater than 6 months while the remaining 7 patients were lost to follow-up. Median follow-up for the 13 patients was 30 months (range 6 to 80). One ranula recurred requiring excision of residual sublingual gland (7%). One patient developed a local infection that was treated with antibiotics (7%). No long term complications were reported. CONCLUSION: Simple transoral excision of the sublingual gland with ranula drainage is sufficient for treatment of plunging ranulas. It is essential to obtain a full resection of the gland to prevent relapse. This limited approach has low rates of complications and ranula recurrence.

Differential immunohistochemical expression of type I collagen and matrix metalloproteinase 2 among major salivary glands of young and geriatric mice.

OBJECTIVE: This study aimed to demonstrate the immunohistochemical changes associated with MMP-2 and type 1 collagen separately for the first time in the major salivary glands (the parotid, submaxillary, and sublingual glands) that occur with aging in mice. MATERIAL AND METHODS: Fourteen Balb/c white mice (50-80 g) were used in this study. The animals were divided into two equal groups. Group I consisted of young animals (2-month-old) (n=7) and Group II consisted of older animals (18-month-old) (n=7). After routine histological follow-ups, Hematoxylin-eosin (H&E), Masson's Trichrome staining and immunohistochemical staining was performed for type I collagen and MMP-2. RESULTS: We observed that there were age-related decreases in the number of acinar cells, increase in eosinophilic zymogen granules in cells, collagen accumulation in fibrotic areas and dilatation in interlobular ducts. Also, while type I collagen and MMP-2 immunoreactivity were moderate in the salivary glands of the young mice, they were high in the salivary glands of the old mice (p=0.001). In the H-score assessment, MMP-2 immunoreactivity was lower at a significant level in young mice than in old mice (p=0.001). CONCLUSIONS: This study showed that anatomical, physiological and morphological abnormalities occur in all three major salivary glands as a natural consequence of aging.

Differential immunohistochemical expression of type I collagen and matrix metalloproteinase 2 among major salivary glands of young and geriatric mice

Abstract Objective This study aimed to demonstrate the immunohistochemical changes associated with MMP-2 and type 1 collagen separately for the first time in the major salivary glands (the parotid, submaxillary, and sublingual glands) that occur with aging in mice. Material and Methods Fourteen Balb/c white mice (50-80 g) were used in this study. The animals were divided into two equal groups. Group I consisted of young animals (2-month-old) (n=7) and Group II consisted of older animals (18-month-old) (n=7). After routine histological follow-ups, Hematoxylin-eosin (H&E), Masson's Trichrome staining and immunohistochemical staining was performed for type I collagen and MMP-2. Results We observed that there were age-related decreases in the number of acinar cells, increase in eosinophilic zymogen granules in cells, collagen accumulation in fibrotic areas and dilatation in interlobular ducts. Also, while type I collagen and MMP-2 immunoreactivity were moderate in the salivary glands of the young mice, they were high in the salivary glands of the old mice (p=0.001). In the H-score assessment, MMP-2 immunoreactivity was lower at a significant level in young mice than in old mice (p=0.001). Conclusions This study showed that anatomical, physiological and morphological abnormalities occur in all three major salivary glands as a natural consequence of aging.

Enhanced salivary secretion by interferential current stimulation in patients with dry mouth: a pilot study.

OBJECTIVE: This pilot study tested the effects of submandibular and sublingual gland stimulation by interferential current stimulation (IFCS), a noninvasive mode of electrical stimulation. STUDY DESIGN: Three groups were enrolled in this study: 20 young adults, 19 older adults, and 21 patients with dry mouth. Four electrodes were attached to the submandibular area, and the secreted saliva was collected by using Salivette cotton rolls (Sarstedt K. K., Tokyo, Japan) for 15 minutes, either with or without IFCS. Patients were randomly chosen to receive IFCS. Each subject rated pain and discomfort on the Visual Analogue Scale (VAS) after each experiment. Saliva chromogranin A levels were measured as a stress marker. To compare data between conditions with and without IFCS, a two-sample Student t test analysis was performed. RESULTS: Saliva flow was slightly increased in those in the dry mouth group receiving IFCS compared with those who did not receive IFCS (approximately 130%). However, no such difference was found in the young and older adult groups. There was no significant difference in the VAS values of pain and discomfort or in the stress marker levels between patients who received or did not receive IFCS in the three groups. CONCLUSIONS: IFCS delivered to submandibular and sublingual glands may promote saliva secretion in persons who suffer from dry mouth in a manner that does not induce pain or physical stress.

