Showing papers on "Major Salivary Gland published in 2018"
TL;DR: How various diseases and medical treatment including commonly prescribed medications and cancer therapies can affect salivary gland structure and function is focused on.
Abstract: Saliva is a complex fluid produced by 3 pairs of major salivary glands and by hundreds of minor salivary glands. It comprises a large variety of constituents and physicochemical properties, which are important for the maintenance of oral health. Saliva not only protects the teeth and the oropharyngeal mucosa, it also facilitates articulation of speech, and is imperative for mastication and swallowing. Furthermore, saliva plays an important role in maintaining a balanced microbiota. Thus, the multiple functions provided by saliva are essential for proper protection and functioning of the body as a whole and for the general health. A large number of diseases and medications can affect salivary secretion through different mechanisms, leading to salivary gland dysfunction and associated oral problems, including xerostomia, dental caries and fungal infections. The first part of this review article provides an updated insight into our understanding of salivary gland structure, the neural regulation of salivary gland secretion, the mechanisms underlying the formation of saliva, the various functions of saliva and factors that influence salivary secretion under normal physiological conditions. The second part focuses on how various diseases and medical treatment including commonly prescribed medications and cancer therapies can affect salivary gland structure and function. We also provide a brief insight into how to diagnose salivary gland dysfunction.
214 citations
TL;DR: The purpose of this review is to provide a succinct image-rich article illustrating relevant anatomy and pathology of the salivary glands via an extensive review of the primary literature.
Abstract: The major and minor salivary glands of the head and neck are important structures that contribute to many of the normal physiologic processes of the aerodigestive tract. The major salivary glands are routinely included within the field of view of standard neuroimaging, and although easily identifiable, salivary pathology is relatively rare and often easy to overlook. Knowledge of the normal and abnormal imaging appearance of the salivary glands is critical for forming useful differential diagnoses, as well as initiating proper clinical workup for what are often incidental findings. The purpose of this review is to provide a succinct image-rich article illustrating relevant anatomy and pathology of the salivary glands via an extensive review of the primary literature. In Part 1, we review anatomy as well as provide an in-depth discussion of the various infectious and inflammatory processes that can affect the salivary glands.
51 citations
TL;DR: Treatment strategies rely on oncologic resection of the primary site with negative margins as well as adjuvant radiotherapy in patients with high-risk features, such as high-grade histology, advanced T class, or perineural invasion in patients With clinically node-negative disease at high risk for occult nodal metastases.
Abstract: Salivary gland malignancies are rare tumors that comprise multiple histologic entities with diverse clinical behavior Mucoepidermoid carcinoma is the most frequent primary salivary malignancy, followed by adenoid cystic and acinic cell carcinoma Although most salivary malignancies are asymptomatic, presentation with a rapidly enlarging mass may be accompanied by pain, functional neurologic deficits, soft-tissue invasion, or nodal enlargement Assessment of clinical behavior and physical exam greatly contributes to diagnostic workup Preoperative imaging, to include ultrasound, computed tomography, or magnetic resonance imaging, may assist with surgical planning Limitations of preoperative fine-needle aspiration cytology mean that, in some cases, definitive histologic diagnosis may not be established until therapeutic surgery is undertaken Treatment strategies rely on oncologic resection of the primary site with negative margins as well as adjuvant radiotherapy in patients with high-risk features, such
47 citations
TL;DR: Gene ontology analyses revealed that the highly expressed genes common to all glands were associated with global functions, while many of the genes expressed in a single gland play a major role in the function of that gland.
Abstract: RNA-Seq was used to better understand the molecular nature of the biological differences among the three major exocrine salivary glands in mammals. Transcriptional profiling found that the adult mu...
32 citations
TL;DR: SUS examination of parotid and submandibular glands on one side is sufficient to predict classification of patients according to the ACR-EULAR criteria, and only hypoechogenic areas can be scored to increase feasibility of sUS in outpatient clinics worldwide.
