Structured Reporting of Head and Neck Sonography Achieves Substantial Interrater Reliability.

Purpose Ultrasound examinations are often criticized for having higher examiner dependency compared to other imaging techniques. Compared to free-text reporting, structured reporting (SR) of head and neck sonography (HNS) achieves superior time efficiency as well as report quality. However, there are no findings concerning the influence of SR on the interrater reliability (IRR) of HNS. Materials and Methods Typical pathologies (n=4) in HNS were documented by video/images by two certified head and neck ultrasound instructors. Consequently, structured reports of these videos/images were created by n=9 senior physicians at departments of otolaryngology or maxillofacial surgery with DEGUM instructors on staff. Reports (n=36) were evaluated regarding overall completeness and IRR. Additionally, user satisfaction was assessed by a visual analog scale (VAS). Results SR yielded very high report completeness (91.8%) in all four cases with a substantial IRR (Fleiss' κ 0.73). Interrater agreement was high at 87.2% with very good user satisfaction (VAS 8.6). Conclusion SR has the potential to ensure high-quality examination reports with substantial comparability and very high user satisfaction. Furthermore, big data collection and analysis are facilitated by SR. Therefore, process quality, workflow, and scientific output are potentially enhanced by SR.

Toxic retrobulbar neuritis due to recurrent nonsteroidal antiinflammatory drug-exacerbated respiratory disease-based chronic sinusitis in the left sphenoid sinus: a case report.

BACKGROUND: Abrupt visual impairment constitutes a medical urgency, necessitating an interdisciplinary diagnostic and therapeutic approach owing to the broad spectrum of potential etiologies, thereby engaging numerous medical specialties. CASE PRESENTATION: A 21-year-old Mixed White and Asian female patient, with medical history of nonsteroidal antiinflammatory drug-exacerbated respiratory disease necessitating previous sinus surgery, reported sudden monocular vision loss. Unremarkable ophthalmological examination of the fellow eye and hematological parameters, save for a slight elevation in lymphocytes and eosinophils, were observed. Imaging studies indicated recurrence of bilateral chronic rhinosinusitis with nasal polyps and a mucocele in the left sphenoid sinus, accompanied by bony structural deficits. Emergency revision sinus surgery, guided by navigation, was promptly performed. The patient received treatment with methylprednisolone, ceftriaxone, cyanocobalamin, pyridoxine, thiamine, and acetylsalicylic acid. During the hospital stay, she developed steroid-induced glaucoma, which was subsequently managed successfully. Negative microbiological swabs, along with pathohistological evidence of increased tissue eosinophilia and the patient's clinical history, led to the diagnosis of toxic retrobulbar neuritis secondary to recurrent nonsteroidal antiinflammatory drug-exacerbated respiratory disease-associated chronic rhinosinusitis of the left sphenoid sinus. CONCLUSIONS: In cases of acute unilateral vision loss, optic neuritis is a highly probable differential diagnosis and may be induced by pathologies of the paranasal sinuses. Nonsteroidal antiinflammatory drug-exacerbated respiratory disease, a subtype of chronic rhinosinusitis, is associated with type 2 inflammation, which is increasingly recognized for its role in the pathogenesis of bronchial asthma, eosinophilic esophagitis, and atopic eczema. Clinicians should consider chronic rhinosinusitis as a potential differential diagnosis in unilateral visual loss and be cognizant of the rising significance of type 2 inflammations, which are relevant to a variety of diseases.

Neutrophil Extracellular Traps Drive Dacryolithiasis.

