Research status and prospects of acupuncture for prevention and treatment of chemo- and radiotherapy-induced salivary gland dysfunction in head and neck cancer.

Salivary gland dysfunction (SGD) induced by chemo- and radiotherapy for head and neck cancer (HNC) has always been a difficult problem in modern medicine. The quality of life of a large number of HNC patients is severely impaired by SGD such as xerostomia and dysphagia. In recent years, several studies have found that acupuncture can improve patients' salivary secretion, but it has not yet been approved as an alternative therapy for SGD. For this reason, we collected the clinical study reports on acupuncture in the treatment of SGD induced by chemo- and radiotherapy in HNC patients in the past 20 years, and analyzed and discussed the advantages and disadvantages of these studies with respect to tumor types, group setting, intervention modality, acupoints selection, outcome evaluation, and safety. We believed that acupuncture is beneficial for SGD, but the existing objective evidence is insufficient to support its effectiveness. Therefore, improving the Standards for Reporting Interventions in Clinical Trials of Acupuncture, selecting the optimal combination of acupoints through scientific and rigorous study design, and exploring the potential mechanism of acupuncture in the treatment of diseases combined with the meridian theory may be effective ways to promote the acceptance of acupuncture as an alternative therapy for SGD in future. The significance of this review is to provide a reference for researchers to carry out high-quality clinical trials of acupuncture in the treatment of SGD in future from the perspective of the combination of modern medicine and traditional Chinese medicine.

Gemigliptin suppresses salivary dysfunction in streptozotocin-induced diabetic rats.

Patients with diabetes commonly experience hyposalivation, which induces discomfort in eating, swallowing, dryness, smell, and speaking, as well as increases the incidence of periodontal disease. Dipeptidyl peptidase-4 (DPP4) inhibitors are frequently used as antidiabetic drugs that lower glucose levels by utilizing similar mechanisms; however, additional protective functions of each gliptin have been discovered. In this study, the protective roles of gemigliptin, a DPP4 inhibitor, against salivary dysfunction under diabetic conditions were investigated. Streptozotocin-induced diabetic rats received gemigliptin 10 mg/kg or 100 mg/kg via oral gavage for 3 weeks. The weights of salivary gland tissues, saliva secretion, and antioxidant capacity in salivary glands were reduced after diabetes induction, but were significantly preserved following gemigliptin treatment. In salivary gland analysis, expression of apoptotic proteins, as well as amylase and aquaporin-5 (AQP5) protein expression, were increased following gemigliptin treatment. Furthermore, the number of TUNEL-positive cells decreased after gemigliptin treatment. Therefore, gemigliptin has protective roles against salivary dysfunction observed in diabetes, mediated via antioxidant, anti-apoptotic, and salivary secretion mechanisms. These results may help in selecting a suitable drug for patients with diabetes experiencing salivary dysfunction.

Long Term Delta-9-tetrahydrocannabinol Administration Inhibits Proinflammatory Responses in Minor Salivary Glands of Chronically Simian Immunodeficieny Virus Infected Rhesus Macaques.

HIV/SIV-associated oral mucosal disease/dysfunction (HAOMD) (gingivitis/periodontitis/salivary adenitis) represents a major comorbidity affecting HIV patients on anti-retroviral therapy. Using a systems biology approach, we investigated molecular changes (mRNA/microRNA) underlying HAOMD and its modulation by phytocannabinoids (delta-9-tetrahydrocannabinol (∆9-THC)) in uninfected (n = 5) and SIV-infected rhesus macaques untreated (VEH-untreated/SIV; n = 7) or treated with vehicle (VEH/SIV; n = 3) or ∆9-THC (THC/SIV; n = 3). Relative to controls, fewer mRNAs were upregulated in THC/SIV compared to VEH-untreated/SIV macaques. Gene enrichment analysis showed differential enrichment of biological functions involved in anti-viral defense, Type-I interferon, Toll-like receptor, RIG-1 and IL1R signaling in VEH-untreated/SIV macaques. We focused on the anti-ER-stress anterior gradient-2 (AGR2), epithelial barrier protecting and anti-dysbiotic WAP Four-Disulfide Core Domain-2 (WFDC2) and glucocorticoid-induced anti-inflammatory TSC22D3 (TSC22-domain family member-3) that were significantly downregulated in oropharyngeal mucosa (OPM) of VEH-untreated/SIV macaques. All three proteins localized to minor salivary gland acini and secretory ducts and showed enhanced and reduced expression in OPM of THC/SIV and VEH/SIV macaques, respectively. Additionally, inflammation associated miR-21, miR-142-3p and miR-29b showed significantly higher expression in OPM of VEH-untreated/SIV macaques. TSC22D3 was validated as a target of miR-29b. These preliminary translational findings suggest that phytocannabinoids may safely and effectively reduce oral inflammatory responses in HIV/SIV and other (autoimmune) diseases.

