Surgical management of thyroid cancer.

Thyroid cancer is the most common endocrine neoplasm; however, it only accounts for less than 1% of all human malignances. Thyroid cancers are divided into well differentiated and non-well differentiated cancers, according to their histology and behavior. The surgical management options of well-differentiated thyroid cancer include total or near-total thyroidectomy, subtotal thyroidectomy and lobectomy plus isthmusectomy. The extent of surgery for thyroid cancer continues to be an area of controversy. Complications associated with thyroid surgery are directly proportional to the extent of thyroidectomy and inversely proportional to the experience of the operating surgeon. They occur less frequently with good surgical technique and better understanding of surgical anatomy, and include wound healing and infections (seroma, hematoma and wound infection), nerve injury, hypoparathyroidism, hypothyroidism, postoperative hemorrhage and respiratory obstruction.

Thyroid disorders in patients treated with radiotherapy for head-and-neck cancer: a retrospective analysis of seventy-three patients.

PURPOSE: To evaluate the incidence of thyroid disorders and dose distribution to the thyroid in patients treated with radiotherapy for head-and-neck carcinomas. METHODS AND MATERIALS: A retrospective evaluation of data from 73 patients treated for head-and-neck cancers in our department was performed. Thyroid function was evaluated mainly by the measurement of thyrotropin (thyroid stimulating hormone [TSH]). A retrospective analysis of treatment plans was performed for 57 patients. Percentages of thyroid glandular volume absorbing 10, 30, and 50 Gy (V10, V30, and V50 respectively) were considered for statistical analysis. RESULTS: A majority of patients (61%) had a normal thyroid function whereas 19 patients (26%) had hypothyroidism. Mean thyroid volume was 30.39 cc. Point 3 (located at isthmus) absorbed lower doses compared with other points (p < 0.0001). Median values of V10, V30, and V50 were 92% (range, 57-100%), 75% (range, 28.5-100%), and 35% (range, 3-83%) respectively. Gender was associated with toxicity (presence of any kind of thyroid disorders) (p < 0.05), with females displaying higher levels of TSHr (relative TSH = patient's value/maximum value of the laboratory range) (p = 0.0005) and smaller thyroid volume (p = 0.0012) compared with male population. TSHr values were associated with thyroid volume, and the presence of midline shielding block in the anterior field was associated with relative free thyroxine (FT4r = patient's value/maximum value of the laboratory range) values. CONCLUSIONS: Gender and thyroid volume seem to play an important role in the occurrence of thyroid toxicity, but further studies on dose-effect relationship for radiotherapy-induced thyroid toxicity are needed.

Randomized trial of fenretinide (4-HPR) to prevent recurrences, new localizations and carcinomas in patients operated on for oral leukoplakia: long-term results.

We assessed the efficacy of fenretinide at preventing relapses, new lesions and carcinomas after surgical excision of oral leukoplakia. In a controlled multicenter study, 170 patients operated on for oral leukoplakias with benign postoperative histology were randomized to 200 mg fenretinide daily for 1 year vs. no intervention. Preliminary analysis indicated that fenretinide had good tolerability and was effective at preventing relapses and new lesions during treatment. Analysis after 5-year follow-up suggested that fenretinide protected against relapses and new lesions up to 19 months after randomization, with both limits of the 95% hazard ratio CI for fenretinide vs. control below 1 for 7 months after randomization. There was also a protective effect against all first events, including cancer, for 25 months, with both limits of the 95% CI below 1 up to 11 months after randomization. Subsequently, risk ratio estimates were unstable. Fenretinide was well tolerated and effective at preventing relapses and new leukoplakias during treatment and after. The trial had to be stopped prematurely for very low recruitment and had insufficient power to reveal any protective effect against oral carcinoma; nevertheless, continuing studies on this promising chemopreventive are justified.

Major surgery in elderly head and neck cancer patients: immediate and long-term surgical results and complication rates.

BACKGROUND: Evaluation of immediate and long-term surgical results in major surgery for the head and neck tumours in elderly patients and identification of tumour and patient related factors that affect the incidence and severity of surgical and medical complications. METHODS: Retrospective analysis of a series of 24 consecutive patients aged 70 and over with head and neck tumours undergoing extensive surgical resections with reconstruction with/without osseous and/or soft tissue transfer. Patients' demographics and surgery and tumour related data were extracted from appropriate charts and recorded. Pre-existent comorbid conditions, immediate and long-term surgical and medical complications were analysed. Pre-existing comorbidities were graded and staged using the Comorbidity Data Collection Form. Postoperative surgical and medical complications were scored according to their severity. RESULTS: Overall complication rate in present study was 63% and 54% of patients experienced clinically important surgical and/or medical complications. However, medium admission time remained at 16 days. Presence of advanced comorbidity, longer operative times and advanced stage of disease seemed to influence the development of surgical or medical complications. CONCLUSIONS: Major surgery for head and neck tumours is of great value even in elderly patients providing very good surgical results with acceptable complication rates. The choice of treatment modality should be based on all factors affecting the treatment outcomes. In particular, the presence of the co-existent underlying diseases should be assessed meticulously and in cases with clinically important comorbidities the surgical treatment stress should be reduced to minimum.

