The Need for Studies on Oral Corticosteroids After Sialendoscopy for Obstructive Salivary Gland Disease: Systematic Review.

OBJECTIVES: This qualitative systematic review evaluates the evidence in support of the use of oral corticosteroids in patients undergoing sialendoscopy for the treatment of obstructive sialadenitis. DESIGN: Qualitative systematic review. METHODS: A literature search was conducted from January 1985 and September 2020. Inclusion criteria embraced peer-reviewed articles in which adult patients undergoing interventional sialendoscopy for obstructive salivary gland disease received oral corticosteroids. The results were initially screened based on title and abstract, and the remaining articles were reviewed for eligibility. RESULTS: About 218 papers were selected by title and abstract, 96 were selected for full-text review, and 9 met the inclusion criteria. Eight published reports were retrospective observational studies and 1 was a prospective comparative study. Overall, the heterogeneity of clinical data stood out in this systematic review. The pooled success rate in the studies was 873/979 (89%). Only 5 studies described a rationale for oral corticosteroid use as part of the post-operative management. In 4 studies, a prednisone total daily dose of 40 to 50 mg was used. One study clearly showed a lower recurrence rate in patients who received oral steroids for more than 7 days in addition to sialendoscopy for management of ductal stenoses. CONCLUSION: This systematic review showed that most centers that prescribe oral corticosteroids after sialendoscopy are unaware of the specific results with this treatment. For ductal stenoses, only 1 paper clearly showed the benefits of oral corticosteroids after sialendoscopy but more high-quality evidence is required in the form of a comparative study or randomized controlled trial, with appropriate long-term follow up.

Successful treatment of a dog with phenobarbital-responsive sialadenosis and an oesophageal stricture.

BACKGROUND: Phenobarbital-responsive sialadenosis (PRS) can cause nausea and vomiting, and is rarely reported in dogs. OBJECTIVES: An 8-year-old neutered, male Pomeranian dog was presented to our teaching hospital with vomiting that began 2 years ago. The clinical signs repeatedly improved and deteriorated despite treatment. METHODS: The only abnormality found on physical examination was salivary gland enlargement, and no specific findings were observed on blood analysis and imaging tests. The results of the fine needle aspirate cytology from the salivary glands revealed possible sialadenosis. Phenobarbital was prescribed, and the patient's symptoms resolved. However, upon discontinuing drug, the patient's clinical signs recurred and did not improve even after re-introduction of phenobarbital and the addition of other anticonvulsant drugs. An oesophageal stricture was observed on an oesophagram, and fibrosis was confirmed endoscopically. A balloon dilation was performed to expand the stenosis. RESULTS: After the first procedure, the patient's clinical signs initially improved, but relapsed 2 weeks later. A total of three oesophageal dilation procedures were performed using a sequentially larger diameter balloon. After the third procedure, the patient's clinical signs were managed without recurrence. The cause of recurrent gastrointestinal signs following the initial successful treatment of phenobarbital-responsive sialadenosis was due to oesophageal stricture formation. CONCLUSIONS: This case report demonstrates the successful management of PRS with subsequent oesophageal stricture formation in a dog.

Clinical efficacy of botulinum toxin in salivary duct stenosis: A preliminary study of six cases.

INTRODUCTION: Salivary duct stenosis is the second most common cause of obstructive pathology after lithiases, and it primarily affects the parotid gland. Salivary duct stenosis is treated with drug therapy and/or sialendoscopy. If unsuccessful, surgical removal of the gland is indicated, but it is associated with a high risk of facial morbidity. The aim of this study is to evaluate the clinical efficacy of an alternate treatment, botulinum toxin, in salivary duct stenosis. MATERIAL AND METHODS: In a preliminary retrospective study from January 2011 to December 2014, six patients with parotid duct stenosis received 50IU of botulinum toxin in three injections in the parotid gland. The frequency of relapses and the intensity of pain and swelling were recorded before and after treatment. The onset of action and duration of efficacy were also assessed. RESULTS: Four of six patients showed a decrease in the frequency of swelling episodes and greater pain relief during the first year of treatment, but to a lesser extent after 2years. The mean duration of efficacy was 3.5months with an interval between two injections of 5.7months. Only one parotidectomy had to be performed. No major side effects were observed, with only one case of local infection at the injection site. CONCLUSION: Botulinum toxin appears to be a viable alternative in treating salivary duct stenosis before resorting to surgical gland removal.

