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This systematic review aimed to assess the literature for management strategies and economic impact of salivary gland hypofunction and xerostomia induced by cancer therapies and to determine the quality of evidence-based management recommendations. The electronic databases of MEDLINE/PubMed and EMBASE were searched for articles published in English since the 1989 NIH Development Consensus Conference on the Oral Complications of Cancer Therapies until 2008 inclusive. For each article, two independent reviewers extracted information regarding study design, study population, interventions, outcome measures, results, and conclusions. Seventy-two interventional studies met the inclusion criteria. In addition, 49 intensity-modulated radiation therapy (IMRT) studies were included as a management strategy aiming for less salivary gland damage. Management guideline recommendations were drawn up for IMRT, amifostine, muscarinic agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer. There is evidence that salivary gland hypofunction and xerostomia induced by cancer therapies can be prevented or symptoms be minimized to some degree, depending on the type of cancer treatment. Management guideline recommendations are provided for IMRT, amifostine, muscarinic agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer. Fields of sparse literature identified included effects of gustatory and masticatory stimulation, specific oral mucosal lubricant formulas, submandibular gland transfer, acupuncture, hyperbaric oxygen treatment, management strategies in pediatric cancer populations, and the economic consequences of salivary gland hypofunction and xerostomia.

Oral complications are commonly experienced by patients undergoing cancer therapies. The Oral Care Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) has completed nine systematic reviews including Bisphosphonate Osteonecrosis of the Jaw, Odontogenic/Periodontal Infection, Dysgeusia, Oral Fungal Infection, Osteoradionecrosis, Trismus, Oral Pain, Oral Viral Infection, and Xerostomia. The aims of these reviews were to determine the prevalence of each oral complication, relationship with quality of life, economic impact, and formulation of guidelines based on the quality of the literature. The present article described the details of the methodology and statistical analysis utilized in these nine systematic reviews. Additionally, a summary of the quality of the literature from these oral complications is presented. Oral complications associated with cancer therapies are common among cancer patients. The systematic reviews by the Oral Care Study Group of MASCC/ISOO provide a thorough assessment of the available literature for these oral complications.

The purpose was to review relevant scientific papers written since 1989 which focused on the prevalence and management of dysgeusia as an oral side effect of cancer treatment. Our literature search was limited to English language papers published between 1990 and 2008. A total of 30 papers were reviewed; the results of 26 of these papers were included in the present systematic review. A structured assessment form was used by two reviewers for each paper. Studies were weighted as to the quality of the study design, and treatment recommendations were based on the relative strength of each paper. A wide range in reported prevalence of dysgeusia was identified with the weighted prevalence from 56–76%, depending on the type of cancer treatment. Attempts to prevent dysgeusia through the prophylactic use of zinc sulfate or amifostine have been of limited benefit. Nutritional counseling may be helpful to some patients in minimizing the symptoms of dysgeusia. Dysgeusia is a common oral side effect of cancer therapy (radiotherapy, chemotherapy, or combined modality therapy) and often impacts negatively on quality of life. From the current literature, there does not appear to be a predictable way of preventing or treating dysgeusia.

MEDLINE/PubMed and EMBASE.The review included papers published between January 1, 1990 and December 31, 2008. The primary outcome was to retrieve all literature containing original data on dental caries, periodontal disease and pre-cancer dental clearance protocols in cancer patients undergoing head and neck radiotherapy, chemotherapy or combined treatment modalities. Excluded studies included systematic and non-systematic reviews, microbiology studies, growth and development studies, organ transplant studies, studies eliciting dental complications through questionnaires, studies reporting data from previous publications, phase I and II trials, opinion papers, case reports, articles published before 1990, and publications from the 1990 National Cancer Institute Monographs, which were based on the 1989 National Institutes of Health Development Consensus Conference on the Oral Complications of Cancer Therapies.Each article was independently evaluated by two reviewers with pilot-tested collection forms customised for reviewing dental disease data. Dental caries was assessed by the presence (Y/N), DMFT/dmft (decayed, missing, and filled teeth: DMFT for permanent adult teeth and dmft signifying deciduous teeth), and DMFS/dmfs indexes (decayed, missing, and filled surfaces: DMFS for permanent adult teeth and dmfs signifying deciduous teeth), if available. In addition, periodontal health was assessed using the plaque and gingival indexes. Further data collected for each article such as type of study, blinding, presence of control group, scale validity, and sample size were used to determine quality outcomes utilised to determine the weighted prevalence of caries and dental infection.Sixty-four published papers between 1990 and 2008 were reviewed. The weighted overall prevalence of dental caries was 28.1%. The overall DMFT for patients who were post-antineoplastic therapy was 9.19 (n=457). The overall plaque index for patients who were post-antineoplastic therapy was 1.38 (n=189). The gingival index for patients who were post-chemotherapy was 1.02 (n=162). The weighted prevalence of dental infection/abscess during chemotherapy was reported in three studies and was 5.8%.Patients who were post-radiotherapy had the highest DMFT. The use of fluoride products and chlorhexidine rinses is beneficial in patients who are post-radiotherapy. There continues to be a lack of clinical studies on the extent and severity of dental disease that are associated with infectious complications during cancer therapy.

