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Introduction: The aim of this study was to correlate structural, histomorphological damage of the salivary gland with scintigraphic findings during fractioned radiotherapy., Methods: The head and neck area of 27 WAG/RijH rats was irradiated with (60)Co-gamma-rays (60 Gy/30f/6 weeks). A port-system was implanted and (99m)Tc-pertechnetat applied at different stages of irradiation (0, 16, 30, 46, 60 Gy and 6 months post irradiation)., Results: After the application of 16 Gy an intra- and extra-cellular oedema developed in the salivary glands. The progressive vacuolisation (30 Gy) passed over into lipomatosis (46 Gy) and necrosis (60 Gy) in the parotid and mandibular glands. Six months after irradiation treatment, the chronic histomorphological damage corresponded to stage II according to Seifert. The corresponding loss in gland function was 13% (16 Gy); 26% (30 Gy); 57% (46 Gy); 75% (60 Gy) and 66.5% (6 months post irradiation)., Conclusion: This animal model demonstrates the correlation between histomorphological and scintigraphic findings.

Clinical studies show that amifostine can reduce xerostomia and mucositis during radiotherapy of head and neck cancers. The aim of this study was to evaluate the radioprotective potency of amifostine with respect to late toxicity of salivary glands of rats. The head-neck-area of 8 male WAG/RijH rats (295 +/- 7 g) were irradiated with 60Co-gamma-rays (60 Gy/30 f/6 weeks). Amifostine (250 mg/m2 body surface) was applied via a venous port 15 min before each irradiation. Rats of a control group were irradiated with the same schedule with equal volumes of physiological saline. The morphological and sialoscintigraphical findings clearly demonstrate that amifostine has a remarkable cytoprotective effect on the late toxicity of irradiated salivary glands.

Background: High-dose radioiodine therapy following total thyroidectomy is standard for patients suffering from differentiated thyroid carcinoma and contributes significantly to their favourable prognosis. Due to active iodine accumulation, high focal radiation doses are received by the salivary glands., Patients/result: Report on two patients, who received multiple high-dose radioiodine treatments because of a differentiated metastatic thyroid carcinoma. A few years later, they developed a mucoepidermoid carcinoma of the salivary glands. Due to the high cumulative radiation dose, radiation-induced secondary malignancies following radiation-induced sialadenitis appears likely, although no causal connection could be proven., Conclusion: Consistent protection of the salivary glands during radioiodine therapy as well as the follow-up of the many long-term survivors of differentiated thyroid carcinomas is desirable to further lower the salivary gland-related side effects and to detect secondary malignancies as early as possible.

The extent of radiogenic salivary gland damage depends on the radiation dose, the fractionation, and the localization of the gland in the radiation field. Because extracellular matrix proteins, for example collagen IV, belong to the main components of basement membranes (BM), which are considered to posses cell- and structure-regulating functions, this study set out to describe radiogenic BM changes. The staining profile of collagen IV was studied in 110 female rat mandibular glands depending on age (1 year vs. 1 1/2 years), dosage (2 Gy/d; total dosages 20, 40, or 60 Gy), the radiation field (inside vs. outside), and on the latency period (1/2 year vs. 1 year), using immunohistochemical methods. The stainings were assessed semiquantitatively and differences were evaluated using multivariate analysis. The staining pattern of the polyclonal antibody in rat tissues did not differ from the pattern found in human salivary glands. Collagen IV was detected at variable levels in the glandular and nerve tissue and in vascular walls (negative: adventitia). Irradiated tissues were stained more strongly than non-irradiated, and differences were significant in salivary glands exposed to more than 20 Gy. Age and the latency period had no significant effect on staining. The BM constituent collagen IV showed dose-dependent increasing expression analogous to the salivary gland damage, which could contribute to disturbed cell-matrix interactions following salivary gland radiation exposure. Several tissue structures may be more sensitive to possible scattered radiation. Information on the pretreatment status is mandatory in histopathological studies on the BM of salivary glands.