Mucopeptide concretions, previously called dacryoliths, are macroscopic stones that commonly obstruct the lacrimal sac. The mechanism behind dacryolithiasis remains unclear; however, the involvement of various immune cells, including neutrophils, has been confirmed. These findings remain limited, and no information on neutrophil extracellular traps (NETs), essentially involved in the pathogenesis of other lithiases, is available yet. Here, we employ microcomputed tomography, magnetic resonance tomography, histochemistry, mass spectrometry, and enzyme activity analyses to investigate the role of neutrophils and NETs in dacryolithiasis. We classify mucopeptide concretions into three types, with respect to the quantity of cellular and acellular material, polysaccharides, and mucosubstances. We propose the role of neutrophils and NETs within the existing model of gradual formation and growth of mucopeptide concretions, with neutrophils contributing to the initial stages of dacryolithiasis, as they localized on the inner (older) parts of the tissue. As NETs localized on the outer (newer) parts of the tissue, we link their role to the late stages of dacryolithiasis, presumably maintaining the proinflammatory environment and preventing efficient clearance. An abundance of IgG on the surface indicates the involvement of the adaptive immune system later as well. These findings bring new perspectives on dacryolithiasis, in which the innate and adaptive immune system are essentially involved.

Moonlighting chromatin: when DNA escapes nuclear control.

Extracellular chromatin, for example in the form of neutrophil extracellular traps (NETs), is an important element that propels the pathological progression of a plethora of diseases. DNA drives the interferon system, serves as autoantigen, and forms the extracellular scaffold for proteins of the innate immune system. An insufficient clearance of extruded chromatin after the release of DNA from the nucleus into the extracellular milieu can perform a secret task of moonlighting in immune-inflammatory and occlusive disorders. Here, we discuss (I) the cellular events involved in the extracellular release of chromatin and NET formation, (II) the devastating consequence of a dysregulated NET formation, and (III) the imbalance between NET formation and clearance. We include the role of NET formation in the occlusion of vessels and ducts, in lung disease, in autoimmune diseases, in chronic oral disorders, in cancer, in the formation of adhesions, and in traumatic spinal cord injury. To develop effective therapies, it is of utmost importance to target pathways that cause decondensation of chromatin during exaggerated NET formation and aggregation. Alternatively, therapies that support the clearance of extracellular chromatin are conceivable.

Pneumoparotid: Practical impact of Surgeon performed Ultrasound in an effective Diagnostic Approach.

OBJECTIVES: Pneumoparotid is characterized by air inclusions in the parotid duct system. Use of ultrasound has proved valuable for evaluating air inclusions in various parts of the body; the diagnostics of this condition has not been systematically analyzed, however. The aim of this study was to evaluate the value of ultrasound in the detection of air inclusions along the parotid duct system and its closer characterization. METHODS: Retrospective analysis was carried out of patients diagnosed with pneumoparotid between 2005 and 2020 in a salivary gland center. Ultrasound was performed in all cases, and features of air inclusions were described. Reference standard was the clinical demonstration of foamy saliva after gland massage and/or sialendoscopic evidence of intraductal air inclusions. RESULTS: Twenty-one patients were identified (48.8 ± 3.8 years). Two were associated with wind instruments; seven were iatrogenic, following treatment for duct stenosis; one after radiotherapy; four with known bruxism and seven were idiopathic and without associated conditions. On ultrasound examination, pneumoparotid was characterized by three phenomena: flattened, mobile hyperechoic reflexes, dirty shadows with reverberation or "sunbeam effect," and shifting shadows during gland massage. CONCLUSIONS: Ultrasound was useful for characterizing pneumoparotid in a fast and practical way and could serve as imaging tool of first choice.

Calcification in Salivary Gland Cancer Mimicking Sialolithiasis-A Diagnostic Pitfall on Imaging: Report of Two Cases and Brief Review of the Literature.

Objectives: Sialolithiasis is the most common cause of calcifications detected with ultrasound in patients with chronic inflammatory symptoms and swellings of the salivary glands. Other differential diagnoses of calcifications are extremely rare and mostly benign. Methods: Case report and literature review. Results: Two rare cases of malignant parotid gland tumors with calcifications in a localization typical for sialolithiasis, which were mistaken for salivary calculi based on image findings, are presented. Conclusions: This report intends to highlight the pitfalls in the imaging of parotid gland diseases. Even if malignant tumors of the parotid gland with calcifications are extremely rare, in ambiguous cases, differential diagnoses should be considered carefully. A high suspicion index of the need for further diagnostics in cases with calcifications is practical and could include missing periprandial symptoms, no obstruction signs in the proximal duct, and missing evidence of sialolithiasis in sialendoscopy.

