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PURPOSE: Critically review and summarise existing knowledge on prevalence of oral, dental, and craniofacial side-effects of antineoplastic treatment in childhood cancer survivors (CCS). METHODS: A literature search was conducted for studies reporting on children aged 4-19 years treated for any type of malignancy up to the age of 15 years and for whom, at the time of the examination, more than 8 months have elapsed since the end of treatment. Data regarding dental late effects on teeth and craniofacial complex were collected and mean prevalence of each defect was reported. RESULTS: From the 800 articles identified, 17 studies fulfilled inclusion criteria and were included. A total of 983 CCS were examined, with the total number of healthy controls being 1266 children. Haematological malignancy was the most prevalent diagnosis with the age at diagnosis ranging between 0-15 years. Multiple antineoplastic protocols were implemented with the elapsed time being 8 months up to 17 years. One-third of CCS experienced at least one late effect, with corresponding value for the control group being below 25%. Among the defects identified clinically, microdontia, hypodontia and enamel developmental defects were recorded in 1/4 of CCS. Impaired root growth and agenesis were the two defects mostly recorded radiographically. The effect on dental maturity and on salivary glands was unclear. CONCLUSION: CCS are at risk of developing dental late effects because of their disease and its treatment and therefore, routine periodic examinations are essential to record their development and provide comprehensive oral healthcare.

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Periodontal conditions and salivary levels of immunoglobulins sIgA, IgM, and IgG subclass distribution and albumin, quantified by enzyme-linked immunosorbent assay, were determined in 20 patients with Down syndrome and 19 healthy controls. Gingival inflammation was more extensive (P < 0.05) among Down syndrome subjects compared to controls as well as the occurrence of periodontal pockets (> 4 mm) (P < 0.05). The immunoglobulin levels of sIgA, IgM, the sum of IgG subclasses, and the concentration of albumin did not differ significantly between the 2 groups. However, the proportion of IgG1 expressed as percentage of the sum of total IgG was significantly higher (P < 0.01) in the Down syndrome group compared to controls. On the contrary, the proportion of IgG2, IgG3, and IgG4 subclasses in saliva did not differ between the 2 groups. The results indicate an altered distribution of IgG subclasses in saliva, with a higher proportion of IgG1 in Down syndrome individuals compared to controls.

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The levels of prostaglandin E2 (PGE2) and interleukin-1 beta (IL-1 beta) were determined in gingival crevicular fluid (GCF) collected from patients with gingivitis: 15 Down syndrome children and 15 controls. The mean level of PGE2 in GCF was significantly higher (P < 0.05) in the Down syndrome group (10.0 pg/microliters GCF) than in the control group (4.6 pg/microliters GCF). In GCF samples collected from sites characterized as noninflamed, the mean level of PGE2 was significantly higher (P < 0.001) in the Down syndrome group than in the controls. The mean level of PGE2 in samples from inflamed sites, on the other hand, did not differ between the two groups. The mean level of IL-1 beta was not significantly higher in the Down syndrome group than in the controls. This study shows that the level of PGE2 detected in GCF from Down syndrome patients is increased, a fact that may be of importance in the pathogenesis of the periodontal disease frequently seen in these patients.

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Levels of Actinobacillus actinomycetemcomitans, Capnocytophaga and Porphyromonas gingivalis were determined in subgingival plaque samples from 37 adolescents with Down's syndrome and 37 healthy controls matched with respect to age and sex. Gingival inflammation, supra- and subgingival calculus, periodontal pockets ( > 4 mm) and alveolar bone loss were registered. Alveolar bone loss was more frequent in Down's syndrome subjects (32%) than in the controls (3%). A. actinomycetemcomitans was detected in the subgingival plaque in 35% of the Down's syndrome adolescents and in 5% of the controls. On site level, A. actinomycetemcomitans and Capnocytophaga were more frequent in the subgingival plaque samples of Down's syndrome children than in those of controls. Comparing Down's syndrome subjects positive or negative for A. actinomycetemcomitans and Capnocytophaga, no significant differences were found in terms of gingival inflammation, periodontal pockets ( > 4 mm) or number of sites with alveolar bone loss. The results indicate an altered microbial composition of the subgingival plaque of Down's syndrome subjects compared with healthy controls, with higher frequency of A. actinomycetemcomitans.

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The object of this prospective study was to compare the clinical behavior of composite and amalgam restorations with respect to anatomical form, marginal adaptation, caries adjacent to margin, and post-operative sensitivity. We selected children (n = 43) with an average age of 6.4 yr exhibiting proximal caries lesions in primary molars distributed on both left and right sides. In each child, one amalgam and one composite side were randomly chosen, resulting in 64 fillings for composite and 55 for amalgam. After a two-year period, significantly (p less than 0.05) more composite fillings (88%) were clinically classified as satisfactory compared with amalgam fillings (68%). No significant relationship was found between the success rate of proximal fillings and the caries activity of the individuals. The results indicate that composite can be used successfully as a class II filling material in primary molars in children.

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The histological appearance of the gingiva in children with Down's syndrome (DS) was studied with special reference to inflammatory involvement and innervation. A dense infiltration of inflammatory cells was seen in the propria of most of the DS patients, including a few polymorphonuclear leucocytes. A hyperplasia of the epithelium was also found. The innervation of the gingiva was studied using immunohistochemistry. Nerve fibers as well as nerve bundles immunoreactive to neurofilament (NF) were seen in the propria, while occasionally intraepithelial NF fibers were observed. Calcitonin gene-related peptide (CGRP)-immunoreactive fibers and fiber bundles were also visualized, but they were less abundant than NF fibers. The density of NF and CGRP fibers and fiber bundles was estimated by semiquantitative evaluation. A higher density of NF and CGRP immunoreactive structures was observed in the propria of DS patients compared to the control subjects, while no obvious alteration was seen in their distribution in the propria. In addition, sparsely distributed fibers immunoreactive to peptide histidine isoleucine amide (PHI) and vasoactive intestinal polypeptide (VIP) fibers as well as neuropeptide Y (NPY) and tyrosine hydroxylase (TH) were seen, mainly surrounding blood vessels. A few substance P (SP) fibers were also found, mostly close to the epithelium. No obvious differences of these sparsely distributed fibers were seen in the DS patients compared to controls. Thus, a profound inflammatory involvement of the gingiva of DS patients is seen concomitant with a hyperinnervation of the presumed sensory component of the gingival innervation. In contrast, no alterations were seen in the density of neuronal markers related to autonomic nerve fibers. The sensory hyperinnervation observed is probably not specifically related to DS, but may be due to a sprouting of afferent nerves induced by the inflammatory reaction. However, factors released from the sensory afferents could contribute to the gingival inflammation seen in DS.

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