This systematic review aims to examine the prevalence of bisphosphonate osteonecrosis (BON) in the cancer population, prevention and treatment protocols, and quality of life issues. A search of MEDLINE/PubMed and EMBASE form October 2003 to December 31, 2008 was conducted with the objective of identifying publications that contained original data regarding BON. A total of 28 publications fulfilled inclusion criteria, but only 22 were used for prevalence analysis. No randomized controlled clinical trials, meta-analysis, or quality of life papers were found that contained information regarding either prevalence or treatment protocols for the management of BON. The overall weighted prevalence of BON included a sample of 39,124 patients with a mean weighted prevalence of 6.1%. The weighted prevalence was 13.3% for studies with documented follow-up with a sample size of 927 individuals. The weighted prevalence in studies with undocumented follow-up was 0.7% in a sample of 8,829 chart reviews. Epidemiological studies evaluated a total of 29,368 individual records, and the weighted BON prevalence was 1.2%. High-quality studies are needed to accurately characterize the prevalence of BON, and to determine effective treatment protocols.

Objective To identify key target genes and activated signaling pathways associated with the pathogenesis of Sjogren's syndrome (SS) by conducting a systems analysis of parotid glands manifesting primary SS or primary SS/mucosa-associated lymphoid tissue (MALT) lymphoma phenotypes. Methods A systems biology approach was used to analyze parotid gland tissue samples obtained from patients with primary SS, patients with primary SS/MALT lymphoma, and subjects without primary SS (non–primary SS controls). The tissue samples were assessed concurrently by gene-expression microarray profiling and proteomics analysis, followed by weighted gene-coexpression network analysis. Results Gene-coexpression modules related to primary SS and primary SS/MALT lymphoma were significantly enriched with genes known to be involved in the immune/defense response, apoptosis, cell signaling, gene regulation, and oxidative stress. Detailed functional pathway analyses indicated that primary SS–associated modules were enriched with genes involved in proteasome degradation, apoptosis, signal peptides of the class I major histocompatibility complex (MHC), complement activation, cell growth and death, and integrin-mediated cell adhesion, while primary SS/MALT lymphoma–associated modules were enriched with genes involved in translation, ribosome biogenesis and assembly, proteasome degradation, class I MHC signal peptides, the G13 signaling pathway, complement activation, and integrin-mediated cell adhesion. Combined analyses of gene expression and proteomics data implicated 6 highly connected “hub” genes for distinguishing primary SS from non–primary SS, and 8 hub genes for distinguishing primary SS/MALT lymphoma from primary SS. Conclusion Systems biology analyses of the parotid glands from patients with primary SS and those with primary SS/MALT lymphoma revealed pathways and molecular targets associated with disease pathogenesis. The identified gene modules/pathways provide further insights into the molecular mechanisms of primary SS and primary SS/MALT lymphoma. The identified disease-hub genes represent promising targets for therapeutic intervention, diagnosis, and prognosis.

The aim of this study was to analyze retrospectively effects of exercise therapy on trismus related to head and neck cancer or as a consequence of its treatment, and to compare these effects with trismus not related to head and neck cancer. Medical records of patients referred to the department of physical therapy with the diagnosis trismus were retrieved and analyzed. Data of 27 patients with trismus related to head and neck cancer and data of eight patients with trismus not related to cancer were found. The number and type of exercises were registered from the records, as was the extent of mouth opening before and after exercise therapy. The median (IQR) number of exercise treatments was 4 (3-9.3). Exercises included active range of motion exercises, hold relax techniques, manual stretching and joint distraction. The increase in mouth opening was significantly (p

