Arjan Vissink

Bio: Arjan Vissink is an academic researcher from University Medical Center Groningen. The author has contributed to research in topics: Implant & Medicine. The author has an hindex of 78, co-authored 668 publications receiving 22780 citations. Previous affiliations of Arjan Vissink include Lund University & University of Groningen.

Oral Sequelae of Head and Neck Radiotherapy

Abstract: In addition to anti-tumor effects, ionizing radiation causes damage in normal tissues located in the radiation portals. Oral complications of radiotherapy in the head and neck region are the result of the deleterious effects of radiation on, e.g., salivary glands, oral mucosa, bone, dentition, masticatory musculature, and temporomandibular joints. The clinical consequences of radiotherapy include mucositis, hyposalivation, taste loss, osteoradionecrosis, radiation caries, and trismus. Mucositis and taste loss are reversible consequences that usually subside early post-irradiation, while hyposalivation is normally irreversible. Furthermore, the risk of developing radiation caries and osteoradionecrosis is a life-long threat. All these consequences form a heavy burden for the patients and have a tremendous impact on their quality of life during and after radiotherapy. In this review, the radiation-induced changes in healthy oral tissues and the resulting clinical consequences are discussed.

Rituximab treatment in patients with primary Sjögren's syndrome: an open-label phase II study.

Abstract: Objective To investigate the safety and efficacy of B cell depletion treatment of patients with active primary Sjogren's syndrome of short duration (early primary SS) and patients with primary SS and mucosa-associated lymphoid tissue (MALT)-type lymphoma (MALT/primary SS). Methods Fifteen patients with primary SS were included in this phase II trial. Inclusion criteria for the early primary SS group were B cell hyperactivity (IgG >15 gm/liter), presence of autoantibodies (IgM rheumatoid factor, anti-SSA/SSB), and short disease duration ( Results Significant improvement of subjective symptoms and an increase in salivary gland function was observed in patients with residual salivary gland function. Immunologic analysis showed a rapid decrease of peripheral B cells and stable levels of IgG. Human anti-chimeric antibodies (HACAs) developed in 4 of 15 patients (27%), all with early primary SS. Three of these patients developed a serum sickness-like disorder. Of the 7 patients with MALT/primary SS, complete remission was achieved in 3, and disease was stable in 3 and progressive in 1. Conclusion Findings of this phase II study suggest that rituximab is effective in the treatment of primary SS. The high incidence of HACAs and associated side effects observed in this study needs further evaluation.

Effectiveness of rituximab treatment in primary Sjögren's syndrome: a randomized, double-blind, placebo-controlled trial.

Abstract: 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.

Prevention and treatment of the consequences of head and neck radiotherapy.

Abstract: The location of the primary tumor or lymph node metastases dictates the inclusion of the oral cavity, salivary glands, and jaws in the radiation treatment portals for patients who have head and neck cancer. The clinical sequelae of the radiation treatment include mucositis, hyposalivation, loss of taste, osteoradionecrosis, radiation caries, and trismus. These sequelae may be dose-limiting and have a tremendous effect on the patient's quality of life. Most treatment protocols to prevent these sequelae are still based on clinical experience, but alternatives based on fundamental basic and clinical research are becoming more and more available. Many of these alternatives either need further study before they can be incorporated into the protocols commonly used to prevent and treat the radiation-related oral sequelae or await implementation of these protocols. In this review, the various possibilities for prevention and/or treatment of radiation-induced changes in healthy oral tissues and their consequences are discussed.

