Personalizing dental screening and prevention protocols in dentulous patients with oropharyngeal cancer undergoing radiotherapy: A retrospective cohort study.

Objectives: Patients with head and neck cancer are routinely screened for dental foci prior to radiotherapy (RT) to prevent post- RT tooth extractions associated with an increased risk of osteoradionecrosis. We evaluated the risk factors for post-RT tooth extraction to personalise dental screening and prevention protocols prior to RT. Materials and methods: This retrospective cohort study included dentulous patients diagnosed with oropharyngeal cancer who had undergone radiation therapy at doses 60-70 Gy and achieved a disease-free survival of ≥ 1 year (N = 174). Risk factors were assessed using Cox regression models. Results: The cumulative incidence of post-RT tooth extraction was 30.7 % at 5 years. Main indications for extraction (n = 62) were radiation caries (n = 20) and periodontal disease (n = 27). Risk factors associated (p < 0.05) with radiation caries-related extractions included active smoking, alcohol abuse, poor oral hygiene, parotid gland irradiation, and mandibular irradiation. A high-dose volume in the mandible was associated with periodontal disease events. Conclusion: Post-RT extractions due to radiation caries were influenced by lifestyle factors and RT dose in the mandible and parotid glands. Periodontal disease-related extractions were primarily associated with the mandibular dose. During dental screening these post-RT risk factors should be taken into account to prevent osteoradionecrosis.

Late Complications in Long-Term Childhood Cancer Survivors: What the Oral Health Professional Needs to Know.

With diagnostic and therapeutic advances, over 80% of children diagnosed with cancer become long-term survivors. As the number of childhood cancer survivors (CCS) continues to increase, dental practitioners become more likely to have CCS among their patients. CCS may develop late complications from damage caused by their cancer treatment to endocrine, cardiovascular, musculoskeletal, and other organ systems. These complications may surface decades after the completion of treatment. Adverse outcomes of childhood cancer treatment frequently involve oral and craniofacial structures including the dentition. Tooth development, salivary gland function, craniofacial growth, and temporomandibular joint function may be disturbed, increasing oral health risks in these individuals. Moreover, CCS are at risk of developing subsequent malignancies, which may manifest in or near the oral cavity. It is important that dental practitioners are aware of the childhood cancer history of their patients and have knowledge of potential late complications. Therefore, this narrative review aims to inform dental practitioners of late oral complications of cancer treatment modalities commonly used in pediatric oncology. Furthermore, selected common non-oral late sequelae of cancer therapy that could have an impact on oral health and on delivering dental care will be discussed.

The effect of conditioning regimen and prescribed medications on hyposalivation in haematopoietic cell transplantation (HCT) patients: an 18-month prospective longitudinal study.

OBJECTIVES: Haematopoietic cell transplantation (HCT) preceded by a conditioning regimen is an established treatment option for (non)malignant haematologic disorders. We aim to describe the development of hyposalivation over time in HCT recipients, and determine risk indicators. MATERIALS AND METHODS: A multi-centre prospective longitudinal observational study was conducted. Unstimulated (UWS) and stimulated (SWS) whole saliva was collected before HCT, early post-HCT, and after 3, 6, 12, and 18 months. The effect of type of transplantation (allogeneic vs autologous) and intensity (full vs reduced) of the conditioning regimen on hyposalivation (UWS < 0.2 mL/min; SWS < 0.7 mL/min) was explored. RESULTS: A total of 125 HCT recipients were included. More than half of the patients had hyposalivation early post-HCT; a quarter still had hyposalivation after 12 months. The conditioning intensity was a risk indicator in the development of hyposalivation of both UWS (OR: 3.9, 95% CI: 1.6-10.6) and SWS (OR: 8.2, 95% CI: 2.9-24.6). After 3 and 12 months, this effect was not statistically significant anymore. CONCLUSIONS: Hyposalivation affects the majority of patients early post-HCT. The conditioning intensity and the type of transplantation were significant risk indicators in the development of hyposalivation. The number of prescribed medications, total body irradiation as part of the conditioning regimen and oral mucosal graft-versus-host disease did not influence hyposalivation significantly. CLINICAL RELEVANCE: Because of the high prevalence of hyposalivation, HCT recipients will have an increased risk of oral complications. It might be reasonable to plan additional check-ups in the dental practice and consider additional preventive strategies.

Oral health in patients scheduled for hematopoietic stem cell transplantation in the Orastem study.