Background: With the advents of new processing techniques and new graft survival theories in fat grafting, the question is: Which processing technique is of preference? This study systematically reviewed literature regarding current techniques for processing fat grafts. Methods: PubMed, Embase, Cinahl, and Cochrane databases were searched until August 2015. Studies comparing different fat grafting processing techniques were included. Outcomes were viability of adipocytes, number of adipose-derived stromal/stem cells (ASC) and growth factors in vitro, volume and quality of the graft in animal studies, and satisfaction and volume retention in human studies. Results: Thirty-five studies were included. Adipocyte viability and ASC numbers were the best using the gauze/towel technique (permeability principle) compared to centrifugation. With regard to centrifugation, the pellet contained more ASCs compared to the middle layer. The animal studies' and patients' satisfaction results were not distinctive. The only study assessing volume retention in humans showed that a wash filter device performed significantly better than centrifugation. Conclusion: In this study, processing techniques using permeability principles proved superior to centrifugation (reinforced gravity principle) regarding viability and ASC number. Due to the variety in study characteristics and reported outcome variables, however, none of the processing techniques in this study demonstrated clinical evidence of superiority. (C) 2015 Published by Elsevier Ltd on behalf of European Association for Cranio-Maxillo-Facial Surgery.

Sicca complaints (sensation of dry mouth and/or eyes) are present in about a quarter of the individuals above the age of 65 years old and are mainly due to medication. However, physiological changes that occur during aging might also lead to a diminished glandular function. These age-related changes are, at least in part, to be the consequence of decreased androgen levels. In addition to these physiological effects that occur during normal aging, sicca complaints can also be caused by Sjogren's syndrome (SS): a systemic auto-inflammatory disorder mainly affecting exocrine glands. Genetic factors, lowered levels of gonadal hormones and (viral) infections appear to contribute to the etiology of the syndrome. The incidence of SS is higher among aged individuals, which might be due to earlier diagnosis, as the onset of SS in an individual with age-related exocrine gland dysfunction lowers the threshold for sicca complaints. On the other hand, physiological aging might be considered as a risk factor for development of SS, resulting in a faster development of the syndrome. Differentiating physiological sicca complaints from SS in the elderly can be challenging, since apparently healthy individuals might present with auto-antibodies and lymphocytic infiltrates in salivary glands might be present as well. The drop in the level of androgens and estrogens upon aging, immunosenescence and pro-inflammatory features of the aging immune system may all contribute to the etiology of pSS in the elderly. In this review, we describe the physiological effects of aging and the influence of SS on exocrine gland morphology and function.

B cell depletion therapy with rituximab (RTX; 2 weekly infusions of 1000 mg, premedication: 100 mg prednisolone) in primary Sjogren's syndrome (pSS) patients is effective in reducing subjective and objective symptoms.1 As B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are important cytokines involved in B cell survival and activation, we assessed in pSS patients included in a double-blind, randomised, placebo-controlled trial1 the effects of RTX on serum BAFF and APRIL levels up to 48 weeks after RTX. Serum concentrations of BAFF and APRIL were measured by ELISA using kits from RD median 1277 pg/ml (range 907–3802 pg/ml)) compared with healthy controls (n=10; median 983 pg/ml (range 600–1564 pg/ml)); p

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. …

Xerostomia is the subjective feeling of oral dryness. The major causes are Sjögren's syndrome (SS), medication and radiotherapy to the head and neck. SS is a chronic systemic autoimmune disease characterized by infiltration of the exocrine glands, the salivary and lacrimal ones in particular. The pathogenesis involves systemic B cell hyperactivity and T cell lymphocytes targeting glandular epithelial cells. About 7.5% of patients with SS develop malignant B cell lymphoma, mostly mucosa-associated tissue lymphomas. Certain classes of drugs can induce hyposalivation and/or xerostomia by, e.g., targeting neurotransmitters and receptors. As a result, amongst others the production of fluid and electrolytes in salivary glands can be reduced and the salivary composition can change. During head and neck radiotherapy, the administration of high doses to the major salivary glands, which are located in the periphery of the head, leads to progressive loss of glandular function and a diminished salivary output. Reduction of the dose and the volume of irradiated salivary glands by advanced radiotherapy techniques can be highly beneficial for patients.

Salivary gland biopsy is a technique broadly applied for the diagnosis of Sjogren's syndrome (SS), lymphoma accompanying SS, sarcoidosis, amyloidosis, and other connective tissue disorders. SS has characteristic microscopic findings involving lymphocytic infiltration surrounding the excretory ducts in combination with destruction of acinar tissue. This article focuses on the main techniques used for taking labial and parotid salivary gland biopsies in the diagnostic workup of SS with respect to their advantages, their postoperative complications, and their usefulness for diagnostic procedures, monitoring disease progression, and treatment evaluation.