An immunohistochemistry-based study on aquaporin (AQP)-1, 3, 4, 5 and 8 in the parotid glands, submandibular glands and sublingual glands of Sjögren's syndrome mouse models chronically administered cevimeline.

Cevimeline is a muscarinic agonist that promotes saliva secretion and is used to treat Sjögren's syndrome (SS), an autoimmune disorder in which the exocrine glands that produce saliva are destroyed. Cevimeline is thought to affect the composition of saliva in part by regulating the localization of aquaporins (AQPs). In this study, we investigated the effects of chronic Cevimeline administration in the salivary glands of SS mice on the immunohistochemical localization of aquaporin (AQP)-1, 3, 4, 5 and 8. We used Cevimeline-untreated SS mice, treated SS mice, discontinued SS mice and untreated normal mice. AQP-5 was found in the apical and lateral membranes of acinar cells in the parotid and submandibular glands of cevimeline-treated SS mice and untreated normal mice. Saliva secretion and AQP-5 localization were sustained in SS mice who were chronically administered Cevimeline and at four weeks after discontinuation. Unlike AQP-5, the localization of AQP-1, 3, 4 and 8 were not affected by Cevimeline administration. Our findings demonstrated that administration of Cevimeline maintains the proper localization of AQP-5 in the acinar cells of the salivary gland, which may promote salivation in chronically treated SS mice. Clinically, this suggests that chronic Cevimeline administration may be useful therapeutically for SS patients suffering from a decrease in saliva secretion by improving the disordered AQP-5 localization.

Avaliação do fenótipo e da proliferação celular das estruturas ductiformes no processo de envelhecimento de glândulas sublinguais humanas / Evaluation of the phenotype and the proliferation capacity of duct-like structures in the aging process of human sublingual glands

São várias as alterações microscópicas decorrentes do processo de envelhecimento das glândulas salivares, dentre elas o aumento no número de estruturas ductiformes. O objetivo deste trabalho é estudar o fenótipo e o índice de proliferação celular das mesmas. Sessenta glândulas sublinguais de cadáveres humanos foram divididas em dois grupos segundo a aixa etária dos indivíduos (0-30 anos e 61-90 anos). O fenótipo foi estimado pela imunomarcação da citoqueratina 19 (CK 19), da proteína S-100 e pela evidenciação dos polissacarídeos mucina e glicogênio. A avaliação do índice de proliferação de células epiteliais das estruturas ductiformes se deu por meio da imunomarcação do Ki-67. As técnicas histoquímicas consistiram no ácido periódico de Schiff (PAS) e Azul de Alcian pH 2,5. Em cada campo microscópico capturado foram contadas as estruturas ductiformes para estabelecer o perfil de marcação em percentual. A análise estatística foi realizada por meio dos testes t de Student, Mann-Whitney e correlação de Pearson (p < 0,05). Comparando os dois grupos, apenas a imunomarcação para CK 19 mostrou diferença estatisticamente significante (p = 0,033), sendo sua expressão mais forte no grupo de idosos. Não houve diferença significante entre os marcadores PAS e Azul de Alcian (p = 0,270). Nos dois grupos a imunomarcação para CK 19 foi mais forte do que para S-100 (p = 0,004; p < 0,001), sendo a correlação entre os dois imunomarcadores ausente (ρ = -0,163; p = 0,315). Não houve imunomarcação para o Ki-67 em nenhuma estrutura ductiforme. Concluiu-se que as estruturas ductiformes demonstram um perfil fenotípico ductal e não apresentam atividade proliferativa celular. Elas podem representar um processo regressivo com origem nos ácinos ou resultarem de metaplasia.