Transoral floor of mouth lipoma resection: A technical multimedia analysis.

Lipomas are common benign mesenchymal tumors that originate from mature adipocytes throughout the body, with 13-20% occurring in the head and neck region, however only 1-4.4% affect the oral cavity, where they are found predominately in the cheek, followed by the tongue, lips, palatal mucosa, gingiva, and floor of the mouth. Herein, we present a multimedia analysis of transoral floor of mouth lipoma resection in a 58-year-old female. Learning points include (1) Identification and stenting of Wharton's ducts in order to facilitate their functional preservation and to minimize risk of postoperative sialocele; (2) postoperative observation with airway monitoring due to expected floor of mouth edema; (3) utilization of a midline incision to minimize injury to Wharton's ducts and maximize bilateral access to the floor of mouth.

Hiposialia y Xerostomía Post Irradiación: Terapias Innovadoras en el Campo Biomolecular / Hyposialia and Xerostomy Post Irradiation: Innovative Therapies in the Biomolecular Field

Las glándulas salivales humanas pueden ser gravemente lesionadas por la radioterapia utilizada contra neoplasias de cabeza y cuello, produciendo hiposialia y xerostomía, las cuales afectan la salud oral y sistémica, mermando la calidad de vida de la persona. Los tratamientos convencionales actuales están diseñados para disminuir los síntomas, sin actuar sobre los cambios fisiopatológicos que se dan a nivel glandular. Esta revisión intenta analizar aquellas terapias preventivas y/o curativas que están desarrollándose en el campo biomolecular y que tienen un futuro prometedor por sus características innovadoras: terapia génica, terapia con células madre y terapia con factores de crecimiento. Se evidencia un aporte adicional de la nanotecnología, la cual está mejorando las vías de aplicación de los tratamientos.

Human salivary glands can be seriously injured by the radiotherapy used against head and neck neoplasms, producing hyposialia and xerostomy, which affect oral and systemic health, diminishing the person's quality of life. Current conventional treatments are designed to reduce symptoms, without acting on the pathophysiological changes that occur at the glandular level. This review attempts to analyze those preventive and /or curative therapies that are developing in the biomolecular field and that have a promising future due to their innovative features: Gene therapy, stem cell therapy and growth factor therapy. An additional contribution of nanotechnology is evident, which is improving the routes of treatment application.

Fucoidan attenuates radioiodine-induced salivary gland dysfunction in mice.

