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Background/Aim. Rectal cancer still presents a major health problem. Although a surgery is the mainstay of the rectal cancer treatment, there is now widespread agreement that combined modality therapy is often indicated. Around 20% of T3N0 rectal cancer patients develop distant or local relapse of the disease. There is a need for prognostic biomarkers that could help us determine the subgroup of patients with a high risk for recurrence. The aim of this study was to determine the prognostic potential of vascular endothelial growth factor (VEGF) in patients with T3N0 rectal carcinoma. Methods. This retrospective study included 163 selected T3N0 rectal cancer patients, operated on the Department for Colorectal Surgery of the Clinic for Digestive Surger (First Surgical Clinic), Clinical Centre of Serbia, Belgrade. VEGF expression was immunohistochemically assessed. Oncological outcome was analyzed using data from prospectively designed data base. Parameters of interest were: distant metastases, the disease free and overall survival. Survival and time to recurrence were evaluated using Kaplan Meier`s method and the factors were compared with the long-rank test. Results. There were 102 men and 61 women. The median age was 62 years (age range, 31?88 years). Median follow-up interval was 81 months (range, 4-177 months). During the follow-up period 6 patients developed local recurrence, in 31 patients distant metastases occurred. Three factors were found to be associated with distant metastases: VEGF expression, mucinous adenocarcinoma and tumor differentiation (p < 0.05). In patients with positive VEGF expression, the disease free survival and overall survival were significantly worse than in negative ones (65% and 59%, respectively) (log-rank test, p < 0.05). Conclusion. High VEGF expression in T3N0 rectal carcinomas together with some standard histopathological tumor features can give us enough information to identify subgroup of patients with high risk for recurrence and poorer prognosis.

Anaplastic thyroid carcinoma (ATC) is a rare but highly aggressive human malignancy. It is known that disturbances in apoptotic pathways have a great impact on tumor progression and aggressiveness. In this study the apoptosisrelated molecules Bcl-2 (antiapoptotic), Bax (proapoptotic) and survivin (an inhibitor of apoptosis) were analyzed immunohistochemically in thirty archival cases of ATC. In situ apoptotic cell death was analyzed by the TUNEL method. Mean Bcl-2 staining score (calculated from individual scores from 0-3) was low compared to those for Bax and survivin (p

Background: Preoperative localization of pancreatic neuroendocrine tumors (NET) is usually very difficult. Noninvasive, imaging tests, such as abdominal ultrasound, CT or MRI are not sensitive enough as well as selective angiography. The aim of the study was to clarify the usefulness of the EUS in preoperative localization of the pancreatic NET. Methods: From September 1998 - March 2005, EUS was performed in 1600 patients. Among them, in 10 (0,7%), this examination was carried out due to previous biochemical tests, which diagnosed the pancreatic NET. We studied the location, the size and echo-pattern of the neoplasm. The results were compared with operation and histology or EUS- FNA guided pancreatic biopsy in 9/10 patients. All EUS examinations were performed using Olympus GIF-130 videoecho-endoscope with 7,5 /12MHz switch able radial probe. Results: EUS correctly localized the pancreatic NET in 7/8 cases, (sensitivity:87,5%). In 2 patients, EUS accurately excluded pancreatic NET. There were no false positive findings (specificity 100%). Six tumors were benign (75%), and two were malign (25%). We localized 6 insulinomas and single pancreatic carcinoid tumor. The median tumor size detected by EUS was 21mm. Conclusion: EUS is highly accurate in preoperative localization of the pancreatic NET-s and We confirmed it in our study. EUS presents the method of choice for preoperative localization of the pancreatic NET.

