Arjan Vissink

Oral Sequelae of Head and Neck Radiotherapy

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.

Effectiveness of Rituximab Treatment in Primary Sjogren's Syndrome A Randomized, Double-Blind, Placebo-Controlled Trial

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 Sjögrens 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 > or =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

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 patients 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.

Treatment outcome of immediate, early and conventional single-tooth implants in the aesthetic zone: a systematic review to survival, bone level, soft-tissue, aesthetics and patient satisfaction

AIM This study evaluated, through a systematic review of the literature, the outcome of single-implant restorations in the aesthetic zone with natural adjacent teeth, thereby addressing immediate, early and conventional implant approaches. MATERIAL AND METHODS MEDLINE (1950-2008), EMBASE (1966-2008), and CENTRAL (1800-2008) were searched to identify eligible studies. Two reviewers independently assessed the methodological quality using specific study-design-related assessment forms. RESULTS Out of 86 primarily selected articles, 19 studies fulfilled the inclusion criteria. A meta-analysis showed an overall survival rate of 95.5% [95% confidence interval: (93.0-97.1)] after 1 year. A stratified meta-analysis revealed no differences in survival between immediate, early and conventional implant strategies. Little marginal peri-implant bone resorption was found together with low incidence of biological and technical complications. No significant differences in outcome measures were reported in clinical trials comparing immediate, early or conventional implant strategies. CONCLUSION The included literature suggested that promising short-term results could be achieved for immediate, early and conventional single-implants in the aesthetic zone. However, important parameters as aesthetic outcome, soft-tissue aspects, and patient satisfaction were clearly underexposed. The question whether immediate and early single-implant therapies would result in better treatment outcomes remained inconclusive due to lack of well-designed controlled clinical studies.

A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: prevalence, severity and impact on quality of life

PurposeThis systematic review aimed to assess the literature for prevalence, severity, and impact on quality of life of salivary gland hypofunction and xerostomia induced by cancer therapies.MethodsThe 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. Two independent reviewers extracted information regarding study design, study population, interventions, outcome measures, results and conclusions for each article.ResultsThe inclusion criteria were met by 184 articles covering salivary gland hypofunction and xerostomia induced by conventional, 3D conformal radiotherapy or intensity-modulated radiotherapy in head and neck cancer patients, cancer chemotherapy, total body irradiation/hematopoietic stem cell transplantation, radioactive iodine treatment, and immunotherapy.ConclusionsSalivary gland hypofunction and xerostomia are induced by radiotherapy in the head and neck region depending on the cumulative radiation dose to the gland tissue. Treatment focus should be on optimized/new approaches to further reduce the dose to the parotids, and particularly submandibular and minor salivary glands, as these glands are major contributors to moistening of oral tissues. Other cancer treatments also induce salivary gland hypofunction, although to a lesser severity, and in the case of chemotherapy and immunotherapy, the adverse effect is temporary. Fields of sparse literature included pediatric cancer populations, cancer chemotherapy, radioactive iodine treatment, total body irradiation/hematopoietic stem cell transplantation, and immunotherapy.

Clinical management of salivary gland hypofunction and xerostomia in head-and-neck cancer patients: Successes and barriers

The most significant long-term complication of radiotherapy in the head-and-neck region is hyposalivation and its related complaints, particularily xerostomia. This review addresses the pathophysiology underlying irradiation damage to salivary gland tissue, the consequences of radiation injury, and issues contributing to the clinical management of salivary gland hypofunction and xerostomia. These include ways to (1) prevent or minimize radiation injury of salivary gland tissue, (2) manage radiation-induced hyposalivation and xerostomia, and (3) restore the function of salivary gland tissue damaged by radiotherapy.

Protocol for the Prevention and Treatment of Oral Sequelae Resulting from Head and Neck Radiation Therapy

In addition to the desired antitumor effects, head and neck radiation therapy induces damage in normal tissues that may result in oral sequelae such as mucositis, hypo‐salivation, radiation caries, taste loss, trismus, soft‐tissue necrosis, and osteoradionecrosis. These sequelae may be dose‐limiting and have a tremendous effect on the patients quality of life, Current policies to prevent these sequelae primarily are based on clinical experience and show great diversity. A protocol for the prevention and treatment of oral sequelae resulting from head and neck radiation therapy, based on fundamental research and data derived from the literature, is presented. The protocol is particularly applicable in centers with a dental team. This team should be involved at the time of initial diagnosis so that a successful preventive regimen is an integral part of the overall cancer treatment regimen.

Augmentation of localized defects of the anterior maxillary ridge with autogenous bone before insertion of implants

PURPOSE This study evaluated the applicability of intraorally harvested autogenous bone grafts for the augmentation of the narrow maxillary alveolar ridge to enable insertion of implants for single tooth replacement. MATERIALS AND METHODS Local defects of the anterior maxilla were reconstructed in 27 patients with autogenous bone grafts from the mandibular symphysis (n = 12), maxillary tuberosity (n = 8), or mandibular retromolar area (n = 7). Three months after grafting, either Branemark (n = 23) or ITI Bonefit implants (n = 8) were inserted. RESULTS At the time of implantation, all grafted sites showed sufficient bone volume for insertion of the implants. Twenty-four to 68 months after insertion, all implants were functioning well. CONCLUSION Augmentation of local alveolar defects in the maxilla with intraorally harvested autogenous bone grafts appears to be a reliable method to enable implant placement.

A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: management strategies and economic impact

PurposeThis 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.MethodsThe 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.ResultsSeventy-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.ConclusionsThere 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.

Periodontal inflamed surface area: quantifying inflammatory burden

BACKGROUND Currently, a large variety of classifications is used for periodontitis as a risk factor for other diseases. None of these classifications quantifies the amount of inflamed periodontal tissue, while this information is needed to assess the inflammatory burden posed by periodontitis. AIM To develop a classification of periodontitis that quantifies the amount of inflamed periodontal tissue, which can be easily and broadly applied. MATERIAL AND METHODS A literature search was conducted to look for a classification of periodontitis that quantified the amount of inflamed periodontal tissue. A classification that quantified the root surface area affected by attachment loss was found. This classification did not quantify the surface area of inflamed periodontal tissue, however. Therefore, an Excel spreadsheet was developed in which the periodontal inflamed surface area (PISA) is calculated using clinical Attachment Level (CAL), recessions and bleeding on probing (BOP). RESULTS The PISA reflects the surface area of bleeding pocket epithelium in square millimetres. The surface area of bleeding pocket epithelium quantifies the amount of inflamed periodontal tissue. A freely downloadable spreadsheet is available to calculate the PISA. CONCLUSION PISA quantifies the inflammatory burden posed by periodontitis and can be easily and broadly applied.