ATYPICAL CARCINOID OF THE LARYNX AND MULTIFOCAL METASTASES.

Neuroendocrine carcinoma (NEC) of the larynx is the most frequent neuroendocrine neoplasm of the head and neck and the most common nonsquamous carcinoma of the larynx. It usually occurs in the supraglottic area, in smoking men. We report a case of a 58-year-old woman with no history of smoking who presented with an atypical carcinoid, arising in the right piriform sinus of the larynx. During the 5-year follow-up, the patient developed metastases in the lymph nodes, palatine tonsils, parotid glands, breasts and skin. For this reason the patient underwent several surgical procedures, radiotherapy and eventually was qualified for chemotherapy. Our case shows that NEC of the larynx can have an atypical presentation. The diagnosis requires careful pathological evaluation with immunohistochemistry and a wide spectrum of imaging. The serum concentration of chromogranin A seems to be not useful in the diagnosis and follow-up of laryngeal NEC.

131I thyroid activity and committed dose assessment among family members of patients treated with radioactive iodine.

The main goal of the present study was estimation of an internal contamination of 131I among family members of patients treated with radioactive iodine. Thyroid activity measurements of 131I in examined volunteers were performed using a whole-body spectrometer at the institute of nuclear physics, Polish academy of sciences. During this research, 20 relatives of patients treated with 131I were examined: eight women and 12 men with an age in the range from 3 to 72 years. In the case of nine individuals, the activity of 131I in the thyroid was below the detection limit, but among the remaining 11 individuals, the activity varied from (9 ± 3) Bq up to (1140 ± 295) Bq. Subsequently, based on the measurements of thyroid 131I activities, the corresponding doses were assessed. The highest estimated effective dose reached 218 µSv, while the thyroid equivalent dose was 2.4 mSv. In addition, the experimental data obtained were statistically analysed together with the results of surveys of the individuals participating in the study by means of correspondence analysis and nonparametric tests: Mann-Whitney, gamma, χ2 and Yule Phi coefficient. These analyses revealed relationships between 131I activities in the thyroids of the examined individuals and their housing conditions as well as consumption of meals prepared by the patients.

Transcriptomic population markers for human population discrimination.

BACKGROUND: Numerous studies have demonstrated significant differences in the expression level across continental human populations. Most of published results were performed on B-cell lines materials examined under specific laboratory conditions, without further validation in a primary biological material. The goal of our study was to identify mRNA markers characterized by a significant and stable difference in the gene expression profile in Caucasian and Chinese populations, both in the commercially available B-lymphocyte cell lines and in the primary samples of the peripheral blood. RESULTS: The preliminary selection of population-differentiating transcripts was based on Illumina expression microarray analysis of the representative group of ethnically-specified B-lymphocyte cell lines. Twenty genes with the inter-population difference in the mean expression characterized by the at least 1.5-fold change and FDR <  0.05 were identified. Subsequently, a two-step validation procedure was carried out. In the first step, a subset of selected population- differentiating transcripts was tested in the independent set of B-lymphocyte cell lines, using TLDA cards. Based on TLDA analysis, three transcripts representing Fch > 2 were chosen for validation. The differentiating status was confirmed for all of them: UTS2, UGT2B17 and SLC7A7. The mean expression of UTS2 was higher in CHB (25.8-fold change compared to CEU), while the expression of UGT2B17 and SLC7A7 was higher in CEU (3.2- and 2.2-fold change, respectively). In the next validation step, two transcripts were verified in the primary biological material. As an ultimate result of our study, two mRNA markers (UTS2 and UGT2B17) exhibiting population differences in the expression level in both B-cell line and in the blood were identified. Further statistical analysis confirmed the discriminatory potential of these two markers. CONCLUSIONS: An inter-population differences on the level of gene expression were identified in both B-cell lines and peripheral blood samples. These findings may have a practical application in the field of forensic science. In particular, these transcripts, targeted by specific probes, may be used as population-specific targets in the efforts aiming to separate mixture of blood from individuals of different populations. Notwithstanding, these results have to be confirmed on extended population group.

Papillary thyroid carcinoma in a boy with familial tuberous sclerosis complex attributable to a TSC2 deletion-a case report.

