[A PhD completed. Long-term effects of childhood cancer therapy on oral health]. / Serie: Hora est. Langetermijneffecten van de behandeling van kinderkanker op de mondgezondheid.

In recent years, the five-year survival rate for childhood cancer has increased to about 80%. However, childhood cancer therapy can have serious long-term adverse effects on general health later in life. Of survivors, 75% experience 1 or more late effects. This PhD research aimed to gain more insight into the long-term effects on oral health of childhood cancer therapy, 15 years or more after diagnosis. This study, which is part of the Dutch Childhood Cancer Survivor Study Late Effects 2 (DCCSS LATER 2 Study), showed that oral complications such as dental developmental disorders and hyposalivation occur frequently. Most important risk factors were head and neck radiotherapy of the salivary glands, (alkylating) cytostatic agents, and age at the time of the cancer diagnosis. Dentists should be aware of childhood cancer in the medical history of their patient and of the type of therapy received. Regular dental visits are an essential part of long-term follow-up care of childhood cancer survivors.

[Oral chronic graft versus host disease, what is it and how is it treated?] / Orale chronische graft-versus-hostziekte, wat is het en hoe wordt het behandeld?

Allogeneic stem cell transplantation can cause chronic graft versus host disease (cGVHD). A number of patients manifest cGVHD in and around the mouth. It can present itself as clinically as mucosal lesions and/or salivary gland dysfunction and/or sclerotic changes. Cheeks and tongue are most commonly affected, but the palate, gingiva and lips can also be impacted. Oral cGVHD is associated with mucosal sensitivity, pain, (severe) oral dryness, altered taste, restricted mouth opening and difficulty swallowing, all of which may contribute to a significant decrease of the patient's quality of life. Patients also run an increased risk of developing squamous cell carcinoma of the oral mucosa. The diagnosis of cGVHD is almost always based on the patient's medical history and clinical picture. Treatment of symptoms is based on the patient's problem(s). Dental professionals can provide patients with supportive preventive care aimed at reducing symptoms and preventing further deterioration of oral health.

[Oral graft-versus-host-disease: implications for dental professionals]. / Orale graft-versus-hostziekte: implicaties voor mondzorgverleners.

Graft-versus-host disease (GVHD) is a serious complication after allogeneic hematopoietic stem cell transpl antation, which frequently affects the mouth. GVHD is the result of an immunological attack of donor-derived cells against the tissue of patients. Chronic oral GVHD can affect the mucosa and/or damage salivary glands and can cause sclerotic changes to the head and neck area. Patients can experience painful oral and gingival mucosa, dry mouth, taste changes and limited mouth opening. Due to painful mucosa and salivary glands, and limited mouth opening, performing oral hygiene and dental interventions can be difficult. Immunosuppression in combination with altered salivary production increases the risk of secondary infectious complications, such as dental caries and candida infections. Dental professionals can play an important role in the prevention of oral complications.

Diversity and compositional differences in the oral microbiome of oral squamous cell carcinoma patients and healthy controls: a scoping review.

Objectives: The human oral microbiome may play a role in the development of oral squamous cell carcinoma. The aim of this scoping review was to examine microbial diversity and differences in the composition of the oral microbiome between OSCC patients and healthy controls. Methods: A literature search (in PubMed and Embase.com) was performed on January 9, 2023. The outcome variables used from the included studies of this review were alpha- and beta diversity and oral microbiome composition profiles for each taxonomic level (phylum-, class-, order-, genus- and species level). Results: Thirteen out of 423 studies were included in this review compromising 1,677 subjects, of which 905 (54.0%) were OSCC patients and 772 (46.0%) were healthy controls. Most studies found a higher alpha diversity in the OSCC patient group and significantly different beta diversities between OSCC patient samples and healthy control samples. Studies reported more abundant Fusobacteria (on phylum level), Fusobacterium (on genus level), Fusobacterium nucleatum, Porphyromonas endodontalis and Prevotella intermedia (on species level) in OSCC patients. The healthy control group had more abundant Actinobacteria (on phylum level), Streptococcus and Veilonella (on genus level) and Veilonella parvula (on species level) according to most studies. Conclusions: Our findings show differences in oral microbiome diversity and composition in OSCC patients. Clinical implications demand continuing study. Development of internationally accepted standard procedures for oral sample collection and oral microbiota analysis is needed for more conclusive and clinically relevant comparisons in future research.