Ethanol Ablation of Ranulas: Short-Term Follow-Up Results and Clinicoradiologic Factors for Successful Outcome.

BACKGROUND AND PURPOSE: Surgical excision of an affected sublingual gland for treatment of a ranula can carry a potential of a nerve damage or postoperative complications. However, there have been little studies about effective minimally invasive therapeutic method, yet. Our aim was to evaluate the efficacy and safety of ethanol ablation of ranulas and the clinicoradiologic factors that can predict outcome. MATERIALS AND METHODS: This retrospective study evaluated 23 patients with ranulas treated by percutaneous ethanol ablation. Treatment outcome was assessed in 20 patients followed for at least 6 months. The duration of symptoms before ethanol ablation, pretreatment volume, and parapharyngeal extension on sonography and/or CT were correlated with the outcome. The Mann-Whitney U test and Fisher exact test were used for comparison of the factors according to the outcome. RESULTS: The study evaluated 14 males and 9 females with a median age of 26 years (range, 3-41 years). Among 20 patients who were followed for at least 6 months (median, 20 months; range, 6-73 months), 9 patients (45%) demonstrated complete disappearance of the ranulas and 11 (55%) showed an incomplete response. When the patients were divided according to the duration of symptoms before ethanol ablation, the complete response rate was significantly higher in patients with ≤12 months of symptoms (73%, 8/11) than that in others (11%, 1/9) (P = .010). Pretreatment volume and parapharyngeal extension were not significantly different between the 2 groups. CONCLUSIONS: Ethanol ablation is a safe and noninvasive treatment technique for ranulas with a significantly better outcome in patients with ≤12 months of symptoms. Therefore, it could be considered an alternative nonsurgical approach for ranulas with recent onset of symptoms.

Botulinum toxin therapy: functional silencing of salivary disorders.

Botulinum toxin (BTX) is a neurotoxic protein produced by Clostridium botulinum, an anaerobic bacterium. BTX therapy is a safe and effective treatment when used for functional silencing of the salivary glands in disorders such as sialoceles and salivary fistulae that may have a post-traumatic or post-operative origin. BTX injections can be considered in sialoceles and salivary fistulae after the failure of or together with conservative treatments (e.g. antibiotics, pressure dressings, or serial aspirations). BTX treatment has a promising role in chronic sialadenitis. BTX therapy is highly successful in the treatment of gustatory sweating (Frey's syndrome), and could be considered the gold standard treatment for this neurological disorder.

The Significance of Matrix Metalloproteinases in Oral Diseases.

Matrix metalloproteinases (MMPs) belong to a family of structurally related zinc-dependent proteolytic enzymes that are known to play a key role in the catabolic turnover of extracellular matrix (ECM) components. Research studies to date have indicated that MMPs regulate the activity of several non-ECM bioactive substrates, including growth factors, cytokines, chemokines and cell receptors, which determine the tissue microenvironment. Disruption of the balance between the concentration of active matalloproteinases and their inhibitors (TIMPs) may lead to pathological changes associated with uncontrolled ECM turnover, tissue remodeling, inflammatory response, cell growth and migration. This brief review presents some information on MMPs' role in inflammatory, metabolic and cancer abnormalities related to the salivary glands, as well as MMP-related aspects that lead to the formation of human dentinal caries lesions. In oral diseases, the most relevant biological fluid commonly used for diagnosing periodontal diseases is saliva. In diseased patients with significantly higher levels of MMPs in their saliva than healthy people, most extracellular matrix components undergo digestion to lower molecular weight forms. Conventional treatment successfully reduces the levels of MMPs inhibits the progressive breakdown of gingival and periodontal ligament collagens. Beside inflammatory abnormalities like Sjögren's syndrome (SS), a large group of disorders is comprised of cancers, most of them involving the parotid gland.

