Search Results (322)

The submandibular glands (SMGs), along with the parotid and sublingual glands, generate the majority of saliva and play critical roles in maintaining oral and systemic health. Despite their physiological importance, long-term therapeutic options for salivary gland dysfunction remain limited, highlighting the need for a deeper molecular understanding of SMG biology, particularly in humans. To address this knowledge gap, we have performed transcriptomic- and epigenomic-based analyses and molecular characterization of the human SMG. Our integrated analysis of multiorgan RNA-sequencing datasets has identified an SMG-enriched gene expression signature comprising 289 protein-coding and 75 long non-coding RNA (lncRNA) genes that include both known regulators of salivary gland function and several novel candidates ripe for future exploration. To complement these transcriptomic studies, we have generated chromatin immunoprecipitation sequencing (ChIP-seq) datasets of key histone modifications on human SMGs. Our epigenomic analyses have allowed us to identify genome-wide enhancers and super-enhancers that are likely to drive genes and regulatory pathways that are important in human SMG biology. Finally, comparative analysis with mouse and human SMG and other tissue datasets reveals evolutionary conserved gene and regulatory networks, underscoring fundamental mechanisms of salivary gland biology. Collectively, this study offers a valuable knowledge-based resource that can facilitate targeted research on salivary gland dysfunction in human patients. Full article

Background: The majority of parotid gland tumors are benign, while malignant forms are uncommon, affecting fewer than 1 in 100,000 individuals. The main challenge resides in the histopathological complexity and the clinical overlap between benign and malignant parotid tumors, which frequently results in misdiagnosis. Aim: The objective of this research was to evaluate the clinical and histopathological characteristics of parotid gland tumors at a Romanian healthcare center. Materials and methods: A five-year retrospective study was conducted, with the inclusion criterion being the presence of complete clinical, pathological, and surgical records. Results: Of 156 patients included in the study, 67.3% were found to have benign lesions (male/female ratio 1.14:1), and there was a slight male predominance (53.3%). Partial parotidectomy was the most common surgical intervention for benign parotid tumors (59.6%), whereas total parotidectomy was predominantly indicated for malignant tumors, with facial nerve sacrifice occurring in 20% of cases to ensure complete tumor excision. Patients with benign tumors were found to be younger. Malignant tumors were commonly diagnosed at stage III (36.4%), indicative of more advanced disease at the time of diagnosis. Clinical diagnosis showed a high specificity of 96.9%, indicating high accuracy in malignancy suspicion, yet the sensitivity of 56% indicates that a significant number of malignancies were not detected during the initial evaluation. Tumor size was found to be influenced by gender and correlated with surgical methods, suggesting that patient characteristics and tumor biology may impact surgical strategy. Conclusions: This retrospective study highlights differences in gender, tumor size, and surgical approach between benign and malignant parotid gland tumors, offering valuable contributions in terms of diagnostic accuracy and treatment patterns despite a limited number of malignant cases. Full article

Objectives: Lepidium meyenii Walpers (LMW), a high-altitude plant, is known to stimulate hormone release, counteract neurodegeneration, and protect against oxidative stress. Saliva is vital for oral health, and reduced production leads to xerostomia, often caused by aging, radiation, or Sjögren’s syndrome. Key pathological features include mesenchymal fibrosis and acinar atrophy, largely regulated by the TGF-β1 pathway. Current treatments are limited, with many patients relying on artificial saliva. Developing therapies to restore salivary function could offer significant benefits. Methods: In this study, we assessed the protective effects of LMW extract (LMWE) in irradiated C57BL/6J mice and TGF-β1-treated rat parotid acinar cells (Par-C10) using histological, molecular, bioenergetic, and 3D organoid analyses to evaluate salivary gland regeneration and lineage-specific differentiation. Results: LMWE significantly restored gland weight, shortened secretion lag time, and increased amylase activity in irradiated mice. Histological and molecular analyses showed reduced acinar atrophy and fibrosis, preservation of epithelial polarity, and upregulation of Mist1, AQP5, and amylase. In vitro, LMWE protected Par-C10 cells from TGF-β1-induced senescence, preserved mitochondrial membrane potential, and improved epithelial barrier function. In 3D organoid cultures of Par-C10 cells embedded in matrix, (1E,4Z)-1-(2,4-dihydroxyphenyl)-5-(3,4-dihydroxyphenyl) penta-1,4-dien-3-one (DHPPD) and (Z)-N-phenyldodec-2-enamide (E4Z-PD)-selectively enhanced acinar and ductal lineage differentiation, respectively. Conclusions: These results suggest that LMWE promotes salivary gland regeneration through antioxidative and lineage-specific mechanisms and may represent a safe and effective therapeutic strategy for xerostomia. Full article