There are several age-related microscopic changes in the salivary glands, including the increase in the number of duct-like structures. The aim of this study is to evaluate the phenotype and the cell proliferation index of these structures. Sixty sublingual glands obtained from human cadavers were divided into two groups according to the individuals age (0-30 and 61-90 years old). The phenotype was estimated by the immunostaining for cytokeratin 19 (CK 19), S-100 protein and by the disclosure of the polysaccharides mucin and glycogen. The cell proliferation index was determined by Ki-67 immunostaining. The histochemical techniques consisted of periodic acid-Schiff (PAS) and Alcian Blue pH 2.5. Ineach captured microscopic field, the duct-like structures were counted to establish the staining profile in percentage. Statistical analysis was done by Students t-test, Mann-Whitney test and Pearsons correlation coefficient (p < 0.05). Comparing the two groups, only the immunostaining for CK 19 showed significant statistical difference (p = 0.033), with strongest expression in the elderly group. There was no significant difference between the markers PAS and Alcian Blue (p = 0.270). In both groups the immunostaining for CK 19 was stronger than for S-100 (p = 0.004; p < 0.001), but there was no correlation between the two immunomarkers (ρ = -0.163; p = 0.315). There was no immunostaining for Ki-67 in any ductlike structure. We concluded that the duct-like structures demonstrate a ductal phenotypic profile and do not present cell proliferation activity. They may represent a regressive process arising from acini or a result of a metaplasia.

Avaliação do fenótipo e da proliferação celular das estruturas ductiformes no processo de envelhecimento de glândulas sublinguais humanas / Evaluation of the phenotype and the proliferation capacity of duct-like structures in the aging process of human sublingual glands

São várias as alterações microscópicas decorrentes do processo de envelhecimento das glândulas salivares, dentre elas o aumento no número de estruturas ductiformes. O objetivo deste trabalho é estudar o fenótipo e o índice de proliferação celular das mesmas. Sessenta glândulas sublinguais de cadáveres humanos foram divididas em dois grupos segundo a aixa etária dos indivíduos (0-30 anos e 61-90 anos). O fenótipo foi estimado pela imunomarcação da citoqueratina 19 (CK 19), da proteína S-100 e pela evidenciação dos polissacarídeos mucina e glicogênio. A avaliação do índice de proliferação de células epiteliais das estruturas ductiformes se deu por meio da imunomarcação do Ki-67. As técnicas histoquímicas consistiram no ácido periódico de Schiff (PAS) e Azul de Alcian pH 2,5. Em cada campo microscópico capturado foram contadas as estruturas ductiformes para estabelecer o perfil de marcação em percentual. A análise estatística foi realizada por meio dos testes t de Student, Mann-Whitney e correlação de Pearson (p < 0,05). Comparando os dois grupos, apenas a imunomarcação para CK 19 mostrou diferença estatisticamente significante (p = 0,033), sendo sua expressão mais forte no grupo de idosos. Não houve diferença significante entre os marcadores PAS e Azul de Alcian (p = 0,270). Nos dois grupos a imunomarcação para CK 19 foi mais forte do que para S-100 (p = 0,004; p < 0,001), sendo a correlação entre os dois imunomarcadores ausente (ρ = -0,163; p = 0,315). Não houve imunomarcação para o Ki-67 em nenhuma estrutura ductiforme. Concluiu-se que as estruturas ductiformes demonstram um perfil fenotípico ductal e não apresentam atividade proliferativa celular. Elas podem representar um processo regressivo com origem nos ácinos ou resultarem de metaplasia.

There are several age-related microscopic changes in the salivary glands, including the increase in the number of duct-like structures. The aim of this study is to evaluate the phenotype and the cell proliferation index of these structures. Sixty sublingual glands obtained from human cadavers were divided into two groups according to the individuals age (0-30 and 61-90 years old). The phenotype was estimated by the immunostaining for cytokeratin 19 (CK 19), S-100 protein and by the disclosure of the polysaccharides mucin and glycogen. The cell proliferation index was determined by Ki-67 immunostaining. The histochemical techniques consisted of periodic acid-Schiff (PAS) and Alcian Blue pH 2.5. Ineach captured microscopic field, the duct-like structures were counted to establish the staining profile in percentage. Statistical analysis was done by Students t-test, Mann-Whitney test and Pearsons correlation coefficient (p < 0.05). Comparing the two groups, only the immunostaining for CK 19 showed significant statistical difference (p = 0.033), with strongest expression in the elderly group. There was no significant difference between the markers PAS and Alcian Blue (p = 0.270). In both groups the immunostaining for CK 19 was stronger than for S-100 (p = 0.004; p < 0.001), but there was no correlation between the two immunomarkers (ρ = -0.163; p = 0.315). There was no immunostaining for Ki-67 in any ductlike structure. We concluded that the duct-like structures demonstrate a ductal phenotypic profile and do not present cell proliferation activity. They may represent a regressive process arising from acini or a result of a metaplasia.