Usefulness of minor salivary gland biopsy in the diagnosis of IgG4-related disease: a case report.

Although considered essential for diagnosing IgG4-related disease (IgG4-RD), biopsy of target organs is often difficult to perform. Such was the case of a 56-year-old man admitted with general malaise and weight loss. Computed tomography revealed swelling of the submandibular gland, mild dilatation of the main pancreatic duct, renal involvement, periaortitis, and swelling of the lymph nodes in the abdominal cavity. Laboratory testing revealed elevated serum IgG4 level. These findings were suggestive of IgG4-RD; however, the patient refused consent for biopsy of the target organs for a definitive diagnosis for the invasiveness. Therefore, we tried to perform a biopsy from minor salivary gland, which revealed no sign of clinical abnormality because the biopsy is not an invasive diagnostic procedure. As a result, the biopsy revealed significant IgG4-positive plasma cell infiltration, allowing for definitive IgG4-RD diagnosis. Administration of oral prednisolone (30 mg/day) effectively improved all symptoms. These findings indicate that minor salivary gland biopsy is an effective means of IgG4-RD diagnosis in patients for whom biopsy of target organs is difficult even if there were no sign of clinical abnormality in appearance.

Chronic inflammation in the pancreas and salivary glands--lessons from similarities and differences in pathophysiology and treatment modalities.

The pancreas and salivary glands have similar anatomical structures and physiological functions producing bicarbonate-rich fluid containing digestive enzymes and other components to be delivered into the gut. Despite these similarities, the two organs are also different in numerous respects, especially regarding the inflammatory diseases affecting them. This article will summarize the pathophysiology and current and potential pharmacological treatments of chronic inflammatory diseases such as chronic pancreatitis, autoimmune pancreatitis, Sjögren's syndrome and irradiation-induced salivary gland atrophy. Despite the differences, in both organs the inflammatory process is accompanied by epithelial tissue destruction and fibrosis. Both in pancreatic and in salivary research, an important task is to stop or even reverse this process. The utilization of stem/progenitor cell populations previously identified in these organs and the application of mesenchymal stem cells are very promising for such regenerative purposes. In addition, gene therapy and tissue engineering research progressively advance and have already yielded clinically beneficial preliminary results for salivary gland diseases. For the hard-to-access, hard-to-regenerate pancreas these developments may also offer new solutions, especially since salivary and pancreatic progenitors are very similar in characteristics and may be mutually useful to regenerate the respective other organ as well. These novel developments could be of great significance and may bring new hope for patients since currently used therapeutic protocols in salivary and in pancreatic chronic inflammatory diseases offer primarily symptomatic treatments and limited beneficial outcome.

IgG4-related disease: a novel, important but easily missed condition.

Immunoglobulin G4-related disease (IgG4-RD) is a multisystem, fibroinflammatory condition unrecognised in medical science until the last decade. It is characterised by progressive scarring and dysfunction of affected organs and tissues including the pancreas, hepatobiliary tree, kidneys, salivary glands, retroperitoneum and lungs. The diagnosis is made with the presence of numerous IgG4 positive plasma cells within a histologically-distinct chronic inflammatory process; most patients also have elevated serum IgG4. Though early cases were all identified in Japan, subsequent reports clearly demonstrate that IgG4-RD exists worldwide. There are no data confirming the prevalence of IgG4-RD in the West but it is thought to be very rare. Limited awareness of the condition and its heterogeneous presentation frequently results in misdiagnosis. Prompt and correct diagnosis is critical, as a rapid reversal of even advanced disease is often seen with corticosteroid therapy. We present three cases that illustrate some of the typical features of this condition.