The three most frequently diagnosed salivary gland diseases are salivary gland infections, sialolithiasis and mucoceles. Salivary gland infections are usually of bacterial or viral etiology and can be divided into acute and chronic types. Occasionally they can result from obstruction of the salivary duct, an autoimmmune disease or cancer therapy. Infections can occur in all types of salivary glands and are observed at all ages. Sialolithiasis is characterized by the development of calcified structures in the salivary glands, especially in the submandibular gland. Sialoliths are generally attributed to retention of saliva and are usually accompanied by swelling and pain when a salivary stimulus is applied. Mucoceles can be differentiated into mucus extravasation phenomenon or mucus escape reaction, mucus retention cysts and ranulas. They result from extravasation of saliva into the surrounding soft tissues or from retention of saliva within the duct.

Objective: Sialography is commonly used for the diagnosis of Sjogren's syndrome, although its invasive nature is often regarded as a serious drawback for routine usage. The aim of this study was to evaluate the morbidity and acceptability of parotid sialography using oil-based contrast fluid. Study Design: Twenty-four consecutive sialographic procedures were evaluated in terms of morbidity and the patient's acceptance of the procedure, assessed with a standardized questionnaire. Information was also obtained by recording relevant physical parameters during the procedure. Results: There was good acceptance of the sialographic procedure, and the morbidity was low. No signs of overfilling or false route were observed in any of the sialograms. On average, 0.74 mL of contrast fluid was infused with a velocity of 0.01 mL/s. The whole procedure was completed within 12 minutes. Conclusions: Parotid sialography appears less invasive than is often thought. It had a low morbidity rate and was well accepted by the patients. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001;92:572-5)

Objectives: To report the successful use of rituximab on salivary gland immunohistology and function in a patient with Sjogren's syndrome ( SS) and associated MALT lymphoma.Case report: The patient was a 42 year old woman with primary SS and associated MALT lymphoma located in the parotid gland and the hard palate. Four infusions of rituximab ( 375 mg/m(2)) weekly resulted in complete remission of the lymphoma. An incision biopsy of the parotid gland before and after treatment showed improvement of the ( immuno) histopathological characteristics of SS, with possible regeneration of salivary gland tissue. Furthermore, salivary analysis showed decreased inflammatory characteristics and increased stimulated salivary flow.Discussion: Rituximab is a promising agent in the treatment of SS associated MALT lymphoma. In addition to the effect on MALT lymphoma, B cell depletion by rituximab may also attenuate the activity of SS. This case report is the first to describe the effect of rituximab on histological and sialometric/ chemical characteristics of SS. The efficacy of rituximab in the treatment of SS warrants further investigation.

Het vaststellen en vastleggen van de aard en de omvang van de parodontale afwijking is niet alleen van diagnostisch belang. Een zorgvuldige vastlegging is ook belangrijk voor het bepalen van de prognose en het maken van een behandelplan.

Alle drie soorten hebben een lokale en een gegeneraliseerde vorm. Over de oorzaak van de verschillende vormen van early onset parodontitis is nogal wat onzekerheid.

Het parodontium en het endodontium zijn nauw met elkaar verbonden door dentinetubuli, accessoire en laterale wortelkanaaltjes en het foramen apicale.

Mucogingivale aandoeningen zijn aandoeningen van het mondslijmvlies waarbij ook de gingiva is betrokken. Deze aandoeningen kunnen ontstaan als gevolg van trauma’s, irritatie, infecties, medicatie, kwaadaardige ontaarding en systeemafwijkingen. De indeling geschiedt meestal op basis van uiterlijke kenmerken zoals kleur en vorm.

Sjogren’s syndrome (SjS) is an autoimmune inflammatory disorder of exocrine glands that has a particular predilection for the lacrimal and salivary glands. Dry mouth and dry eyes are frequently proffered as presenting symptoms [1, 2]. These are in many cases accompanied by several nonspecific symptoms, such as malaise and fatigue [3]. In addition, extraglandular manifestations such as purpura, polyneuropathy, and arthritis can be present even as presenting signs of the disease [2]. The occurrence of lymphomas is another important issue in SjS that requires timely diagnosis and treatment [4]. This enlarges the possibilities for therapies aimed to slow down, stop, or even reverse the further development of SjS. This chapter describes experimental therapies that are aimed at reducing disease activity or reversing the progression of SjS [5].

Aangezien parodontitis door plaque wordt veroorzaakt en primair beschouwd een bacteriele infectie is, kan worden gesteld dat zonder plaque geen parodontitis ontstaat.

De vorming van tandplaque is een complex dynamisch proces, waarbij het mondmilieu, het dieet, anatomische factoren en het lokale immuunsysteem belangrijk zijn.