Abstract: Objective To assess whether ultrasonographic scoring of (i) both parotid and submandibular salivary glands and (ii) all individual components of the Hocevar scoring system, is needed for classifying patients as primary Sjogren’s syndrome (pSS). Methods Ultrasound examination of the major salivary glands (sUS) was performed in 204 consecutive patients clinically suspected (n=171) or diagnosed (n=33) with pSS. Parenchymal echogenicity, homogeneity, hypoechogenic areas, hyperechogenic reflections and salivary gland posterior border were scored in left and right parotid and submandibular glands. Logistic regression analyses were performed to assess which glands and sUS components contributed significantly to classification as pSS or non-pSS according to the 2016 American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) criteria. Results 116 (57%) patients were classified as pSS, the remaining as non-pSS. Instead of scoring both sides (area under the curve; AUC=0.856, Nagelkerke R 2 =0.526), multivariate analysis showed that sUS scoring of only right (AUC=0.850; R 2 =0.518) or left (AUC=0.852; R 2 =0.511) parotid and submandibular glands is sufficient to predict ACR-EULAR classification. Moreover, all individual components of the Hocevar scoring system significantly predicted classification. Multivariate analysis showed that parenchymal echogenicity and hypoechogenic areas contributed independently to ACR-EULAR classification (AUC=0.857; R 2 =0.539). Scoring these components in one parotid and one submandibular gland highly predicted ACR-EULAR classification (AUC=0.855; R 2 =0.539). Scoring only hypoechogenic areas on one side showed almost similar results (AUC=0.846; R 2 =0.498). Conclusion sUS examination of parotid and submandibular glands on one side is sufficient to predict classification of patients according to the ACR-EULAR criteria. To further increase feasibility of sUS in outpatient clinics worldwide, only hypoechogenic areas can be scored.
30 citations
TL;DR: The scanning technique and normal sonographic anatomy of major Salivary glands and overviews typical sonographic appearances of salivary pathologies, including infective and inflammatory conditions, sialolithiasis, and neoplasms are reviewed.
29 citations
TL;DR: The data suggest that chronic MeHg exposure in low-daily doses is able to induce cellular damage in rat salivary glands, and showed that cell MT production is not enough to protect gland tissue against cellular structural damage seen by reducing marking of cytoskeletal proteins as CK18 and α-SMA.
Abstract: Environmental and occupational mercury exposure is considered a major public health issue. Despite being well known that MeHg exposure causes adverse effects in several physiologic functions, MeHg effects on salivary glands still not completely elucidated. Here, we investigated the cellular MeHg-induced damage in the three major salivary glands (parotid, submandibular, and sublingual) of adult rats after chronic, systemic and low doses of MeHg exposure. Rats were exposed by 0.04 mg/kg/day over 60 days. After that, animals were euthanized and all three glands were collected. We evaluated total Hg accumulation, metallothionein I/II (MT I/II), α-smooth muscle actin (α-SMA), and cytokeratin 18 (CK18) immune expression. Our results have showed that MeHg is able to disrupt gland tissue and to induce a protective mechanism by MT I/II expression. We also showed that cell MT production is not enough to protect gland tissue against cellular structural damage seen by reducing marking of cytoskeletal proteins as CK18 and α-SMA. Our data suggest that chronic MeHg exposure in low-daily doses is able to induce cellular damage in rat salivary glands.
27 citations
TL;DR: This study is the first to identify a molecular signal directing transition of naïve oral epithelium toward salivary gland identity, and shows that retinoic acid regulates salivARY gland initiation.
Abstract: In mammals, the epithelial tissues of major salivary glands generate saliva and drain it into the oral cavity. For submandibular salivary glands (SMGs), the epithelial tissues arise during embryogenesis from naive oral ectoderm adjacent to the base of the tongue, which begins to thicken, express SOX9 and invaginate into underlying mesenchyme. The developmental mechanisms initiating salivary gland development remain unexplored. In this study, we show that retinoic acid (RA) signaling activity at the site of gland initiation is colocalized with expression of retinol metabolic genes Rdh10 and Aldh1a2 in the underlying SMG mesenchyme. Utilizing a novel ex vivo assay for SMG initiation developed for this study, we show that RDH10 and RA are required for salivary gland initiation. Moreover, we show that the requirement for RA in gland initiation involves canonical signaling through retinoic acid receptors (RAR). Finally, we show that RA signaling essential for gland initiation is transduced specifically through RARα, with no contribution from other RAR isoforms. This is the first study to identify a molecular signal regulating mammalian salivary gland initiation.
26 citations
Journal Article•
TL;DR: It is examined the possible utility for US to monitor patient response to therapy in both clinical research and standard clinical care and the possibility that US may be of value in disease stratification.