Background/Objectives: Magnetic resonance elastography (MRE) is a noninvasive imaging technique that quantitatively characterizes tissue mechanical properties. This study aimed to establish and validate a feasible parotid MRE protocol using 3T MRI, with potential relevance for oral and maxillofacial surgery (OMFS) and otorhinolaryngology practice. Methods: This study included 21 healthy volunteers (18 women, 3 men; mean age, 49 years) examined between January and May 2024. MRE was performed using a 3.0 Tesla MRI system (Discovery MR750w, GE Healthcare, Waukesha, WI, USA) with a passive driver positioned over the parotid gland in a 16-channel head/neck coil. Two radiologists independently analyzed axial magnitude images drawing regions of interest (ROIs) encompassing the entire gland while excluding intraparotid lymph nodes and vascular structures. Mean and maximum stiffness values (kPa) were recorded for each gland. Interobserver agreement was assessed using intraclass correlation coefficients (ICCs) and Bland–Altman analysis. Results: Mean stiffness was 1.209 ± 0.240 kPa (Radiologist 1) and 1.146 ± 0.233 kPa (Radiologist 2); maximum stiffness was 1.595 ± 0.532 kPa and 1.563 ± 0.528 kPa, respectively. ICCs were 0.638 for mean stiffness and 0.918 for maximum stiffness, indicating moderate-to-excellent agreement. Conclusions: MRE is a technically feasible and reproducible method for evaluating parotid stiffness using standard imaging infrastructure. This feasibility study in healthy volunteers provides normative stiffness values for the parotid gland and supports MRE as a potential tool for “radiological palpation” to aid in the differentiation of salivary gland lesions and post-treatment assessment in OMFS and otorhinolaryngology practice. Full article

Background: Hospital-based data can complement registry estimates for cranio-maxillofacial (CMF) oncology, particularly in under-reported regions. We aimed to describe the institutional case-mix of CMF tumor diagnoses, standardized to ICD-10 sites, and to quantify trends using visit-normalized indicators. Methods: We conducted a retrospective, observational, single-center, hospital-based study of diagnosis-level encounters (2012–2016). Diagnoses were recoded to ICD-10 and restricted to CMF sites (lip, oral cavity, major salivary glands, oropharynx/hypopharynx, nasal cavity/middle ear, paranasal sinuses, eye/adnexa). The primary indicator uses a strict CMF set (malignant CMF codes plus D00.0 and D14.1); odontogenic cysts and non-neoplastic jaw lesions (K09–K10) were excluded, while benign CMF neoplasms are reported descriptively for site distributions. Results: We identified 2729 malignant CMF diagnoses over 2012–2016, peaking in 2014 (n = 751) and lowest in 2016 (n = 367). The combined malignant rate (per 1000 total visits) was 30.6, 43.9, 52.6, 34.4, and 26.7 for 2012→2016. The proportion of malignancies within the strict CMF set was 99.2%, 97.3%, 97.9%, 96.8%, and 95.1%, respectively (overall 97.4%). The most frequent malignant sites cumulatively were the palate (n = 416), parotid gland (n = 376), floor of mouth (n = 344), gingiva (n = 282), and mouth, unspecified (n = 179). Conclusions: After ICD-10 recoding and restriction to CMF sites, malignant tumors predominated within the institutional, diagnosis-level case-mix, with a 2014 peak followed by a decline. These indicators are case-mix monitors and not population incidences; interpretation should consider coding practices and service-mix changes across years. Full article