Salivary proteomic and genomic biomarkers for primary sjögren's syndrome

Abstract: Sjogren’s syndrome (SS), which was first described in 1933 by the Swedish physician Henrik Sjogren (1), is a chronic autoimmune disorder clinically characterized by a dry mouth (xerostomia) and dry eyes (keratoconjunctivitis sicca). The disease primarily affects women, with a ratio of 9:1 over the occurrence in men. While SS affects up to 4 million Americans, about half of the cases are primary SS. Primary SS occurs alone, whereas secondary SS presents in connection with another autoimmune disease, such as rheumatoid arthritis or systemic lupus erythematosus (SLE). Histologically, SS is characterized by infiltration of exocrine gland tissues by predominantly CD4 T lymphocytes. At the molecular level, glandular epithelial cells express high levels of HLA–DR, which has led to the speculation that these cells are presenting antigen (viral antigen or autoantigen) to the invading T cells. Cytokine production follows, with interferon (IFN) and interleukin-2 (IL-2) being especially important. There is also evidence of B cell activation with autoantibody production and an increase in B cell malignancy. SS patients exhibit a 40-fold increased risk of developing lymphoma. SS is a complex disease that can go undiagnosed for several months to years. Although the underlying immune-mediated glandular destruction is thought to develop slowly over several years, a long delay from the start of symptoms to the final diagnosis has been frequently reported. SS presumably involves the interplay of genetic and environmental factors. To date, few of these factors are well understood. As a result, there is a lack of early diagnostic markers, and diagnosis usually lags symptom onset by years. A new international consensus for the diagnosis of SS requires objective signs and symptoms of dryness, including a characteristic appearance of a biopsy sample from a minor or major salivary gland and/or the presence of autoantibody such as anti-SSA (2–4). However, establishing the diagnosis of primary SS has been difficult in light of its nonspecific symptoms (dry eyes and mouth) and the lack of both sensitive and specific biomarkers, either body fluid– or tissue-based, for its detection. It is widely believed that developing molecular biomarkers for the early diagnosis of primary SS will improve the application of systematic therapies and the setting of criteria with which to monitor therapies and assess prognosis (e.g., lymphoma development). Saliva is the product of 3 pairs of major salivary glands (the parotid, submandibular, and sublingual glands) and multiple minor salivary glands that lie beneath the oral mucosa. Human saliva contains many informative proteins that can be used for the detection of diseases. Saliva is an attractive diagnostic fluid because testing of saliva provides several key advantages, including low cost, noninvasiveness, and easy sample collection and processing. This biologic fluid has been used for the survey of general health and for the diagnosis of diseases in humans, such as human immunodeficiency virus, periodontal diseases, and autoimmune diseases (5–8). Our laboratory is active in the comprehensive analysis of the saliva proteome (for more information, see www.hspp.ucla.edu), thus providing the technologies and expertise to contrast proteomic constituents in primary SS with those in control saliva (9–11). Thus far, we have identified over 1,000 proteins in whole saliva (WS). In addition, we have recently identified and cataloged ~3,000 messenger RNAs (mRNA) in human WS (12). These studies have provided a solid foundation for the discovery of biomarkers in the saliva of patients with primary SS. We have previously demonstrated proteome- and genome-wide approaches to harnessing saliva protein and mRNA signatures for the detection of oral cancer in humans (13,14). There have been continuous efforts in the search for biomarkers in human serum or saliva for the diagnosis of primary SS. Some gene products were found at elevated levels in SS patient sera or saliva, including β2-microglobulin (β2m), soluble IL-2 receptor, IL-6, anti-Ro/SSA, anti-La/SSB, and anti–α-fodrin autoantibodies (15–20). However, none of them individually is sensitive or specific enough to use for the confirmative diagnosis of SS (15). Therefore, it is crucial to use emerging proteome- and genome-wide approaches to discover a wide spectrum of informative and discriminatory biomarkers that can be combined to improve the sensitivity and specificity for the detection of primary SS.

A review of saliva: Normal composition, flow, and function

Abstract: An adequate supply of saliva is critical to the preservation and maintenance of oral tissue. Clinicians often do not value the many benefits of saliva until quantities are decreased. Much is written on the subject of salivary hypofunction, but little attention is paid to normal salivary flow and function. This article is a brief, up-to-date overview of the literature on the basics of normal salivary composition, flow, and function. A review of the literature was conducted using MEDLINE and Healthstar (1944 through 1999); articles were selected for inclusion on the basis of relevance and significance to the clinician.

Clinical practice guidelines in oncology

Abstract: Ductal carcinoma in situ (DCIS) of the breast represents a heterogeneous group of neoplastic lesions in the breast ducts. The goal for management of DCIS is to prevent the development of invasive breast cancer. This manuscript focuses on the NCCN Guidelines Panel recommendations for the workup, primary treatment, risk reduction strategies, and surveillance specific to DCIS.

Platelet-Rich Plasma From Basic Science to Clinical Applications

Abstract: Platelet-rich plasma (PRP) has been utilized in surgery for 2 decades; there has been a recent interest in the use of PRP for the treatment of sports-related injuries. PRP contains growth factors and bioactive proteins that influence the healing of tendon, ligament, muscle, and bone. This article examines the basic science of PRP, and it describes the current clinical applications in sports medicine. This study reviews and evaluates the human studies that have been published in the orthopaedic surgery and sports medicine literature. The use of PRP in amateur and professional sports is reviewed, and the regulation of PRP by antidoping agencies is discussed.