Objective. To study the efficacy and safety of B cell depletion with rituximab, a chimeric murine/human anti-CD20 monoclonal antibody, in patients with primary Sjogren's syndrome (SS) in a double-blind, randomized, placebo-controlled trial.Methods. Patients with active primary SS, as determined by the revised American-European Consensus Group criteria, and a rate of stimulated whole saliva secretion of >= 0.15 ml/minute were treated with either rituximab (1,000 mg) or placebo infusions on days 1 and 15. Patients were assigned randomly to a treatment group in a ratio of 2: 1 (rituximab: placebo). Followup was conducted at 5, 12, 24, 36, and 48 weeks. The primary end point was the stimulated whole saliva flow rate, while secondary end points included functional, laboratory, and subjective variables.Results. Thirty patients with primary SS (29 female) were randomly allocated to a treatment group. The mean +/- SD age of the patients receiving rituximab was 43 +/- 11 years and the disease duration was 63 +/- 50 months, while patients in the placebo group were age 43 +/- 17 years and had a disease duration of 67 +/- 63 months. In the rituximab group, significant improvements, in terms of the mean change from baseline compared with that in the placebo group, were found for the primary end point of the stimulated whole saliva flow rate (P = 0.038 versus placebo) and also for various laboratory parameters (B cell and rheumatoid factor [RF] levels), subjective parameters (Multidimensional Fatigue Inventory [MFI] scores and visual analog scale [VAS] scores for sicca symptoms), and extraglandular manifestations. Moreover, in comparison with baseline values, rituximab treatment significantly improved the stimulated whole saliva flow rate (P = 0.004) and several other variables (e.g., B cell and RF levels, unstimulated whole saliva flow rate, lacrimal gland function on the lissamine green test, MFI scores, Short Form 36 health survey scores, and VAS scores for sicca symptoms). One patient in the rituximab group developed mild serum sickness-like disease.Conclusion. These results indicate that rituximab is an effective and safe treatment strategy for patients with primary SS.

The purpose of this study is to review the evidence base from 1990 to 2008 to (1) clarify the impact of cancer therapies on prevalence of osteoradionecrosis (ORN) in head and neck cancer patients, and to (2) evaluate management strategies and their consequences on quality of life and cost of care. Articles were selected for the time period beginning after 1989, excluding the 1990 NCI monograph articles from the 1989 NIH-sponsored Oral Complications in Cancer Therapy Symposium that was published in 1990. The search included both Medline/PubMed and Embase and was limited to humans. The search was limited to publications in the English language. No abstracts were utilized in the current review. Each article was evaluated by two reviewers. A weighted prevalence was calculated for the prevalence of ORN while incorporating predetermined quality measures. The level of evidence, recommendation grade, and guideline (if possible) were provided for published preventive and management strategies for ORN. A total of 43 articles between 1990 and 2008 were reviewed. The weighted prevalence for ORN included conventional radiotherapy (RT) = 7.4%, intensity modulated RT (IMRT) = 5.1%, chemoradiotherapy (CRT) = 6.8%, and brachytherapy = 5.3%. Hyperbaric oxygen may contribute a role in management of ORN. However, no clear guideline recommendations could be established for the prevention or treatment of ORN based on the literature reviewed. New cancer treatment modalities such as IMRT and concomitant CRT have had minimal effect on prevalence of ORN. No studies to date have systematically addressed impact of ORN on either quality of life or cost of care.

We present the findings of a structured systematic review of the literature assessing orofacial pain induced by malignant disease and/or its therapy (excluding mucositis). This evaluation of the literature published after the 1989 NIH Development Consensus conference on the oral complications of cancer therapies is an effort to assess the prevalence of pain, quality of life and economic impact, and management strategies for cancer therapy-induced orofacial pain. A systematic medical literature search was conducted with assistance from a research librarian in MEDLINE/PubMed and EMBASE databases for articles published between January 1, 1990 and December 31, 2008. Each study was independently assessed by two reviewers with expertise in the field of oral oncology. Thirty-nine studies assessed pain in the head and neck region. The measure was commonly embedded in quality of life studies. Most of these studies described pain in head and neck cancer (HNC) patients, which therefore became the focus of the report. Pain is common in patients with HNC and is reported by approximately half of patients prior to cancer therapy, 81% during therapy, 70% at the end of therapy, and by 36% at 6 months after treatment. Pain is experienced beyond the 6-month period by approximately one third of patients and is typically more severe than pre-treatment cancer-induced pain. This systematic review identified the presence of pain before cancer therapy, likely attributable to the cancer; an increase in pain during therapy and the common persistence of pain following cancer treatment. Continuing research should use validated tools to prospectively assess orofacial pain, its causes and pathophysiology, and its effect on quality of life and economic impact. Clinical trials of pain management in this setting are also warranted.