Simultaneous Application of Ultrasound and Sialendoscopy and its Value in the Management of Sialolithiasis.

OBJECTIVE: Ultrasound (US) and sialendoscopy (SE) are routinely used in patients presenting with sialolithiasis in the submandibular (SMG) and parotid gland (PG). The objective was to assess the value of the simultaneous application of US and SE in the management of sialolithiasis. STUDY DESIGN: Retrospective study. SETTING: Tertiary referral center for salivary gland diseases. PARTICIPANTS: Patients in whom US and SE as single investigation tools were neither conclusive nor useful in the management of sialolithiasis were investigated using both methods simultaneously (simUS + SE). MAIN OUTCOME MEASURES: Establishment of the final diagnosis and/or contribution to the planning/performing of treatment in sialolithiasis. RESULTS: 74 patients were examined by simUS + SE (58.1 % SMG and 41.9 % PG). In all patients (unclear) hyperechoic reflexes were assessed and/or localized by SE-controlled US navigation. 68.9 % of the patients were investigated for diagnostic or differential-diagnostic reasons including distinguishing extraductal from intraductal calcifications and/or to exclude residual stones after therapy. In 52.7 % simUS + SE was used to plan and/or perform further treatment, in 20.3 % to enable performing a combined approach (all PG) and in 29.7 % to evaluate and plan the most adequate therapy (mainly intraductal vs. extracorporeal shock wave lithotripsy, 68.2 % of these SMG). In two cases SE-controlled and US-guided stone extraction was performed. CONCLUSION: SimUS + SE is an innovative approach which proved to be very useful in managing sialolithiasis. It added valuable information regarding the establishment of a diagnosis or differential diagnosis, planning and performing the most adequate treatment, intraoperative control of therapy and postoperative follow-up.

Intraductal Fragmentation in Sialolithiasis Using Pneumatic Lithotripsy: Initial Experience and Results.

OBJECTIVE: To report initial experience in using a pneumatic lithotripter to treat salivary stones. STUDY DESIGN: Level IV retrospective study. SETTING: University hospital and tertiary referral center. METHODS: A pneumatic lithotripter was used to treat salivary stones after these were diagnosed. Probes with diameters of 0.7 mm were used. Total fragmentation was intended in all stones. Stone fragments were removed using several instruments in serial sialendoscopies to achieve complete stone clearance. RESULTS: A total of 62 patients with 77 stones were treated. Forty-three submandibular stones were treated in 34 patients, and 34 parotid stones were treated in 28 patients. An operating pressure of 2.5 bar and a single frequency mode were used. Complete fragmentation was achieved in all but one of the treated stones in both glands (98.7%). Among the patients, 90.32% became stone free and 100% symptom free. Multiple stones were treated in 24.19% of the patients, and multimodal therapy was also carried out in 24.19%. All of the glands were preserved. CONCLUSIONS: The pneumatic lithotripter proved to be effective in the treatment of sialolithiasis. Stone size, location, and the gland involved were important clinical factors. The device was sufficient to achieve success without any increased risk for complications in the patients or damage to the sialendoscopes.

Histopathological comparison of pleomorphic adenomas of the parotid and submandibular gland.

OBJECTIVE: The aim of this study was to investigate and compare the histopathological findings in pleomorphic adenomas (PA) of the parotid and submandibular gland with emphasis on the histological subtype and capsular characteristics. MATERIALS AND METHODS: The histopathological specimens of all patients with PAs of the parotid and submandibular gland between 2000 and 2020 were re-examined by an experienced head and neck pathologist. Patients without representative slides allowing evaluation of the whole periphery of the PA were excluded from our study sample. RESULTS: Nine hundred and thirty-four patients formed our study sample (327 men, 607 women, male-to-female ratio: 0.53:1). Eight hundred and forty-four cases had a PA in the parotid gland and the remaining 90 in the submandibular gland. Our comparative analysis showed that submandibular PAs are characterized by the consistent presence of an intact anatomical capsule, infrequent occurrence of pseudopodia and satellite nodules, and a low proportion of the high-risk myxoid subtype. CONCLUSION: Our study highlights significant differences between PAs of the parotid and submandibular glands in their histopathological characteristics. Their differences likely underlie the favorable surgical outcome observed in PAs of the submandibular glands and may explain the propensity of PAs of the parotid glands for local recurrences.

