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Biomedical subjects

K Kuzdak

Publications and source records attributed to K Kuzdak.

At least 19 recordsLinked to original sources

Detection of lymph node metastases of papillary thyroid cancer-comparison of the results of histopathology, immunohistochemistry and reverse transcription-polymerase chain reaction-a preliminary report.

BACKGROUND: The range of lymphadenectomy in differentiated thyroid cancer remains still a matter of controversy because of the lack of reliable diagnostic methods for nodal metastases, other than histopathology. AIM: To compare the results of detection of lymph node metastases of papillary thyroid cancer by conventional histopathology and immunohistochemistry with the results of reverse transcription-polymerase chain reaction for thyroglobulin mRNA. PATIENTS AND METHODS: Each of 166 cervical lymph nodes obtained from 21 patients was divided into two halves: one was used for conventional histopathology and immunohistochemistry, the other part was investigated by molecular examination. RESULTS: We obtained different results from examination of the lymph nodes in six (28.6%) patients. In four patients (19.1%) reverse transcription-polymerase chain reaction (RT-PCR) was more sensitive in detection of positive lymph nodes; in two patients (9.5%) it revealed fewer metastasised lymph nodes than did histopathology. The rest of the patients did not have any differences: 12 (57.1%) of them had negative lymph nodes and three (14.3%) had positive lymph nodes in all examinations. CONCLUSIONS: (1) Thyroglobulin (Tg) RT-PCR is an appropriate method of detection for thyroid cancer cells. (2) In combination with histopathology, it might help to qualify patients' nodal status better.

Adenocarcinoma, Papillary↗

P53 concentration and soluble FasL (sFasL) serum level as indicators of apoptosis in patients with benign and malignant thyroid tumors.

During embryonal development and morphogenesis, apoptosis may be induced by two pathways. The first is an external protein signal originating from other cell--also named as "death signal". The another one is a specific cell reaction to external stress factors. Plasma concentration of proteins regulating both apoptosis pathways may be useful in early diagnosis and staging of thyroid tumors. The aim of the study was to evaluate p53 and sFasL plasma concentration in patients with benign and malignant thyroid tumors. The study population was composed of 33 patients with thyroid carcinoma and 10 patients with follicular carcinoma (tumor types were verified by fine-needle biopsy). All patients underwent surgical procedures. p53 and sFasL levels were evaluated before surgery. Control group consists of 10 adult healthy volunteers. The results revealed high p53 and sFasL plasma concentration in patients with benign and malignant thyroid tumors. Such results confirm a significant role of p53 and sFasL in apoptosis in thyroid tumors. Expression of both proteins may be an indicator of an increased apoptosis and useful in preoperative diagnosis in thyroid tumors (Tab. 1, Ref. 31).

Adolescent↗

HMGI(Y) gene expression as a potential marker of thyroid follicular carcinoma.

BACKGROUND: We assessed HMGI(Y) gene expression in thyroid tumors, control thyroid tissue and in the blood of patients diagnosed with papillary and follicular thyroid cancers to try to differentiate between malignant and benign disease. METHODS: HMGI(Y) gene expression was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) in 60 cases of thyroid tumors. Among this number 11 were diagnosed as papillary carcinoma, 37 as follicular carcinoma, and 12 as follicular adenoma. All carcinoma cases selected for this study were classified according to the tumor, lymph node metastases, distant metastases (TNM) classification. RESULTS: HMGI(Y) gene expression was detected only in follicular carcinomas, whereas in papillary carcinomas, follicular adenomas and control tissues there was no positive reaction. In follicular carcinomas the percentage of positive cases (number of samples with presence of HMGI(Y) gene transcript) was the highest and reached approximately 84. There was no statistical dependence between the presence of HMGI(Y) gene expression and tumor size or the presence of lymph node and distant metastases. HMGI(Y) gene expression was also analyzed in whole blood taken from a selected group of patients diagnosed with papillary or follicular carcinomas. Among follicular carcinomas there were 83% of positive cases, whereas among papillary carcinomas there were only 6%. CONCLUSIONS: On the basis of our study, we conclude that HMGI(Y) gene expression analysis could be helpful in differentiation between follicular carcinoma and adenoma.