Despite advances in transplant medicine, prevalence of complications after hematopoietic stem cell transplantation (HSCT) remains high. The impact of pre-HSCT oral health factors on the incidence and severity of complications post-HSCT is poorly understood. The aim of this prospective, observational study was to analyze oral health in patients planned for HSCT. Patients ≥18 years requiring HSCT were included from five sites between 2011-2018. General health, oral findings and patient-reported symptoms were registered in 272 patients. Oral symptoms around disease onset were reported by 43 patients (15.9%) and 153 patients (58.8%) reported oral complications during previous chemotherapy. One third of patients experienced oral symptoms at the oral examination before conditioning regimen and HSCT. In total, 124 (46.1%) patients had dental caries, 63 (29.0%) had ≥one tooth with deep periodontal pockets, 147 (75.0%) had ≥one tooth with bleeding on probing. Apical periodontitis was observed in almost 1/4 and partially impacted teeth in 17 (6.3%) patients. Oral mucosal lesions were observed in 84 patients (30.9%). A total of 45 (17.4%) of 259 patients had at least one acute issue to be managed prior to HSCT. In conclusion, oral symptoms and manifestations of oral disease were prevalent in patients planned for HSCT. The extent of oral and acute dental diseases calls for general oral screening of patients pre-HSCT.

Taste and smell disturbances in patients with chronic oral graft vs. host disease: An observational study.

Background: A common complication of allogeneic hematopoietic stem cell transplantation (alloHSCT) is chronic oral graft vs. host disease (cGvHD). Oral cGvHD may present as mucosal lesions, salivary gland dysfunction, and trismus. Moreover, taste and smell ability may be affected, but the prevalence, nature and severity of altered taste and smell function, and their impact on quality of life (QoL) are understudied. Aim: To identify the prevalence, nature, and severity of taste and smell disturbances, their impact on QoL and to assess whether altered taste/smell ability is associated with oral mucosal cGvHD or hyposalivation. Materials and methods: AlloHSCT recipients at least 100 days post-HSCT and referred for oral cGvHD-related oral complaints were eligible for participation in this cross-sectional study. Manifestations of oral mucosal cGvHD were scored, the (un)stimulated salivary flow was measured, and objective taste and smell ability was evaluated. Subjective taste and smell alterations, and overall and oral health (OH)-related QoL were assessed. Results: In total, 45 patients were included, of which objective reduced taste ability (hypogeusia) was identified in 68.9%; 28.9% had reduced smell ability and 11.1% had complete loss of smell. Nevertheless, only 31.1% of patients reported severe taste alterations and 22% reported moderate taste alterations indicating that not all the patients were aware of their altered taste sense. Taste/smell disturbances were not related to oral mucosal cGvHD or hyposalivation. Most alloHSCT recipients reported a decreased OH-related QoL. However, a relation between taste/smell ability and global or OH-related QoL could not be identified. Conclusion: Taste and smell disturbances are prevalent among alloHSCT recipients. Most patients reported a decreased OH-related QoL, but the specific impact of taste and smell disturbances remains to be elucidated.

Tooth Formation as Experimental Model to Study Chemotherapy on Tissue Development: Effect of a Specific Dose of Temozolomide/Veliparib.

BACKGROUND: Chemotherapy treatment of cancer in children can influence formation of normal tissues, leading to irreversible changes in their structure and function. Tooth formation is susceptible to several types of chemotherapy that induce irreversible changes in the structure of enamel, dentin and dental root morphology. These changes can make the teeth more prone to fracture or to caries when they have erupted. Recent studies report successful treatment of brain tumors with the alkylating drug temozolomide (TMZ) in combination with veliparib (VLP) in a glioblastoma in vivo mouse model. Whether these drugs also affect tooth formation is unknown. AIM: In this study the effect of TMZ/VLP on incisor formation was investigated in tissue sections of jaws from mice and compared with mice not treated with these drugs. MATERIALS AND METHOD: The following aspects were studied using immunohistochemistry of specific protein markers including: (1) proliferation (by protein expression of proliferation marker Ki67) (2) a protein involved in paracellular ion transport (expression of tight junction (TJ) protein claudin-1) and (3) in transcellular passage of ions across the dental epithelium (expression of Na+, K+ 2Cl- cotransporter/NKCC1). RESULTS: Chemotherapy with TMZ/VLP strongly reduced immunostaining for claudin-1 in distal parts of maturation ameloblasts. No gross changes were found in the treated mice, either in cell proliferation in the dental epithelium at the cervical loop or in the immunostaining pattern for NKCC1 in (non-ameloblastic) dental epithelium. The salivary glands in the treated mice contained strongly reduced immunostaining for NKCC1 in the basolateral membranes of acinar cells. DISCUSSION/CONCLUSIONS: Based on the reduction of claudin-1 immunostaining in ameloblasts, TMZ/VLP may potentially influence forming enamel by changes in the structure of TJs structures in maturation ameloblasts, structures that are crucial for the selective passage of ions through the intercellular space between neighboring ameloblasts. The strongly reduced basolateral NKCC1 staining seen in fully-grown salivary glands of TMZ/VLP-treated mice suggests that TMZ/VLF could also influence ion transport in adult saliva by the salivary gland epithelium. This may cause treated children to be more susceptible to caries.

