Cervico-facial irradiation and orthodontic treatment.

Cancers during infancy and childhood affect 1 to 3% of children under the age of 15. Among these cancers the most frequent are malignant hemopathies, and in particular, acute lymphoblastic leukemia, which represents 80% of infant leukemias, with a peak of incidence around the age of 3-4. The overall prognosis for infant malignant hemopathies has improved significantly thanks to progress made in chemotherapy and radiotherapy. However, these anti-cancer treatments, particularly radiotherapy, when performed early, generally before 5 years of age, can have harmful effects that interfere with overall growth and particularly cranio-facial growth, and also with the child's oro-dental development. Some effects such as mandibular retrognathia, macrodontia, microdontia, agenesis and delayed eruption could increase the need for orthodontic treatment, while other complications, particularly the reduced height of the alveolar processes, short thin roots and modification of the superficial and profound periodontium, are likely to make such treatment more difficult. The aim of this review of the literature is to identify the essential factors that must be analyzed before orthodontic treatment is proposed for subjects who have undergone radiotherapy at an early age, and the precautions to be taken before and during orthodontic treatment.

Late effects of orbital enucleation and radiation on maxillofacial prosthetic rehabilitation: A clinical report.

The retinoblastoma is one of the most common tumors of the eye diagnosed in childhood. The treatment for patients with retinoblastoma includes surgical removal of the lesion along with adjunctive chemotherapy and radiotherapy. If the tumor is controlled, these treatments can have secondary adverse effects pertaining to the growth and development of orofacial structures in young patients. This clinical report describes the prosthetic rehabilitation of a patient who underwent enucleation followed by radiation therapy and adjunctive chemotherapy to treat the primary diagnosis of retinoblastoma. This therapy resulted in a combination of dental and facial growth and developmental abnormalities.

Disturbances in dental development and craniofacial growth in children treated with hematopoietic stem cell transplantation.

OBJECTIVES: To investigate the correlation between age, degree of disturbances in dental development, and vertical growth of the face in children treated with hematopoietic stem cell transplantation (HSCT). PATIENTS: 39 long-term survivors of HSCT performed in childhood and transplanted before the age of 12, at a mean age of 6.8±3.3 years. METHODS: Panoramic and cephalometric radiographs were taken at a mean age of 16.2 years. For each patient two age- and sex-matched healthy controls were included. The area of three mandibular teeth was measured and a cephalometric analysis was performed. RESULTS: The mean area of the mandibular central incisor, first and second molar was significantly smaller in the HSCT group, and the vertical growth of the face was significantly reduced, especially in the lower third, compared to healthy controls. A statistically significant correlation between age at HSCT, degree of disturbances in dental development, and vertical growth of the face was found. Children subjected to pre-HSCT chemotherapy protocols had significantly more growth reduction in vertical craniofacial variables compared to children without pre-HSCT chemotherapy. Conditioning regimens including busulfan or total body irradiation had similar deleterious effects on tooth area reduction and craniofacial parameters. CONCLUSIONS: The younger the child is at HSCT, the greater the impairment in dental and vertical facial development. This supports the suggestion that the reduction in lower facial height found in SCT children mainly is a result of impaired dental development and that young age is a risk factor for more severe disturbances.

Correlation of Hsp110 expression with caspase-3 and -9 during apoptosis induced by in vivo embryonic exposition to retinoic acid or irradiation in early mouse craniofacial development.

OBJECTIVE: To analyze the expression and role of three proteins (HSP110, caspase-3 and caspase-9) during craniofacial development. DESIGN: Seven pregnant C57Bl/6J mice received, by force-feeding at gestation day 9 (E9), 80 mg/kg of all-trans retinoic acid mixed to sesame oil. Seven pregnant NMRI mice received two grays irradiation at the same gestation day. Control mice of both strains (seven mice for each strain) were not submitted to any treatment. Embryos were obtained at various stages after exposition (3, 6, 12 and 24 h), fixed, dehydrated and embedded. Coronal sections (5 microm) were made. Slide staining occurred alternatively using anti-Hsp110, anti-caspase-3 and anti-caspase-9 immunohistochemistry. RESULTS: Expression of HSP110, caspase-3 and caspase-9 was found in cells of well-known locations of programmed cell death. After retinoic acid exposure, expressions were increased especially in neural crest cells of mandibular and hyoid arches. Quantification of positive cells shows that caspase-9 and Hsp110 were expressed before caspase-3. After irradiation, the expression of the three proteins quickly increased with a maximum 3 h after irradiation. For all three models of apoptosis (physiological, retinoic-induced and irradiation-induced) HSP110 positive cells were more numerous than caspase-3 positive cells. Caspase-3 positive cells were more numerous than caspase-9 positive cells especially in mesectodermal irradiation-induced apoptotic cells. CONCLUSION: The findings show a potential function of HSP110 in apoptosis during embryo development. Caspase-3-expressing cells are more numerous than cells expressing caspase-9, especially irradiation-induced apoptotic neural crest cells. This suggests that other caspases, still to be identified, may activate caspase-3 in this model.