Adenocarcinoma, Follicular↗

Soluble intracellular adhesion molecules (sICAM-1, sVCAM-1) in peripheral blood of patients with thyroid cancer.

The growth of a neoplasm and its ability to form metastases is a multistep process dependent on angiogenesis and immunological reactions of the organism. In this process adhesive factors are also involved. The aim of this work was estimation of the concentration of soluble intercellular adhesion molecules (sICAM-1) and vascular cellular adhesion molecules (sVCAM-1) in the serum of peripheral blood of patients with thyroid cancer before operation. The study comprised 48 patients ( 38 women and 10 men) aged from 18 to 87 years, in whom thin needle aspiration biopsy revealed cancer of the thyroid. Postoperative histopathological examination showed papillary cancer in 35 patients, oxyphilic cancer in 5 patients, anaplastic cancer in 4 and medullary cancer in 4 patients. In those patients, using the immunoenzymatic method ELISA, the concentration of sICAM-1 and sVCAM-1 in the serum of peripheral blood was determined. The control group comprised 26 healthy persons. We found statistically significant increase of sICAM-1 concentration in serum in all forms of cancer, in comparison with the control group. Mean concentrations of sICAM-1 were as follows: in papillary cancer patients 455.23+/-28.66 vs. 299.62+/-11.54 ng/ml, p<0.05; in oxyphilic cancer 455.60+/-95.21 vs. 299.62+/-11.54 ng/ml, p<0.05; in anaplastic cancer 570.00+/-170.89 vs. 299.62+/-11.54 ng/ml, p<0.05; and in medullary cancer 512.00+/-11.46 vs. 299.62+/-11.54 ng/ml, p<0.05. The mean concentration of sVCAM-1 in serum was statistically significantly higher than in the control group only in case of anaplastic cancer (1033.75+/-86.30 vs. 644.58+/-27.30 ng/ml; p<0.05). We evaluated the correlation coefficient between the concentration of sICAM-1 and sVCAM-1 in the serum of patients with thyroid cancer. Positive correlation was observed between the concentration of sICAM-1 and sVCAM-1. The obtained results confirm essential role of the investigated adhesive factors in the process of thyroid cancer growth.

Adolescent↗

Expression of C-ERBB2 and P65 genes and their protein products in follicular neoplasms of thyroid gland.

C-ERBB2 and P65 gene expression was investigated by reverse transcriptase polymerase chain reaction method (RT-PCR) in thirty follicular thyroid cancers and twenty follicular adenomas. Additionally, the cancers and adenomas were stained by immunohistochemistry for the expression of their protein products. We did not observe P65 gene expression in any of the analyzed follicular cancers (n=30) but it was observed in 13 out of 20 (65%) follicular adenomas. The presence of C-ERBB2 gene expression was found in 18 (90%) follicular adenomas but not in cancers. There were 10 (50%) adenomas and 11 (36.7%) cancers with positive staining for C-ERBB2 protein and 15 (75%) adenomas and 2 (6.7%) cancers with positive staining for P65 protein. We conclude that expression of C-ERBB2 and P65 genes is associated with follicular adenoma but not with cancer of thyroid gland.

Adenocarcinoma, Follicular↗

Angiogenesis of endocrine gland tumours--new molecular targets in diagnostics and therapy.