Abstract: Salivary gland ultrasonography (US) has recently been re-discovered as a useful tool to assess salivary gland involvement in primary Sjogren's syndrome (SS). In this review, we discuss US of the major salivary glands in the diagnosis of primary SS and analyse the possible added value of inclusion in classification criteria. We review the literature concerning associations between US of the major salivary glands, salivary gland histology and serology, with the possibility that US may be of value in disease stratification. We also examine the possible utility for US to monitor patient response to therapy in both clinical research and standard clinical care.
22 citations
TL;DR: Five low‐grade intraductal carcinoma cases with prominent oncocytic change in the major salivary glands are described.
Abstract: Aims Low-grade intraductal carcinoma (LG-IDC) is a clinically indolent malignant tumour of the salivary glands. Because of its rarity, the histological variants of LG-IDC have not been well characterised. Herein, we describe five LG-IDC cases with prominent oncocytic change in the major salivary glands. Methods and results We examined five cases, three males and two females (mean age = 63 years), of LG-IDC with oncocytic change. The sites affected by LG-IDC were the parotid and submandibular glands. The lesions were macroscopically unilocular or multilocular cysts with a solid tumour arising from the cyst wall. Smaller tumour cell nests were also observed. As with classic LG-IDC, the cyst wall was surrounded by myoepithelial cells with no invasive component. The tumour cells had abundant oncocytic cytoplasm and proliferated in a low-papillary, tubular or cribriform pattern. Immunohistochemically, the tumour cells were diffusely positive for pan-cytokeratin, S100, mammaglobin and antimitochondria antibody, and were negative for androgen receptor and gross cystic disease fluid protein-15. Unlike classic LG-IDC, some of these cases demonstrated focal invagination of myoepithelial cells in the intraductal tumour. Conclusion Oncocytic LG-IDC should be recognised as a histologically unique variant of LG-IDC. Awareness of this entity is important to avoid erroneous diagnosis and inappropriate treatment for histological mimics.
20 citations
TL;DR: The data report a novel role of Irf6 in exocrine gland development and support a rationale for performing exocrine functional tests for patients with IRF6-damaging mutations.
Abstract: Interferon regulatory factor 6 ( IRF6) acts as a tumor suppressor and controls cell differentiation in ectodermal and craniofacial tissues by regulating expression of target genes. Haploinsufficiency of IRF6 causes Van der Woude and popliteal pterygium syndrome, 2 syndromic forms of cleft lip and palate. Around 85% of patients with Van der Woude express pits on the lower lip that continuously or intermittently drain saliva, and patients with the common cleft lip and palate have a higher prevalence of dental caries and gingivitis. This study aims to identify the role of IRF6 in development of exocrine glands, specifically the major salivary glands. Our transgenic mouse model that expresses LacZ reporter under the control of the human IRF6 enhancer element showed high expression of IRF6 in major and minor salivary glands and ducts. Immunostaining data also confirmed the endogenous expression of IRF6 in the developing ductal, serous, and mucous acinar cells of salivary glands. As such, we hypothesized that Irf6 is important for proper development of salivary glands and potentially other exocrine glands. Loss of Irf6 in mice causes an increase in the proliferation level of salivary cells, disorganized branching morphogenesis, and a lack of differentiated mucous acinar cells in submandibular and sublingual glands. Expression and localization of the acinar differentiation marker MIST1 were altered in Irf6-null salivary gland and pancreas. The RNA-Seq analysis demonstrated that 168 genes are differentially expressed and confer functions associated with transmembrane transporter activity, spliceosome, and transcriptional regulation. Furthermore, expression of genes involved in the EGF pathway-that is, Ereg, Ltbp4, Matn1, Matn3, and Tpo-was decreased at embryonic day 14.5, while levels of apoptotic proteins were elevated at postnatal day 0. In conclusion, our data report a novel role of Irf6 in exocrine gland development and support a rationale for performing exocrine functional tests for patients with IRF6-damaging mutations.
TL;DR: To evaluate the stiffness of parotid and submandibular glands using elastography ultrasound and to correlate it with B‐mode ultrasonographical, clinical and serological features, salivary profibrotic and inflammatory chemokines, and Salivary gland fibrosis.