Dental and maxillofacial abnormalities following treatment of malignant tumours in children.

There is a wide range of malignant tumours with an embryonic origin that can affect children in their early childhood including Rhabdomyosarcoma, Osteosarcoma, Chloroma, Retinoblastoma and neuroblastoma. Different protocols have been developed over the past years to treat these tumours and different combinations of radiotherapy, surgery and chemotherapy were used. This improved the survival rate considerably. This treatment has a marked effect on growth of soft and hard tissues in the affected regions of the head and face, leading to facial and dental abnormalities that become evident with growth. The great effect of radiotherapy and chemotherapy on craniofacial skeletal growth should be considered in all cases undergoing treatment for tumours. The resulting dental and maxillofacial abnormalities should be expected in all cases and its management require involvement of different members of the medical team including maxillofacial surgeon, restorative dentist, orthodontist, psychologist, dietician, speech therapist, the patient and the parents in order to achieve maximum results. This paper presents four patients who underwent radiotherapy and chemotherapy for treatment of embryonic tumours and discusses the main side effects of the treatment.

Effects of therapy on dentofacial development in long-term survivors of head and neck rhabdomyosarcoma: the memorial sloan-kettering cancer center experience.

PURPOSE: To describe potential effects of multimodality therapy on dental and facial development in long-term survivors of head and neck rhabdomyosarcoma. PATIENTS AND METHODS: The medical records of all patients aged 20 years or less presenting between 1985 and 1996 with a diagnosis of rhabdomyosarcoma and treated by protocol were reviewed. Head and neck rhabdomyosarcoma patients who were followed in the Dental Service and were alive and free of disease with at least a 5-year follow-up were included in the review. Ten patients satisfied the inclusion criteria and form the basis of this report. The median age at diagnosis of the 10 patients was 4.3 years (range 10 months to 19.5 years). All patients were treated with chemotherapy, two patients underwent surgery, and all but one patient received external beam radiation therapy. RESULTS: Clinical or radiographic dentofacial abnormalities were observed in 8 of the 10 (80%) patients. Abnormalities included enamel defects, bony hypoplasia/facial asymmetry, trismus, velopharyngeal incompetency, tooth/root agenesis, and disturbance in root development. Bony hypoplasia and disturbance in root formation were the most common findings. CONCLUSIONS: Multimodality therapy for head and neck rhabdomyosarcoma can result in dentofacial abnormalities that affect the patient's quality of life. The care of the long-term survivor requires a multidisciplinary approach, including early involvement of the dental team.

Functional rehabilitation using orthognathic surgery, bone transplants and implants after irradiation of malignancy in early childhood.

Functional rehabilitation has been carried out in four young patients by use of orthognathic surgery, bone grafting and implants. All four patients had been successfully treated for malignant tumours in the midface during early childhood by use of full dose irradiation. Retarded growth of the maxilla together with missing root formation of permanent teeth prevented the alveolar process to develop. Bimaxillary osteotomies with inlay bone graft have been made in two cases and maxillary osteotomy le Fort I with interpositional and inlay grafting in two individuals. Implants surgery has been made in a second stage surgery. A total of eighteen implants has been inserted and during five years follow-up two implants have been lost (survival rate 90%). All patients have been successfully rehabilitated with fixed bridge prosthesis.

Effects of cancer therapy on dental and maxillofacial development in children: report of case.

Malignant lymphoma is one of the most common hematological diseases of children. The prognosis is fairly good with multimodal cancer therapy. We reported a boy with Burkitt's lymphoma in the nasal cavity who received chemotherapy and irradiation of the head and neck area at four years of age. During seven years of follow-up, we studied the developmental effects of cancer therapy, including general growth, maxillofacial bones, and dentition. Compared with boys of matching age, the development of his entire body and maxillofacial bones was delayed. In the irradiated areas, the roots of teeth were short or poorly developed and the root apices showed premature closure. After the patient was in remission from the tumor in his early childhood, the long-term effects of cancer therapy on dental and maxillofacial development are worth our further evaluation and follow-up.

[Direct and indirect effects of medication (including chemotherapy) and irradiation on the pulp]. / Influence directe et indirecte de la médication (chimiothérapie y comprise) et de l'irradiation sur la pulpe.