BACKGROUND: Radioiodine (RI) treatments can destroy the cellular components of salivary glands (SG) and disrupt their function. This study investigated whether fucoidan could attenuate radioiodine-induced SG dysfunction in a mouse model. METHODS: Female C57BL/6 mice (n = 36) were classified into three groups; i) a normal (control) group, ii) an RI-treated group (0.2 mCi/20 g mouse, administered orally), and iii) a fucoidan and RI-treated group. Mice in each group were classified into three subgroups and sacrificed at 2, 4, and 12 weeks after RI treatment. The measurements of salivary flow rates and lag times and histomorphologic examinations were performed, and apoptotic assays were conducted. Changes in salivary 99mTechnetium (Tc)-pertechnetate parameters using single-photon emission computed tomography were followed. RESULTS: Salivary flow rates and lag times in the fucoidan group were improved compared to the RI-treated group. Histologic examinations of SGs in the fucoidan group showed mucin-rich parenchymal areas and reduced periductal fibrosis as compared to the RI-treated group. Moreover, compared with the RI-treated group, fucoidan-treated groups showed evidence of cytoprotection, with a greater number of salivary epithelial cells and myoepithelial cells being observed. Fewer apoptotic cells were observed in the fucoidan group as compared to the RI group. The extent of 99mTc pertechnetate excretion in the fucoidan group was similar to that of the control group. CONCLUSION: Our results demonstrate that fucoidan administration before RI treatment could attenuate RI-induced SG damage and provides a possible candidate for preventing SG damage induced by RI.

Protective Effect of Ginseng on Salivary Dysfunction Following Radioiodine Therapy in a Mouse Model.

BACKGROUND: Following radioiodine (RI) therapy, oxidative stress is a putative damage mechanism resulting in salivary gland (SG) dysfunction. Since ginseng is a known anti-oxidative herb, we examined the SG radioprotective effects of Korea red ginseng (KRG) in a mouse model, when administered prior to RI. METHODS: Four-week-old mice (n = 60) were divided into four groups: (1) normal control, (2) RI only treated (0.01 mCi/g, orally), (3) KRG administered (0.2 mg/g, intraperitoneal injection) 0.5 and 24 hours before RI, and (4) amifostine-treated group (0.2 mg/g, intraperitoneally) 0.5 hour before RI. The salivary lag times and flow rates were assessed, and sampled tissues were subjected to histologic examinations including hematoxylin and eosin and immunohistochemical staining. Apoptosis was examined by the terminal deoxynucleotidyl transferase biotin-dUDP nick end labeling (TUNEL) assay, and excretion changes in salivary 99mTc pertechnetate were evaluated by single-photon emission computed tomography. RESULTS: The body weight of the KRG group was similar to the control group. Salivary lag times and flow rates in the RI + KRG group were faster than in the RI only group. There was no significant intergroup difference in the SG weight. The RI + KRG group exhibited more mucin-containing parenchyma and less fibrotic tissues than the RI only group. Salivary epithelial (aquaporin 5) and myoepithelial (smooth muscle actin) cells of the RI + KRG group were protected from radiation damage. Low 8-OhdG (oxidative stress biomarker) and high superoxide dismutase 2 (reactive oxygen species scavenger) immunostaining reactivity was detected in the RI + KRG group when compared with the RI only group. Fewer apoptotic cells were observed in the RI + KRG or amifostine group compared to the RI only group in the TUNEL assay. The 99mTc pertechnetate excretion level recovered in the KRG group. CONCLUSION: Pretreatment with KRG before RI therapy is potentially beneficial in protecting against RI-induced salivary dysfunction.

Is accurate contouring of salivary and swallowing structures necessary to spare them in head and neck VMAT plans?

BACKGROUND AND PURPOSE: Current standards for organ-at-risk (OAR) contouring encourage anatomical accuracy which can be resource intensive. Certain OARs may be suitable for alternative delineation strategies. We investigated whether simplified salivary and swallowing structure contouring can still lead to good OAR sparing in automated head and neck cancer (HNC) plans. MATERIALS AND METHODS: For 15 HNC patients, knowledge-based plans (KBPs) using RapidPlan™ were created using: (1) standard clinical contours for all OARs (benchmark-plans), (2) automated knowledge-based contours for the salivary glands, with standard contours for the remaining OARs (SS-plans) and (3) simplified contours (SC-plans) consisting of quick-to-draw tubular structures to account for the oral cavity, salivary glands and swallowing muscles. Individual clinical OAR contours in a RapidPlan™ model were combined to create composite salivary/swallowing structures. These were matched to tube-contours to create SC-plans. All plans were compared based on dose to anatomically accurate clinical OAR contours. RESULTS: Salivary gland delineation in SS-plans required on average 2 min, compared with 7 min for manual delineation of all tubular-contours. Automated atlas-based contours overlapped with, on average, 71% of clinical salivary gland contours while tube-contours overlapped with 95%/75%/93% of salivary gland/oral cavity/swallowing structure contours. On average, SC-plans were comparable to benchmark-plans and SS-plans, with average differences in composite salivary and swallowing structure dose ≤2 Gy and <1 Gy respectively. CONCLUSIONS: Simplified-contours could be created quickly and resulted in clinically acceptable HNC VMAT plans. They can be combined with automated planning to facilitate the implementation of advanced radiotherapy, even when resources are limited.