Angiogenesis is one of the key stages in the development of neoplastic tumours, in which a small group of mutated cells transforms into a large malignant tumour metastasising to the neighbouring tissues and organs. The studies on the significance of neoangiogenesis in the progression of endocrine gland neoplasms have recently become one of the most rapidly evolving branches of molecular endocrinology. The induction of angiogenesis has been demonstrated to result from the imbalance between positive and negative factors which control this process. Our paper presents the results of current studies on the role of factors such as molecular markers of angiogenesis (e.g. vascular endothelial growth factor and basic fibroblast growth factor), metalloproteinases (which regulate the decomposition of the extracellular matrix) and their inhibitors, and adhesive molecules (e.g. soluble vascular cellular adhesion molecule-1 and soluble intracellular adhesion molecule-1) in the pathogenesis and diagnostics of endocrine gland tumours in humans. Also, we discuss new therapeutic strategies for inhibiting the growth of neoplasms by blocking the formation of blood vessels using angiogenesis antagonists, which inhibit various stages of angiogenesis. More and more data are being accumulated suggesting that these preparations could, in the near future, be used in the pharmacotherapy of some endocrine gland neoplasms.

Clinical Trials as Topic↗

The influence of a single acetic acid and lactic acid injection on rat normal thyroid tissue.

Until now, the use of acetic and lactic acid for the treatment of thyroid nodular lesions, as well as histopathologic changes in the thyroid tissue after their intrathyroidal injections has not been described. The aim of this study is to evaluate macro- and microscopic changes in rat normal thyroid tissue induced by single intrathyroidal injection of acetic acid (AA) and lactic acid (LA) in different concentrations, as well as the influence of intrathyroidal acid injection on function of the recurrent laryngeal nerves. Male Wistar rats were divided into two groups of 50 (Group A and B). Rats of each group were divided into the subgroups of five. In each subgroup of Group A and B, AA and LA water solutions of different concentrations (0%, 2.5%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 80%), respectively, were injected into the right thyroid lobe. From Group A and B, 7 and 8 rats died, respectively (after injections of 50-80% AA and LA solutions). After 4 weeks post AA or LA injection the thyroid along with the surrounding tissues was excised and assessed macro- and microscopically in all rats that survived. Before the injection and just before the second operation, the vocal cord function was evaluated. Our results show that both, acetic and lactic acid of different concentrations damage rat normal thyroid tissue after a single intrathyroidal injection. The minimal concentrations of acetic and lactic acid that cause lethal changes in rat normal thyroid tissue are 20% and 10%, respectively. Acetic and lactic acid in the concentrations of 40% and 50%, respectively, and higher can cause injury of the tissues adjacent to the thyroid.

Acetic Acid↗

Carcinogenic effect of combined administration of 2,4-diaminoanisole sulfate, 4,4'-thiodianiline and N,N'-diethylthiourea in male Wistar rats.

Male Wistar rats were divided into two groups. Rats of group 1 were fed basal powdered diet containing 610 ppm 2,4- diaminoanisole sulfate (DAAS), 46 ppm 4,4'-thiodianiline (TDA) and 200 ppm N,N'-diethylthiourea (DETU) for 52 weeks (DTD treatment). Rats of group 2 were maintained on basal diet throughout the experiment as controls. At 52 weeks all surviving rats were sacrificed and subjected to an autopsy. Thyroid, lungs, stomach, liver, spleen, kidneys, testes and all gross lesions suspected of being a tumor were removed. After DTD treatment, the incidence of thyroid hyperplasia and papillary thyroid carcinoma was 59% (10/17) and 65% (11/17), respectively. Hepatocellular adenoma was induced in 2 of 17 rats (12%). Papillary thyroid carcinoma metastasis was found in the lung of 1 rat. No neoplastic tumors were found in kidney, spleen, stomach and testis tissue.

Adenoma, Liver Cell↗

Usefulness of VEGF, MMP-2, MMP-3 and TIMP-2 serum level evaluation in patients with adrenal tumours.