A direct or indirect effect of the intake of medication on the pulp itself has not yet been described in the literature. The effect of local anesthetics on the pulp, on the other hand, has been documented. Although local anaesthesia has been employed in dentistry for many years, most investigations of its action have only considered the effect on the nerves within the pulp using traditional methods. Recently it has become clear that the nerves and blood vessels of the pulp do not act in isolation but are closely related. In this respect it has been shown that there exists a direct relationship between the length of the flow cessation and the concentration of vasoconstrictor used. Therefore care should be taken when using vasoconstrictors especially where pulpal injury is apt to occur when dental procedures such as full crown preparations are performed immediately following a ligamental injection. The anaesthetic efficacy of intraosseous injection is well documented. The effect, however, on the dental pulpal circulation still remains subject of further investigation. Radiotherapy involving the oral cavity and salivary glands and chemotherapy (in a lesser degree) induce alterations in the oral tissues and the salivary gland functions. Some of these side effects are transient. However there are side effects such as the xerostomia which are very drastic for the dentition resulting in radiation caries and dental hypersensitivity. Tooth anomalies in the developing dentition are also described. Due to the rapid progression of the radiation caries a monitoring of the oral cavity with strict application of preventive measurements and systematic follow-up can reduce the incidence of the complications. Unfortunately most of the patients belonging to this group consult with the complications of their radiotherapy and chemotherapy. In this respect endodontic treatment of the severely decayed teeth is an important part of dental treatment. Moreover, extraction is regularly contraindicated as osteoradionecrosis is then one of the major sequels.

Dento-maxillofacial sequelae in a child treated for a rhabdomyosarcoma in the head and neck. A case report.

This case report describes severe dento-maxillofacial defects after chemoradiation therapy in a child aged 9 years 6 months with a parameningeal rhabdomyosarcoma. A clinical and radiologic (apical dental radiographs, orthopantograph, lateral skull roentgenogram) dental follow-up over 4 years showed such dental abnormalities as root blunting, mild to severe root shortening, premature closure of the root apices, and severe radiation caries. Craniofacial morphology evaluated by cephalometric analysis and dental models showed deficiency with mandibular and maxillary hypoplasia.

Craniofacial growth in children treated for malignant diseases.

With the improving cure rate in childhood malignancies, increasing interest has been focused on the long-term survivors of childhood cancer and the quality of their life. The severity of long-term disturbances in dental and craniofacial development is dependent on the age of the child at diagnosis, if chemotherapy is combined with radiation or not. With regard to craniofacial development combination chemotherapy has no effects compared with healthy controls, whereas children treated cranial irradiation before 5 years of age exhibit a reduced growth of the mandible. Conditioning before bone marrow transplantation with total body irradiation results in a significantly reduced growth of the craniofacial skeleton. The mandible was four times more radiosensitive compared with the maxilla. With attention to the dental and craniofacial development, occlusion and craniomandibular function, children in risk groups should be followed, and given prophylactic treatment and intervention at appropriate times to reduce the consequences of the disease itself and the therapy given.

[Skeletal changes induced by radiotherapy. A study of subjects with retinoblastoma. II]. / Alterazioni scheletriche indotte dalla radioterapia. Studio di soggetti affetti da retinoblastoma. Parte II.

The authors examine the dental and skeletal alterations consequent to the use of radiotherapy as the elective method of treating retinoblastoma, an endobulbar neuroectodermal tumour typical of early infancy. The authors revise the basic concepts of radiobiology and the modifications induced by radiation in developing tissues with reference to both alterations at a microscopic (histological) level and those at a macroscopic level, namely of a morphological and structural nature. In the first part of the study the authors examine the damage to dental structures relating to both developing tissues and damage to mature tissue. The second part of the paper analyses radiation damage on cartilage and bone tissues in the process of formation and the authors present their documentation in the form of iconographic and radiographic material together with an esthetic face analysis performed using Rickettz's method in three cases referred to their attention.

Long-term effects of antineoplastic chemotherapy and radiotherapy on dental development.

Advances in treatment protocols over the past 20 years have resulted in much improved survival rates for children with cancer. As more children survive, the emphasis has moved from "saving children at all costs' to saving children "at least cost to the child' and protocols are continually reviewed with this in mind. As more dental practitioners are likely to encounter children who have survived malignant disease, this paper looks at the long-term effects of treatment modalities on the dentoalveolar complex.

[The significance of preventive CNS irradiation during antineoplastic therapy in childhood with regard to late odontogenic and mandibulofacial injuries]. / Die Bedeutung einer präventiven ZNS-Bestrahlung im Rahmen einer antineoplastischen Therapie im Kindesalter hinsichtlich dentogener und mandibulofazialer Spätschäden.