Tuberous sclerosis complex (tsc), a phacomatosis, is a rare genetic disease (autosomal dominant; incidence: 1 in 6,800-17,300) associated with mutations in the TSC1 and TSC2 genes, 70% of which are sporadic. The disease causes benign tumours in the brain, kidneys, heart, lungs, skin, and eyes; thyroid lesions are extremely rare. A 13-year-old euthyroid boy with a hereditary form of tsc (del 4730G in TSC2, also seen in 2 sisters and the father) was admitted to hospital with a thyroid nodule. Physical examination revealed a nodular left lobe with increased consistency. Thyroid ultrasonography revealed a heterogeneous left lobe, predominantly hypoechoic with multiple microcalcifications and the presence of suspicious cervical lymph nodes on the left side. A macrocalcification was observed on the right lobe. Fine-needle biopsy results showed a few groups of cells with discrete atypical characteristics, including abundant cytoplasm, nuclei with conspicuous nucleoli, intra-nuclear inclusions, and nuclear grooves. The patient underwent total thyroidectomy with lymphadenectomy. Histopathology examination confirmed papillary thyroid carcinoma. The coincidence of endocrine neoplasia including thyroid cancer and tsc is rare, and tsc with papillary thyroid carcinoma has never been described in a child. Studies of mutations in the tumour suppressor genes TSC1, TSC2, and STK11, activating the mtor (mammalian target of rapamycin) pathway, might support their role in the pathogenesis of thyroid cancer.

miRNAs with the potential to distinguish follicular thyroid carcinomas from benign follicular thyroid tumors: results of a meta-analysis.

The detection of somatic mutations in indeterminate or follicular proliferation fine-needle aspiration cytologies (FNACs) is able to clarify only a subgroup of those FNACs. Therefore, further markers to differentiate this problematic FNAC category by the identification of mutation negative thyroid cancers and benign nodules are urgently needed. Our objective was to evaluate previously published miRNA markers and discover novel ones from all publicly available miRNA expression profiling data sets. By literature review and data repository search we gathered 3 data sets describing human miRNA expression profiles of follicular thyroid cancer (FTC) and follicular adenoma (FA) samples. Literature review summarized 27 previously published miRNAs, which were validated in the 3 available data sets. By means of uniform statistical analysis 6 further miRNAs were identified and tested in an independent, previously published microarray data set. Meta-analysis confirmed 7 out of 27 previously published, and 4 out of 6 de novo identified miRNAs. The low confirmation rate of previously published miRNA markers was induced by low numbers of samples in the analyzed studies and high false discovery rates that were higher than 0.2. Finally, miR-637, miR-181c-3p, miR-206, and miR-7-5p were discovered as de novo potential FTC markers and validated in at least one independent, previously published data set. Two out of these new identified miRNAs (miR-7-5p and miR-206) were validated by qPCR in an independent sample set of 32 FTC and 46 FA samples. Especially miR-7-5p was able to differentiate benign and malignant thyroid tumors in several datasets.

A gene expression signature distinguishes normal tissues of sporadic and radiation-induced papillary thyroid carcinomas.

BACKGROUND: Papillary thyroid cancer (PTC) incidence increased dramatically in children after the Chernobyl accident, providing a unique opportunity to investigate the molecular features of radiation-induced thyroid cancer. In contrast to the previous studies that included age-related confounding factors, we investigated mRNA expression in PTC and in the normal contralateral tissues of patients exposed and non-exposed to the Chernobyl fallout, using age- and ethnicity-matched non-irradiated cohorts. METHODS: Forty-five patients were analysed by full-genome mRNA microarrays. Twenty-two patients have been exposed to the Chernobyl fallout; 23 others were age-matched and resident in the same regions of Ukraine, but were born after 1 March 1987, that is, were not exposed to ¹³¹I. RESULTS: A gene expression signature of 793 probes corresponding to 403 genes that permitted differentiation between normal tissues from patients exposed and from those who were not exposed to radiation was identified. The differences were confirmed by quantitative RT-PCR. Many deregulated pathways in the exposed normal tissues are related to cell proliferation. CONCLUSION: Our results suggest that a higher proliferation rate in normal thyroid could be related to radiation-induced cancer either as a predisposition or as a consequence of radiation. The signature allows the identification of radiation-induced thyroid cancers.

Optimization of the method of RNA isolation from paraffin blocks to assess gene expression in breast cancer.