OBJECTIVE: To estimate serum levels of vascular endothelial growth factor (VEGF), metalloproteases MMP-2 (gelatinase A), MMP-3 (stromyelisine 1) and metalloprotease tissue inhibitors (TIMP-2) in patients with various benign and malignant adrenal tumours before and after surgery, as well as to evaluate if there is a correlation between serum levels of these agents and tumour types. METHODS: Serum levels of VEGF, MMP-2, -3 and TIMP-2 were estimated in 43 patients with adrenal tumour at the admission and, in case of surgery, again one month after surgery. The patients were divided into 6 groups according to the type of the tumour (I - patients with adrenal cortex carcinoma, II - with benign hormonally active adrenocortical adenomas, III - with benign, hormonally inactive adenocortical adenomas (incidentaloma), IV - with benign, hormonally active phaeochromocytomas, V - with hormonally quiescent phaeochromocytomas, VI - hormonally inactive adrenal tumours of extraglandular origin. The control group consisted of 10 healthy individuals. RESULTS: There was no correlation between MMP-2 serum levels and tumour types and no significant difference between MMP-2 level before and after surgery. There were no significant differences between TIMP-2 serum levels in patients with adrenal tumours and the control values. Significant increase of serum MMP-3 level was found in patients with cortex cancer and hormonally active benign adrenocortical tumours. The MMP-3 mean serum level was also significantly higher in patients with malignant incidentalomas than in those with benign ones. In all groups of patients with adrenal tumours the means serum VEGF level was significantly higher than in control patients, and it was also significantly higher in patients with malignant incidantalomas than in those with benign ones. After surgery the VEGF level decreased significantly in patients with extraglandular tumours and cortex cancers who had no recurrence. CONCLUSIONS: Since MMP-3 and VEGF serum levels were found significantly higher in patients with malignant adrenal incidentalomas than in those with benign ones, they might be applied as markers of malignancy of incidentalomas. VEGF and MMP-3 levels decreased after tumour resection in all patients with malignant tumors and increased significantly in patients with recurrence. Therefore, they are supposed to be of prognostic value in these patients.

Adenoma↗

[The influence of thyroidectomy of serum VEGF levels in patients with Graves disease].

Angiogenic cytokines, including vascular endothelial growth factor (VEGF), play an important role in patients after surgery because they facilitate proper wound healing. The aim of the paper was the comparison of serum VEGF levels in patients before and after thyroidectomy due to Graves disease (Gd). A serum VEGF level was determined by means of ELISA method before the operation as well as 3 and 7 days after it in 24 patients. The mean serum VEGF level was 61.2 pg/ml (range, 33.7-105.0 pg/ml) before the operation and increased after the operation to 115.6 pg/ml (range, 36.3-214.2 pg/ml). After thyroidectomy, the mean level of serum VEGF level in all patients rose by for 79.5% (range, 7.7-115.4%). These results suggest that serum VEGF level increases in patients with Gd after subtotal thyroidectomy, although disorder in secreting cytokines is observed in Gd patients and they were administered thyrostatics up to the operation, which have an immunosuppressive activity.

Adult↗

p53, MDM2, bcl-2 staining in follicular neoplasms of the thyroid gland.

Sixty-two follicular adenomas of the thyroid were investigated by immunohistochemistry for the expression of p53, MDM2 and bcl-2 proteins. The wild type of 393 aminoacid nuclear p53 phosphoprotein is the product of a gene located on the short arm of chromosome 17. The p53 protein controls the growth of transformed cells in a culture and thus termed a suppressor gene product. Mouse double minute 2 (MDM2) gene product has been described to occur in malignant epithelial tissue, the protein product of this gene binds to and presumably inactivates the growth suppressive effect of wild type p53 protein. Bcl-2 is an oncogene whose product inhibits apoptosis in many cells types. Some scattered nuclei in two adenomas (3.2%) stained positively for p53. The adenomas with positive staining for p53 were subserially sectioned, but no signs of invasion were found, both patients are alive and well. In 12 adenomas (19%) there was positive reaction for MDM2 protein, whereas none of them where p53 positive. All cases were strongly positive for bcl-2 staining. We conclude that p53 protein expression is not confined to follicular adenomas, while MDM2 and bcl-2 genes products are.