The aim of the present study was to determine the adverse effects of antineoplastic chemotherapy and radiotherapy on tooth development, i.e., on dentition in general and on craniofacial growth. The patients studied consisted of 26 children with solid tumors treated with chemotherapy alone and 34 patients with acute lymphoblastic leukemia (ALL) who were treated with intensive and follow-on radiation therapy (18 and 24 Gy) to the neurocranium as a constituent of central nervous system prophylactics in treatment protocols for ALL. The treatment protocol employed in these children is known as the BFM (Berlin, Frankfurt, Münster) protocol. At the time of diagnosis the children ranged in age from 3 to 52 months. All treated patients had microdontia, enamel dysplasia, thinning and tapering of apical roots portions, and marked shortening of the roots. These defects were more pronounced in children treated for ALL, but it was not possible to establish statistically relevant evidence on the influence of adjuvant radiotherapy in this group. This indicates that there is a catch up in craniofacial growth 9 years after therapy and that the most serious long-term adverse effects are on dentition.

A longitudinal study of the effects of surgery, radiation, growth hormone, and orthodontic therapy on the craniofacial skeleton of a patient evidencing hypopituitarism and a Class II malocclusion: report of a case.

Facial growth is an important factor for the orthodontists in the timing of treatment of the patient with a Class II malocclusion who has a potential for retarded growth. This patient had an isolated idiopathic growth hormone deficiency and hypothyroidism and was treated during a circumpubertal growth spurt in two phases. The first phase involved a functional appliance and the second was accomplished with fixed appliances. The case report affords one of the rare opportunities to document and analyze the multifactorial effects of surgery, radiation, growth and thyroid hormones, and orthodontic treatment on the craniofacial growth of a patient evidencing a Class II, Division 1 malocclusion (retrognathic mandible). Hand-wrist, panoramic, cephalometric radiographs, dental, and skeletal height and weight measurements are employed. Six-year posttreatment dental and craniofacial skeletal changes and management problems are presented as well.

Histologic changes in dental morphology induced by high dose chemotherapy and total body irradiation.

Disturbances in dental development were studied with the use of radiography and histology in a patient with acute lymphoblastic leukemia who was treated with induction chemotherapy at 2.3 years of age and bone marrow transplantation at 4.3 years of age. The follow-up 9.5 years after bone marrow transplantation showed evidence of short tapered roots, enamel hypoplasia, microdontia, and aplasia. A histologic examination of two extracted permanent teeth showed that the crown of the maxillary lateral incisor exhibited numerous incremental lines that corresponded closely to the treatment periods with cytotoxic drugs. The maxillary second premolar exhibited regularly spaced incremental lines in the enamel and dentine. A gross hypoplasia was seen in the cervical part of the crown corresponding to the time of administration of 10 Gy total body irradiation. The results indicate that chemotherapy mainly induces qualitative disturbances in dentine and enamel, whereas total body irradiation induces both qualitative and quantitative changes.

Dental management of the pediatric oncology patient.

Acute oral problems that frequently occur during oncologic therapy include mucositis, infection, and hemorrhage. Certain chemotherapeutic agents consistently produce significant mucositis. Herpes simplex virus infection is a frequent cause of oral ulceration. Gram-negative oral bacilli can cause severe local necrosis of oral tissues and lethal bacteremia and sepsis. Sepsis with oral streptococci is common in the early postengraftment period following bone marrow transplant. A case report describes the successful use of a new hemostatic agent to control hemorrhage in a patient with severe thrombocytopenia in leukemic relapse. Long-term dental complications of oncologic therapy include abnormal dental and craniofacial development. Dental abnormalities in children treated for acute lymphoblastic leukemia are more severe if oncologic therapy begins before 5 years of age and if cranial irradiation is used. The combination of high-dose cranial irradiation (2400 cGy) and chemotherapy before 5 years of age results in deficient mandibular growth. In children with reduced growth hormone production and deficient mandibular growth due to treatment with bone marrow transplantation, stimulation of mandibular condylar growth is reported following the use of growth hormone.

[Esthetic and functional rehabilitation in a young irradiated patient]. / Réhabilitation esthétique et fonctionnelle chez un jeune patient irradié.

The authors present the prosthetic rehabilitation of a young patient nineteen years old, radiated at four years old, during the treatment of right nasal fossa malignant tumour. Only metallic mandibular and maxillary dentals coverage can be considered after the realization of temporary supra-dental resin removable dentures, testing the possibilities of treatment, on esthetic and functional points of view.

Craniofacial growth in bone marrow transplant recipients treated with growth hormone after total body irradiation.

The effect of growth hormone (GH) treatment on craniofacial development was studied in five children exhibiting growth retardation following bone marrow transplantation. Linear and angular measurements were made on lateral radiographic cephalograms taken prior to the start of GH treatment and after an average treatment time of 1.2 yr. The results showed that the mean growth increments of mandibular length in the GH treated children, exceeded the corresponding values of the control group by 150% during the period of investigation. It is suggested that this dimensional increase in the patients was due to GH stimulation on the chondral growth process in the mandibular condyles.