Our aim was to evaluate the literature for the prevalence of and interventions for oral viral infections and, based on scientific evidence, point to effective treatment protocols. Quality of life (QOL) and economic impact were assessed if available in the articles reviewed. Our search of the English literature focused on oral viral infections in cancer patients within the timeframe of 1989-2007. Review methods were standardized. Cohort studies were used to determine the weighted prevalence of oral viral infection in cancer patients. The quality of selected articles were assessed and scored with respect to sources of bias, representativeness, scale validity, and sample size. Interventional studies were utilized to determine management guidelines. Literature search included measures of QOL and economic variables. Prevalence of oral herpes simplex virus (HSV) infection in neutropenic patients was higher than in patients treated with radiotherapy for head and neck cancer (49.8% vs. 0%, respectively). In patients treated with radiochemotherapy for head and neck cancer, the prevalence of oral HSV infection increases up to 43.2% (CI, 0-100%). Prevalence of HSV infection was higher when oral ulcers existed. Information about other oral viral infections is sparse. There was a significant benefit of using acyclovir to prevent HSV oral infection (at 800 mg/day). Various dosing protocols of valacyclovir achieved prevention of HSV reactivation (500 or 1,000 mg/day). The prevalence of HSV reactivation was similar for acyclovir and valacyclovir. No information about impact on QOL and economic burden was available. Acyclovir and valacyclovir are equally effective in preventing oral HSV infection. Neutropenic patients, who were primarily treated for hematological malignancies in the studies reviewed, are at a greater risk for viral infection.

Objective. To compare health-related quality of life (HR-QOL), employment and disability of primary and secondary SS (pSS and sSS, respectively) patients with the general Dutch population.Methods. HR-QOL, employment and disability were assessed in SS patients regularly attending the University Medical Center Groningen (n=235). HR-QOL, employment and disability were evaluated with the Short Form-36 questionnaire (SF-36) and an employment and disability questionnaire. Results were compared with Dutch population data (matched for sex and age). Demographical and clinical data associated with HR-QOL, employment and disability were assessed.Results. Response rate was 83%. SS patients scored lower on HR-QOL than the general Dutch population. sSS patients scored lower on physical functioning, bodily pain and general health than pSS patients. Predictors for reduced HR-QOL were fatigue, tendomyalgia, articular involvement, use of artificial saliva, use of anti-depressants, comorbidity, male sex and eligibility for disability compensation (DC). Employment was lower and DC rates were higher in SS patients compared with the Dutch population.Conclusion. SS has a large impact on HR-QOL, employment and disability.

Radiation therapy and chemotherapy for malignant tumors in the head and neck region are inevitably associated with injury to oral tissues, including the salivary glands. This often results in salivary gland hypofunction. Until now there has been no effective method of preventing damage caused by cancer therapies. Although not yet supported by sufficient evidence, there are some clinical trials indicating a potential benefit from radical scavengers and saliva stimulants. Other developments are in gene transfer to regain salivary gland function and stem cell transplantation to regenerate a diseased salivary gland. While irradiation on salivary gland tissue is irreversible to a large extent, hyposalivation associated with chemotherapy is usually less severe and reversible. In case of significant residual secretory capacity, supportive care is indicated. These patients are advised to stimulate their salivary glands by mechanical or gustatory stimuli. Alternatively, salivary flow can be stimulated by cholinergic stimulation (eg, pilocarpine or cevimeline). In the case of little or no residual capacity, palliative treatment is the only option. In such patients, nocturnal oral dryness can be alleviated by spraying oral surfaces with water or by applying a saliva substitute, particularly a substitute with gellike properties. During the day, the application of mouthwashes and saliva substitutes is indicated if moistening of oral surfaces with water is not sufficient. Recent developments are focusing on bioactive saliva substitutes and mouthwashes containing antimicrobial peptides to protect oral tissues against microbial colonization and to suppress or cure mucosal and gingival inflammation.