Pharmacological interventions for preventing dry mouth and salivary gland dysfunction following radiotherapy.

BACKGROUND: Salivary gland dysfunction is an 'umbrella' term for the presence of either xerostomia (subjective sensation of dryness), or salivary gland hypofunction (reduction in saliva production). It is a predictable side effect of radiotherapy to the head and neck region, and is associated with a significant impairment of quality of life. A wide range of pharmacological interventions, with varying mechanisms of action, have been used for the prevention of radiation-induced salivary gland dysfunction. OBJECTIVES: To assess the effects of pharmacological interventions for the prevention of radiation-induced salivary gland dysfunction. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 14 September 2016); the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 8) in the Cochrane Library (searched 14 September 2016); MEDLINE Ovid (1946 to 14 September 2016); Embase Ovid (1980 to 14 September 2016); CINAHL EBSCO (Cumulative Index to Nursing and Allied Health Literature; 1937 to 14 September 2016); LILACS BIREME Virtual Health Library (Latin American and Caribbean Health Science Information database; 1982 to 14 September 2016); Zetoc Conference Proceedings (1993 to 14 September 2016); and OpenGrey (1997 to 14 September 2016). We searched the US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. SELECTION CRITERIA: We included randomised controlled trials, irrespective of their language of publication or publication status. Trials included participants of all ages, ethnic origin and gender, scheduled to receive radiotherapy on its own or in addition to chemotherapy to the head and neck region. Participants could be outpatients or inpatients. We included trials comparing any pharmacological agent regimen, prescribed prophylactically for salivary gland dysfunction prior to or during radiotherapy, with placebo, no intervention or an alternative pharmacological intervention. Comparisons of radiation techniques were excluded. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 39 studies that randomised 3520 participants; the number of participants analysed varied by outcome and time point. The studies were ordered into 14 separate comparisons with meta-analysis only being possible in three of those.We found low-quality evidence to show that amifostine, when compared to a placebo or no treatment control, might reduce the risk of moderate to severe xerostomia (grade 2 or higher on a 0 to 4 scale) at the end of radiotherapy (risk ratio (RR) 0.35, 95% confidence interval (CI) 0.19 to 0.67; P = 0.001, 3 studies, 119 participants), and up to three months after radiotherapy (RR 0.66, 95% CI 0.48 to 0.92; P = 0.01, 5 studies, 687 participants), but there is insufficient evidence that the effect is sustained up to 12 months after radiotherapy (RR 0.70, 95% CI 0.40 to 1.23; P = 0.21, 7 studies, 682 participants). We found very low-quality evidence that amifostine increased unstimulated salivary flow rate up to 12 months after radiotherapy, both in terms of mg of saliva per 5 minutes (mean difference (MD) 0.32, 95% CI 0.09 to 0.55; P = 0.006, 1 study, 27 participants), and incidence of producing greater than 0.1 g of saliva over 5 minutes (RR 1.45, 95% CI 1.13 to 1.86; P = 0.004, 1 study, 175 participants). However, there was insufficient evidence to show a difference when looking at stimulated salivary flow rates. There was insufficient (very low-quality) evidence to show that amifostine compromised the effects of cancer treatment when looking at survival measures. There was some very low-quality evidence of a small benefit for amifostine in terms of quality of life (10-point scale) at 12 months after radiotherapy (MD 0.70, 95% CI 0.20 to 1.20; P = 0.006, 1 study, 180 participants), but insufficient evidence at the end of and up to three months postradiotherapy. A further study showed no evidence of a difference at 6, 12, 18 and 24 months postradiotherapy. There was low-quality evidence that amifostine is associated with increases in: vomiting (RR 4.90, 95% CI 2.87 to 8.38; P < 0.00001, 5 studies, 601 participants); hypotension (RR 9.20, 95% CI 2.84 to 29.83; P = 0.0002, 3 studies, 376 participants); nausea (RR 2.60, 95% CI 1.81 to 3.74; P < 0.00001, 4 studies, 556 participants); and allergic response (RR 7.51, 95% CI 1.40 to 40.39; P = 0.02, 3 studies, 524 participants).We found insufficient evidence (that was of very low quality) to determine whether or not pilocarpine performed better or worse than a placebo or no treatment control for the outcomes: xerostomia, salivary flow rate, survival, and quality of life. There was some low-quality evidence that pilocarpine was associated with an increase in sweating (RR 2.98, 95% CI 1.43 to 6.22; P = 0.004, 5 studies, 389 participants).We found insufficient evidence to determine whether or not palifermin performed better or worse than placebo for: xerostomia (low quality); survival (moderate quality); and any adverse effects.There was also insufficient evidence to determine the effects of the following interventions: biperiden plus pilocarpine, Chinese medicines, bethanechol, artificial saliva, selenium, antiseptic mouthrinse, antimicrobial lozenge, polaprezinc, azulene rinse, and Venalot Depot (coumarin plus troxerutin). AUTHORS' CONCLUSIONS: There is some low-quality evidence to suggest that amifostine prevents the feeling of dry mouth in people receiving radiotherapy to the head and neck (with or without chemotherapy) in the short- (end of radiotherapy) to medium-term (three months postradiotherapy). However, it is less clear whether or not this effect is sustained to 12 months postradiotherapy. The benefits of amifostine should be weighed against its high cost and side effects. There was insufficient evidence to show that any other intervention is beneficial.