Significant salivary changes in relation to oral mucositis following autologous hematopoietic stem cell transplantation.

The aim of this multicentre, longitudinal study was to determine salivary changes in relation to oral mucositis (OM) in multiple myeloma patients following high-dose melphalan and autologous hematopoietic stem cell transplantation (ASCT). Unstimulated and stimulated whole-mouth saliva samples (UWS and SWS) were collected before ASCT, 1×/wk during the hospitalisation phase, and 3 and 12 months post-ASCT. During the hospitalisation period OM was scored 3×/wk (WHO system). Flow rate, pH, total protein concentration (Nanodrop), albumin, lactoferrin, neutrophil defensin-1 (HNP1), total IgA and S100A8/A9 (ELISA) were determined. Mixed models were used to evaluate differences between ulcerative (u)OM (≥2 WHO, n = 20) and non-uOM (n = 31) groups. Until 18 days after ASCT, flow rate, pH, total IgA and HNP1 levels decreased in UWS and/or SWS, while log lactoferrin levels were significantly increased (UWS: p = 0.016 95% CI [0.36, 3.58], SWS: p < 0.001 95% CI [1.14, 3.29]). Twelve months post-ASCT, salivary protein levels were similar to baseline except for log total IgA, which was higher (UWS: p < 0.001 95% CI [0.49, 1.29], SWS: p < 0.001 95% CI [0.72, 1.45]). No differences between uOM and non-uOM groups were observed. Changes in salivary proteins indicated an inflammatory reaction in salivary glands coinciding with mucosal and systemic reactions in response to high-dose melphalan.

[Tooth development disturbances following haematopoietic stem cell transplantation]. / Langetermijneffecten op de gebitsontwikkeling na stamceltransplantatie.

Forty children treated with allogenic haematopoietic stem cell transplantation for haematological malignancies, were examined at least 2 years after transplantation. The researchers collected information concerning subjective oral symptoms, the results of a panoramic radiograph and the findings of an oral examination. Nearly all children had tooth development disturbances, including missing teeth, shortened roots, and arrested root development. The study group showed a significantly higher prevalence of missing teeth than the standard values for first and second premolars in both maxilla and mandible, as well as for second molars in the mandible. Children younger than 3 years of age at the start of the treatment missed significantly more teeth than older children. The mean root-crown length ratios of several tooth types were lower when compared with a control group of healthy Finnish children. The mean dental age was higher than the mean chronological age due to early final apical root formation.

Long-term adverse effects of hematopoietic stem cell transplantation on dental development in children.

PURPOSE: The purpose of this study was to assess late effects of cytotoxic therapy with hematopoietic stem cell transplantation (HCT) on dental development in survivors of childhood cancer. MATERIALS AND METHODS: Forty children who underwent allogeneic HCT for a variety of hematological malignancies were evaluated at a minimum of 2 years after transplantation. We obtained information on oral symptoms, exposed panoramic radiographs (PRG), and performed an oral examination. PRGs were scored for agenesis and root and/or crown abnormalities. The root-crown ratio was calculated, and dental age was assessed using Demirjian' s method. MAIN RESULTS: The studied group showed a significantly higher prevalence of tooth agenesis compared to normative data for first and second premolars in both the maxilla and mandible, as well as the second molars in the mandible (all p values <0.001). Children who were <3 years old at the time of cancer treatment had significantly more missing teeth than older children, F(2,37) = 7.58, p < 0.002. Root-crown ratios were lower in the study sample than those from normative data. In addition, the mean dental age was higher (as a result of earlier apical root closure) than the mean chronological age, t(28) = 2.47, p < 0.020. CONCLUSIONS: Nearly all children examined had dental development disturbances, including agenesis, short roots, and arrested root development. An oral/dental evaluation and preventative oral supportive care regimens should be part of programs monitoring late effects in long-term survivors of childhood cancer.