Adenoma↗

Thyroid cryotherapy in an experimental rat model-topography of temperature during therapy and functional results.

The aim of this study was to investigate post cryotherapy thyroid function status of normal rat thyroid tissue and to determine the topography of temperature of cryotreated tissues and of tissues adjacent to them. Nitrous oxide cryotherapy was performed in 40 male Wistar rats. They were divided into four groups of 10. In group I, the right thyroid lobe was subjected to cryotherapy and the left lobe was not frozen. In group II, both thyroid lobes were cryotreated. In group III, the right lobe was frozen and the left lobe was excised. In group IV, the thyroid was subjected to neither cryotherapy nor surgery. During cryotherapy, the temperature in various places of the thyroid and in the surrounding tissues was measured. Serum thyrotropin concentrations were determined before an experiment and 4 weeks after in all rats. The results of temperature measurements proved that it is possible to limit cryotherapy to certain areas of thyroid tissue and to spare the neighboring tissues, because they are not subjected to temperatures that are damaging. The effectiveness of cryotherapy was confirmed by functional effect. Cryotherapy changed function of thyroid tissue. There was a statistically significant difference between mean baseline and follow-up concentrations in rats of groups II and III. In both groups hypothyroidism occurred post cryotherapy.

Animals↗

[Treatment of solitary toxic thyroid nodules with the use of percutaneous ethanol injections].

Twenty women aged 18-76 years (mean 42 +/- 23 years) with solitary benign toxic thyroid nodule were treated with intranodular percutaneous 96%-ethanol injection, performed under ultrasound guidance. 1 ml of ethanol was instilled per 1 cm3 of nodule tissue. 2-5 (mean 3.1) sessions were conducted every month. The early follow-up evaluation of the results (the evaluation of nodule size by means of clinical and ultrasound examination) was performed in 6 months, and the long-term one in 2 years after last injection. A morphological evaluation was conducted according to the following scale: 1--nodule disappearance, 2--cicatricial nodule (solid structure and less than 0.5 cm in diameter), 3--nodule smaller by [symbol: see text] 50% of its initial dimensions, 4--nodule smaller by < 50% of its initial dimensions. A functional evaluation was carried out according to the following scale: I--permanent euthyroidism, II--permanent decrease of hyperthyroidism, III--no functional effect. A final follow-up evaluation revealed: nodule disappearance in 2 (10%) patients (Group 1), cicatricial nodule in 8 (40%) patients (Group 2), nodules smaller by [symbol: see text] 50% of its initial dimensions in 2 (10%) patients (Group 3) and nodules smaller by < 50% of initial dimensions in 8 (40%) patients (Group 4). The results in Group 1 and 2 were defined as good (50%), in Group 3 as satisfactory (10%) and in Group 4 as bad; and I--permanent euthyroidism in 16 (80%) patients, II--permanent decrease of hyperthyroidism in 1 (5%) patient, III--no functional effect in 3 (15%) patients. 2 patients in whom new nodules appeared and 1 patient with bad morphological and no functional treatment effects were operated on. A histological examination revealed haemorrhagic necrosis surrounded by fibrous tissue in removed nodules. The following complications were observed: 1) pain during and after the injection in 15 (75%) patients, 2) subfebrile body temperature in 3 (15%) patients and fever up to 39 degrees C on the 1-st day after the injection in 1 (5%) patient, 3) local ecchymosis in 1 (5%) patient, 4) temporary dysphonia in 1 (5%) patient. It seems that percutaneous ethanol injection treatment can be an useful treatment method of solitary benign toxic thyroid nodules in patients who do not give their consent to surgical or 131I treatment or with contraindications to an operation or radioiodine therapy.

Adolescent↗

Thyroid cryotherapy in an experimental rat model.