Goals of work: Growth factors and cytokines may be useful in preventing chemotherapy (CT)- and radiotherapy (RT)-induced oral and gastrointestinal mucositis. Two systematic reviews of the medical literature on growth factors and cytokines for the amelioration of CT- and RT-induced mucositis throughout the alimentary tract were performed by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology. The aim of these evidence-based scientific reviews was to critically evaluate the literature and create evidence-based guidelines for the use of growth factors and cytokines in the prevention or treatment of CT- and RT-induced mucositis. Method: The two reviews covered articles on clinical trials from January 1966 through May 2002 and preclinical studies from June 2002 through May 2005, respectively. The systematic review process was based on a well-established method for evaluating scientific literature. Main results: The number of articles in the first review was 29. In the second review, 23 articles were evaluated, 14 preclinical and 9 clinical studies. It was concluded from the first review that there was no sufficient evidence to provide any recommendations for clinical practice guidelines regarding growth factors and cytokines. From the second review, a guideline could be presented recommending the use of recombinant human keratinocyte growth factor-1 (palifermin) to prevent oral mucositis in patients receiving high-dose CT and total body irradiation followed by stem cell transplantation for haematological malignancies. A guideline could also be provided suggesting that granulocyte macrophage colony-stimulating factor mouthwash not be used for the prevention of oral mucositis in the transplant setting with high-dose CT and autologous or allogeneic stem cell transplantation. Conclusions: These systematic reviews have provided clarity and shown exciting new results. Further studies will provide new options for this debilitating side-effect of cancer therapy.

Little is known about the relationship between lachrymal and salivary gland involvement in Sjögren's syndrome (SS). It is also of interest to know which eye test contributes most to the diagnosis of SS. We investigated the performance of different tear tests and how these tests relate to common serologic and salivary tests in SS.In patients suspected of SS, the tear breakup time and the tear mucus score were evaluated in addition to the routine tests. Eighty consecutive patients were included, categorized into primary SS (pSS), secondary SS (sSS), and negative for SS.The tear breakup time and mucus score both performed insufficiently in diagnosing SS, in contrast to the Rose Bengal score. In pSS and sSS patients, a clear correlation was noted between tear and saliva quality and secretion rate, and between the Rose Bengal score and parotid sialography. Increased Rose Bengal scores also correlated significantly with hyperglobulinemia and presence of SSB antibodies in serum, with duration of subjective eye dryness, and with decreased tear gland function.The Rose Bengal score remains the eye test of choice having the highest specificity for SS. Hyperglobulinemia and especially positive SSB serology may warrant close monitoring of the eyes, since these serum findings appear to relate to the severity of ocular surface damage. Theoretically, a positive evaluation of either the ocular or oral component, in addition to positive serology or histopathology, could be sufficient to diagnose the syndrome for clinical purposes.

The annual incidence of cancer in the world is estimated at more than 11 million cases with at least 1.3 million in the United States of America [1, 2]. Earlier cancer detection and advances in cancer therapies have provided important management advances to improve survival and quality of life. Common cancer treatment strategies include surgical resection, chemotherapy, radiotherapy, and hematopoietic stem cell transplantation. The goal of such treatments is to cure the patient from the cancer. However, side effects from these therapies can limit the effectiveness of treatment and have a marked impact on the patient’s quality of life both during and after completion of the cancer therapy. The oral cavity is a common site of complications related to cancer therapies. The Surgeon General’s report on Oral Health in America estimates that more than 30–35% (400,000 annually) of patients undergoing cancer treatment will develop oral complications [3]. The Surgeon General’ sr eport—Oral Health in America— calls for both the building of the science and evidence base and the application of science effectively to improve oral health. This recommendation development process aims to effectively transfer research findings in the field of oncology, including oral complications seen with cancer therapies and oral management prior to the start of cancer therapy, to the public and health professionals. Well developed, evidencebased management recommendations have the potential to enhance the appropriateness of clinical practice, improve the quality of oral health care, lead to better patient outcomes, improve cost-effectiveness, and identify areas of further research needs. In order to effectively change perceptions of the burden of illness of oral complications from cancer therapies, a complete understanding of the impact of these complicationsisvital.Concern for underestimating the impact of oral complications may result in avoidance or delay in appropriate care for cancer patients.

A case of primary sialoangiectasia, which in this case was initially misdiagnosed as Sjogren's syndrome, is described. Other diseases, including HIV infection, psoriatic arthritis, and acute parotitis, may cause glandular changes similar to the changes found in the syndrome. Therefore, sialography must be combined with other methods of assessment of the oral cavity when suspicion is high for Sjogren's syndrome. Properly applied, sialography provides essential information regarding the severity of glandular damage and the progression of the disease.

