Marek Dedecjus

Selective embolization of thyroid arteries as a preresective and palliative treatment of thyroid cancer

Although many tumours of head and neck have been successfully embolized, the number of publications on the application of selective embolization of thyroid arteries (SETA) is limited. The aim of the present study is to evaluate the safety, efficacy and possible indications and contraindications for preresective or palliative SETA in thyroid cancer. The study group comprised 20 patients with thyroid tumours: 7 cases of advanced inoperable anaplastic thyroid cancer (ATC) and 13 cases of differentiated thyroid carcinoma (DTC). All the patients underwent SETA of the superior and/or inferior thyroid arteries. After SETA, selective angiographies of thyroid arteries were performed to ensure that the targeted arteries had been completely occluded. In all the cases, SETA decreased the blood flow through the thyroid. Preresective SETA limited bleeding during surgery and decreased operating time. We observed a massive increase of thyroglobulin (Tg) concentrations in cases of DTC that started 36-48 h after SETA and did not occur in cases of ATC. Although SETA had no influence on the mortality of ATC patients, they reported improvements in swallowing, breathing and decrease of the pain. Concluding, SETA is minimally invasive and safe method limiting blood flow through thyroid tumours. In DTC patients, SETA causes ischaemic necrosis of the gland which results in important increases in serum concentrations of Tg. Therefore, thyroidectomy should be performed during the first 36 h after preresective embolization. Moreover, SETA may become an attractive option of palliative treatment for ATC patients with intractable bleeding, pain or signs of tracheal and oesophageal compression.

Cyclin E expression in papillary thyroid carcinoma: relation to staging.

Cyclin E plays a pivotal role in the regulation of G1‐S transition and relates to malignant transformation of the cells. However, the clinical significance of cyclin E expression in patients with papillary thyroid carcinoma (PTC) remains unknown. We examined by immunohistochemistry the expression of cyclin E in 41 resected PTCs in pathologic stages from pT1a to pT4 and analyzed its relation to clinicohistopathologic factors. The positive staining was divided into 3 grades: no expression if less than 10%, expression if 11–50% and overexpression if more than 50% of the nuclei of tumor cells were stained positively. Cylin E expressions were observed in 75.6% of analyzed PTCs but only 60% of papillary microcarcinomas (PMCs) were immunopositive for cyclin E expression. However, cyclin E staining was observed in 90.4% of PTCs in a group with TNM higher than pT1a. The staining index was significantly different between the PMCs and the rest of the cancers investigated (14.91% ± 14.4% vs. 34.03% ± 23.44%, respectively; p < 0.005) and we observed positive relation between the staining index and factor T of staging of PTCs. All the lymph node metastases coexisted with cyclin E expression and most, but not all, of them coexisted with cyclin E overexpression. These findings indicate that cyclin E may play a key role for the oncogenesis and biologic behavior of PTC. If our results are confirmed in a larger study, a high level of cyclin E expression may become a new prognostic marker for PTCs.

Thyroid Hormones Influence Human Dendritic Cells' Phenotype, Function, and Subsets Distribution

BACKGROUND Dendritic cells (DCs) are the most effective antigen-presenting cells and key regulators of immune response. The immunoregulatory properties of DCs strongly depend on the microenvironment in which DCs have been matured and activated. Thyroid hormones are an important part of this environment and regulate many vital processes including growth and cellular metabolism. The aim of the study was an analysis of the influence of thyroid hormones on blood DC subtypes ex vivo, including the surface expression of molecules involved in antigen presentation, costimulation, and maturation, as well as on functional properties of DCs in vitro. METHODS Blood samples for the quantitative and phenotypic analysis of peripheral blood plasmacytoid and myeloid DC subtypes were collected from thyroidectomized patients at two time points: (i) at the time of the so-called stimulation with endogenous thyrotropin-a group of hypothyroid patients after l-thyroxine (L-T(4)) withdrawal (pretreatment group)-and (ii) after 2 months of L-T(4) administration for thyrotropin suppression-a posttreatment group. The phenotype of DCs including HLA-DR, costimulatory molecules (CD40, CD80, and CD86), and maturation marker CD83 was assessed by flow cytometry. The influence of isolated peripheral blood DCs on autologous peripheral blood mononuclear cell proliferation and cytokine secretion (interferon alpha, interleukin-12) under triiodothyronine (T(3)) deficiency or T(3) excess was investigated in culture experiments. RESULTS The percentage of peripheral blood plasmacytoid and myeloid DCs was higher after L-T(4) administration when compared with the pretreatment group. Moreover, the expression of CD86 on both DC subtypes was higher in the L-T(4) treated than in the hypothyroid patients. In the in vitro experiments, T(3) stimulation increased CD86 expression on cultured DCs. The phenotypic difference was paralleled by enhanced ability of T(3)-stimulated DCs to activate interleukin-12 secretion and proliferation of autologous peripheral blood mononuclear cells (PBMLs) in coculture experiments. CONCLUSIONS In the present study, we provide for the first time an evidence that the thyrometabolic status has an influence on the phenotype and function of human peripheral blood DCs. This observation may be of potential importance for the understanding of the pathogenesis of immune and endocrine disorders.