In recent years cryotherapy has been more and more frequently used for the treatment of tumors of different organs. Until now, the use of cryotherapy for the treatment of thyroid lesions, as well as histopathologic changes in thyroid tissue after cryotherapy, has not been described. Nitrous oxide cryotherapy of one thyroid lobe in twenty 12-week male Wistar rats was performed. After 2 and 4 weeks, the cryotreated thyroid lobe and the second lobe along with a part of the trachea, esophagus, and the subhyoid muscles adhering to the thyroid were excised and assessed macro- and microscopically. The macroscopic evaluation, performed 2 and 4 weeks postcryotherapy, revealed atrophy of the cryotreated lobe in 4 and 3 rats, respectively, and reduction of the cryotreated lobe dimensions in 6 and 7 rats, respectively. In the specimens of the lobes excised 2 weeks following cryotherapy, examined microscopically, necrosis, granulomatous inflammation, hemorrhages, and hemosiderin deposits were found most often, whereas in the specimens of the lobe excised after 4 weeks lymphocytic inflammation and fibrosis were mainly observed. No microscopic changes were observed in the thyroid lobes that were not frozen or in the parathyroid glands located inside these lobes or extrathyroidally, either ipsilaterally or contralaterally to the cryotreated thyroid lobes. There was no microscopic damage to other tissues adjacent to the thyroid gland. No rat developed vocal cord dysfunction after cryotherapy and no significant changes in serum calcium level before and after cryotherapy were observed. The results obtained show that it is possible to cryoblate thyroid tissue without damaging the tissues adjacent to the thyroid, as well as to spare function of the recurrent laryngeal nerves and parathyroid glands.

Animals↗

The surgical treatment of adrenal gland tumors--incidentaloma.

Analysis of 32 patients operated on because of accidentally discovered adrenal tumors "incidentaloma" is presented. In 12 of them there was subclinical hormonal activity, in 9 of them tumors turned out to be pheochromocytoma and 3 of them were cortex adenoma. There were 20 hormonally inactive tumors, in 5 of them there were malignant lesions (4 of the cortex and 1 of the medulla). For evaluation of hormonal activity of adrenal tumors evaluation of chromogranin A and cortisol serum blood level or urine free cortisol level is recommended. For precise localization of the tumor beside USG also CT examination is of use. According to the high percentage of malignant lesions in "incidentaloma" type tumors, surgery treatment without delay is recommended. BAC or DHES in blood serum examinations were not found helpful in preoperative evaluating the lesions as benign or malignant. In case of preoperatively found subclinical hormonal hyperactivity of medulla pharmacological treatment with alpha and beta blockers in surgery preparation is recommended. Lateral extraperitoneal access for adrenalectomy is considered safe and provides good operational view. Laparoscopic procedure because of high percentage of malignant lesions in this group of patients is not justified.

Adenoma↗

Percutaneous ethanol injection in treatment of benign nonfunctional and hyperfunctional thyroid nodules.

In recent years a new method of treatment of thyroid disorders, percutaneous ethanol injection (PEI), has been successfully used as an alternative to surgery for the management of benign nodules. In this study 103 females and 5 males (34.4 +/- 11.3 yrs) with nonfunctional cystic (23) or solid (38) nodules, and also 47 with hyperfunctional solid nodules, were treated with single or repeated ethanol injections. In all patients, the cytological studies, ultrasound evaluation and the levels of free triiodothyronine (fT3), free thyroxine (fT4), and thyrotropin or thyroids-stimulating hormone (TSH) before and after ethanol administration, were determined. The patients were followed up for 12-36 months. The size of the benign nonfunctional nodules was totally reduced in 49.9% of cases with solid and in 60.9% of patients with cystic nodules. Hyperthyroidism was cured in 91.5% of patients. The PEI procedure was connected with a few significant complications only, in relation to the localization of nodules. It was cheap, possible on an outpatient basis, easy to perform and acceptable to patients. Since the cost of thyroidectomy is high and the complication rate significant, PEI is a suitable substitute treatment especially for some patients with small toxic benign nodules of the thyroid gland.

Administration, Cutaneous↗