INTRODUCTION Endogenous Cushing's syndrome is a clinical state resulting from prolonged, inappropriate exposure to excessive endogenous secretion of Cortisol and hence excess circulating free cortisol, characterized by loss of the normal feedback mechanisms of the hypothalamo-pituitary-adrenal axis and the normal circadian rhythm of cortisol secretion [2]. The etiology of Cushing's syndrome may be excessive ACTH secretion from the pituitary gland, ectopic ACTH secretion by nonpituitary tumor, or excessive autonomous secretion of cortisol from a hyperfunctioning adrenal adenoma or carcinoma. Other than this broad ACTH-dependent and ACTH-independent categories, the syndrome may be caused by ectopic CRH secretion, PPNAD, MAH, ectopic action of GIP or catecholamines, and other adrenel-dependent processes associated with adrenocortical hyperfunction. CASE REPORT A 31 year-old men with b-month history of hyperpigmentation, weight gain and proximal myopathy was refereed to Institute of Endocrinology for evaluation of hypercortisolism. At admission, patient had classic cushingoid habit with plethoric face, dermal and muscle atrophy, abdominal strie rubrae and centripetal obesity. The standard laboratory data showed hyperglycaemia and hypokaliemia with high potassium excretion level. The circadian rhythm of cortisol secretion was blunted, with moderately elevated ACTH level, and without cortisol suppression after low-dose and high-dose dexamethason suppression test. Urinary 5HIAA was elevated. Abdominal and sellar region magnetic resonance imaging was negative. CRH stimulation resulted in ACTH increase of 87% of basal, but without significant increase of cortisol level, only 7%. Thoracal CT scan revealed 14 mm mass in right apical pulmonary segment. A wedge resection of anterior segment of right upper lobe was performed. Microscopic evaluation showed tumor tissue consisting of solid areas of uniform, oval cells with eosinophilic cytoplasm and centrally located nuclei. Stromal tissue was scanty, and mitotic figures were infrequent. Tumor cells were immunoreactive for synaptophysin, neuron-specific enolase, and ACTH. The postoperative course was uneventful and the patient was discharged on glucocorticoid supplementation. Signs of Cushing's syndrome were in regression, and patient remained normotensive and normoglycaemic without therapy. DISCUSSION A multitude of normal nonpituitary cells from different organs and tissues have been shown to express the POMC gene from which ACTH is derived. The tumors most commonly associated the ectopic ACTH syndrome arise from neuroendocrine tissues, APUD cells. POMC gene expression in non-pituitary cells differs from that in pituitary cells both qualitatively and quantitatively [8], Aggressive tumors, like small cell cancer of the lung (SCCL) preferentially release intact POMC, whereas carcinoids rather overprocess the precursor, releasing ACTH and smaller peptides like CLIP. Some tumors associated with ectopic ACTH syndrome express other markers of neuroendocrine differentiation like two specific prohormone convertases (PCs). Assessment of vasopressin (V3) receptor gene expression in ACTH-producing nonpituitary tumors revealed bronchial carcinoid as a particular subset of tumors where both V3 receptor and POMC gene may be expressed in pattern indistinguishable from that in corticotroph adenoma [9]. In most, but not all, patients with ectopic ACTH syndrome, cortisol is unresponsive to high-dose dexamethason suppression test, what is used as diagnostic tool. It is not clear if the primary resistance resulted from structural abnormality of the native glucocorticoid receptor (GR), a low level of expression, or some intrinsic property of the cell line [9]. It appears that ectopic ACTH syndrome is made of two different entities. When it is because of highly differentiated tumors, with highest level of pituitary-like POMC mRNA, expressing PCs, high level of V3 receptors and GR, like bronchial carcinoids, it might be called ectopic corticotroph syndrome. In contrast, when it is caused by aggressive, poorly differentiated tumors, with much lower expression of V3 receptor, like SCCL, it might be called aberrant ACTH secretion syndrome. Carcinoid tumors have been reported in a wide range of organs but most commonly involve the lungs, bronchi, and gastrointestinal tract. They arise from neuroendocrine cells and are characterized by positive reactions to markers of neuroendocrine tissue, including neuron specific enolase, synaptophysin, and chromogranina [11]. Carcinoid tumors are typically found to contain numerous membrane-bound neurosecretory granules composed of variety of hormones and biogenic amines. One of the best characterized is serotonin, subsequently metabolized to 5-hydrohy-indolacetic acid (5-HIAA), which is excreted in the urine. In addition to serotonin, carcinoid tumors have been found to secrete ACTH, histamine, dopamine, substance P, neurotensin, prostaglandins and kallikrein. The release of serotonin and other vasoactive substances is thought to cause carcinoid syndrome, which manifestations are episodic flushing, weezing, diarrhea, and eventual right-sided valvular heart disease. These tumors have been classified as either well-differentiated or poorly differentiated neuroendocrine carcinomas. The term ?pulmonary tumorlets" describes multiple microscopic nests of neuroendocrine cells in the lungs [12]. Pulmonary carcinoids make up approximately 2 percents of primary lung tumors. The majority of these tumors are perihilar in location, and patients often presents with recurrent pneumonia, cough, hemoptisis, or chest pain. The carcinoid syndrome occurs in less than 5 percent of cases. Ectopic secretion of ACTH from pulmonary carcinoid accounts for 1 percent of all cases of Cushing's syndrome. They are distinct clinical and pathologic entity, generally peripheral in location. Although they are usually typical by standard histologie criteria, they have mush greater metastatic potential than hormonally quiescent typical carcinoids [13]. Surgical treatment therefore should be one proposed for more aggressive malignant tumors. In all cases of ACTH-dependent Cushing's syndrome with regular pituitary MRI and bilateral inferior petrosal sinus sampling, thin-section and spiral CT scanning of the chest should be routine diagnostic procedure [14], We present thirty-one year old patient with typical pulmonary carcinod with ACTH ectopic secretion consequently confirmed by histology.