Low cholesteryl ester transfer protein (CETP) concentration but normal CETP activity in serum from patients with short‐term hypothyroidism Lack of relationship to lipoprotein abnormalities

objectives Hypothyroidism is associated with a number of abnormalities in lipoprotein metabolism. Although alterations in neutral lipid exchanges among plasma lipoproteins might be one characteristic feature of hypothyroidism, a few human studies of cholesteryl ester transfer protein (CETP) activity have led to heterogeneous and fragmentary observations. The aim of the present study was to analyse the influence of short‐term hypothyroidism on CETP activity, as well as on the structure and composition of lipoproteins.

Comparison of Lateral Thermal Spread Using Monopolar and Bipolar Diathermy, and the Bipolar Vessel Sealing System ThermoStapler™ During Thyroidectomy

UNLABELLED Electric devices enabling the maintenance of haemostasis during surgery have found application in modern thyroidectomy procedures. The haemostatic effect is associated with generation of heat, which apart from the intended result may bring about thermal tissue injury. The aim of the study was to determine the thermal spread around the active tip of electric devices in the operating field during total thyroidectomy, and the safe temperature range during the operation of studied devices. MATERIALS AND METHODS Over 14 months from December 2009 until January 2011, 76 total thyroidectomy procedures were analysed. The surgeries employed mono- and bipolar diathermy as well as the ThermoStapler™ bipolar vessel sealing system. During the procedures, the thermal spread around the active tips of used electric devices was recorded with the use of high-definition camera. Comparable 5-second periods of electric device use at two power ranges (30 W and 50 W) were selected from the recorded material. The highest temperature of the active tip of electric devices was determined, and the 42°C isotherm was found with the use of computer image analysis, thus determining the safe distance of important anatomic structures from the active tip of the electric device. RESULTS The temperature spread around the active tips of electric devices was recorded and the 42°C isotherm was determined. The diameter of this isotherm at the end of operation differed statistically significantly depending on the type of electric devices and power settings. The highest temperature, at both power ranges, was recorded for the bipolar vessel sealing system, while the lowest - for bipolar diathermy; at the same time a significantly lower 42°C isotherm diameter was found for ThermoStapler™ as compared with other devices. In all studied cases, the largest heat spread was found for monopolar diathermy. CONCLUSIONS The mean safe distance of the active tip of an electric device from important anatomic structures is 5 mm and depends on the device type and its power settings. Monopolar diathermy causes the strongest heating of surrounding tissues, and the ThermoStapler™ bipolar vessel sealing system, despite producing the highest temperature during operation, causes relatively small thermal injury to the surrounding tissues.

Evaluation of selective embolization of thyroid arteries (SETA) as a preresective treatment in selected cases of toxic goitre.

Backgroundin recent years, an increasing interest in the application of selective embolization of thyroid arteries (SETA) in the treatment of thyroid diseases is observed. In the present report, we analyse the value, safety and possible indications for preresective SETA in cases of large toxic goitres.Patients and methodthe study group comprised 10 patients with large toxic goitre (thyroid volume 254 ± 50 mL), including one patient with cervicomediastinal goitre and one patient with anti-thyroid drug intolerance in state of overt thyrotoxicosis. All the patients underwent SETA of the superior and/or inferior thyroid arteries, followed by thyroidectomy, performed up to thirty-six hours after SETA (23.1 ± 11 h). After embolization, selective angiographies of thyroid arteries were performed to ensure that the targeted arteries had been completely occluded.Results and conclusionin all the patients, SETA decreased blood flow through the thyroid. Preresective SETA reduced blood loss during and after thyroidectomy and decreased the operating time, but the differences were too small to justify routine applications of preresective SETA as an adjunct to surgical treatment of toxic goitre. On the other hand, SETA is a safe and minimally-invasive technique, which may become an attractive option for quick preparation to surgery in selected patients with toxic goitre, who present anti-thyroid drug intolerance or refuse radioactive iodine treatment.

Diagnostics and treatment of differentiated thyroid carcinoma in children - Guidelines of Polish National Societies.

1Department of Paediatric Endocrinology and Rheumatology, Poznan University of Medical Sciences, Poznan, Poland 2Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Gliwice Branch, Gliwice, Poland. 3Department of Paediatrics and Paediatric Endocrinology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland 4Department of Oncological and Reconstructive Surgery, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Gliwice Branch, Gliwice, Poland 5Department of Oncological Endocrinology and Nuclear Medicine, Centre of Oncology – Maria Sklodowska-Curie Memorial Institute, Warsaw, Poland 6Department of Tumour Pathology, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Gliwice Branch, Gliwice, Poland 7Department of Paediatrics and Endocrinology, Medical University, Warsaw, Poland 8Department of General and Oncological Surgery, Medical University of Lodz, Lodz, Poland 9Private practice, Katowice, Poland 10Department of Paediatric Surgery and Urology, Wroclaw Medical University, Wroclaw, Poland 11Department of Morphometry of Endocrine Glands, Chair of Endocrinology, Medical University of Lodz, Lodz, Poland 12Department of Dental Pathology, Medical University of Lodz, Lodz, Poland 13Department of Tumour Pathology, Poznan University of Medical Sciences, Poznan, Poland 14Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland 15Department of Endocrinology and Metabolic Diseases, Polish Mother’s Memorial Hospital-Research Institute, Medical University of Lodz, Lodz, Poland