Resveratrol attenuates radiation-induced salivary gland dysfunction in mice.

OBJECTIVES/HYPOTHESIS: In our study we investigated the radioprotective effect of resveratrol (RES) in a murine model of radiation-induced salivary gland dysfunction. STUDY DESIGN: Ninety-six Institute of Cancer Research mice were randomly divided into four groups: solvent (group I), RES treated (group II; 20 mg/kg/d), 15 Gy irradiation with solvent treatment (group III), and 15 Gy irradiation with RES treatment (group IV; 15 Gy and 20 mg/kg/d RES). RES (group II and IV) was administered intraperitoneally 3 days prior to irradiation through the conclusion of the experiment. METHODS: Saliva and submandibular gland tissues were obtained for biochemical, morphological, immunohistochemical, and Western blot analyses at 8 hours, 24 hours, and 30 days after localized irradiation. RESULTS: Radiation caused a reduction of saliva secretion, salivary amylase activity, superoxide dismutase, and an elevation of malondialdehyde. Administration of RES reversed the reduction of saliva secretion induced by irradiation and restored salivary amylase and superoxide dismutase activity. In addition, RES could inhibit increases in transforming growth factor-ß1 expression induced by radiation. CONCLUSIONS: RES can protect salivary glands against the negative effects of irradiation and has great potential as a treatment for successful radiotherapy in clinical practice.

Salivary and lacrimal gland dysfunction after remnant ablation with radioactive iodine in patients with differentiated thyroid carcinoma prepared with recombinant human thyrotropin.

