Jan Brzeziński

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.

Expression of Insulin‐like Growth Factor I (IGF‐I) Gene and of Genes for IGF‐Binding Proteins 1, 2, 3, 4 (IGFBP‐1—IGFBP‐4) in Non‐neoplastic Human Thyroid Cells and in Certain Human Thyroid Cancers. Effect of Exogenous IGF‐I on This Expression

Aim: The aim of this study was to examine the expression of the IGF‐I gene and of genes for IGFBP‐1, ‐2, ‐3, and ‐4 in cells from nodular goiters (NG), and from different human thyroid carcinomas (papillary—PTC, anaplastic—ATC, and medullary—MTC), cultured in monolayers. The influence, exerted by exogenous IGF‐I on the expression of these genes, was also investigated. Methods: Thyroid tissue specimens were obtained from 65 patients during subtotal or total thyroidectomies. After approximately 2–3 weeks of culture, thyroid cells were incubated for 24 hours with IGF‐I in concentrations of: 0, 1, 10 and 100 ng/ml. The total mRNA was isolated according to the method described by Chomczyński and Sacchi with our own modifications. Afterwards, mRNA encoding IGF‐I, IGFBP‐1—IGFBP‐4 and glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH), were amplified, using the reverse transcription‐polymerase chain reaction (RT‐PCR); GAPDH gene served as a control gene. PCR products were electrophoresed and then submitted to densitometric analysis. Results and conclusions: Our study has shown that in carcinoma cells (ATC, PTC, MTC), IGF‐I reveals a stimulatory influence on the expression of its own gene, that effect being most distinctive in ATC cells. These facts indicate an important role of IGF‐I in the pathogenesis and invasiveness of the analyzed malignant neoplasms.

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.

Increased thymidine kinase activity in human thyroid toxic adenomas: effects of exposure to epidermal growth factor in vitro.

The activity of thymidine kinase (TK—EC 2.7.1.21)—an enzyme functioning as a part of the pyrimidine salvage pathway of DNA synthesis—is closely related to growth processes. The aim of the study was to measure TK activity in homogenates of human thyroid tissue of the following types: non‐toxic nodular goiter (NTNG)—macroscopically unchanged tissue, non‐toxic adenoma (NTA), and toxic adenoma (TA) (obtained from patients, who—before the surgery—had been treated with thyrostatic drugs for thyrotoxicosis). Thyroid tissue was obtained from female patients subjected to subtotal thyroidectomy at the Department of Endocrine Surgery, Medical University of Łódź. Thyroid homogenates were incubated in the presence of epidermal growth factor (EGF), used in five different concentrations (0.1 ng/ml, 1 ng/ml, 10 ng/ml, 100 ng/ml, 1000 ng/ml). TK activity was estimated by chromatographic measurements of the amount of the main reaction product—deoxythymidine monophosphate. Results: 1) We did not observe any significant difference between TK activity in the homogenates of the thyroid tissue collected from NTNG and NTA; TK activity was clearly higher in the homogenates of adenomatous tissue, collected from the patients with TA; 2) EGF increased TK activity in the homogenates of the macroscopically unchanged tissue, collected—during surgery—from the patients with NTNG, as well as in homogenates of thyroid tissue from NTA; 3) In case of hyperactive thyroid tissue, obtained from TA, EGF tended to increase TK activity, however, without any statistical differences. Our results confirm TK increased activity in hyperactive thyroid tissue. At the same time, the obtained data suggest a certain role of EGF in goiter formation in humans.