Background/Objectives: During kidney failure, chronic hemodialysis therapy (HD) is required to replace lost renal function, and patients on regular HD frequently report xerostomia. This systematic review and meta-analysis aims to compare salivary flow rates between patients with kidney failure on HD and healthy controls and to evaluate acute changes in salivary secretion before and after a dialysis session. Methods: A systematic review was conducted in accordance with PRISMA guidelines. PubMed, Web of Science, and Embase were searched for observational studies quantifying salivary flow rates in adult patients with kidney failure on chronic hemodialysis versus healthy controls or pre- versus post-dialysis. Data on salivary flow rates were extracted and stratified by subtype (whole or gland-specific) and condition (stimulated or unstimulated), along with key study characteristics including participant demographics, saliva collection methods, and dialysis duration. Study quality was appraised using NHLBI tools and categorized as poor, fair, or good. Where ≥2 homogeneous datasets existed, random-effects meta-analyses (α = 0.05) were performed to estimate mean differences (95% CI) for each salivary parameter; heterogeneity was evaluated via I². Results: A total of 20 studies (13 cross-sectional, 7 before-after) met inclusion, of which 17 studies (with a total of 1224 HD patients and 548 controls) were meta-analyzed. Compared with controls, HD patients showed lower secretion rates of unstimulated whole saliva (UWS: MD −0.11 mL/min; 95% CI −0.20 to −0.02; I² = 94%) and stimulated whole saliva (SWS: MD −0.77 mL/min; 95% CI −0.94 to −0.60; I² = 92%), whereas stimulated parotid saliva (SPS) did not differ significantly (MD −0.08 mL/min; 95% CI −0.77 to 0.60; I² = 96%). In before-after analyses, both UWS (MD +0.15 mL/min; 95% CI 0.02–0.28; I² = 90%) and SWS (MD +0.20 mL/min; 95% CI 0.14–0.26; I² = 0%) increased immediately post-HD. Conclusions: Despite methodological challenges and population heterogeneity, the evidence indicates salivary hypofunction in HD patients and improvement after hemodialysis. The magnitude of these effects seems influenced by underlying comorbidities (notably diabetes), HD duration, and methodological factors. Since saliva is of major importance to maintaining good oral health, recognizing and managing dry mouth should therefore be part of the comprehensive care of patients with kidney failure. Full article

Background: The majority of parotid gland tumors are benign, e.g., pleomorphic adenoma (PA) and Warthin’s tumor (WT). From a biomedical point of view, oxidative stress is of significant importance due to its established association with the initiation and progression of various types of cancer, including parotid gland cancers. This study aimed to assess whether blood prooxidant–antioxidant markers could aid in diagnosing and guiding surgery for recurrent malignancies after parotid tumor treatment. Methods: We examined patients (n = 20) diagnosed with WT (n = 14) and PA (n = 6) using histopathological verification and computed tomography (CT) who qualified for surgical treatment. Blood samples were taken before the surgery and again 10 days later for biochemical analysis. The activities of the antioxidant enzymes (SOD, CAT and GPx), the non-enzymatic antioxidants (GSH and UA) and oxidative stress markers (MDA and TOS) were determined in the blood. The activities of CK and LDH and the concentrations of Cor and TAS were measured in the serum. Hb and Ht were determined in whole blood. Results: The patients’ SOD, CAT, and GPx activities after surgery did not differ significantly from their preoperative levels. However, following surgery, their serum TOS levels were significantly elevated in all the patients compared to baseline. In contrast, the plasma MDA concentrations were markedly reduced after surgery. Similarly, the GSH concentrations showed a significant decrease postoperatively. No significant changes were observed in the CK and LDH activities, TAS concentrations, or levels of Hb, Ht and Cor following surgery. Conclusions: The surgical removal of salivary gland tumors did not result in a reduction in oxidative stress at 10 days after surgery. Therefore, further studies are needed to determine the effectiveness of endogenous defense mechanisms in counteracting the oxidative stress induced by salivary gland tumors. Full article