Follicular thyroid cancer is the second most common thyroid malignancy. This tumor has a predisposition for hematogenous dissemination an extrathyroid spread. Accurate cytological diagnosis of follicular thyroid cancer is not possible and this fact highlights the necessity for surgical treatment of any suspicious thyroid nodule. Aggressiveness of this tumor is greater than in the case of papillary thyroid cancer and it is the reason for radical surgical treatment of follicular thyroid cancer. Total thyroidectomy facilitates later adjuvant therapy with thyroid hormones and radioiodine. This procedure improves the outcome and the risk of relapse. Results of our study clearly demonstrate that diagnosis of follicular thyroid cancer in us is established in the early phase of the disease (78.57%), but the significant number of the patients (21.43%) is still in the advanced phase of the disease.

Few subjects in endocrine surgery have generated as much contraversy as the management of thyroid nodule. The contraversial issues include evaluation of labaratory findings and imaging diagnostic procedures in the patient with solitary thyroid nodule. The major issue in relation to controversies is choice of optimal diagnostic workup.

The aim of the study was to show the standards of preoperative management, intraoperative monitoring and postoperative evaluation of patients with thyroid gland carcinoma. It was point out the importance of the preoperative diagnosis of the tumor, and the concurrent diseases. The special attention was paid to difficult airway recognition and resolving this situation. Both, anesthetist?s and surgeon?s point of view of perioperative and postoperative complications were discussed with special interest on early surgical complications and the need for urgent anesthetic treatment. Criteria for minimal and desirable monitoring of vital functions were suggested in order to prevent, recognize and cure complications. Our conclusions were based on recent references from the world literature and on our own experience in Center for endocrine surgery KCS, Belgrade.

Numerous pathohistologic criteria, difficultes and pitfalls in the process of diagnosing of thyroid carcinoma are discussed. Benign hyperplastic papillae may be present in colloidal cystic goiter and hyperplastic goiter. These structures are lined by cells with normochromatic nuclei and do not disturb the thyroid tissue architecture. Papillae in papillary thyroid carcinoma have cells with ground-glass, hypochromatic nuclei. Follicles inspissated in capsula of follicular or even colloidal adenoma may be evaluated as capsular invasion - diagnostic feature of follicular carcinoma. Undifferentiated thyroid carcinoma is sometimes similar to fibrosarcoma and reveal cellular pleomorphism, anaplasia and numerous foci of necrosis. Medullary thyroid carcinoma with scanty stromal amyloid, its papillary variant and carcinoid-like histologic type consist of oval cells with eosinophilic cytoplasm and dark nuclei.

Papillary thyroid cancer is after ovarian cancer the most frequent malignant disease of the endocrine system and because of this fact, early detection and appropriate surgical treatment is essential. Radical surgical treatment lower the risk of the disease relapse and postoperative adjuvant therapy with radio iodine is possible as well as postoperative follow up with tireoglobulin measurement. If the total thyroidectomy is performed in highly specialized institution the risk of postoperative complications is acceptable and therefore is the treatment of choice for papillary thyroid cancer. Only the patients with occult papillary thyroid cancer can be treated with hemythyroidectomy. In our series of 410 patients the majority of the patients (85,12%) were in the early phase of the disease and the degree of successfully performed radical surgery for papillary thyroid cancer was very high (tumor reduction was performed in only 1,46% of cases).

Galectin-3 is a a beta-galactoside binding protein recently proposed to be a promising presurgical molecular marker for distinguishing benign from malignant thyroid neoplasms. We analyzed galectin-3 expression immunohistochemically in papillary areas of hyperplastic lesions of benign thyroid tissue in comparison with malignant papillary projections of papillary thyroid carcinoma (PTC). A monoclonal antibody to galectin-3 and ABC immunohistochemical technique were used to evaluate galectin-3 expression in 26 cases of benign papillary hyperplasia (8 cases of hyperplastic adenoma, 8 cases of hyperplastic colloid goiter, 10 cases of Graves disease) in comparison with 25 cases of PTC. Immunohistochemical results showed no reactivity for galectin-3 in papillary areas of benign hyperplastic lesions. Strong cytoplasmic galectin-3 immunoreactivity was found in all 25 cases of PTC. These results show that galectin-3 expression is a feature of malignant papillary projections but not of benign papillary hyperplasia. Thus, the immunohistochemical evaluation of galectin-3 might contribute to differential diagnosis between malignant and benign thyroid lesions with papillary projections.