Modern management and pathophysiology of ranula: literature review.

BACKGROUND: There is a lack of consensus about the appropriate treatment of ranula. The objective of the present investigation was to produce a scientific basis for treatment. METHODS: A review of the relevant literature is interpreted in the light of improved knowledge about the local anatomy and the pathophysiology of the salivary glands. RESULTS: The oral and plunging ranulas are cystic extravasation mucoceles that arise from the sublingual gland and usually from a torn duct of Rivinus. The sublingual gland is a spontaneous secretor and the salivary flow is resistant to obstruction, which is caused by fibrosis induced by the extravasation. The submandibular gland is not a spontaneous secretor, is less resistant, and does not give rise to ranulas. CONCLUSIONS: Effective treatment is removal of the involved unit of the sublingual gland or inducing sufficient fibrosis to seal the leak through which the mucus extravasates.

Acute microflow changes after stop and restart of intra-aortic balloon pump in cardiogenic shock.

BACKGROUND: The intra-aortic balloon counter pulsation (IABP) is the most frequently used method of mechanical cardiac support in cardiogenic shock (CS). Microcirculatory impairment correlates with outcome in critically ill patients. We therefore investigated the acute influence of IABP therapy on sublingual microflow in patients with CS. METHODS: Sidestream darkfield intravitalmicroscopy was used in 13 patients with severe CS. The sublingual microvascular bed (10-100 microm) was examined according to current guidelines. We measured microflow in means of microvascular flow index at baseline and after intentional stop of IABP support. A computerized model was used for blinded off-line analysis. RESULTS: Microflow in vessels 10-50 microm in diameter was improved during IABP support (P < 0.001). Norepinephrine had a negative effect on the response to IABP related microflow improvement. Cardiac Perfusion Index (product of Cardiac Power index and microflow) correlated best with blood lactate levels. CONCLUSIONS: It was the aim of this study to evaluate the acute influence of IABP therapy on microflow in vivo. In this setting we found that IABP therapy improves sublingual microflow. Future studies should investigate Cardiac Perfusion Index under such conditions with respect to clinical decision making.

O espaço sublingual / The sublingual space

O espaço sublingual é um espaço de forma semilunar situado no soalho da boca. Estende-se desde a superfície interna da margem alveolar até a base da língua. Localiza-se medialmente ao músculo milo-hióideo, que o separa dos espaços submentoniano e submandibular, posteriormente ao complexo hioglosso-estiloglosso e anteriormente ao músculo genioglosso. A presença de tecido conjuntivo frouxo e tecido gorduroso como conteúdo neste espaço confere aspecto característico na tomografia computadorizada e na ressonância magnética, permitindo sua fácil identificação. Contém ainda a glândula sublingual, a porção profunda da glândula submandibular e seu ducto, a artéria e veia lingual, além dos nervos lingual, glossofaríngeo e hipoglosso. Suas relações são de grande importância, uma vez que lesões originadas na orofaringe e na cavidade oral podem envolver esta área. Os autores analisam a anatomia deste espaço e suas estruturas componentes, relacionando-as com enfermidades que o acometem. Os métodos de imagem são úteis na avaliação e compreensão dessas lesões, podendo também orientar condutas terapêuticas

The sublingual space is a semilunar shaped space of the floor of the mouth that extends from the internal surface of the alveolar edge to the base of the tongue. The sublingual space is located medially to the mylohyoid muscle, which separates the sublingual space from the submandibular space, anteriorly to the hyoglossus-styloglossus complex, and is medially bounded by the genioglossus muscle. It contains the sublingual gland, the deep portion of the submandibular gland, the submandibular duct, the lingual artery and vein, the lingual nerve and the cranial nerves IX and XII. The relationships of the sublingual space are very important since lesions originating from the oropharynx and oral cavity can extend into this area whereas lesions arising from the sublingual space readily spread to involve the adjacent submandibular space. The authors present an anatomical and functional description of the structures within the sublingual space and discuss the diseases occurring in this region. Imaging methods are useful in the assessment and understanding of the lesions in the sublingual space and may help in the clinical and surgical management of the patients.