BACKGROUND: One of the adverse effects of radioactive iodine (¹³¹I) treatment in patients with thyroid cancer is damage to the salivary and lacrimal glands. In almost all studies evaluating salivary and lacrimal gland dysfunction, the patients received ¹³¹I after levothyroxine (L-T4) withdrawal. Since the biokinetics of ¹³¹I after recombinant human thyrotropin (rhTSH) is not the same as in hypothyroidism, studies need to evaluate ¹³¹I-induced salivary and lacrimal toxicity after preparation with rhTSH. This prospective study investigated the occurrence of salivary and lacrimal damage after ablation with ¹³¹I using this preparation. METHODS: One hundred forty-eight patients who had a total thyroidectomy were included in the study. The subjects were evaluated after thyroidectomy during L-T4 use to exclude those who already showed symptoms or had a history of ocular or oral disease. Symptoms were investigated 12 and 18 months after ablation. In patients who had persistent symptoms, specific tests were performed to confirm glandular dysfunction and to rule out other causes. RESULTS: Twelve months after ablation, symptoms of salivary or lacrimal dysfunction were observed in 10 (6.7%) patients, including oral symptoms in 8 (5.4%) and ocular symptoms in 6 (4%). Eighteen months after ¹³¹I, symptoms persisted in eight (5.4%) patients, including oral symptoms in seven (4.7%) and ocular symptoms in five (3.4%). In all of the patients, glandular dysfunction was confirmed by specific tests and other causes were ruled out. No symptoms were seen in the patients who received a low ¹³¹I dose (30 mCi). In the patients who received high ¹³¹I doses (100 or 150 mCi), symptoms were noted 12 months after ¹³¹I in 10 patients (9.2%), and 18 months after ¹³¹I in 8 patients (7.4%). CONCLUSIONS: Apparently, the rates of salivary and lacrimal damage were lower than those reported in prospective studies that used similar ¹³¹I activities, but these studies were performed in patients who were hypothyroid at the time of ¹³¹I ablation. Further studies are needed to compare radiotoxicity between patients prepared for ¹³¹I ablation with rhTSH and those prepared for ¹³¹I ablation with L-T4 withdrawal.

Protective effects of resveratrol on salivary gland damage induced by total body irradiation in rats.

OBJECTIVES/HYPOTHESIS: One of the most common acute side effects of irradiation is xerostomia, which results from damage to the salivary gland cells by direct ionization. Resveratrol is a natural compound with profound anti-inflammatory and antioxidant properties. The purpose of the present study was to investigate the potential protective effects of resveratrol on injury to the salivary glands of rats that were exposed to total body irradiation. STUDY DESIGN: An experimental study at the Inonu University School of Medicine. METHODS: Twenty-nine female rats were randomized into four groups: group 1, high-dose (100 mg/kg) resveratrol group (n = 7); group 2, low-dose (10 mg/kg) resveratrol group (n = 7); group 3, control (vehicle) rats (n = 7); and group 4, sham-irradiation group (n = 8). The medications were administered as single doses, and the rats were exposed to total body irradiation 24 hours after the treatment. The animals were sacrificed the following day, and the parotid and submandibular glands were excised. Salivary gland histology and the tissue levels of glutathione (GSH), nitric oxide (NO), and malondialdehyde (MDA) were investigated. RESULTS: The rats in group 1 showed significantly decreased acinar loss and less ductal damage and cell necrosis than those of the control group (P < .05). Antioxidant GSH levels were significantly increased by high doses of resveratrol treatment. The tissue activities of MDA in both the parotid and submandibular glands were significantly reduced in group 1. Low-dose resveratrol treatment did not significantly alter the tissue levels of MDA. CONCLUSIONS: Resveratrol at relatively high doses can reduce the irradiation-dependent salivary gland damage, suggesting that this natural antioxidant may be effectively used to lessen the side effects related to salivary gland dysfunction that is induced by irradiation.

Salivary gland and associated complications in head and neck cancer therapy.

Xerostomia and salivary gland hypofunction are two of the most common and significant complications of head and neck cancer therapy in the head and neck region. This article will provide a brief overview of salivary gland hypofunction and associated complications in head and neck cancer therapy, mainly in radiation therapy. The discussion will include quality of life issues as well as current advances in cancer therapy to reduce xerostomia and salivary gland hypofunction.

Prevention of radiation-induced salivary hypofunction following hKGF gene delivery to murine submandibular glands.