Caries Progression after Haematopoietic Stem Cell Transplantation and the Role of Hyposalivation.

Haematopoietic stem cell transplantation (HSCT) preceded by a conditioning regimen is an established treatment option for many haematological diseases. Decreased salivary flow rates after HSCT may increase caries risk. We aim to estimate the extent to which caries lesions develop or progress in adult HSCT recipients and assess its association with salivary flow rates. A multi-centre prospective observational study was conducted in which patients receiving HSCT were followed up for 18 months. We included 116 patients (median age 56 years, 43% female) from two medical centres in the Netherlands. Unstimulated whole saliva (UWS) and stimulated whole saliva (SWS) were collected, and full caries charts were made before HSCT and 3, 6, 12, and 18 months post-HSCT. Caries was scored according to the ICDAS criteria by trained dentist-examiners. New dentine lesions or lesion progression into dentine (ICDAS ≥4 or cavitated root lesions) occurred in 32% of patients over 18 months. The median number of affected surfaces was 2 (range: 1-12) per patient with caries progression. The influence of hyposalivation of unstimulated saliva (<0.2 mL/min) and stimulated saliva (<0.7 mL/min) at baseline and after 3 months on caries progression was determined with a negative binomial regression model. Hyposalivation of SWS 3 months after HSCT was a significant risk indicator for caries progression (incidence rate ratio: 5.30, 95% CI: 2.09-13.4, p < 0.001), while hyposalivation of SWS at baseline and hyposalivation of UWS were not. We conclude that caries progression is a common oral complication in patients after HSCT, and stimulated hyposalivation shortly after treatment is a significant risk indicator for caries progression.

Long-Term Analysis of Resilience of the Oral Microbiome in Allogeneic Stem Cell Transplant Recipients.

Stem cell transplantation (SCT) is associated with oral microbial dysbiosis. However, long-term longitudinal data are lacking. Therefore, this study aimed to longitudinally assess the oral microbiome in SCT patients and to determine if changes are associated with oral mucositis and oral chronic graft-versus-host disease. Fifty allogeneic SCT recipients treated in two Dutch university hospitals were prospectively followed, starting at pre-SCT, weekly during hospitalization, and at 3, 6, 12, and 18 months after SCT. Oral rinsing samples were taken, and oral mucositis (WHO score) and oral chronic graft-versus-host disease (NIH score) were assessed. The oral microbiome diversity (Shannon index) and composition significantly changed after SCT and returned to pre-treatment levels from 3 months after SCT. Oral mucositis was associated with a more pronounced decrease in microbial diversity and with several disease-associated genera, such as Mycobacterium, Staphylococcus, and Enterococcus. On the other hand, microbiome diversity and composition were not associated with oral chronic graft-versus-host disease. To conclude, dysbiosis of the oral microbiome occurred directly after SCT but recovered after 3 months. Diversity and composition were related to oral mucositis but not to oral chronic graft-versus-host disease.

Surgical treatment of fractures of the zygomaticomaxillary complex: effect of fixation on repositioning and stability. A systematic review.

Management of zygomaticomaxillary complex (ZMC) fractures can be challenging. Consequently, there is a difference in treatment amongst clinicians. In the literature it remains unclear if the number of fixation points affects the quality of the anatomical reduction, stability through time, and potential complications. Therefore, the objective of this study was to assess the outcome of no fixation, one-point fixation and multiple-point fixation of ZMC fractures. MEDLINE, EMBASE and The Cochrane Central Register of Controlled Trials were searched to identify eligible studies. After screening 925 articles, 17 studies fulfilled the inclusion criteria. Based on this systematic review no clear conclusions can be drawn on how stability, repositioning, and postoperative complications are affected by the number of fixation points. Nevertheless, it can be concluded that the advantage of multiple approaches is direct visualisation, and the downside is potentially approach-related complications. This review suggests that intraoperatively assisted cone-beam computed tomography (CBCT) can help improve the quality of the repositioning and by minimising the number of fixation points, the number of postoperative complications could be further reduced.