The potential impact of highly active antiretroviral therapy on the treatment and epidemiology of ranula in human immunodeficiency virus-positive patients.

OBJECTIVE: The study's aim was to assess the potential therapeutic effect of highly active antiretroviral therapy (HAART) on ranulas in human immunodeficiency virus (HIV)-positive patients. STUDY DESIGN: The study includes a retrospective observation of 3 patients who were initially part of a prospective study on the comparative effect of HAART on ranulas in 14 HIV-positive patients. These patients were clinically monitored while pursuing the medical treatment with HAART. Neither a fine needle aspiration nor a surgical procedure was performed. Clinical photographs were used for monitoring of any reduction in the ranula size. The effect of HAART on ranula was assessed at 3, 6 and 12 month. RESULTS: A complete resolution of the ranula lesion was noticed in the 3 HIV-positive selected patients. These results were observed between 6 and 12 months period. CONCLUSION: This study suggests that HAART might present a potential therapeutic effect on ranula in HIV-positive patients.

[Specific tongue involvement revealing sarcoidosis]. / Atteinte linguale spécifique révélatrice d'une sarcoïdose.

BACKGROUND: Sarcoidosis is a multisystem granulomatous disease of unknown aetiology. Tongue involvement is extremely rare. Herein we report a new case. PATIENTS AND METHODS: A 65-year-old woman presented with a 6-month history of painless multiple nodules on the tongue. The patient also complained of xerostomia. Besides nodules on the tongue, physical examination revealed erythematous nodules on the dorsum of the hands and feet. A diagnosis of sarcoidosis with tongue, cutaneous and salivary gland involvement was made on the basis of these findings and further investigations performed. The patient's condition showed improvement with partial regression of tongue lesions after oral steroid therapy. DISCUSSION: Tongue involvement in sarcoidosis is exceedingly rare. It may be isolated or part of a generalized multisystem sarcoidosis. Nodules, indurations and swelling are the most common clinical manifestations. Management of tongue sarcoidosis is not consensual. Oral corticosteroids appear to be the most effective therapy. CONCLUSION: Sarcoidosis of the tongue should be considered when chronic unexplained nodules are noted. Diagnosis can easily be confirmed by a histological examination of mucosal biopsy.

[Antihomotoxic therapy in patients with inflammatory and dystrophic salivary gland diseases].

Traumeel S was used as monotherapy for salivary glands inflammatory and dystrophic disorders. The study showed the drug to be especially efficient by exacerbation of the recurrent disease but the results were poor by indolent disease and on the latter stages of dystrophic disorder. Traumel S may be recommended to be used in combined therapy for salivary glands inflammatory and dystrophic disorders treatment.

Activation of transient receptor potential vanilloid subtype 1 increases expression and permeability of tight junction in normal and hyposecretory submandibular gland.

Tight junction (TJ) is an important structure that regulates material transport through the paracellular pathway across the epithelium, but its significance in salivary physiology and pathogenesis of salivary dysfunctional diseases is not fully understood. We previously demonstrated that a functional transient receptor potential vanilloid subtype 1 (TRPV1) expresses in submandibular gland (SMG). However, association of TRPV1-induced saliva secretion with TJ remains unknown. Here we explored the effect of TRPV1 activation on expression and function of TJ of rabbit SMG in vitro and in vivo. RT-PCR and western blot analysis revealed that capsaicin upregulated expression of zonula occludin-1 (ZO-1), claudin (Cldn)-3, and -11, but not Cldn-1, -2, -4, -5, and -7 in cultured SMG cells. Capsaicin also increased the entering of 4 kDa FITC-dextran into the acinar lumen, induced redistribution of cytoskeleton F-actin under confocal microscope, and these effects were abolished by preincubation of capsazepine, a TRPV1 antagonist, indicating that activation of TRPV1 increases expression and permeability of TJ in SMG. Additionally, in a hyposecretory model induced by rabbit SMG transplantation, the expression of ZO-1, Cldn-3, and -11 was decreased, whereas other TJs remained unaltered. The structure of TJ was impaired and the width of apical TJs was reduced under transmission electron microscope, concomitant with diminished immunofluorescence of F-actin in peri-apicolateral region, indicating impaired TJ expression and decreased paracellular permeability in the transplanted SMG. Moreover, topical capsaicin cream increased secretion, decreased TJ structural injury, reversed TJ expression levels, and protected F-actin morphology from disarrangement in transplanted SMGs. These data provide the first evidence to demonstrate that TJ components, particularly ZO-1, Cldn-3, and -11 have important roles in secretion of SMG under both physiological and pathophysiological conditions. The injury in TJ integrity was involved in the hypofunctional SMGs, and TRPV1 might be a potential target to improve saliva secretion through modulating expression and function of TJs.