Patterns of cyclin A and B1 immunostaining in papillary thyroid carcinoma

INTRODUCTION AND OBJECTIVES Cyclin A, encoded by CCNA (cyclin A) gene with locus in chromosome 4q27, and cyclin B1, encoded by CCNB1 (cyclin B1) gene with locus in chromosome 5q12, are proteins that play a key role in the passage through the restriction point in G2 phase of the cell cycle. The aim of the study was to analyse immunohistochemically the expression of cyclins A and B1 in different variants of papillary thyroid carcinoma (PTC). MATERIAL AND METHODS The immunostaining patterns of the proteins in question in the tissue of 40 resected PTC (20 cases of classic variant of PTC, 9 cases of PTC follicular variant and 11 cases of other non-classic variants of PTC) were investigated. RESULTS On analyzing cyclin A and B1 expression, positive staining in 90% cases of PTC were observed. The study revealed a significant difference in expression of cyclins A and B1 between classic and non-classic variants of PTC. The expression of both examined cyclins was weaker in the classic variant of PTC. In the group of follicular variant of PTC, the expression of cyclins was of medium intensity and in the group of other non-classic variants of PTC, the expression was clearly higher. CONCLUSIONS The results of the presented study suggest that cyclins A and B1 expression may have a characteristic pattern of immunostaining for particular variants of PTC. If the obtained results are confirmed in a larger group of patients, the diagnostic panel constructed of the antibodies against these proteins may increase the diagnostic accuracy in PTC cases.

A rare case of Hodkin's lymphoma of the mediastinum imitating retrosternal goiter--retrospective analysis of the diagnostic process.

Primary extranodal sites of development of lymphoid neoplasms are rare and concern about 5% of patients with Hodgkins lymphoma. Extranodal development is more common in non Hodgkins lymphoma and may reach 33%. A 27-year-old woman was diagnosed by a cardiologist for a short breath. On the physical examination no other abnormalities were observed. Echocardiography, performed by cardiologist, revealed a large tumor, overlaying the right ventricle and compressing the pulmonary trunk. Chest X-ray, ultrasound and CT-scan confirmed diagnosis. In fine needle aspiration clear, lucid fluid was obtained. Scintygraphy of the neck and thorax showed accumulation of the marker in the properly placed but enlarged thyroid gland. Patient was qualified for surgical treatment - cervicotomy and sternothomy were performed. The histopatological exam of the tumor revealed Hodgkins lymphoma of the mediastinum (classical subtype NS-1). Following the surgery, adjuvant therapy was instituted. After the treatment PET-CT-scan did not show any kind of non-physiological radiomarkers accumulation in the monitored regions of the body and in in three-years follow-up the patient shows no signs of recurrence.

Evaluation of the effectiveness of iodine prophylaxis in Poland based on over 20 years of observations of iodine supply in school-aged children in the central region of the country

Introduction Due to the mild-to-moderate iodine deficiency in Poland, in 1997 iodine prophylaxis based on obligatory salt iodization was introduced. We attempted to evaluate the effectiveness of such prophylaxis, based on over 20 years of observations of iodine supply in school-aged children in Opoczno district (Central Poland). Material and methods A group of 603 children (316 girls and 287 boys), aged 6–14, was examined at 4 time points: in the years 1994, 1999, 2010 and 2016. The children were tested for urine iodine concentration (UIC) and in each child the thyroid volume was measured ultrasonographically. Results The median UIC in 1994 (45.5 μg/l) indicated moderate iodine deficiency, while after introducing prophylaxis it corresponded to adequate values (1999 – 101.1 μg/l, 2010 – 100.6 μg/l, 2016 – 288.3 μg/l); however, the last value was higher than the previous two. The thyroid size, assessed by ultrasonography and presented as volume/body surface area (V/BSA), in 1994 was 6.55 × 10–6 m; this value was higher than at other time points (2.73 × 10–6 m in 1999, 2.73 × 10–6 m in 2010, and 2.70 × 10–6 m in 2016). Conclusions Iodine prophylaxis has proved effective in eliminating iodine deficiency. In recent years, the diversification of iodine sources, despite the reduction of salt consumption, has led to an increase in median UIC to values close to the upper limit of UIC, accepted as normal. Further increase in iodine supply may be unfavourable for health; therefore constant monitoring of iodine prophylaxis is required.