[Haematopoietic stem cell transplantation and oral complications]. / Hematopoëtische stamceltransplantaties en orale problemen.

New haematopoietic stem cell transplantation procedures make the treatment available to patients who previously did not qualify, such as the elderly. In addition, the spectrum of oral complications associated with haematopoietic stem cell transplantation has altered as a result of the recent developments. This article is a review of the main principles of haematopoietic stem cell transplantation and provides information on oral complications which may develop, such as mucositis, infections, bleeding, graft-versus-host disease, xerostomia, hyposalivation, altered taste, secondary tumors, osteoporosis, osteonecrosis and growing and developing disturbancies. Finally, the role of dental care providers in cases of haematopoietic stem cell transplantation is addressed.

CD4 to CD8 ratio and in vitro lymphoproliferative responses during experimental gingivitis in pregnancy and post-partum.

The absolute numbers and percentages of peripheral T, B, and NK cells were assessed in 7 women, both during the second trimester of pregnancy and 6 months post-partum. Furthermore, the in vitro responses of peripheral blood lymphocytes (PBL) to several mitogens and a preparation of Prevotella intermedia were compared in a period of experimentally-induced gingivitis during pregnancy and post-partum. Clinically, the periodontal pocket bleeding index (PPBI) was found to be higher during pregnancy than post-partum. The absolute numbers of CD3, CD4, and CD19 positive cells appeared to be decreased during pregnancy as compared to post-partum. However, the results did not indicate any evidence for a reduced in vitro PBL response to several mitogens and a preparation of P. intermedia during pregnancy.

Experimental gingivitis during pregnancy and post-partum: immunohistochemical aspects.

The histoimmunological response of 8 individuals was studied longitudinally in relation to the development of experimental gingivitis during pregnancy and post-partum. At day 0 as well as at day 14 of experimental gingivitis the mean periodontal pocket bleeding index (PPBI) was higher during pregnancy than post-partum, whereas the amount of plaque that accumulated was similar. The number of CD1 positive cells (mainly Langerhans) in the oral epithelium was found to be higher during pregnancy. In the sulcular epithelium, however, the number of these cells tended to decrease during pregnancy as compared to post-partum. The number of CD4 positive cells in oral and sulcular epithelium was increased during pregnancy (P < 0.05). It was speculated that this increase in the number of CD4 positive cells is confined to the Th-1 subset, since the number of CD14 positive cells (mainly macrophages and granulocytes) together with the number of B cells was found to be decreased during pregnancy. Th-1 cells are known to be cytotoxic against these HLA class II antigen bearing cells. Consequently, cytotoxicity directed against B cells and macrophages may result in diminished immunoresponsiveness in pregnancy gingivitis.

Stimulation of lymphocytes in vitro by Bacteroides intermedius and Bacteroides (Porphyromonas) gingivalis sonicates.

The present study was designed to assess whether the in vitro stimulation of lymphocytes by sonicates of Bacteroides intermedius and Bacteroides (Porphyromonas) gingivalis is antigen specific or non-specific. In addition, the role of T and B lymphocytes in these responses was assessed. Peripheral blood lymphocytes obtained from healthy volunteers were cultured in the presence of these bacterial preparations and the proliferative response was measured. In similar experiments the response of umbilical cord blood lymphocytes did not exceed background values. In limiting dilution experiments only 1:4000, 1:6800, and 1:8200 of the lymphocytes initially reacted to B. intermedius, which strongly argues for the antigen-specificity of the response. Purified T cells, in the presence of monocytes, proliferated when stimulated with B. intermedius and B. gingivalis. As for B cell stimulation, the bacterial extracts were capable of inducing IgM production, which appeared to be T cell dependent. These findings support the notion that B. intermedius and B. gingivalis induce specific T cell activation; secondarily, a T cell dependent, polyclonal B cell activation may occur.