[Reactive-dystrophic processes in salivary glands (sialoadenoses) running on the background of metabolic syndrome].

Basing upon comprehensive checkup of 82 patients with metabolic syndrome authors made diagnostics of different forms of sialoadenosis in them. The disease proceeded on the background of abdominal adiposity, lipid metabolism derangements, glucose toleration disturbances and diabetes mellitus of the 2nd type with reduction of tissue sensitivity to insulin (insulin resistivity). Results of the fulfilled patient treatment showed that it was necessary to include in the complex of therapeutic measures metformine (glukofagee) producing positive effect upon carbohydrate metabolism and also to normalize the work of glands increasing their secretory activity.

Genetic and pharmacologic inhibition of the Ca2+ influx channel TRPC3 protects secretory epithelia from Ca2+-dependent toxicity.

BACKGROUND & AIMS: Excessive Ca2+ influx mediates many cytotoxic processes, including those associated with autoimmune inflammatory diseases such as acute pancreatitis and Sjögren syndrome. Transient receptor potential (canonical) channel (TRPC) 3 is a major Ca2+ influx channel in pancreatic and salivary gland cells. We investigated whether genetic or pharmacologic inhibition of TRPC3 protects pancreas and salivary glands from Ca2+-dependent damage. METHODS: We developed a Ca2+-dependent model of cell damage for salivary gland acini. Acute pancreatitis was induced by injection of cerulein into wild-type and Trpc3-/- mice. Mice were also given the Trpc3-selective inhibitor pyrazole 3 (Pyr3). RESULTS: Salivary glands and pancreas of Trpc3-/- mice were protected from Ca2+-mediated cell toxicity. Analysis of Ca2+ signaling in wild-type and Trpc3-/- acini showed that Pyr3 is a highly specific inhibitor of Tprc3; it protected salivary glands and pancreas cells from Ca2+-mediated toxicity by inhibiting the Trpc3-mediated component of Ca2+ influx. CONCLUSIONS: TRPC3-mediated Ca2+ influx mediates damage to pancreas and salivary glands. Pharmacologic inhibition of TRPC3 with the highly selective TRPC3 inhibitor Pyr3 might be developed for treatment of patients with acute pancreatitis and Sjögren syndrome.

Local drug delivery for oral mucosal diseases: challenges and opportunities.

There are few topical formulations used for oral medicine applications most of which have been developed for the management of dermatological conditions. As such, numerous obstacles are faced when utilizing these preparations in the oral cavity, namely enzymatic degradation, taste, limited surface area, poor tissue penetration and accidental swallowing. In this review, we discuss common mucosal diseases such as oral cancer, mucositis, vesiculo-erosive conditions, infections, neuropathic pain and salivary dysfunction, which could benefit from topical delivery systems designed specifically for the oral mucosa, which are capable of sustained release. Each condition requires distinct penetration and drug retention profiles in order to optimize treatment and minimize side effects. Local drug delivery may provide a more targeted and efficient drug-delivery option than systemic delivery for diseases of the oral mucosa. We identify those mucosal diseases currently being treated, the challenges that must be overcome and the potential of novel therapies. Novel biological therapies such as macromolecular biological drugs, peptides and gene therapy may be of value in the treatment of many chronic oral conditions and thus in oral medicine if their delivery can be optimized.