Flow cytometry in the differential diagnostics of Hashimoto’s thyroiditis and MALT lymphoma of the thyroid

INTRODUCTION A combination of traditional cytology methods with fluorescence activated cell sorting (FACS) analysis of fine-needle aspiration biopsy (FNAB) material is considered a powerful diagnostic tool in the differential diagnosis of thyroid lesions suspected of mucosa-associated lymphoid tissue lymphoma (MALT-L). The aim of this study was to demonstrate the FACS-based diagnostic process of thyroid lesions in a clinical situation where ultrasound and cytological examinations did not allow differentiation between Hashimotos thyroiditis (HT) and MALT-L. MATERIAL AND METHODS The patients analysed in this study presented significantly different clinical courses of thyroid disease: quickly enlarging painless tumour of the thyroid right lobe in the first case, and chronic HT with palpable tumour in the thyroid isthmus in the second patient. Due to the suspicion of MALT-L resulting from indeterminate ultrasound and FNAB-cytology results, FNAB material was obtained from all the previously examined thyroid lesions and directly subjected to FACS assessment, encompassing κ/λ light chain restriction analysis, as well as measurements of B and T cell surface antigens. RESULTS The FACS analysis of FNAB material obtained from our patients did not show any definite signs of light chain restriction. Although one of the samples showed a borderline value of κ/λ ratio (κ/λ = 0.31), further immunophenotyping confirmed clonal expansion in none of the examined thyroid regions. Histopathological findings documented the diagnosis of HT in both clinical cases. CONCLUSION We believe that FACS represents a useful and reliable complementary diagnostic measure in FNAB-based differential diagnosis of lymphoproliferative thyroid disorders.

Silver-staining nucleolar organizer region quantification in pituitary adenomas

Nucleolar organizer regions (NORs) are segments of DNA, encoding for ribosomal RNA. They are associated with argyrophilic proteins and, thus, they can be localized through silver staining. A correlation has been shown between the number, the size, or the intranuclear localization of AgNORs, and the proliferative activity of cells. The aim of this study was to examine numerous features of AgNORs in pituitary adenomas and to relate them to immunohistochemical typing of tumor. Histologic slides from 32 pituitary tumors and one normal pituitary were silver-stained and analyzed with a computerized system for microscopic image analysis, supported by an AgNORmeter95 program. All the tumors were also immunocyto chemically characterized. We have found that gonadotropinomas, when compared with plurihormonal adenomas, revealed a lower proportion of nuclei with a single AgNOR and a higher percentage of marginal dots. Recurrent adenomas, when compared with primary adenomas, showed a higher proportion of nuclei with three AgNOR dots, a larger total area of dots in the nuclei, and a higher standard deviation of the AgNOR dot area in the nucleus. Adenomas immunopositive for prolactin, when compared with immunonegative ones, showed a larger mean area of the AgNOR dot, a larger area of the biggest dot in the nucleus, and a higher proportion of nuclei within a single dot. These results suggest that the estimated parameters of AgNOR dots differ according to tumor aggressiveness and to the hormone immunopositivity of pituitary adenomas.

Effect of L-thyroxine treatment on peripheral blood dendritic cell subpopulations in patients with Hashimoto's thyroiditis.

Recent reports suggested dendritic cells (DCs) to be important players in the pathogenesis of autoimmune thyroid processes in humans. However, there are virtually no data addressing the influence of thyroid autoaggression-associated disturbances of thyrometabolic conditions on DCs biology. The aim of the study was to evaluate the influence of L-thyroxine supplementation on conventional and plasmacytoid peripheral blood DCs subtypes in patients with hypothyroidism due to Hashimotos thyroiditis (HT). Eighteen patients with newly diagnosed hypothyroidism due to HT were included into the study. All patients received L-thyroxine treatment with doses adjusted to reach euthyroidism. Peripheral blood DC subtypes structure and immunoregulatory phenotype were analyzed by flow cytometry in the same patient prospectively at two time points: (i) before and (ii) 3 months after beginning of L-thyroxine treatment (hypothyroidism vs. euthyroidism, respectively). Percentage of plasmacytoid DCs in peripheral blood mononuclear cells fraction was significantly decreased in the course of L-thyroxine treatment (0.27 ± 0.19 vs. 0.11 ± 0.08; p < 0.05), whereas we did not observe any changes in the number of conventional DCs. However, the phenotypic analysis showed a significant increase of conventional DCs expressing CD86 and CD91 (64.25 ± 21.6% vs. 86.3 ± 11%; p < 0.05 and 30.75 ± 11.66% vs. 44.5 ± 13.3%; p < 0.05; respectively) in euthyroid patients. Standard L-thyroxine supplementation in HT patients exerted significant immunoregulatory effects, associated with quantitative and phenotypic changes of peripheral blood DC subpopulations.