Oral chronic graft-versus-host disease: What the general dental practitioner needs to know.

BACKGROUND: Long-term survivors of allogeneic hematopoietic cell transplantation will increasingly seek care from dental providers. METHODS: The authors highlight the importance of minimizing oral symptoms and complications associated with oral chronic graft-versus-host-disease (cGVHD). RESULTS: Chronic GVHD is the result of an immune response of donor-derived cells against recipient tissues. Oral cGVHD can affect the mucosa and damage salivary glands and cause sclerotic changes. Symptoms include sensitivity and pain, dry mouth, taste changes, and limited mouth opening. Risk of developing caries and oral cancer is increased. Food intake, oral hygiene, and dental interventions can represent challenges. Oral cGVHD manifestations and dental interventions should be managed in close consultation with the medical team, as systemic treatment for cGVHD can have implications for dental management. CONCLUSIONS: General dental practitioners can contribute substantially to alleviating oral cGVHD involvement and preventing additional oral health deterioration. PRACTICAL IMPLICATIONS: Frequent examinations, patient education, oral hygiene reinforcement, dry mouth management, caries prevention, and management of dental needs are indicated. In addition, oral physical therapy might be needed. Invasive dental interventions should be coordinated with the transplantation team. Screening for oral malignancies is important even years after resolution of GVHD symptoms. Management of the oral manifestations of cGVHD might require referral to an oral medicine professional.

Exploring the role of oral microorganisms in the pathogenesis of mucositis by assessing their impact on metabolic activity and reproductive capacity of epithelial cells in vitro.

PURPOSE: Clinical and in vitro studies showed selected oral microorganisms to be related to delayed wound healing and ulcerative oral mucositis. However, it is not known whether this effect is due to reduced metabolism and/or the reduced reproductive capacity of epithelial cells. Therefore, we studied the influence of the oral microorganisms Porphyromonas gingivalis, Candida glabrata, and Candida kefyr on cell metabolism and reproductive capacity of oral epithelial cells, aimed to further unravel the pathogenesis of oral mucositis. METHODS: Oral epithelial cells were exposed to different concentrations of P. gingivalis, C. glabrata, and C. kefyr as mono-infections or mixed together. An MTT assay was performed to determine the effect on cell metabolism. A clonogenic assay was used to study the effect on the reproductive capacity of oral epithelial cells. RESULTS: The metabolism of oral epithelial cells was reduced when the microorganisms were present in high concentrations: P. gingivalis at a multiplicity of infection (MOI) of 1000 and the Candida spp. at MOI 100. No statistical difference was observed in the ability of a single epithelial cell to grow into a colony of cells between control and P. gingivalis, C. glabrata, and C. kefyr, independent of the concentrations and combinations used. CONCLUSION: P. gingivalis, C. glabrata, and C. kefyr lowered the metabolic activity of oral epithelial cells in high concentrations, yet they did not influence the reproductive capacity of epithelial cells. Their impact on ulcerative oral mucositis is likely due to an effect on the migration, proliferation, and metabolism of epithelial cells.

Microbial changes in relation to oral mucositis in autologous hematopoietic stem cell transplantation recipients.

The aim of this prospective, two center study was to investigate the dynamics of the microbial changes in relation to the development of ulcerative oral mucositis in autologous SCT (autoSCT) recipients. Fifty-one patients were diagnosed with multiple myeloma and treated with high-dose melphalan followed by autoSCT. They were evaluated before, three times weekly during hospitalization, and three months after autoSCT. At each time point an oral rinse was collected and the presence or absence of ulcerative oral mucositis (UOM) was scored (WHO scale). Oral microbiome was determined by using 16S rRNA amplicon sequencing and fungal load by qPCR. Twenty patients (39%) developed UOM. The oral microbiome changed significantly after autoSCT and returned to pre-autoSCT composition after three months. However, changes in microbial diversity and similarity were more pronounced and rapid in patients who developed UOM compared to patients who did not. Already before autoSCT, different taxa discriminated between the 2 groups, suggesting microbially-driven risk factors. Samples with high fungal load (>0.1%) had a significantly different microbial profile from samples without fungi. In conclusion, autoSCT induced significant and reversible changes in the oral microbiome, while patients who did not develop ulcerative oral mucositis had a more resilient microbial ecosystem.