The Translational Role of MUC8 in Salivary Glands: A Potential Biomarker for Salivary Stone Disease?

Mucin (MUC) 8 has been shown to play an important role in respiratory disease and inflammatory responses. In the present study, we investigated the question of whether MUC8 is also produced and secreted by salivary glands and whether it may also play a role in the oral cavity in the context of inflammatory processes or in the context of salivary stone formation. Tissue samples from parotid and submandibular glands of body donors (n = 6, age range 63-88 years), as well as surgically removed salivary stones from patients (n = 38, age range 48-72 years) with parotid and submandibular stone disease were immunohistochemically analyzed targeting MUC8 and TNFα. The presence of MUC8 in salivary stones was additionally analyzed by dot blot analyses. Moreover, saliva samples from patients (n = 10, age range 51-72 years), who had a salivary stone of the submandibular gland on one side were compared with saliva samples from the other "healthy" side, which did not have a salivary stone, by ELISA. Positive MUC8 was detectable in the inter- and intralobular excretory ducts of both glands (parotid and submandibular). The glandular acini showed no reactivity. TNFα revealed comparable reactivity to MUC8 in the glandular excretory ducts and also did not react in glandular acini. Salivary stones demonstrated a characteristic distribution pattern of MUC8 that differed between parotid and submandibular salivary stones. The mean MUC8 concentration was 71.06 ng/mL in female and 33.21 ng/mL in male subjects (p = 0.156). Saliva from the side with salivary calculi contained significantly (15-fold) higher MUC8 concentration levels than saliva from the healthy side (p = 0.0005). MUC8 concentration in salivary stones varied from 4.59 ng/mL to 202.83 ng/mL. In females, the MUC8 concentration in salivary stones was significantly (2.3-fold) higher, with an average of 82.84 ng/mL compared to 25.27 ng/mL in male patients (p = 0.034). MUC8 is secreted in the excretory duct system of salivary glands and released into saliva. Importantly, MUC8 salivary concentrations vary greatly between individuals. In addition, the MUC8 concentration is gender-dependent (♀ > ♂). In the context of salivary stone diseases, MUC8 is highly secreted in saliva. The findings support a role for MUC8 in the context of inflammatory events and salivary stone formation. The findings allow conclusions on a gender-dependent component of MUC8.

Ultrasound in Inflammatory and Obstructive Salivary Gland Diseases: Own Experiences and a Review of the Literature.

Background: Ultrasound is established as a diagnostic tool in salivary glands for obstructive diseases such as sialolithiasis and tumors. Concerning inflammatory diseases and in non-sialolithiasis-caused obstruction, much fewer data are available. In recent years, technical development has allowed a better assessment of the gland parenchyma, and knowledge about intraductal pathologies has increased considerably, which has provided new insights and a new interpretation of ultrasound findings. Objectives: To provide a comprehensive review of the literature that includes our own experiences and to point out the state of the art in ultrasound in the diagnostics of inflammatory and obstructive salivary gland diseases, taking adequate techniques and recent technical developments into consideration. Data sources and study eligibility criteria: A systematic literature search was performed in Pubmed using various specific key words. Results: According to the literature results, including our own experiences, ultrasound is of value in up to >90% of cases presenting with inflammatory and/or obstructive diseases. Technical developments (e.g., elastography) and the application of modified ultrasound techniques (e.g., transoral ultrasound) have contributed to these results. Today, ultrasound is considered a first-line diagnostic tool in these diseases. However, in some inflammatory diseases, the final diagnosis can be made only after inclusion of the anamnesis, clinical symptoms, serologic blood tests, or histopathologic investigation. Conclusions: Ultrasound can be considered as a first-line diagnostic tool in obstructive and inflammatory salivary gland diseases. In obstructive diseases, it may be sufficient for diagnostics in >90% of cases. In inflammatory diseases, ultrasound is at least an excellent screening method and can be used to establish the diagnosis in cases of an early suspicion. In all diseases ultrasound can contribute to better management and can be used for monitoring during follow-up.