Abstract: Aim To evaluate the stiffness of parotid and submandibular glands using elastography ultrasound and to correlate it with B-mode ultrasonographical, clinical and serological features, salivary profibrotic and inflammatory chemokines, and salivary gland fibrosis. Methods We performed B-mode and elastography ultrasound of major salivary glands of 26 patients with primary Sjogren's syndrome. We registered the shear wave velocity (SWV) and correlated it with the morphologic ultrasonographic changes assessed by the Hocevar scale. We assessed the European League Against Rheumatism (EULAR) Sjogren's Syndrome Disease Activity Index (ESSDAI), EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI), non-stimulated whole salivary flow rate (NSWSF), C3 and C4 levels, anti-Ro/La antibodies, salivary inflammatory (C-X-C motif ligand 13 [CXCL13], CXCL10, CXCL8, C-C motif ligand 2 [CCL2], interleukin 10 [IL-10] and IL-6) and pro-fibrotic (CXCL14, CCL28, tumor necrosis factor-related apoptosis-inducing ligand and transforming growth factor β) chemokines and cytokines and evaluated the presence of fibrosis in the minor salivary gland. Results Ninety-two percent of patients were women; mean age was 51.1 ± 11 years; median disease duration was 6.1 years; 92.3% had oral symptoms and 26.9% fibrosis. The median B-mode score was 22.2 points and the median SWV 2.5 m/s (τ = 0.53, P = 0.001). The SWV correlated with the NSWSF (τ = -0.53, P = 0.001), ESSDAI (τ = 0.31, P = 0.03), glandular ESDDAI domain (τ = 0.36, P = 0.02), C4 levels (τ = -0.32, P = 0.04), salivary CXCL13 (τ = 0.29, P = 0.03) and CXCL10 (τ = 0.30, P = 0.003), but not with age and fibrosis. Conclusion WV correlated with the B-mode ultrasound score, systemic and glandular activity and in a large degree with CXCL10, an inflammatory chemokine, but not with fibrosis. An increased SWV might represent chronic glandular inflammation rather than fibrotic changes in these patients.
TL;DR: Determine demographics, clinical characteristics, and survival rates for children with primary salivary gland malignancies.
Abstract: Objectives/hypothesis Determine demographics, clinical characteristics, and survival rates for children with primary salivary gland malignancies. Study design Retrospective, population-based cohort study. Methods All cases of primary salivary gland malignancies diagnosed between the years of 2002 and 2013 in patients ages 0 to 19 years were extracted from the National Cancer Institute's Surveillance, Epidemiology, and End Results database. Additional variables collected included age, gender, ethnicity, tumor histological subtype, tumor size, treatment modality, vitality status, and follow-up time. Kaplan-Meier survival curves were generated. Results Two hundred forty-five primary salivary gland malignancies were identified (220 parotid, 25 submandibular). Median age at diagnosis was 15 years. Most patients were female (59%), white (74%), and non-Spanish/Hispanic/Latino (81%). Among parotid tumors, mean tumor size was 2.3 cm, and there were 109 (50%) mucoepidermoid carcinomas and 86 (39%) acinic cell carcinomas. Most patients underwent surgery (n = 212, 96%) and 64 (29%) received adjuvant radiation. At a mean follow-up of 62.4 months, 10 patients (5%) were deceased. Kaplan-Meier survival curves illustrated that black children exhibited higher mortality rates than white children (15.8% vs. 4.6%, log-rank = 0.0260) as did those who underwent adjuvant radiation (15.73% vs. 3.2%, log-rank = 0.0209). Among submandibular tumors, mean tumor size was 3.1 cm, and there were 11 (44%) mucoepidermoid carcinomas. All patients underwent surgery and most received adjuvant radiation (n = 15, 60%). At a mean follow-up of 51.25 months, one patient was deceased. Conclusions Salivary gland malignancies in children and adolescents are rare. Overall survival for both parotid and submandibular tumors in children is good. Level of evidence 4. Laryngoscope, 128:1126-1132, 2018.
TL;DR: The results showed that porcine parotid glands were pure serous glands and the expression pattern of TJ proteins in salivary glands is similar between human and miniature pig, which may be a candidate animal for studies onSalivary gland TJ function.