Background/Objectives: The aim of our study was to evaluate clinical outcomes in patients with small pleomorphic adenoma (PA) after extracapsular dissection (ED) versus superficial parotidectomy (SP). Methods: Following the PRISMA guidelines, a systematic review covering the years from 1950 to 2025 was conducted using the Pubmed/MEDLINE, Cochrane Library, Scopus, Ovid MEDLINE and Embase databases. A single-arm meta-analysis was performed to evaluate intraoperative capsular rupture, recurrence, transient and permanent facial nerve palsy, Frey’s syndrome, salivary fistula, seroma and hematoma of patients who underwent ED vs. those who underwent SP, and funnel plots were constructed to evaluate the robustness of the findings. Results: Of the 1793 identified papers, 21 articles met the inclusion criteria. The meta-analysis (2507 patients) reported the following: (1) the risk of recurrence is similar in patients treated with ED and SP; (2) the transient facial nerve palsy rate is lower after ED (p < 0.05), while the permanent facial nerve palsy rate is similar with ED and SP; (3) post-operative complications, especially Frey’s syndrome (p < 0.05), are more common after SP. Conclusions: Given the similar recurrence rate and the lower morbidity compared to SP, ED could be considered the treatment of choice for pleomorphic adenomas of the parotid gland that are up to 3 cm in size, mobile and located in the superficial lobe of the parotid gland. Full article

Xerostomia, the subjective complaint of a dry mouth, is frequently associated with salivary flow reduction and/or salivary gland hypofunction. This condition significantly impacts an individual’s quality of life and oral health, including difficulties in speaking, chewing, and swallowing. Xerostomia may be caused by autoimmune diseases, xerogenic medications, and radiation therapy. Our objective was to identify differentially expressed proteins in the saliva of patients with medication and autoimmune disease-associated xerostomia compared to non-xerostomic control subjects. Two groups of individuals (N = 45 total) were recruited: non-xerostomic subjects (NX-group; n = 18) and xerostomic patients (XP-group; n = 27). Dried saliva spot samples were collected from major salivary glands, i.e., parotid (left and right) and submandibular glands. Proteomic analysis was performed by deep nanoLC-MS/MS. Differential protein expression in the XP-group relative to the NX-group was determined by the Mann–Whitney U-test with FDR Benjamini–Hochberg correction (p_adj < 0.05). The Search Tool for Recurring Instances of Neighboring Genes (STRING_v12.0) was used to generate interaction networks and perform pathway analysis. A total of 1407 proteins were detected. Of these, 86 from the left parotid gland, 112 from the right parotid gland, and 73 from the submandibular gland were differentially expressed proteins (DEPs). Using STRING analysis, we identified, for the first time, several neurodegenerative disease-associated networks, primarily involving the downregulation of the 20S proteasome core complex and glyoxalase proteins across salivary glands. In this study, we determined neuronal dysregulation and impaired methylglyoxal (MGO) detoxification, possibly through reduced protein expression of glyoxalase Parkinson’s Disease (PD) Protein 7 (encoded by the PARK7 gene) in major salivary glands of xerostomic patients. Indeed, impaired MGO detoxification has been previously shown to cause salivary gland dysfunction in a mouse model of type 2 diabetes. Based on other DEPs associated with neurodegenerative disorders, our results also suggest a possible deficiency in the parasympathetic nervous system innervation of salivary glands, warranting further investigation. Full article