The current value of quantitative shear wave sonoelastography in parotid gland tumors.

BACKGROUND: The preoperative differentiation between salivary gland tumor entities using computed tomography, magnetic resonance imaging (MRI) and ultrasound (US) is still limited. Biopsies are often regarded as indispensable for properly characterizing these various lesions. The aim of this study was to analyze the value of acoustic radiation force impulse (ARFI) sonoelastography as an US differentiation tool when examining parotid gland (PG) lesions. METHODS: We included 104 patients with PG masses in this study, employing two different US devices using quantitative ARFI-sonoelastography (Siemens Acuson-S3000, n=59; Siemens Acuson-Sequoia, n=45). The ability of sonoelastographic measurements to differentiate between different neoplasms was compared and analyzed for both US machines. RESULTS: Quantitative shear wave sonoelastography is limited in its ability to reliably differentiate between tumor entities of the PG as a stand-alone parameter. Measurement results were unsystematically distributed and not transferable between the two US devices. A significant differentiation of benign and malignant lesions was not possible with either US machine (S3000: P=0.770, Sequoia: P=0.382). A differentiation between pleomorphic adenomas (PA) and Warthin tumors was only possible with the Acuson S3000 system (P=0.001, Spearman-Rho =0.492, sensitivity 73.9%, specificity 65.0%). CONCLUSIONS: A reliable identification and differentiation of PG tumors as well as clinical treatment decisions cannot be made with the sole use of ARFI-sonoelastography. The results emphasize the device-dependence and high error-proneness of this US technique when examining lesions of the PG.

Patients with COVID-19: in the dark-NETs of neutrophils.

SARS-CoV-2 infection poses a major threat to the lungs and multiple other organs, occasionally causing death. Until effective vaccines are developed to curb the pandemic, it is paramount to define the mechanisms and develop protective therapies to prevent organ dysfunction in patients with COVID-19. Individuals that develop severe manifestations have signs of dysregulated innate and adaptive immune responses. Emerging evidence implicates neutrophils and the disbalance between neutrophil extracellular trap (NET) formation and degradation plays a central role in the pathophysiology of inflammation, coagulopathy, organ damage, and immunothrombosis that characterize severe cases of COVID-19. Here, we discuss the evidence supporting a role for NETs in COVID-19 manifestations and present putative mechanisms, by which NETs promote tissue injury and immunothrombosis. We present therapeutic strategies, which have been successful in the treatment of immunο-inflammatory disorders and which target dysregulated NET formation or degradation, as potential approaches that may benefit patients with severe COVID-19.

Intraductal Lithotripsy in Sialolithiasis Using the Calculase III™ Ho:YAG Laser: First Experiences.