The aim of the present paper was to study some characteristics and posibility of surgery of anaplastic thyroid cancer. During five years period in Center for endocrine surgery, we found anaplastic thyroid cancer in 65 patienst (44 female and 21 male), median age 63 years (from 37 to 88 years). Surgical treatment was peerformed in one half (32) anaplastic thyroid cancer patients, at majority of them operative biopsy or tumor reduction only. Radical syrgery was performed in about 10% patients. Posibility of surgery in anaplastic thyroid cancer are very limited. In one third patients there were longstanding goter or thyroid nodul or histological verified dediferentiation of papillary thyroid cancer. This patienst should be operated formerly, before anaplastic transformation.

Thyroid carcinomas arise from follicular cells (papillary, follicular, Hurthle, anaplastic), parafollicular cells (medullary) and stroma (lymphoma, sarcoma?). Gradation and prognostic factors are different for every one of histological type. Most patients with papillary and follicular thyroid cancer have an excellent prognosis. At the other extreme is anaplastic thyroid cancer whose usual mean survival can be measured in months. Exposure to external radiation and living in endemic goiter area increase the frequency of thyroid cancer. Medullary thyroid carcinoma is often familial and may occur in associations with the multiple endocrine neoplasia syndromes.

Medullary thyroid cancer (MTC) is uncommon thyroid tumor with specific characteristics which undoubtedly divide this tumor from other thyroid malignances. Patients with sporadic or hereditary form of MTC differ in clinical presentation, recurrence of the disease and outcome. The aim of study was to establish surgical characteristics of MTC as well as clinical factors that influence surgical treatment. The study group consisted of 68 patients with MTC managed at the Center for Endocrine Surgery between 1987. and 1999. Retrospective analysis included clinical form of the disease, general data, histological and other tumor characteristics. Mean age of the patients were 47.3 years (female/male ratio: 1.5:1). Mean size of tumor was 80.5 cm3, 72.1% patients had tumor greater than 4 cm. in diameter or extrathyroid spread. The majority of patients were in II and III stadium of the disease. Primary operation (at least total thyroidectomy) was performed in 57 (84%) patients. 2(3%) had postoperatively temporally nerve palsy and 7(10.29%) temporally hypoparathyroidism. The overall survival was 46.8 + 9.9% after 9 years and 63.6 + 7.2% at 5 years. Postoperative calcitonin value is significant predictor of survival /Spearman's coefficient (R=0.7048)/, worse prognosis is in correlation with high postoperative calcitonin values. The treatment of choice is at least total thyroidectomy and central lymph nodes resection if enlarged lymph nodes are found. Precise operative technique lowers the risk of postoperative complications. Complex approach to the patient with MTC includes all available methods in pre and postoperative evaluation as well as surgeon's knowledge and skill.

Primary thyroid lymphomas are rare. Surgery is seldom indicated. The aim of the study is to find out the main characteristics of primary thyroid lymphomas in our patients, indications for surgery and the possibility of treatment, frequency and characteristics of rare thyroid tumors. Method: retrospective study of 1044 patient operated for malignant thyroid tumor. Results: From 1995 to may 2003, we operated upon 15 patients with primary thyroid lymphomas, 2 men and 13 women mean age of 50.12 years (from 22 to 74 years), also one patient of age 69 with insular thyroid cancer. Reason for surgery was thyroid tumor in all, compressive disturbances in 9, among them 4 with asphyxia. Radical total thyroidectomy was performed in 4 (26.7%), whole in others some residual tumor tissue was could not be removed in spite of thyroidectomy in 3, hemithyroidectomy in 2, tumor debulking in 5 and only open biopsy was performed in one patient. There was no operative mortality, no postoperative hypocalcaemia and no recurrent nerve palsy. Histological type of tumor was Non-Hodgkin lymphoma in 13 patients, Hodgkin disease in 2 female patients of age 22 and 24. Hashimoto thyroiditis was present in 3 patients. After surgery, 13 patients were treated with chemotherapy, one patient died one month after the operation and one patient refused chemotherapy. Follow-up data are available for 9 patients and the mean follow-up period was 20 months (1-48months). Three patients died after a month, 2 and 3 years after surgery. Six patients are without local relapse. In one patient who refused chemotherapy, a year after thyroid surgery, resection of large intestine was performed because of lymphoma of the colon. Conclusion: Malignant thyroid lymphomas are rare. They present with rapidly growing thyroid tumor, compression and asphyxia. Surgery is only temporarily effective and it is necessary to start with chemo-radiotherapy as soon as possible. Rare forms of thyroid cancer have to be histological recognized in order to choose the best way of treatment.