Background and Clinical Significance: Herein, we describe the clinical case of a 17-year-old patient with psychotic disorder secondary to cerebral venous thrombosis due to primary thrombophilia, which was related to protein S deficiency and a heterozygous MTHFR gene mutation with the p.Ala222Val variant. Case presentation: A 17-year-old female, with no history of previous illnesses, was admitted to the emergency service department due to a psychotic break. Psychiatric evaluation detected disorganized thought, euphoria, ideas that were fleeting and loosely associated, psychomotor excitement, and deviant judgment. On the fifth day, an inflammatory process in the parotid gland was detected, pointing out a probable viral meningoencephalitis, prompting antiviral and antimicrobial treatment. One week after antiviral and steroidal anti-inflammatory treatments, the symptoms’ improvement was minimal, which led to further neurological workup. MRI venography revealed a filling defect in the transverse sinus, consistent with cerebral venous thrombosis. Consequently, anticoagulation treatment with enoxaparin was initiated. The patient’s behavior improved, revealing that the encephalopathic symptoms were secondary to thrombosis of the venous sinus. Hematological studies indicated the cause of the venous sinus thrombosis was a primary thrombophilia caused by a heterozygous MTHFR mutation variant p.Ala222Val and a 35% decrease in plasmatic protein S. Conclusions: This case highlights the possible relationship between psychiatric and thrombotic disorders, suggesting that both the MTHFR mutation and protein S deficiency could lead to psychotic disorders. Early detection of thrombotic risk factors in early-onset psychiatric disorders is essential for the comprehensive management of patients. Full article

Background/Objectives: Pleomorphic adenomas (PAs) are the most common salivary gland tumors, with a known risk of recurrence, especially after inadequate surgical excision. Understanding how surgical approach influences recurrence remains essential to optimize management. This study aimed to synthesize recurrence rates of PAs based on different surgical techniques and to illustrate the implications of surgical strategy through a representative case of multifocal deep lobe recurrence. Methods: A systematic review was conducted according to PRISMA 2020 guidelines. Three electronic databases (PubMed, Cochrane, and Google Scholar) were searched for studies published in the last ten years, reporting recurrence rates of PAs by surgical approach. Data were extracted on recurrence, complications, and tumor characteristics. Additionally, a complex clinical case of recurrent deep lobe PA (DLPA) was presented to contextualize the findings. Results: Fifteen studies were included, comprising a total of 2095 patients. Recurrence rates were 3.27% after extracapsular dissection (ED), 0.73% after partial superficial parotidectomy (PSP), and 2.41% after superficial parotidectomy (SP). Recurrent PA (RPA) is often multifocal and associated with increased risks of facial nerve palsy and positive surgical margins. The presented case involved five surgical procedures, with ultimate total parotidectomy and facial nerve preservation despite infiltrative recurrence in the prestyloid space. Conclusions: Techniques such as ED and PSP have demonstrated their efficacy and safety compared to more invasive approaches, although their application should be carefully evaluated based on tumor size and location. RPA remains a challenging entity to treat. Avoiding outdated techniques and ensuring evidence-based decision making may improve long-term outcomes in PA management. Full article

This study aimed to perform ultrasonography of the tympanic bulla in healthy, non-sedated camelids for the first time. In the first step, dissection and sonography in cadaver specimens allowed the essential identification of the anatomical structures of the region of interest. Ultrasonography of the tympanic bulla was then performed on 71 healthy llamas and alpacas, and the length of the visible lateral bulla wall was measured sonographically. The reproducibility of measuring was determined between two examiners. Differences in length and the influences of gender, age, and body condition scores were monitored. A 10 MHz linear probe was positioned in the rostrocaudal and dorsoventral directions caudal to the mandibular ramus and ventral to the base of the ear using a lateral approach. The equipment used proved to be appropriate to visualize the tympanic bulla, the zygomatic bone, the paracondylar process, the external ear canal, and the parotid gland in the cadaver specimens and all live animals. Llamas revealed a significantly longer visible lateral bulla wall than alpacas, but its length was not influenced by gender, body condition score, or age. In alpacas, older females showed a significantly shorter tympanic bulla wall. The intra- and inter-observer reliability yielded a significant agreement. Based on this study’s results, ultrasonography may serve as a non-invasive diagnostic tool for detecting osseous and soft-tissue changes in camelids with otitis media. Full article

