Ej Sgravenmade

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.

A functional and chemical study of radiation effects on rat parotid and submandibular/sublingual glands

The aim of this study was to monitor composition and rate of secretion of rat parotid and submandibular/sublingual saliva following local single doses of X-rays ranging from 5 to 20 Gy. Pilocarpine-stimulated samples of parotid and submandibular/sublingual saliva were simultaneously collected with miniaturized Lashley cups before and 1-30 days after irradiation. The lag phase (period between injection of pilocarpine and start of the secretion) and flow rate were recorded and the concentrations of sodium, potassium, calcium, phosphate, and amylase were measured. With increasing dose and time, the salivary flow rate as well as sodium concentration decreased, while potassium concentrations increased throughout the follow-up period. The lag phase and the concentration of amylase reached their maximum at 3 and 10 days after irradiation, respectively. The changes in lag phase and flow rate were most obvious after doses of 15 or 20 Gy and showed a great similarity for parotid and submandibular/sublingual saliva. No dose-response relationship was observed for the changes in concentrations of calcium and phosphate. It is concluded that for radiation doses of 10 Gy and above, irreversible changes (lag phase, flow rate, potassium, sodium) were observed. A saturation of the irradiation effects (lag phase, flow rate) seems to exist at doses larger than 15 Gy. No significant differences were observed between the radiation-induced functional changes in parotid and submandibular/sublingual salivary gland tissue.

Wetting Properties of Human Saliva and Saliva Substitutes

Contact angle measurements were employed so that we could study the wetting properties of human whole saliva and saliva substitutes containing mucins or carboxymethylcellulose (CMC) on human oral mucosa (in vivo) and on ground and polished human enamel (in vitro). A new approach was introduced for measuring contact angles on human oral mucosa in vivo. It was shown that the wetting properties of CMC- and mucin-containing saliva substitutes on human enamel were significantly better than those of human whole saliva. On human oral mucosa, the wetting properties of CMC-containing saliva substitutes and human whole saliva were comparable, but were surpassed by those of the mucin-containing saliva substitutes. Mucin-containing substitutes thus provide good wetting properties on ground and polished enamel as well as on oral mucosa.

REHARDENING PROPERTIES OF MUCIN-CONTAINING OR CMC-CONTAINING SALIVA SUBSTITUTES ON SOFTENED HUMAN-ENAMEL - EFFECTS OF SORBITOL, XYLITOL AND INCREASING VISCOSITY

The rehardening of artificially softened human enamel by nine different saliva substitutes and four control solutions in vitro has been investigated by microhardness measurements. The saliva substitutes were all based on the same formula, containing mucins or carboxymethylcellulose (CMC) as the main macromolecules, and phosphate, calcium and fluoride as the main electrolytes, and sorbitol or xylitol. All the saliva substitutes had a rehardening potential. The largest reduction of the rehardening potential was observed after addition of high concentrations of CMC or mucins and the addition of sorbitol. The best rehardening properties were observed for low viscous mucin- or CMC-containing saliva substitutes with xylitol.

In vivo Study on the Prevention of Postradiation Caries

Postradiation caries is usually prevented by the application of topical fluorides (F) at high concentrations. The aim of this study was to develop an optimal preventive program for postradiation caries by evaluating the effects of F concentration and application procedures in subjects with radiation-related xerostomia. Six ground enamel slabs were mounted on each side of the lower denture of each of 7 xerostomia patients. Four procedures were used: no F exposure (control), neutral F gel applied every 2nd day or weekly, and a daily rinse with a F mouthwash for a period of 6 weeks. The enamel slabs were analyzed at weekly intervals by scanning optical monitoring, longitudinal microradiography, and scanning electron microscopy. In addition, hardness measurements were performed on the slabs. F analyses of the enamel slabs were done prior to their insertion in the appliances and after 6 weeks of intraoral exposure. In the control experiments severe demineralization of enamel occurred within 6 weeks. Application of F gel or the use of the F mouthrinse resulted in a significant inhibition of the demineralization process. Of the procedures evaluated, F gel applied every 2nd day was the most effective in preventing the onset of postradiation caries.