Abstract: Tight junction (TJ) proteins play a dynamic role in paracellular fluid transport in salivary gland epithelia. Most TJ studies are carried out in mice and rats. However, the morphology of rodent salivary glands differs from that of human glands. This study aimed to compare the histological features and the expression pattern of TJ proteins in porcine salivary glands with those of human and mouse. The results showed that porcine parotid glands were pure serous glands. Submandibular glands (SMGs) were serous acinar cell-predominated mixed glands, whereas sublingual glands were mucous acinar cell-predominated. Human SMGs were mixed glands containing fewer mucous cells than porcine SMGs, whereas the acinar cells of murine SMGs are seromucous. The histological features of the duct system in the porcine and human SMGs were similar and included intercalated, striated and excretory ducts, but the murine SMG contained a specific structure, the granular convoluted tubule. TJ proteins, including claudin-1 to claudin-12, occludin and zonula occludin-1 (ZO-1), were detected in the porcine major salivary glands and human SMGs by RT-PCR; however, claudin-6, claudin-9 and claudin-11 were not detected in the murine SMG. As shown by immunofluorescence, claudin-1, claudin-3, claudin-4, occludin and ZO-1 were distributed in both acinar and ductal cells in the porcine and human SMGs, whereas claudin-1 and claudin-3 were mainly present in acinar cells, and claudin-4 was mainly distributed in ductal cells in the murine SMG. In addition, 3D images showed that the TJ proteins arranged in a honeycomb-like structure on the luminal surface of the ducts, whereas their arrangements in acini were irregular in porcine SMGs. In summary, the expression pattern of TJ proteins in salivary glands is similar between human and miniature pig, which may be a candidate animal for studies on salivary gland TJ function.
TL;DR: The function, embryologic development, anatomy, and normal imaging features of the major salivary glands are outlined, and the commonly used cross-sectional techniques used for evaluating thesalivary gland are discussed.
TL;DR: Elective neck dissection is unnecessary for all patients with salivary gland ACC of head and neck and Neck dissection might be applied to ACC of MiSGs, which has a higher cervical lymph node metastases rate in ACC.
Abstract: Background The purpose of this research was to determine whether neck dissection is necessary for the adenoid cystic carcinoma (ACC) of head and neck. Materials and methods This article screened the abstract and full-text papers that investigated salivary gland primary ACC of head and neck. Two independent reviewers searched for articles published before October 2017 in three databases (Web of Science, PubMed, and Ovid), having no limits in date and language. Statistical data were analyzed statistically by Review Manager 5.3. Results In total, 18 studies involving 2993 patients were included in the analysis. Of the 2993 patients, 473 patients had cervical lymph node metastasis, with a merge frequency of 16% (95% CI: 13-19). Among included articles, only 4 involved cervical lymph node occult metastases, with a merge frequency of 14% (95% CI: 9-20). There were 5 articles containing minor salivary glands (MiSGs) involving 370 patients of which 92 patients had cervical lymph node metastases and the merge frequency was 25% (95% CI: 11-38). Moreover, there were 4 studies on major salivary glands involving 904 patients of which 158 patients had cervical lymph node metastases and the merge frequency was 17% (95% CI: 15-20). Conclusion Elective neck dissection is unnecessary for all patients with salivary gland ACC of head and neck. Moreover, compared with major salivary glands, MiSGs have a higher cervical lymph node metastases rate in ACC. The overall cervical lymph node metastases rate of MiSGs is 25%, which is enough to attract our attention. Therefore, we suggest that neck dissection might be applied to ACC of MiSGs.
TL;DR: A comprehensive review of congenital and acquired disorders that affect the major salivary glands in the pediatric population is presented, highlighting the imaging findings that are important in defining the appropriate diagnosis or narrowing of the differential diagnosis.
TL;DR: The clinical, pathologic and molecular features of salivary neuroendocrine carcinomas focusing on high-grade major salivARY gland tumors are reviewed and the difficulty in separating salvary tumors from metastatic Merkel cell carcinoma will be highlighted.
Abstract: Salivary neuroendocrine carcinomas are rare and the overwhelming majority is high-grade. The parotid gland is the most commonly involved site followed by the submandibular gland. Most arise de novo but rare examples occurring as a high-grade transformation of another type of salivary gland neoplasm exist. There is significant morphologic and immunophenotypic overlap with neuroendocrine carcinomas of other sites, especially the skin. Like cutaneous neuroendocrine (or Merkel cell) carcinomas, approximately three-fourths are cytokeratin 20 positive. Cytokeratin 20 positive salivary neuroendocrine carcinomas are often referred to as being of the ‘Merkel cell type’ since most other non-cutaneous neuroendocrine carcinomas are cytokeratin 20 negative. Salivary neuroendocrine carcinomas may be challenging to separate from Merkel cell carcinomas of the head and neck on pathologic grounds because the latter often metastasize to the parotid gland. Clinical history is often relied upon to separate primary salivary tumors from cutaneous metastases but may not be helpful in all cases. Here we review the clinical, pathologic and molecular features of salivary neuroendocrine carcinomas focusing on high-grade major salivary gland tumors. The difficulty in separating salivary tumors from metastatic Merkel cell carcinoma will be highlighted.