PURPOSE: Salivary glands are significantly affected when head and neck cancer patients are treated by radiation. We evaluated the effect of human keratinocyte growth factor (hKGF) gene transfer to murine salivary glands on the prevention of radiation-induced salivary hypofunction. EXPERIMENTAL DESIGN: A hybrid serotype 5 adenoviral vector encoding hKGF (AdLTR(2)EF1α-hKGF) was constructed. Female C3H mice, 8 weeks old, were irradiated by single (15 Gy) or fractionated (6 Gy for 5 days) doses to induce salivary hypofunction. AdLTR(2)EF1α-hKGF or AdControl was administered (10(8) - 10(10) particles per gland) to both submandibular glands (SG) by retrograde ductal instillation before irradiation (IR). Salivary flow was measured following pilocarpine stimulation. Human KGF levels were measured by ELISA. SG cell proliferation was measured with bromodeoxyuridine labeling. Endothelial and progenitor or stem cells in SGs were measured by flow cytometry. The effect of SG hKGF production on squamous cell carcinoma (SCC VII) tumor growth was assessed. RESULTS: In 3 separate single-dose IR experiments, salivary flow rates of mice administered the AdLTR(2)EF1α-hKGF vector were not significantly different from nonirradiated control mice (P > 0.05). Similarly, in 3 separate fractionated IR experiments, the hKGF-expressing vector prevented salivary hypofunction dramatically. Transgenic hKGF protein was found at high levels in serum and SG extracts. AdLTR(2)EF1α-hKGF-treated mice showed increased cell proliferation and numbers of endothelial cells, compared with mice treated with AdControl. hKGF gene transfer had no effect on SCC VII tumor growth ± radiation. CONCLUSIONS: hKGF gene transfer prevents salivary hypofunction caused by either single or fractionated radiation dosing in mice. The findings suggest a potential clinical application.

The use of quality of life measures in oral medicine: a review of the literature.

OBJECTIVES: To explore the use of patient reported quality of life measures in oral medicine, to highlight the importance of use of these measures in oral medicine practice and to provide guidance for the selection of such measures in the future. METHODS: A detailed literature review was undertaken to investigate the use of quality of life measures in oral medicine. The databases searched were MEDLINE (through PubMed), EMBASE, CINDHL, Web of Science Citation Index and the Cochrane Database of Systematic Reviews and randomised controlled trials. RESULTS: The initial literature search yielded a total of 5310 citations; however, only 63 of these fulfilled the inclusion criteria. Twenty-two articles were regarding oral mucosal conditions, 14 related to orofacial pain disorders and 27 were regarding salivary gland-related conditions. CONCLUSIONS: The evaluation of quality of life in oral medicine has a broad applicability, providing information in treatment-based studies and population-based studies. A predominance of generic and oral health specific quality of life measures are being used to a limited extent in oral medicine practice. A scarcity of reports of the development, validation or use of disease specific measures is evident.

Modeling of salivary production recovery after radiotherapy using mixed models: determination of optimal dose constraint for IMRT planning and construction of convenient tools to predict salivary function.

PURPOSE: The mathematical relationship between the dose to the parotid glands and salivary gland production needs to be elucidated. This study, which included data from patients included in a French prospective study assessing the benefit of intensity-modulated radiotherapy (RT), sought to elaborate a convenient and original model of salivary recovery. METHODS AND MATERIALS: Between January 2001 and December 2004, 44 patients were included (35 with oropharyngeal and 9 with nasopharyngeal cancer). Of the 44 patients, 24 were treated with intensity-modulated RT, 17 with three-dimensional conformal RT, and 2 with two-dimensional RT. Stimulated salivary production was collected for 40 Gy. CONCLUSION: The results of this study show that the recommendation of a dose constraint for intensity-modulated RT planning should be established at the volume of the contralateral parotid gland receiving >40 Gy rather than the mean dose. For complete salivary production recovery after 24 months, the volume of the contralateral parotid gland receiving >40 Gy should be <33%. Our results permitted us to establish two convenient tools to predict the saliva production recovery function according to the dose received by the contralateral parotid gland.

A focused salivary gland infection with attenuated MCMV: an animal model with prevention of pathology associated with systemic MCMV infection.