UNLABELLED: Molecular oncology increasingly needs the assessment of tumor gene expression profile (transcriptome), most commonly by determination of RNA-based molecular markers employing the technique of quantitative real-time polymerase chain reaction (Q-PCR). However, as all are methods based on RNA, to date, the experience in Q-PCR is mostly limited to freshly collected material frozen at -80 degrees C, i.e. showing no signs of RNA degradation. The aim of the present study was to implement into practice a method of RNA isolation from formalin-fixed and paraffin-embedded (FFPE) breast carcinoma samples collected during routine surgical and histopathological procedure, to further employ it in expression analysis by Q-PCR. The RNA isolation kit RNeasy FFPE (QIAGEN) was used. It was demonstrated that in samples subjected to DNAse digestion, the mean concentration of the obtained RNA was low (46 ng/microl), while during the isolation performed using solely gDNA Eliminator columns, the authors obtained RNA with an almost fourfold higher concentration value. A comparison was made between isolation effectiveness using varying amounts of input material. It was noted that isolation efficacy was lower when three sections were employed (the concentration value of 178 ng/microl) as compared to 5-8 sections (279 and 302 ng/microl, respectively). RNA quality assessment was also performed employing the method of capillary electrophoresis by the "lab-on-a-chip" technology of Agilent Bioanalyzer 2100. Freshly prepared material yielded in single cases samples containing RNA18S and RNA28S populations, while in samples isolated from archival paraffin blocks, the obtained RNA showed more considerable degradation, thus, was of lesser quality. In the analysis of 20 samples from the second collected series, the majority of samples were characterized by the RNA Integrity Number (RIN) values in the range of 2-2.5, still indicative of a substantial degree of RNA degradation. The mean isolation effectiveness in the second series was 885 ng/microl. In 10 of 20 blocks isolated, we succeeded in obtaining sufficient RNA concentration, above 500 ng/microl. It was also noted that the storage time did not affect the amount of RNA obtained from a block: while isolating RNA from freshly prepared blocks, we achieved similar concentrations as when analyzing the archival material. CONCLUSIONS: the key in preserving RNA quality in paraffin blocks is the timing of material collection and fixing. Routine paraffin blocks allow for obtaining RNA for molecular studies, yet with features of considerable degradation.

131I INTERNAL CONTAMINATION AND COMMITTED DOSE ASSESSMENT AMONG NUCLEAR MEDICINE MEDICAL PERSONNEL.

This study presents 131I thyroid activity measurements of 56 employees of the Department of Nuclear Medicine and Endocrine Oncology, Centre for Oncology in Gliwice. The research instrument was a whole-body spectrometer. In 44 out of 56 examined staff members, the determined 131I activity was found to be above the detection limit. The measured activities ranged from 6 ± 2 to 457 ± 118 Bq. The maximum estimated committed effective dose reached was 1.5 mSv/y. The results were compared with previous measurements conducted in another Polish nuclear medical unit. From this comparison, we can see that radiological safety among nuclear medicine personnel can be improved by appropriate work organisation. Reducing exposure of workers can be achieved by properly organised turnovers concerning the most vulnerable worksites. In addition, to lower the radiation risk, it is essential to comply strictly with the isolation regime for the patients.

Prevalence of RAS point mutations in papillary thyroid carcinoma; a novel mutation at codon 31 of K-RAS.

The aim of this study was to assess the incidence of point mutations in RAS oncogenes of papillary thyroid carcinoma (PTC). Tumour specimens were obtained from 29 PTCs. The fragments of exons 1 and 2 of RAS oncogenes family (H- RAS, K- RAS, N- RAS) were amplified and then, point mutations were detected by SSCP and/or by RFLP analysis. Several DNA samples were directly sequenced to confirm the results. Two mutations were found in this study (GAA/CAA at codon 31 of K- RAS and CAA/CAC at codon 61 of N- RAS oncogene). These data confirm the results of previous studies, showing that RAS mutations are more rarely found in PTC than in follicular neoplasms. The influence of a novel mutation at codon 31 of K- RAS oncogene on the development of PTC needs further studies.

Is there a need to redefine the upper normal limit of TSH?

Mild forms of hypothyroidism--subclinical hypothyroidism--have recently been discussed as being a risk factor for the development of overt thyroid dysfunction and for a number of clinical disorders. The diagnosis critically depends on the definition of the upper normal limit of serum TSH as, by definition, free thyroxine serum concentrations are normal. Cut-off levels of 4-5 mU TSH/l have been conventionally used to diagnose an elevated TSH serum concentration. Recent data from large population studies have suggested a much lower TSH cut-off with an upper limit of 2-2.5 mU/l but application of strict criteria for inclusion of subjects from the general population studies aiming at assessing TSH reference intervals (no personal or family history of thyroid disease, no thyroid antibodies and a normal thyroid on ultrasonography) did not result in an unequivocal upper limit of normal TSH at 2.0-2.5 mU/l. When summarizing the available evidence for lowered upper TSH cut-off values and their potential therapeutic implications there is presently insufficient justification to lower the upper normal limit of TSH and, for practical purposes, it is still recommended to maintain the TSH reference interval of 0.4-4.0 mU/l. Classifying subjects with a TSH value between 2 and 4 mU/l as abnormal, as well as intervening with thyroxine treatment in such subjects, is probably doing more harm than good.

Risk of malignant tumors in first-degree relatives of patients with differentiated thyroid cancer -- a hospital based study.