A four-year-old female patient was admitted for evaluation after a mass on the right side of her neck was noticed during straining (Valsalva maneuver). The family first observed the mass when the patient was one year old, and noted that it gradually increased in size over time. A family history assessment revealed no known genetic disorders. The patient underwent neck ultrasonography and computed tomography angiography (CTA), which revealed two aneurysms in a right-sided communicating vein. One aneurysm was located above the jugular notch, and the other was located in the retro-parotid region. The presence of two venous aneurysms in a right-sided communicating vein—one above the jugular notch and the other in the retro-parotid region—suggests a rare and apparently benign congenital anomaly. The progressive enlargement of these malformations warrants close monitoring and surgical intervention, and long-term follow-up may be necessary to prevent complications such as thrombosis, rupture, or compression of adjacent structures. Full article

Background/Objectives: Obstructive salivary gland disorders—primarily sialolithiasis and ductal stenosis—remain a significant source of morbidity, often requiring surgical intervention. Sialendoscopy has emerged as a minimally invasive, gland-preserving technique for both diagnosis and treatment. This retrospective study aimed to evaluate diagnostic and interventional sialendoscopy outcomes in a Romanian patient cohort and to identify gland-specific considerations in the management of salivary gland obstruction; Methods: A total of 89 patients with confirmed obstructive salivary gland disease (parotid or submandibular) were included. The most common indications included lithiasis, ductal stenosis, sialadenitis, and mixed pathologies; two cases of juvenile recurrent parotitis (JRP) were also managed. All patients underwent clinical evaluation, imaging (ultrasound, CBCT, CT, MR sialography), and sialendoscopic treatment between 2021 and 2025 in two centers. Data on demographics, imaging, calculus size, procedural technique, anesthesia, and complications were collected and analyzed using descriptive and inferential statistics; Results: The submandibular gland was more frequently involved (70.8%), with larger calculi compared to the parotid (mean 7.6 mm vs. 5.1 mm; p = 0.004). Minimally invasive techniques were predominantly used: sialolithotomy and intracorporeal lithotripsy were each performed in 32.6% of cases. Submandibulectomy was required in only 5.6% of patients. Most procedures (93.3%) were conducted under local anesthesia. Complication rates were low and primarily minor and self-limiting; Conclusions: Sialendoscopy is a safe and effective gland-preserving approach in managing obstructive salivary gland disorders. Gland-specific anatomy influences diagnostic pathways and therapeutic choices. These findings support broader adoption of sialendoscopy in routine practice and highlight the need for tailored management protocols based on gland involvement and stone characteristics. However, the study is limited by the absence of standardized post-intervention quality-of-life assessments and structured follow-up data on symptom recurrence. Full article

Background/Objectives: The purpose of this study was to determine the incidence of salivary gland tumors based on age, gender, histological type, and localization over an eleven-year period at the University Hospital of Split. Methods: The medical records of the Department of Otorhinolaryngology with Head and Neck Surgery and the Department of Maxillofacial Surgery at the University Hospital of Split regarding salivary gland tumors were searched from January 2012 to December 2022. The current fifth World Health Organization (WHO) Classification of Head and Neck Tumors and its criteria were considered during that process. Results: Out of 404 patients, 211 (52.20%) were female and 193 (47.77%) male. The mean age was 60. There were four pediatric patients. Six patients had a combination of two different histological types of salivary gland tumors present simultaneously at the exact localization. Therefore, there were 410 histological types in total, 214 related to females and 196 to males. A total of 361 (88.05%) benign and 49 (11.95%) malignant primary salivary gland tumors were detected. The parotid gland was the predominant location (N = 361, 87.8%). There were no cases affecting the sublingual gland. Pleomorphic adenoma was the most common benign histological type (N = 169, 41.2%). The most common malignant histological types were adenoid cystic carcinoma (N = 9, 2.2%) and mucoepidermoid carcinoma (N = 9, 2.2%). The average incidences of salivary gland tumors in the 11 years for the four Dalmatian counties and the Republic of Croatia were 4.45/100,000 and 0.9/100,000, respectively. Conclusions: The results of this study, primarily the ones concerning histological types and localization, do not deviate from general knowledge about salivary gland tumors. Simultaneous and ipsilateral occurrence of different histological types is a rare and extremely valuable finding. The average incidence for Dalmatian counties and the Republic of Croatia is within the range of the International Agency for Research on Cancer estimates. Full article