While the salivary gland has been recognized as an important effector site of the common mucosal immune system, a useful model for studying anti-viral salivary gland immune responses in vivo and for exploring the role of the salivary gland within the common mucosal system has been lacking. Murine cytomegalovirus (MCMV) is a beta-herpesvirus that displays a strong tropism for the salivary gland and produces significant morbidity in susceptible mice when introduced by intraperitoneal (i.p.) inoculation. This study tested the hypothesis that MCMV morbidity and pathology could be reduced by injecting the virus directly the submandibular salivary gland (intraglandular (i.g.)), using either in vivo derived MCMV or the less virulent, tissue-culture-derived MCMV (tcMCMV). Peak salivary gland viral titers were completely unaffected by infection route (i.p vs. i.g.) after inoculation with either MCMV or tcMCMV. However, i.g. tcMCMV inoculation reduced viremia in all systemic tissues tested compared to i.p. inoculation. Furthermore, systemic organ pathology observed in the liver and spleen after i.p. inoculation with either MCMV or tcMCMV was completely eliminated by i.g. inoculation with tcMCMV. Cellular infiltrates in the salivary glands, after i.p. or i.g. inoculation were composed of both B and T cells, indicating the potential for a local immune response to occur in the salivary gland. These results demonstrate that a focused MCMV infection of the salivary gland without systemic organ pathology is possible using i.g. delivery of tcMCMV.

Does lemon candy decrease salivary gland damage after radioiodine therapy for thyroid cancer?

UNLABELLED: Salivary gland dysfunction is one of the common side effects of high-dose radioiodine therapy for thyroid cancer. The purpose of this study was to determine whether an early start of sucking lemon candy decreases salivary gland injury after radioiodine therapy. METHODS: The incidence of the side effects of radioiodine therapy on the salivary glands was prospectively and longitudinally investigated in 2 groups of patients with postsurgical differentiated thyroid cancer with varying regimens for sucking lemon candy. From August 1999 to October 2000, 116 consecutive patients were asked to suck 1 or 2 lemon candies every 2-3 h in the daytime of the first 5 d after radioiodine therapy (group A). Lemon candy sucking was started within 1 h after radioiodine ingestion. From November 2000 to June 2002, 139 consecutive patients (group B) were asked to suck lemon candies in a manner similar to that of group A. In the group B, lemon candies were withheld until 24 h after the ingestion of radioiodine. Patients with salivary gland disorders, diabetes, collagen tissue diseases, or a previous history of radioiodine therapy or external irradiation to the neck were excluded. Thus, 105 patients in group A and 125 patients in group B were available for analysis. There were no statistical differences in the mean age (55.2 y vs. 58.5 y), average levels of serum free thyroxine (l-3,5,3',5'-tetraiodothyronine) (0.40 ng/dL vs. 0.47 ng/dL), and the mean dose of (131)I administered (3.96 GBq vs. 3.87 GBq) between the 2 groups. The onset of salivary side effects was monitored during hospital admission and regular follow-up on the basis of interviews with patients, a visual analog scale, and salivary gland scintigraphy using (99m)Tc-pertechnetate. When a patient showed a persistent (>4 mo) dry mouth associated with a nonfunctioning pattern on salivary gland scintigraphy, a diagnosis of xerostomia was established. RESULTS: The incidences of sialoadenitis, hypogeusia or taste loss, and dry mouth with or without repeated sialadenitis in group A versus group B were 63.8% versus 36.8% (P < 0.001), 39.0% versus 25.6% (P < 0.01), and 23.8% versus 11.2% (P < 0.005), respectively. Permanent xerostomia occurred in 15 patients in group A (14.3%) and 7 patients in group B (5.6%) (P < 0.05). In both groups, bilateral involvement of the parotid gland was the most frequently seen and was followed by bilateral involvement of the submandibular gland. CONCLUSION: An early start of sucking lemon candy may induce a significant increase in salivary gland damage. Lemon candy should not be given until 24 h after radioiodine therapy.