TL;DR: This study was the first that directly compared the validity of ultrasound of major salivary glands (sUS) with parotid gland biopsy outcome and showed that the agreement between sUS andParotid as well as labial gland biopsies was good but was slightly higher for the former.
Abstract: We would like to thank Alegria et al 1 for their letter to the editor commenting on our recent publication entitled ‘Ultrasonography of major salivary glands compared with parotid and labial gland biopsy and classification criteria in patients with clinically suspected primary Sjogren’s syndrome’.2 Our study was the first that directly compared the validity of ultrasound of major salivary glands (sUS) with parotid gland biopsy outcome. We showed that the agreement between sUS and parotid as well as labial gland biopsies was good but was slightly higher for the former.
As noted by Alegria et al ,1 we found different results for the positive predictive value (PPV) and negative predictive value (NPV) between sUS versus parotid and sUS versus labial gland biopsies.2 Although these observations may indeed be caused by discordance between the parotid and labial gland biopsy outcome, there are other factors that may equally well contribute to this discrepancy. First, the parotid glands are assessed during the sUS examination and included in the scoring, whereas the labial glands are not.2 Second, in 6%–15% of the general population, the labial gland biopsy is positive, while in only 5% of the general population, the parotid gland biopsy is positive. …
TL;DR: Sebaceous carcinomas are uncommon malignant cutaneous tumours originating from the pilosebaceous unit that are mostly common in peri‐ocular glands, but other anatomical regions of the head and neck may be affected, including major and minor salivary glands.
Abstract: Aims Sebaceous carcinomas are uncommon malignant cutaneous tumours originating from the pilosebaceous unit. Although its occurrence is mostly common in peri-ocular glands, other anatomical regions of the head and neck may be affected, including major and minor salivary glands. Methods and results We describe a series of sebaceous adenocarcinomas of the parotid and submandibular glands. The mean age was 62.1 (range = 31-90) years. Two patients (20%) presented regional or distant metastasis to mandible and lungs. All cases were positive for cytokeratins (AE1AE3 and CK-5), epithelial membrane antigen and adipophilin and negative for androgen receptor, Factor XIIIa, S-100, vimentin and perforin. MLH1 and MSH2 were expressed in the nuclei of most tumour cells, and one case showed loss of MSH2 expression. Proliferative index (assessed by Ki-67 expression) and microvessel density (CD34-positive vessels) were higher in metastasis-associated cases. P63 expression was noted in the periphery of the tumour nests, in the basaloid cells, with a mean of 69.2% nuclear positivity. Conclusions The sebaceous adenocarcinoma of salivary glands is rare and may show an unfavourable outcome; therefore, its correct diagnosis may be challenging. For this reason, immunohistochemical studies, including adipophilin in particular, constitute an important diagnostic tool.
TL;DR: Insurance status is associated with stage at presentation and survival among patients with salivary gland cancer and only Medicaid status was significantly associated with worse OS.
Abstract: ObjectivesTo evaluate the impact of insurance status on survival among patients with major salivary gland cancer.Study DesignRetrospective cohort study.SettingSEER program.Subjects and MethodsWe in...
TL;DR: 18F-DCFPyL dosimetry in nine patients was obtained using novel models for the lacrimal and salivary glands, two organs with potentially dose-limiting uptake for therapy and diagnosis which lacked pre-existing models.
Abstract: Prostate-specific membrane antigen (PSMA), a type-II integral membrane protein highly expressed in prostate cancer, has been extensively used as a target for imaging and therapy. Among the available PET radiotracers, the low molecular weight agents that bind to PSMA are proving particularly effective. We present the dosimetry results for 18F-DCFPyL in nine patients with metastatic prostate cancer. Nine patients were imaged using sequential PET/CT scans at approximately 1, 12, 35 and 70 min, and a final PET/CT scan at approximately 120 min after intravenous administration of 321 ± 8 MBq (8.7 ± 0.2 mCi) of18F-DCFPyL. Time-integrated-activity coefficients were calculated and used as input in OLINDA/EXM software to obtain dose estimates for the majority of the major organs. The absorbed doses (AD) to the eye lens and lacrimal glands were calculated using Monte-Carlo models based on idealized anatomy combined with patient-specific volumes and activity from the PET/CT scans. Monte-Carlo based models were also developed for calculation of the dose to two major salivary glands (parotid and submandibular) using CT-based patient-specific gland volumes. The highest calculated mean AD per unit administered activity of 18F was found in the lacrimal glands, followed by the submandibular glands, kidneys, urinary bladder wall, and parotid glands. The S-values for the lacrimal glands to the eye lens (0.42 mGy/MBq h), the tear film to the eye lens (1.78 mGy/MBq h) and the lacrimal gland self-dose (574.10 mGy/MBq h) were calculated. Average S-values for the salivary glands were 3.58 mGy/MBq h for the parotid self-dose and 6.78 mGy/MBq h for the submandibular self-dose. The resultant mean effective dose of 18F-DCFPyL was 0.017 ± 0.002 mSv/MBq. 18F-DCFPyL dosimetry in nine patients was obtained using novel models for the lacrimal and salivary glands, two organs with potentially dose-limiting uptake for therapy and diagnosis which lacked pre-existing models.