Do patients benefit from orthognathic surgery? A systematic review on the effects of elective orthognathic surgery on psychosocial functioning and patient satisfaction.

The main purpose of this systematic review was to determine the current state of evidence regarding patient satisfaction with, and the impact of, orthognathic surgery on psychosocial functioning of patients 17 yr of age and older. A secondary aim was to determine whether individuals with psychiatric disorders and mental health conditions are more likely to be dissatisfied with the treatment outcome than those without. We systematically searched PubMed, PsycInfo, and Embase for relevant studies (up to 6 June 2016). After selection of articles we determined the Directness of Evidence (DoE) and Risk of Bias (RoB). We identified 3,948 studies (1,053 studies in Pubmed, 2,023 in Embase, and 872 in PsycInfo). Of these, 87 remained after screening of title and abstract, while after full-text screening only nine remained for DoE and RoB assessment. All nine studies had a high RoB and a low or moderate DoE. The quality of the methods of studies, published to date, on the effects of orthognathic surgery on patient satisfaction or the psychosocial impact carry a high RoB. Therefore, these do not allow inferences on the effects of orthognathic surgery on patient satisfaction or their psychosocial functioning.

Candida and Porphyromonas gingivalis: the effect on wound closure in vitro.

Microorganisms play a role in oral mucositis after cancer therapy. The current study explored the hypothesis that Candida spp. alone and together with Porphyromonas gingivalis cause delayed healing of oral ulcerations due to the inhibition of wound closure. An in vitro scratch assay model was used to study the influence of viable and heat-killed Candida glabrata, Candida kefyr, and Candida albicans on cell migration of oral epithelial cells. Separately, the effect of conditioned medium of Candida spp. and the effect of a mixed infection of Candida spp. with P. gingivalis on wound closure was studied. In the presence of 10 viable C. glabrata or C. kefyr versus one epithelial cell, with a multiplicity of infection (MOI) of 10, the relative closure of the scratch was 26% and 17%, respectively. At a MOI of 1, this was 60% for C. glabrata and 78% for C. kefyr. The inhibition of oral epithelial cell migration challenged with either C. glabrata or C. kefyr together with P. gingivalis was stronger than the inhibition caused by one of both organisms separately. Candida spp. inhibit cell migration in vitro. A combination of Candida spp. and P. gingivalis inhibited cell migration more than either microorganism separately.

Predictors of oral cavity bleeding and clinical outcome after dental procedures in patients on vitamin K antagonists. A cohort study.

Patients on vitamin K antagonists (VKA) often undergo invasive dental procedures. International guidelines consider all dental procedures as low-risk procedures, while bleeding risk may differ between standard low-risk (e. g. extraction 1-3 elements) and extensive high-risk (e. g. extraction of >3 elements) procedures. Therefore current guidelines may need refinement. In this cohort study, we identified predictors of oral cavity bleeding (OCB) and evaluated clinical outcome after low-risk and high-risk dental procedures in patients on VKA. Perioperative management strategy, procedure risk, and 30-day outcomes were assessed for each procedure. We identified 1845 patients undergoing 2004 low-risk and 325 high-risk procedures between 2013 and 2015. OCB occurred after 67/2004 (3.3 %) low-risk and 21/325 (6.5 %) high-risk procedures (p=0.006). In low-risk procedures, VKA continuation with tranexamic acid mouthwash was associated with a lower OCB risk compared to continuation without mouthwash [OR=0.41, 95 %CI 0.23-0.73] or interruption with bridging [OR=0.49, 95 %CI 0.24-1.00], and a similar risk as interruption without bridging [OR=1.44, 95 %CI 0.62-3.64]. In high-risk procedures, VKA continuation was associated with an increased OCB risk compared to interruption [OR=3.08, 95 %CI 1.05-9.04]. Multivariate analyses revealed bridging, antiplatelet therapy, and a supratherapeutic or unobjectified INR before the procedure as strongest predictors of OCB. Non-oral cavity bleeding (NOCB) and thromboembolic event (TE) rates were 2.1 % and 0.2 %. Bridging therapy was associated with a two-fold increased risk of NOCB [OR=1.93, 95 %CI 1.03-3.60], but not with lower TE rates. In conclusion, predictors of OCB were mostly related to perioperative management and differed between low-risk and high-risk procedures. Perioperative management should be differentiated accordingly.