BACKGROUND AND OBJECTIVES: To report the first experiences with a newly available Ho:YAG laser system for the treatment of salivary stones. STUDY DESIGN/MATERIALS AND METHODS: A retrospective study in a tertiary referral center was conducted. Patients diagnosed with sialolithiasis were treated in Erlangen using the Calculase III™ Ho:YAG laser (Karl Storz, Tuttlingen, Germany). Preset parameters had a frequency of 4 Hz and energy of 0.8-1.2 J, resulting in 3.2-4.8 W. Following total fragmentation, one to two serial sialendoscopies were performed to achieve complete fragment clearance. RESULTS: A total of 55 stones in 49 patients were treated; 17 stones in 15 submandibular glands and 38 in 34 parotids. In total, 61 laser lithotripsies (range 1-3 per stone) were performed using various modes (long, short, and burst) and with preset parameters of 4 Hz and energy of 0.8-1.2 J, resulting in effective power of 3.2-4.8 W. Complete fragmentation was achieved in all the accessible stones. Sialendoscopes, fibers, or the mode used had no significant influence on success rates. A multimodal therapy concept was employed to treat stones in 12.24% of the cases; 95.92% of the patients were ultimately stone-free, and all became symptom-free. All glands were preserved. CONCLUSIONS: The new Calculase III™ Ho:YAG laser was effective in the treatment of sialolithiasis with no increased risk of complications in the patients or damage to the sialendoscopes. Clinical factors such as the type of gland involved, or the location and size of stones had a greater impact on success rates than the technical or preset parameters. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Ultrasound in the diagnosis of parotid duct obstruction not caused by sialolithiasis: diagnostic value in reference to direct visualization with sialendoscopy.

OBJECTIVES: The aim of this study was to evaluate the diagnostic value of ultrasound in the obstructive pathology of the parotic gland not caused by sialolithiasis using sialendoscopy as reference standard. METHODS: Retrospective analysis of all patients who presented with suspected diagnosis of obstructive ductal pathology of the parotid gland other than sialolithiasis between January 2011 and December 2017. 538 patients, for a total of 691 parotid glands were included in the study. Ultrasound was performed, followed by sialendoscopy in all cases. Duct diameter and parenchyma echogenicity were assessed. Direct sialendoscopic examination of the parotid duct was regarded as the reference standard. RESULTS: Parotid glands with normal sialendoscopic findings (21.6%, n = 149) had a duct diameter of 0.3 mm (0-2.7 mm) and homogeneous hyperechoic parenchyma on ultrasound in 98.7%. Ductal inflammation/sialodochitis (32.9%, n = 227) on sialendoscopy had significantly larger ductal diameter of 0.7 mm (0-4.3 mm, p = 0.001) and hypoechoic parenchyma in 78.0% (p < 0.001). Parotid glands with stenosis (45.6%, n = 315) had hypoechoic parenchyma in 52.6% and a ductal diameter of 4.1 mm (0-19.0 mm; p = 0.001). The ductal diameter was ≥2.7 mm in 95.6% of the stenosis (AUC 0.886, p = 0.001). Using 5.1 mm as benchmark ductal diameter, stenosis with ductal anomaly (68/315) were identifiable with a sensitivity of 92.6% and a specificity of 96.8% (AUC 0.986, p = 0.001). CONCLUSION: Ultrasound parameters can be used to distinguish different types of obstructive ductal pathology of the parotid gland, supporting the use of this imaging modality as diagnostic tool of first choice.

Extracapsular Dissection in Pleomorphic Adenomas of the Parotid Gland: Results After 13 Years of Follow-up.

OBJECTIVES/HYPOTHESIS: To assess long-term results after the treatment of parotid pleomorphic adenomas (PPAs) using different surgical techniques and focusing on recurrence rates and the risk of adverse effects. STUDY DESIGN: Retrospective analysis. METHODS: Retrospective analysis of 182 patients treated exclusively for PPAs at a tertiary referral center between 2000 and 2004. Thorough follow-up examinations over a mean period of 13 years were possible in 53.8% (n = 98/182). Tumors were categorized according to the European Salivary Gland Society (ESGS) system to improve the comparison of outcomes. After different surgical resection strategies, recurrence rates, postoperative facial nerve paresis (FNP), and incidence of Frey's syndrome were assessed. The follow-up period included clinical examinations and imaging of every patient in the treating department. RESULTS: Of 182 patients, extracapsular dissection (ED) was performed in 29.7%, and other surgical modalities (OSMs), including facial nerve dissection, in 70.3%. After the long-term follow-up, 98% of all the patients (n = 96/98) were recurrence free. When recurrence rates were compared, no significant differences were noted (P < .331). ED resulted in significantly lower FNP rates compared to OSMs (P < .001). FNP rates significantly increased with size and location of the tumors according to ESGS categories (temporary and permanent FNP, P = .04). Surgical invasiveness corresponded to a significant increase in the incidence of Frey's syndrome (P < .001). CONCLUSIONS: ED was associated with the lowest complication rates, but not with a higher risk of recurrence, when compared with OSM in the long-term course. As ED can be performed in the majority of PPAs, it can be regarded as the treatment of choice whenever possible. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E445-E451, 2021.