Objectives: To determine the performance of different tear and salivary tests applied in Sjogren's syndrome (SS) and to disclose how these tests relate to common serologic tests in SS.Design: In addition to the routine ocular and oral tests for diagnosing SS (Schirmer test, rose bengal score, unstimulated whole saliva flow, and parotid sialography), tear breakup time and flow rate of glandular saliva (parotid and submandibular-sublingual [SM/SL]) were evaluated in patients referred for diagnosis of SS. Patients were categorized into primary SS, secondary SS, and non-SS groups according to the revised European classification criteria for SS.Setting: Referral center. Patients: Referred sample of 80 consecutive patients.Main Outcome Measure: Correlation between ocular and salivary measures.Results: Breakup time;performed insufficiently in diagnosing SS, as opposed to the rose bengal score. In patients with primary and secondary SS, a clear correlation was noted between tear and saliva quality and secretion rate, and between the rose bengal score and parotid sialography. Increased rose bengal scores also correlated significantly with hyperglobulinemia and presence of SS-B antibodies in serum, with duration of subjective eye dryness, and with decreased tear-gland function. With regard to the,oral tests, whole, parotid, and SM/SL salivary flow decreased significantly with increasing duration of oral complaints, with the stimulated SM/SL flow rate showing the strongest decrease and being more specific in diagnosing SS. Also, parotid sialography was more specific in excluding patients without SS than the commonly applied diagnostic criterion of secretion of unstimulated whole saliva.Conclusions: The rose bengal score remains the eye test of choice, as it has the highest specificity for SS. Hyperglobulinemia and especially positive serologic findings for SS-B may warrant close monitoring of the eyes, since these serum findings appear to relate to the severity of ocular surface damage. Parotid sialography and stimulated secretion of SM/SL saliva are more specific in diagnosing SS than unstimulated. secretion of whole saliva.

Histopathological assessment of salivary gland biopsies is an important element of the diagnostic work-up of Sjögren's syndrome (SS) (Fox, 2017; Kroese et al., 2018). Microscopic evaluation of salivary glands of primary SS (pSS) patients reveals characteristic periductal lymphocytic infiltrates (foci), which mainly consist of T- and B-lymphocytes, as well as a variety of non-lymphoid cells, including dendritic cells and macrophages. Over time, these infiltrates may become organised to ectopic lymphoid tissue with T/B cell compartmentalisation, presence of CD21+ follicular dendritic cell (FDC) networks and high endothelial venules (Fisher et al., 2017; Kroese et al., 2014; Kroese et al., 2018; Salomonsson et al., 2003).

Fc receptor-like protein 4 (FcRL4) is normally expressed on a small subset of mucosa-associated B-cells, as well as on mucosa-associated lymphoid tissue (MALT) lymphoma B-cells. Primary Sjogren's syndrome (pSS) patients have an increased risk of developing MALT lymphomas, preferentially in the parotid glands. For this reason we studied here by immunohistochemistry and mRNA analysis whether FcRL4 expressing B-cells are present in salivary gland tissue (labial and parotid) of pSS patients (n = 54) and non-pSS sicca patients (n = 16) and whether parotid gland MALT lymphomas in pSS patients (n = 49) also express this receptor. We also studied the effect of treatment (rituximab and abatacept) on the presence of FcRL4(+) B-cells, and whether numbers in labial gland biopsies at time of diagnosis of pSS can predict whether patients are at risk for MALT lymphoma development.We demonstrate that FcRL4(+) cells are present in salivary gland tissue of pSS patients where they are closely associated with ductal epithelial cells forming lymphoepithelial lesions. The glandular FcRL4(+) cells are highly proliferative, genuine PAX5(+) B-cells. These FcRL4(+) B-cells are far more frequent in parotid gland than in labial gland tissue (p = 0.003). We further show that expression of FcRL4 is present in pSS-related parotid MALT lymphomas. The FcRL4 mRNA expression level in parotid MALT lymphoma is increased compared to parotid gland tissue of pSS patients without lymphoma (p = 0.017). However, numbers of FcRL4(+) B-cells in labial gland biopsies taken at the time of pSS diagnosis, are not predictive for later development of MALT lymphoma. Reduction of parotid gland FcRL4(+) B-cells by rituximab, but not abatacept is accompanied by restoration of the glandular epithelium, illustrating the crosstalk between these B-cells with the ductal cells.In conclusion, intraepithelial FcRL4(+) B-cells are present in the salivary glands of pSS patients. These cells are likely involved in the epithelial changes seen in pSS. Their enrichment in parotid glands may explain why MALT lymphomas in pSS patients preferentially develop at this specific location.

In childhood, Hodgkin’s disease presents as a painless mass in the neck in 90% of cases. As can be clearly seen in this volume, the roles of radiotherapy and chemotherapy have not yet been defined, but virtually all children will be treated with one or both of these modalities.