Diagnóstico radiológico de la cavidad ósea de Stafne

La cavidad ósea de Stafne (COS) es un defecto óseo mandibular de evolución estable que constituye una lesión pseudoquística o pseudotumoral. Se describen tres pacientes con COS estudiados por TC. La lesión presenta unas características típicas: localización característica en ángulo mandibular debajo del canal mandibular sin patología asociada y con abertura a cara lingual mandibular. Si los datos de la ortopantomografía sugieren un COS se debe realizar una TC para confirmar el diagnóstico evitando la realización de procedimientos agresivos quirúrgicos (AU)

The roles of apoptosis and mitosis in atrophy of the rat sublingual gland.

The roles of apoptosis and mitosis of acinar and duct cells in the atrophy of the sublingual gland of rat induced by double duct ligation was investigated using immunohistochemistry for proliferating cell nuclear antigen (PCNA), terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end labeling (TUNEL), and transmission electron microscopy (TEM). Many PCNA-positive duct cells were observed 3 days after duct ligation, and the numbers decreased thereafter. At 3 and 5 days, several TUNEL-positive acinar cells were observed and typical apoptotic acinar cells were identified by TEM. Necrotic acinar cells were also observed ultrastructurally. After 7 days, there were few acini but many ducts, as well as many structures representing transition from acinus to duct. These observations demonstrate that acinar cell loss by apoptosis and duct cell proliferation by mitosis occur in atrophic sublingual glands as well as in other atrophic salivary glands. In addition, it appears that the transition from acinar to duct cell and the necrosis of acinar cells play important roles in the atrophy of the sublingual gland.

Submandibular and sublingual salivary gland function in familial dysautonomia.

OBJECTIVE: Drooling in familial dysautonomia (FD) has been attributed to denervation supersensitivity. The aim of this study was to investigate submandibular and sublingual (SM/SL) gland function in FD. STUDY DESIGN: SM/SL saliva was collected from 15 children with FD and from 31 healthy control subjects. The protein and electrolyte content and the salivary flow rate were determined in each subject. RESULTS: Children with FD displayed significantly elevated outputs of chloride, potassium, calcium, phosphorous, magnesium, and total protein. Salivary flow rates were significantly increased. Phosphorous concentration was statistically low. These results imply SM/SL hyperfunction at the acinar and ductal levels. The concentration of lysozyme, the activity of amylase, and the output of both were similar in patients and control subjects. CONCLUSION: SM/SL gland hyperactivity is a newly described abnormality in FD. At the acinar level, this hyperactivity is expressed with increased fluid, electrolyte, and protein output, and at the ductal level, with increased ion secretion and absorption rate. These changes may be the result of ongoing parasympathetic denervation characteristic in FD.

[Effects of upper incisor separation on the submandibular and sublingual glands of young rats].

The effects of upper incisor separation, chronic isoproterenol (IPR) treatment and a combination with both treatments on the submandibular and sublingual glands of rats were examined and compared biochemically, immunohistochemically and radioimmunologically during 7 days after treatment. The findings obtained were as follows: 1. Both submandibular and sublingual glands of rats were significantly enlarged by an orthodontic appliance and chronic IPR treatment, and in combination with both treatments they were much more markedly enlarged additively during 7 days of treatment. This enlargement was followed, in general, by a significant increase of both RNA and DNA contents, and the incorporation of BrdU into the glandular cells, especially acinar cells, with some evidence of hyperplasia and hypertrophy. 2. Enlargement of the submandibular glands induced by orthodontic treatment was mediated via superior cervical ganglion, chorda tympani and lingual nerves, whereas of the sublingual glands mainly via chorda tympani and lingual nerves with some evidence of the mutual interactions among these nerves. 3. The secretory functions of the submandibular glands were significantly reduced at early stages after orthodontic treatment in contrast to those of chronic IPR treatment with and without orthodontic treatment. 4. The synthesis of LM protein, mainly localized in the acinar cells, was increased by orthodontic treatment in combination with adrenergic blockers, prazosin, metoprolol and ICI 118551, whereas in chronic IPR treatment it was significantly reduced by metoprolol, but not by prazosin and ICI 118551. LM protein was secreted into saliva at 6 h after IPR treatment.