Investigation of Sonographic Criteria for Reliable Identification of T1-T2 Low-Grade Malignant Tumors of the Parotid Gland.

The aim of this study was to investigate sonographic findings of low-grade malignant tumors of the parotid gland. The sonographic findings of all patients treated for T1-T2 low-grade carcinomas of the parotid gland between 2003 and 2018 were retrospectively examined and compared with those of patients with pleomorphic adenomas for the following parameters: definition of tumor margins, echotexture, echogenicity, shape and vascularization. Statistical analysis was performed using the χ2 test. A p value of <0.05 was considered statistically significant. A total of 310 patients (62 with T1-T2 low-grade malignant tumors, 248 with pleomorphic adenomas) were evaluated. Our analysis detected a statistically significant difference in the definition of margins, echotexture, echogenicity and shape. Furthermore, we could detect a specific pattern (anechoic islets in a small hypoechoic lesion with distal enhancement) appearing far more frequently in low-grade malignant lesions. It seems that there is still potential to reduce the incidence of the false working hypothesis "benign lesion" on imaging of low-grade malignant tumors.

Neutrophil Extracellular Traps Promote the Development and Growth of Human Salivary Stones.

Salivary gland stones, or sialoliths, are the most common cause of the obstruction of salivary glands. The mechanism behind the formation of sialoliths has been elusive. Symptomatic sialolithiasis has a prevalence of 0.45% in the general population, is characterized by recurrent painful periprandial swelling of the affected gland, and often results in sialadenitis with the need for surgical intervention. Here, we show by the use of immunohistochemistry, immunofluorescence, computed tomography (CT) scans and reconstructions, special dye techniques, bacterial genotyping, and enzyme activity analyses that neutrophil extracellular traps (NETs) initiate the formation and growth of sialoliths in humans. The deposition of neutrophil granulocyte extracellular DNA around small crystals results in the dense aggregation of the latter, and the subsequent mineralization creates alternating layers of dense mineral, which are predominantly calcium salt deposits and DNA. The further agglomeration and appositional growth of these structures promotes the development of macroscopic sialoliths that finally occlude the efferent ducts of the salivary glands, causing clinical symptoms and salivary gland dysfunction. These findings provide an entirely novel insight into the mechanism of sialolithogenesis, in which an immune system-mediated response essentially participates in the physicochemical process of concrement formation and growth.

Papillary stenosis of the submandibular gland caused by dental prostheses.

OBJECTIVES: The aim of this study was to assess diagnosis and treatment of submandibular duct stenosis caused by dental prostheses. STUDY DESIGN: This retrospective study included 9 patients with papillary stenosis caused by physical irritation of the Wharton duct ostium by a mandibular dental prosthesis. Diagnostics included physical examination, as well as transcutaneous and transoral ultrasound examinations. Treatment consisted of duct incision, papillotomy, and subsequent sialendoscopy. After surgery, patients were advised to have the dental prosthesis altered by the dentist and to have regular gland massage. Follow-up data were obtained via telephone interviews. The most important outcome parameter was a symptom-free state. RESULTS: In all 9 patients, the insertion of the sialendoscope was initially impossible because of the stenosis. After duct incision, sialendoscopy ruled out other obstructive causes and inflammatory states, leaving the dental prosthesis as the only underlying cause of the obstruction. Seven of the 9 treated patients were interviewed after a follow-up period of 28.1 (± 25.4) months. The procedures had resulted in all patients being symptom-free, without any reported complications. CONCLUSIONS: Mandibular prostheses can cause stenosis of the papillary region with subsequent submandibular duct obstruction. Surgical therapy is easy to perform and results in excellent long-term outcomes.