The prevention of oral complications in bone-marrow transplantations by means of oral hygiene and dental intervention.

Oral complications cause morbidity and mortality in patients, undergoing allogeneic or autologous bone-marrow transplantation. The clinical features and the pathogenesis of the oral sequelae of bone marrow ablative therapy and graft-versus-host disease are discussed. In addition, a preventive oral care procedure before, during and after bone-marrow transplantation is proposed.

[Prevention of oral side effects in children receiving chemotherapy]. / Cytostatica bij kinderen. Preventie van orale complicaties.

Especially in children the frequency of oral complications associated with cancer chemotherapy is high. The dentist plays an important role in preventing or reducing these sometimes life-threatening problems. Oral symptoms of the underlying disease, oral sequelae from chemotherapy, patient-related factors and a preventive oral care program will be discussed.

[The significance of endocrine factors and microorganisms in the development of gingivitis in pregnant women]. / Znachenie éndokrinnykh faktorov i mikroorganizmov v razvitii gingivita beremennykh.

40-100% of pregnant women suffer from the co-called pregnancy gingivitis. The cause of pregnancy gingivitis is possible multicausal: increased plasma female sex-hormones, alteration in dental plague and perhaps Prevotella intermedia in the subgingival plague, together with alteration of immunoresponse. Increasing levels of progesterone in the gingiva as well as estrogens due to specific receptors affect vascular permeability and exudation, provoke stasis of microcirculation, increase prostaglandine E2 formation in human gingiva. Decreased gingival keratinization and capability of cell regeneration may affect the epithelial barrier. This can perhaps explain the direct dependence between progesterone and estrogens increasing and the intensification of gingivitis clinical manifestation. The experimental gingivitis model of women during pregnancy and post-partum showed identical amounts of dental plague, but clinical manifestations were more intense during pregnancy and they had a relation with increasing P. Intermedia, no statistical significance was shown in the proportion of P. gingivalis. Increasing steroid hormones can substitute for the naphtoquinone requirement of P. intermedia. Optimal oral hygiene performed during pregnancy reduced gingival swelling, redness and bleeding tendency to levels which can be considered as physiologic for the pregnant state.

Longitudinal assessment of hematopoietic stem cell transplantation and hyposalivation.

Hyposalivation is a common adverse effect of anti-neoplastic therapy of head and neck cancer, causing impaired quality of life and predisposition to oral infections. However, data on the effects of hematopoietic stem cell transplantation (HSCT) on salivary secretion are scarce. The present study determined stimulated whole-saliva flow rates in HSCT recipients in comparison with a healthy control group. Stimulated whole-saliva flow rates of 228 allogeneic HSCT recipients (134 males, 94 females; mean age, 43 yrs) were examined pre-HSCT and 6, 12, and 24 months post-HSCT. Healthy individuals (n = 144; 69 males, 75 females; mean age, 46 yrs) served as the control group. Stimulated saliva flow rates (mL/min) were measured and analyzed statistically, stratifying for hematological diagnoses and conditioning therapy. Hyposalivation (≤ 0.7 mL/min) was found in 40% (p < 0.00001), 53% (p < 0.00001), 31% (p < 0.01), and 26% (n.s.) of the recipients pre-HSCT, and 6, 12, and 24 months post-HSCT, respectively, whereas 16% of the control individuals had hyposalivation. Severe hyposalivation (≤ 0.3 mL/min) was found in 11%, 18%, 4%, and 4% of the recipients pre-HSCT, and 6, 12, and 24 months post-HSCT, respectively. Additionally, conditioning regimen and sex had an impact on saliva flow. In conclusion, hyposalivation was observed to be a common but generally reversible complication among HSCT recipients.

Xerostomia and chronic oral complications among patients treated with haematopoietic stem cell transplantation.