TL;DR: Surgery and postoperative radiotherapy resulted in excellent survival outcomes for patients with major salivary gland MEC, however, high-grade tumors contributed to poor DMFS and OS.
Abstract: PURPOSE This study aimed to evaluate the long-term survival outcomes and prognostic factors that affect the clinical outcomes of patients who underwent surgery and postoperative radiotherapy for major salivary gland mucoepidermoid carcinoma (MEC). MATERIALS AND METHODS We retrospectively reviewed the clinical data of 44 patients who underwent surgery followed by radiotherapy for primary MEC of the major salivary glands between 1991 and 2014. The median follow-up period was 9.8 years (range, 0.8 to 23.8 years). RESULTS The overall outcomes at 5 and 10 years were 81.5% and 78.0% for overall survival (OS), 86.2% and 83.4% for disease- free survival, 90.6% and 87.6% for locoregional recurrence-free survival, and both 90.5% for distant metastasis-free survival (DMFS). Histologic grade was the only independent predictor of OS (low vs. intermediate vs. high; hazard ratio = 3.699; p = 0.041) in multivariate analysis. A poorer survival was observed among patients with high-grade tumors compared with those with non-high- grade tumors (5-year OS, 37.5% vs. 91.7%, p < 0.001; 5-year DMFS, 46.9% vs. 100%, p < 0.001). CONCLUSION Surgery and postoperative radiotherapy resulted in excellent survival outcomes for patients with major salivary gland MEC. However, high-grade tumors contributed to poor DMFS and OS. Additional aggressive strategies for improving survival outcomes should be developed for high-grade MEC.
TL;DR: The distinct localization patterns of cytokeratins in conjunction with cell physiology will reveal the roles of epithelial cells insalivary gland formation during the differentiation of serous, mucous or seromucous salivary glands.
Abstract: Embryonic development of the mouse salivary glands begins with epithelial thickening and continues with sequential changes from the pre-bud to terminal bud stages. After birth, morphogenesis proceeds, and the glands develop into a highly branched epithelial structure that terminates with saliva-producing acinar cells at the adult stage. Acinar cells derived from the epithelium are differentiated into serous, mucous, and seromucous types. During differentiation, cytokeratins, intermediate filaments found in most epithelial cells, play vital roles. Although the localization patterns and developmental roles of cytokeratins in different epithelial organs, including the mammary glands, circumvallate papilla, and sweat glands, have been well studied, their stage-specific localization and morphogenetic roles during salivary gland development have yet to be elucidated. Therefore, the aim of this study was to determine the stage and acinar cell type-specific localization pattern of cytokeratins 4, 5, 7, 8, 13, 14, 18, and 19 in the major salivary glands (submandibular, sublingual, and parotid glands) of the mouse at the E15.5, PN0, PN10, and adult stages. In addition, cell physiology, including cell proliferation, was examined during development via immunostaining for Ki67 to understand the cellular mechanisms that govern acinar cell differentiation during salivary gland morphogenesis. The distinct localization patterns of cytokeratins in conjunction with cell physiology will reveal the roles of epithelial cells in salivary gland formation during the differentiation of serous, mucous or seromucous salivary glands.
TL;DR: This article reviews the multimodality diagnostic imaging features of benign neoplastic and nonneoplastic tumors associated with the major salivary glands.
TL;DR: An atlas has been generated to guide clinicians in delineating the CTVs for perineural spread in major salivary gland cancers andVariation in CTV delineation is a recognised problem in a variety of anatomic sites.