Radiation-Induced Cell Proliferation in the Parotid and Submandibular Glands of the Rat

Repopulation of tissues with cells at damaged sites is an important feature in the recovery of radiation-induced tissue injury. To obtain insight into the regenerative process in salivary gland tissue, proliferative activity was measured as a function of time in the different epithelial cell compartments of rat parotid and submandibular glands after local X irradiation with a single dose of 15 Gy. Bromodeoxyuridine-labeling indices were determined before and 10 h and 1, 3, 6, 10, 15, 20 and 30 days after irradiation. In both glands, X irradiation caused cell death and cell cycle delay manifested during the first day. Three days after irradiation, cell proliferation started in the intercalated duct. Six days after irradiation, proliferation was also observed in acinar and granular convoluted tubule cells. The striated ducts showed proliferative activity starting at day 6 (parotid) and day 10 (submandibular), respectively. The results of this study suggest that after 15 Gy of X rays repopulation takes place in all cell compartments. From the present study it cannot deduce if these cells are originating solely from progenitor cells residing in the intercalated duct or if cells of the other compartments are also stimulated. Proliferative activity was found to be higher in the intercalated duct compartment of the parotid gland than of the submandibular gland, which may be related to the suggested greater radiosensitivity and thus a greater demand for cell replenishment in the parotid gland.

The Role of Secretory Granules in Radiation-Induced Dysfunction of Rat Salivary Glands

To investigate the possible role of secretory granules in radiation-induced salivary gland dysfunction, rats were pretreated with isoproterenol (5 mg/kg intraperitoneally) to degranulate salivary gland acini. At maximal depletion, salivary glands were locally irradiated with a single dose of 15 Gy of X rays. Parotid and submandibular/sublingual saliva samples were collected before and 1-10 days after irradiation. The lag phase, flow rate, concentrations of potassium and sodium, and amylase secretion were determined. Sham-treated, isoproterenol-treated and irradiated animals provided reference data. In the parotid gland, but not in the submandibular gland, protection against radiation-induced changes in flow rate and composition of saliva occurred after pretreatment with isoproterenol. Combining morphological data from a previous study with data from the current study, it is suggested that improvement of parotid gland function is attributed predominantly to a proliferative stimulus on acinar cells by isoproterenol and not to its degranulation effect. After pretreatment with isoproterenol, an earlier expression of radiation-induced acinar cell damage leading to death was observed, followed by a faster tissue recovery. Thus the proliferative stimulus on acinar cells may accelerate the unmasking of latent lethal damage, resulting in the earlier replacement of dead cells by new, functionally intact cells.

THE EFFECT OF X-RAY-IRRADIATION ON THE DEMINERALIZATION OF BOVINE DENTAL ENAMEL - A CONSTANT COMPOSITION STUDY

In this study the effect of X-ray irradiation on demineralization of bovine dental enamel in vitro was investigated. Enamel specimens were irradiated with 72 Gy and subsequently demineralized (140 h) under reproducible constant composition conditions at pH = 5 in the presence of methylhydroxydiphosphonate (MHDP). Microhardness measurements after demineralization without MHDP showed significant differences (p less than 0.001) between irradiated and nonirradiated enamel specimens; no significant differences were found in the presence of MHDP. Quantitative microradiography showed that both mineral loss and lesion depth were significantly lower (p less than 0.001) for the irradiated enamel specimens compared with the nonirradiated ones. Surface layer formation was observed in irradiated enamel demineralized in a solution without MHDP. It was shown that X-ray irradiation decreased the enamel acid solubility in vitro.

Enamel defects associated with tuberous sclerosis: A clinical and scanning-electron-microscope study

The clinical and scanning-electron-microscope appearances of enamel defects in six patients with tuberous sclerosis are described. The pit-shaped enamel defects seem to be pathognomonic of the disease. The detection may be an important help in the early diagnosis of this complex syndrome.

AN ADAPTATION OF THE LASHLEY CUP FOR USE IN RAT SALIVA COLLECTION

A miniaturized Lashley cup for collecting rat parotid and submandibular/sublingual saliva is described. The small dimensions of the cup enabled its proper positioning on the orifices of both salivary ducts. The method avoids surgical intervention, causes no tissue damage, allows simultaneous collection of both types of saliva and its appropriate for long-term studies of salivary composition and secretion in the rat.