OBJECTIVE: To assess the severity of xerostomia (subjective dry mouth) in haematopoietic stem cell transplantation (HSCT) patients and to investigate the association of xerostomia with other chronic oral complications. DESIGN: Cross-sectional study.Study participants and methods Participants were 48 patients with a history of HSCT recruited among members of the Dutch Stem Cell Transplantation Contact Group, and a comparison group of 41 age- and sex-matched individuals. Data were collected using the Xerostomia Inventory (XI score) and a seven-item oral health questionnaire. RESULTS: HSCT patients had a higher XI score than the comparison group, and a greater severity of several oral complaints: painful oral mucosa, altered taste, limited opening of the mouth and problems with tooth brushing. HSCT patients did not report greater pain during cold stimulation of teeth, chipped and cracked teeth or bleeding gums. In HSCT patients, the XI score correlated significantly with the severity of oral mucosal pain, altered taste, limited opening of the mouth, painful teeth following cold stimuli, chipped or cracked teeth, problems with tooth brushing and bleeding gums. In the comparison group, no correlations were observed between XI score and these oral problems. CONCLUSION: HSCT patients have more severe xerostomia, which is associated with other oral complaints. Dental professionals should monitor these patients post-transplant for oral complications. Symptoms of dry mouth should be relieved and secondary complications should be prevented.

Current practices for management of oral mucositis in cancer patients.

Many anticancer therapies induce oral mucositis, diminishing the patient's quality of life. Especially in neutropenic patients, it can lead to life-threatening systemic infection. Moreover, it can become a limiting factor in intensive treatment schedules. Many interventions are aimed at reducing trauma and the risk of secondary infection. The institution of good oral hygiene seems to play a crucial part and can be achieved manually or by means of antiseptic agents. More specific antimicrobial therapy may be indicated. In addition, local and/or systemic pain control may be required. The administration of hematological growth factors, cryoprotectants and other agents or measures that may be of help in the management of mucositis are discussed.

Efficient and unbiased estimation of volume and area of tissue components and cell number in gingival biopsies.

Recently, the methodology for volume and cell number estimation from sectioned tissue has undergone rapid progress. To date there are no indications in the literature that investigators in periodontal research are aware of this progress, published mainly in the disciplines of stereology and morphometry. This is unfortunate, as these developments could be profitably exploited in periodontal pathology. In this review we discuss the dangers of some currently used quantitative methods and indicate how simple unbiased methods together with an appropriate systematic sampling scheme lead to an efficient estimation of cell number and volume of tissue or tissue components.

Experimental gingivitis during pregnancy and post-partum: clinical, endocrinological, and microbiological aspects.

The purpose of this study was to assess whether an intensive oral hygiene regimen practised during pregnancy results in a clinically healthy gingival state, and to assess whether experimentally-induced gingivitis differs in severity during pregnancy as compared to post-partum. In addition, levels of black-pigmented Gram negative anaerobes at subgingival and oral mucosal sites and plasma concentrations of free estrogens and prosterone were determined. These parameters were studied during a 14-day episode of experimental gingivitis induced in the 25th week of pregnancy, and again 6 months post-partum. The subjects were selected on shallow pockets < or = 4 mm and interproximal loss of attachment not exceeding 2 mm. As a result of controlled oral hygiene, the gingival condition improved both during pregnancy and post-partum. At day 0 during pregnancy, however, gingival swelling, redness, and bleeding on probing were found to be higher than post-partum. Free plasma levels of estrogens and progesterone were found to be normal throughout the study. It was hypothesized that the increase in severity of gingival symptoms during pregnancy reflect microvascular physiologic effects of increased levels of these hormones. During pregnancy, more swelling, redness and bleeding on probing developed during experimental gingivitis than post-partum, whereas the amount of plaque was similar in both phases. This suggests that as a result of dental plaque accumulation, gingival inflammation develops superimposed on pregnancy-associated physiologic alterations. Microbiological evaluation showed that the mean proportions of Prevotella intermedia in subgingival plaque increased during experimental gingivitis performed during pregnancy, whereas no increase of this micro-organism was found post-partum.