Recurrent thyroid tumors are much less frequent but more aggressive than primary tumors. The aim is to find out their characteristics, aggressiveness and the possibility of radical surgical excision as well as the frequency of complications. Method and material: retrospective study on 69 patients operated for recurrent thyroid tumors. Results: Recurrent tumors were found in 42 patients with papillary, 11 with follicular (8 with Hurthle), 9 with medullary and 7 with anaplastic thyroid tumors. Relapse in thyroid bed on dominant side had 41 patients (59.4%), relapse on the opposite side we found in 19 patients (27.5%) and relapse in lymph nodes outside of thyroid bed in 37 patients (53.6%). In 33/69 patients, the first procedure was incomplete (reduction in 5, partial resection in 19, hemithyroidectomy in 9). The second procedure was incomplete in 14, near total thyroidectomy in 2, total thyroidectomy in 33 and dissection of lymph nodes in 33, among them in 20 with the operation in thyroid bed. Preoperative recurent nerve palsy had 2 patients and transitional recurent nerve palsy occured after second procedure in 2 patients. Among 33 patients after thyroidectomy for recurent tumor, postoperative hypoparathyroidism occured in 8 (24.2%), of whome in 2 permanent (6%). In the group of 54 patients with recurent differentiated thyroid cancer, radioiodine therapy after first operation had received only 7 patients (13%). Conclusion: the main causes of thyroid cancer relapse are incomplete first procedure and agressiveness of cancer. It is not always possible to excise the complete recurrent tumor. After surgery for papillary cancer, radioiodine therapy is seldom used.

BACKGROUND: Galectin-3, a lectin with specificity for beta galactosides, is believed to be implicated in multiple biological processes through interactions with complementary glycoconjugates. Alterations in galectin-3 expression are observed in a variety of human tumors. In thyroid, this lectin has been found to be highly expressed in malignancies of epithelial origin. We analyzed galectin-3 expression in medullary thyroid carcinoma (MTC). MATERIALS AND METHODS: An immunohistochemical study using monoclonal antibody was performed on paraffin sections of twenty cases of sporadic MTC comprising ten cases without and ten cases with lymph node metastases at the time of surgery. RESULTS: Positive cytoplasmic staining for galectin-3 was found in 16/20 cases, but varied in intensity and distribution from weak/focal (7/16) to moderate (7/16) or strong (2/16). Advanced stage of MTC (with lymph node metastases at the time of surgery) showed moderate to strong galectin-3 expression more frequently (8/10) than cases without lymph node metastases (1/10). CONCLUSION: These findings suggest that galectin-3 expression is associated with the advanced stage of disease and that this lection might play a role in the pathobiology of MTC.

Fine-needle aspiration is a low-cost diagnostic tool with principal value in determining which patients with thyroid nodules should undergo surgery. Team work and close cooperation among endocrinologists, surgeons, and pathologists are essential for success. Cytologic criteria for diagnosis of the most frequent conditions (benign cystic lesions), Hashimoto thyroiditis and malignancies found in thyroid aspirates have been provided. The unsolved problem of the so-called "follicular" or oxyphilic lesion or neoplasia will be investigated by immunocytochemistry.

Background: Galectin-3 is an endogenous beta-galactoside binding lectin implicated in neoplastic transformation and tumor progression. High levels of this lectin have recently been found in malignant thyroid tumors, but not in normal or benign thyroid tissue, suggesting galectin-3 as a promising presurgical marker of thyroid malignancy. Methods: We analyzed immunohistochemically galectin-3 expression in thyroid tissue using a monoclonal antibody. The total of 108 tissue specimens included 55 cases of thyroid carcinoma (30 papillary, 15 follicular, and 10 anaplastic type), 15 samples of follicular adenoma, 15 samples of normal thyroid tissue, and 23 thyroid tissue specimens from human fetuses (16 to 37 weeks of intrauterine life). Results: The results showed galectin-3 expression in 20/30 papillary carcinomas, 11/15 follicular carcinomas, 10/10 anaplastic carcinomas, and 4/15 follicular adenomas. Thyroid follicular cells in normal adult and fetal tissue were negative. Conclusions: These results further confirm that galectin-3 expression is a feature of malignant thyroid cells, and that immunohistochemical detection of galectin-3 could be useful in thyroid carcinoma diagnostics. The absence of galectin-3 in thyroid cells during fetal development suggests that galectin-3 is expressed de novo during malignant transformation of thyroid epithelium, thus it should not be considered an oncofetal antigen.