TL;DR: For the first time, h CAP18/LL-37 is demonstrated in isolated human parotid and submandibular/sublingual saliva and expression of hCAP18/ LL-37 in glandular intravascular neutrophils is demonstrated, indicating that neutrophil of the major salivary glands contribute to the LL- 37 content of whole saliva.
Abstract: The human host defense peptide, LL-37, is an important player in the first line of defense against invading microorganisms. LL-37 and its precursor, hCAP18, have been detected in unstimulated whole saliva but no reports showing hCAP18/LL-37 in isolated, parotid, and/or submandibular/sublingual saliva have been presented. Here, we measured the levels of hCAP18/LL-37 in human parotid and submandibular/sublingual saliva and investigated the expression of hCAP18/LL-37 in parotid and submandibular gland tissue. Parotid and submandibular/sublingual saliva was collected from healthy volunteers, and the levels of hCAP18/LL-37 in saliva were analyzed by dot blot, ELISA, and western blotting. Cellular expression of hCAP18/LL-37 in human parotid and submandibular glands was investigated by immunohistochemistry. Immunoreactivity for hCAP18/LL-37 was detected in both parotid and submandibular/sublingual saliva of all individuals. The concentration of hCAP18/LL-37 was similar in parotid and submandibular/sublingual saliva, and was determined by densitometric scanning of each dot and normalization to the total protein concentration of each sample, and by ELISA. Double immunohistochemistry revealed that intravascular neutrophils of both parotid and submandibular glands express hCAP18/LL-37. For the first time, we demonstrate hCAP18/LL-37 in isolated human parotid and submandibular/sublingual saliva and expression of hCAP18/LL-37 in glandular intravascular neutrophils, indicating that neutrophils of the major salivary glands contribute to the LL-37 content of whole saliva.
TL;DR: This work presents a step by step approach to performing pilocarpine stimulated saliva secretion, including tracheostomy and the dissection of the three major murine salivary glands, and aims to improve the reproducibility of these methods.
Abstract: Hyposalivation is commonly observed in the autoimmune reaction of Sjogren's syndrome or following radiation injury to the major salivary glands. In these cases, questions remain regarding disease pathogenesis and effective interventions. An optimized technique that allows functional assessment of the salivary glands is invaluable for investigating exocrine gland biology, dysfunction, and therapeutics. Here, we present a step by step approach to performing pilocarpine stimulated saliva secretion, including tracheostomy and the dissection of the three major murine salivary glands. We also detail the appropriate murine head and neck anatomy accessed during these techniques. This approach is scalable, allowing for multiple mice to be processed simultaneously, thus improving the efficiency of the work flow. We aim to improve the reproducibility of these methods, each of which has further applications within the field. In addition to saliva collection, we discuss metrics for quantifying and normalizing functional capacity of these tissues. Representative data are included from submandibular glands with depressed salivary gland function 2 weeks following fractionated radiation (4 doses of 6.85 Gy).
TL;DR: The postoperative morbidities and outcomes for major salivary gland neoplasms in the series were acceptable and comparable to the results available in the literature.
Abstract: Background and Objectives: Salivary gland neoplasms are relatively uncommon. They have a wide variety of histopathological types with diverse biological behavior. It involves all the major and minor salivary glands in the head and neck. This article focuses on the various types of major salivary gland tumors treated at a tertiary cancer center along with their surgical morbidities and outcomes. Materials and Methods: Data of all the salivary gland neoplasms operated in the head and neck services between January 2012 and December 2013 were retrieved from a prospectively collected database. The clinical, demographic data and types of surgeries along with the morbidities were collated from the database and the details regarding the follow-up were collected from the electronic medical record. Results: Out of 235. cases registered, 107. patients were treated at our institute. The parotid gland was most commonly involved; majority were malignant lesions. Sixty-two patients were treatment naive at presentation. Majority presented with advanced disease. Superficial parotidectomy was the most common surgery performed and neck dissection was done in 27. patients. Facial nerve palsy was the most common complication following surgery. (16%). Sixty patients received adjuvant treatment. All patients on follow-up were alive at their last visit, with 10. patients having recurrence. Factors influencing the disease-free survival were extracapsular spread, tumor grade, and perineural invasion. Conclusion: The postoperative morbidities and outcomes for major salivary gland neoplasms in our series were acceptable and comparable to the results available in the literature. Appropriate treatment of the salivary gland neoplasm will yield good outcomes with acceptable morbidity.
TL;DR: CBCT appears to be an ideal first-line imaging modality for patients with signs and symptoms of obstructed major salivary glands, with an overall accuracy of 92%.