Radiotherapy-induced thyroid disorders.

Despite their specific functional consequences, radiotherapy-induced thyroid abnormalities remain under-estimated and underreported. These sequelae may include primary or central hypothyroidism, thyroiditis, Graves' disease, euthyroid Graves' ophthalmopathy, benign adenomas, multinodular goitre and radiation-induced thyroid carcinoma. Primary hypothyroidism, the most common radiation-induced thyroid dysfunction, affects 20-30% of patients administered following curative radiotherapy to the neck region, with approximately half of the events occurring within the first 5 years after therapy. The relative risk of radiation-induced cancer (mainly well-differentiated tumours) is 15-53-fold higher than in non-irradiated population. The aetiology of radiation-induced thyroid injury includes vascular damage, parenchymal cell damage and auto-immune reactions. Total radiotherapy dose, irradiated volume of the thyroid gland, and the extent of prior thyroid resection are among the most important factors associated with the risk of hypothyroidism. The contribution of other treatment modalities (chemotherapy, endocrine therapy) as well as patient- and tumour-related factors is less clear. Reduction in radiation dose to the thyroid gland and hypothalamic/pituitary complex should be attempted whenever possible. New radiotherapy techniques, such as stereotactic radiosurgery, three-dimensional conformal irradiation, intensity modulated radiotherapy and proton therapy allow generally better dose distribution with lower dose to the non-target organs. The diagnostic approach to thyroid radiation injury includes baseline thyroid function assays in all patients undergoing thyroid or parasellar irradiation. Recommended follow-up procedures include at least annual evaluation with a history for symptoms of thyroid dysfunction, clinical examination, and measurement of thyroid hormones and thyrotropin. Management of overt hypothyroidism is based on hormone replacement therapy. Thyroid hormone therapy is also recommended in cases of subclinical hypothyroidism. Treatment of other radiation-induced thyroid disorders (thyroiditis, Graves' disease, thyroid cancer) is similar to that employed in spontaneously occurring conditions. Further improvements in radiotherapy techniques and progress in endocrine diagnostics and therapy may allow better prevention and management of radiation-related thyroid injury.

Cytogical features of calcifying epithelial odontogenic tumor (Pindborg tumor) with abundant cementum-like material.

Calcifying epithelial odontogenic tumor (CEOT) is a rare tumor, most frequently occurring in the mandible and composed of large sheets of epithelial cells, sometimes showing nuclear pleomorphism. This paper was aimed at reporting of the cytological features of an unusual case of CEOT, affecting a 14-year-old female, with abundant deposition of intercellular calcified material. The cytological preparations were characterized by large clusters of scarcely cohesive, large polyhedral cells and abundant calcified material. The latter consisted of intensely basophilic substance either in large clusters or discrete concretions and, at high-power view, occasional tumor cells also contained calcified material. Histologically, the uncalcified stroma displayed focal Congo Red positivity with the typical birefringence under polarized light. The neoplastic cells were consistently immunoreactive for epithelial membrane antigen, vimentin and, to a lesser extent, for wide spectrum cytokeratins (AE1 AE3) and cytokeratins 8-18 and 19. The cytological features of CEOT are rather characteristic, and the detection of intra- and extracellular calcifications may help to differentiate this neoplasm from others that most commonly arise in this area.

In vitro and in vivo hematopoietic potential of human stem cells residing in muscle tissue.

OBJECTIVE: We studied the in vitro and in vivo hematopoietic potential of human stem cells residing in muscle tissue collected from adults with head and neck cancer. MATERIALS AND METHODS: Adherent muscle cells were cultured in F12 medium with 10% fetal bovine serum and transplanted into immunodeficient mice. RESULTS: On day 12 we obtained a median of 500,000 adherent cells per gram muscle sample. Thy-1, endoglin, HER2/neu, and P1H12 were expressed in the majority of cells. CD34, VEGFR2, c-kit, VCAM-1, and CXCR4 were expressed in 0.5-1.5%, 1-5%, 1-15%, 9-15%, and 30% of cells, respectively. Immunodeficient mice transplanted with fresh muscle cells or less than 500,000 cultured cells showed little or no human engraftment. In mice transplanted with more than 500,000 cultured cells, up to 14% human CD45(+) hematopoietic cells (including myeloid and lymphoid subsets) were detected by flow cytometry. Engraftment was confirmed by polymerase chain reaction, Southern blotting, and DNA sequencing. Liver, muscle, and spleen evaluated for human DNA were positive in the majority of mice showing hematopoietic engraftment in the bone marrow. In vivo hematopoietic engraftment potential was maintained in cultured CD45(-) muscle cells transduced with the green fluorescence protein gene. CONCLUSIONS: Human stem cells residing in muscle tissue can generate multilineage hematopoiesis in immunodeficient mice. Surprisingly, this hematopoietic potential increased in cultured versus fresh cells from muscle tissue.