Treatment of salivary mucocele of the lower lip by OK-432.

OBJECTIVE: The aim of this paper was to evaluate the outcome and complications of the treatment of patients with salivary mucocele by intralesional injection therapy with OK-432. METHODS: We tried OK-432 therapy in 20 patients with salivary mucocele. We injected OK-432 solution into the lesion with a 27-gauge needle to prevent any leakage of the agent from the mucocele. RESULTS: Disappearance of the lesion was observed in 16 of 20 patients. Marked reduction was observed in 4 of 20 patients. No local scarring or deformity of the lower lip occurred in any patients. As side effects, local discomfort at the injection site was observed in two of the patients, but such problems resolved within a few days. We performed this treatment on an outpatient basis without hospitalization. CONCLUSION: Our results confirmed that OK-432 therapy is simple, easy, and relatively safe, and can be used as a substitute for surgery in the treatment of salivary mucocele.

[Applications of botulin]. / Silmä, nenä, suu, kurkku, kaula, kaikki muu --botuliinin käyttömahdollisuuksia.

Among the ailments of the ocular region, the use of botulin has become established in the treatment of blepharospasm and hemifacial spasm in Finland. Botulin has also been used successfully after peripheral facial palsy to improve facial symmetry, reduce lachrymal flow, treat dribbling of saliva as well as spasmodic dysphonia of laryngeal muscles. It may be effective in dysphagia caused by tightness of the upper esophageal sphincter or in several dyshidroses. Gastroenterologic indications include anal fissure and spasm and achalasia of the lower esophageal sphincter. In urology, botulin is effective in overactive bladder and incomplete voiding.

[Alpha-1-blockers (alfuzosin) for obstructive salivary gland diseases]. / Les Alpha-1-Bloquants (alfuzosine) en pathologie salivaire obstructive.

INTRODUCTION: Alpha-blockers are used in urology to treat stenosis and lithiasis. The pathophysiology is similar in salivary glands. We had for aim to assess the safety and effectiveness of an alpha-blocker (Alfuzosin) in patients with ductal stenosis, allergic pseudo-parotitis or sialolithiasis after lithotripsy. PATIENTS AND METHODS: Three hundred and fifty-two patients were included, 194 of whom presented with sialolithiasis fragmented by extracorporeal lithotripsy (112 parotidic and 82 submandibular). Sixty-nine presented with ductal stenosis, and 89 with allergic pseudo-parotitis. This retrospective study lasted 3 years (January 2005 to January 2008) with a mean follow-up of 33 months (18 months to 4 years). Male patients were given 2.5mg tid of the alpha-blocker Alfuzosin and female patients 2.5mg bid for 3 to 24 months. After 6 months and up to 2 years of treatment, patients were assessed every 3 months by US and with a questionnaire on symptoms. RESULTS: Results were similar in male and female patients. Eighty percent of patients with colic-like pain due to stenosis reported a significant improvement after treatment. 78.6% of patients with allergic pseudo-parotitis felt they had improved and noted a sharp decrease of pruritus. Sixty-seven of the patients with residual parotid lithiasis after extracorporeal lithotripsy presented with less ductal lithiasis and fragments were evacuated more rapidly in the two months following lithotripsy. Forty-two percent of the patients treated for residual submandibular lithiasis reported a significant functional improvement and faster evacuation of fragments. Twelve patients out of 352 (3.4%) reported adverse effects. The incidence of orthostatic hypotension was 2.2%. DISCUSSION: A significant improvement of symptoms was observed in patients treated with Alfuzosin for obstructive salivary gland diseases. The drug was well tolerated. These preliminary results are good in terms of effectiveness and inocuity. They should be confirmed with a prospective controlled study.