Background: Extracellular matrix proteins (EMP) form the main components of basement membranes (BM) and associated structures. Basement membranes influence tissue structure, exchange of substances, and cell growth and differentiation. While BM changes have been reported in malignant tumors and in inflammatory diseases, systematic studies of BM changes following irradiation are rare. Because functional and histomorphological damage to the salivary glands is a well known sequela of radiotherapy in humans, our goal was to describe possible BM changes using an experimental model and immunohistochemistry (IH)., Methods: In 59 rat mandibular glands we investigated the distribution of EMP by IH. The animals differed in age from 3 months to 2 years and pre-treatment status (irradiation vs no irradiation). The analyses were performed at selected time points after completion of external irradiation (< 4 months [M]/> or = 4-6 M/> 6 M)., Results: The polyclonal antibodies (anti-laminin [AL], anti-fibronectin [AF], anti-collagen III [AC-III], anti-collagen IV [AC-IV]) identified components of BM (laminin, collagen IV) and BM-associated structures (fibronectin, collagen III) in glandular tissue, in vascular walls, in nerve tissue, and the interstitial connective tissue. Various EMP were detected in different patterns. AL stained nerve tissue moderately and both different gland tissue structures and vascular walls (without adventitia) slightly, while excretory ducts and blood vessel adventitia were distinctly positive for AF. Fibronectin was also present in the connective tissue stroma. Significant differences were seen between irradiated and nonirradiated glands, often with generally stronger and more extensive staining in the irradiated group. For example most tissue structures showed distinctly increasing immunostaining for AL in positive correlation with increasing latency of irradiation up to 6 months. The age was of minor importance., Conclusions: Previous irradiation has to be considered when interpreting the EMP profile of salivary gland tissue, especially in studies both on chronic degenerative diseases and tumor differentiation developing in an area that has undergone radiation therapy.

Background: Damage to the salivary gland (SG) is a well-known sequela of radiotherapy in humans. In many cases irradiation damage causes xerostomia and problems of speech and swallowing. While the functional restriction and the radiogenic SG tissue damage is well documented using histomorphological, electron microscopic and enzyme histochemical methods, immunohistochemical analyses (IH) of the profile of cytokeratins (CK), epithelial differentiation markers, and their alterations in irradiated glands are rare., Methods: In 59 mandibular glands of rats, we investigated the distribution of CK by IH. The animals differed in age from 3 months to 2 years and pretreatment status (irradiation versus no irradiation). The IH were performed at selected time points (< 4 months/> or = 4-6 months/> 6 months)., Results: The monoclonal antibodies (E3, Ks13.1, NCL5D3, K8.12; against CK 17, CK 13, CK 8 and CK 13/15/16, respectively) identified different epithelial structures in rat SG tissue, including excretory duct cells (ECD), striated duct cells (SD), granular convoluted tubules (GTC), intercalated duct cells (ICD), and myoepithelial cells (MC). As typical results, E3 usually stained the ICD, SD, and ECD moderately to strongly and stained the GTC in trace amounts or slightly. K8.12 staining was restricted to ECD and MC. Differences in immunoreactivity were seen between irradiated and non-irradiated glands, predominantly with stronger staining in the irradiated group. A conspicuous finding was the stronger expression of CK 13 in irradiated ECD, ICD, and SD within a latency period of 4-6 months. A similar finding was demonstrated in ICD, ECD, and SD cells after incubation with CK 17 antibodies. In both instances, the staining profile of irradiated glands did not return to nontreatment levels in the long term after exposure., Conclusions: Previous irradiation has to be considered when interpreting IH of salivary gland tissue, especially in studies on chronic degenerative diseases of the salivary glands.

Following high dose radio-iodine therapy, some radiation damage to the salivary glands is to be expected since iodine is taken up by these glands. The great individual variation in the uptake makes it impossible to predict the severity of the damage. T max and maximal excretion capacity after stimulation were therefore estimated by a camera functional scintigram with digital read out in patients following radioiodine therapy (0.1-3.2 Ci); the excretion index was used as an indirect measure of salivary flow. After a dose up to 0.3 Ci there is a change of T max and maximal excretion capacity in 30% of patients; after a dose of 0.5 to 1 Ci it is found in 60 and 80% and after very high doses of 1.1 to 3.2 Ci an abnormal Tmax was found in two-thirds of all patients and reduced or absent excretion capacity in all nine patients in this group. The excretion index also depended significantly on the cumulative dose. All patients who had received very high doses showed marked hyposialia or asialia. The early results of interim examinations suggest, similar to radio-iodine induced hypothyroidism, a cumulative risk of reduced function. In view of the long survival period of patients with differentiated thyroid carcinomas attention should be drawn to this side effect.

We investigated the function of the parotid and submandibular glands in normals and in patients with radiotherapy in the head neck region by scintigraphic methods. The above given doses relate to an application scheme with 200 rd 5 times per week. There is a relatively severe loss of function with small doses from 1000 to 2000 rd. After doses till 3000 rd, there is complete recovery of the gland function in about three months. After 4500 rd, there is in about 80% of the patients a complete recovery after about one year. After irradiation with 5000 or more rd, there is nearly in no person a recovery of the gland function. We did not find a compensatory increase in the function of a spared gland with compensation of irreversibly atrophic glands.