In presented study the risk of incidence of familial differentiated thyroid cancer as well as the risk of other malignant tumors in families of DTC patients was evaluated. 999 patients with differentiated thyroid cancer and 825 persons without any history of malignant disease were evaluated on the occurrence of malignant neoplasm within their families. Information about 6614 first degree relatives of DTC index patients and 4939 first degree relatives of control persons were recorded. The incidence of cancers at various sites was compared between first-degree relatives of index patients and control persons and odds ratio with 95% confidence intervals (CI) were calculated for thyroid cancer and other cancer sites. Within 999 families of thyroid cancer index patients 23 families with more than one case of DTC were found. The risk of the development of thyroid cancer in the first degree was 6 (95% CI 1.8-19) times greater in the index group than in the control group. No increased risk for development of other malignancies was observed. Results of our study confirm previous reports of increased risk of thyroid cancer in first-degree relatives of differentiated thyroid cancer patients. However, the relatively small number of first-degree relatives affected with thyroid cancer (24/6614) does not justify at present any screening in the first-degree relatives of patients affected with differentiated thyroid cancer. Simultaneously, no increased risk of other malignant neoplasm was observed in the differentiated cancer families.

EurEAs_Gplex--A new SNaPshot assay for continental population discrimination and gender identification.

Assays that allow analysis of the biogeographic origin of biological samples in a standard forensic laboratory have to target a small number of highly differentiating markers. Such markers should be easy to multiplex and the assay must perform well in the degraded and scarce biological material. SNPs localized in the genome regions, which in the past were subjected to differential selective pressure in various populations, are the most widely used markers in the studies of biogeographic affiliation. SNPs reflecting biogeographic differences not related to any phenotypic traits are not sufficiently explored. The goal of our study was to identify a small set of SNPs not related to any known pigmentation/phenotype-specific genes, which would allow efficient discrimination between populations of Europe and East Asia. The selection of SNPs was based on the comparative analysis of representative European and Chinese/Japanese samples (B-lymphocyte cell lines), genotyped using the Infinium HumanOmniExpressExome microarray (Illumina). The classifier, consisting of 24 unlinked SNPs (24-SNP classifier), was selected. The performance of a 14-SNP subset of this classifier (14-SNP subclassifier) was tested using genotype data from several populations. The 14-SNP subclassifier differentiated East Asians, Europeans and Africans with ∼100% accuracy; Palestinians, representative of the Middle East, clustered with Europeans, while Amerindians and Pakistani were placed between East Asian and European populations. Based on these results, we have developed a SNaPshot assay (EurEAs_Gplex) for genotyping SNPs from the 14-SNP subclassifier, combined with an additional marker for gender identification. Forensic utility of the EurEAs_Gplex was verified using degraded and low quantity DNA samples. The performance of the EurEAs_Gplex was satisfactory when using degraded DNA; tests using low quantity DNA samples revealed a previously not described source of genotyping errors, potentially important for any SNaPshot-based assays.

The role of FDG-PET in localization of recurrent lesions of differentiated thyroid cancer (DTC) in patients with asymptomatic hyperthyroglobulinemia in a real clinical practice.

INTRODUCTION: Available methods, including serum thyroglobulin (Tg) measurement and whole-body scan (WBS) performed after radioiodine administration, allow for a precise diagnostics in differentiated thyroid cancer (DTC). However, some asymptomatic patients demonstrate negative WBS despite a high Tg serum concentration. In these subjects, fluorodeoxyglucose-positron emission tomography (FDG-PET) should be considered. The primary aim of our study was to evaluate a diagnostic value of FDG-PET in asymptomatic hyperthyroglobulinemia. The secondary one was to determine a prognostic value of a negative FDG-PET result in DTC patients with elevated Tg level. MATERIAL: One hundred and ten FDG-PET/CT scans were retrospectively analyzed, 85 scans were done under TSH stimulation and 25 on LT4 suppressive therapy. Follow-up ranged between 4 and 9 years. RESULTS: The first FDG-PET/CT detected cancer foci in 49 subjects with a global sensitivity of 45%. When the sensitivity was evaluated with reference to TSH stimulation and suppression, its values were 50 and 28% respectively. In 42 patients, FDG-PET failed to diagnose the reason for elevated Tg level. During further follow-up, in 17 of them, DTC recurrence was detected by other methods (CT, MRI, US). Fourteen subjects with asymptomatic hyperthyroglobulinemia were free of DTC progression for at least 4 years. CONCLUSIONS: FDG-PET in DTC patients with asymptomatic hyperthyroglobulinemia constitutes a valuable diagnostic tool. Negative FDG-PET demonstrated a limited prognostic significance, as only every third patient did not show DTC progression. Moreover, negative FDG-PET does not justify less strict DTC monitoring, because it is related to 40% risk of relapse during the 5-year follow-up.

Juvenile differentiated thyroid carcinoma and the role of radioiodine in its treatment: a qualitative review.

Well under 15% of differentiated thyroid carcinoma (DTC) is diagnosed at < or =18 years of age. The population is heterogenous and the differences between prepubertal children and pubertals and adolescents are to be considered. Although very little has been reported on children with sporadic DTC under the age of 10 years, juvenile DTC has at least some undeniable differences with adult DTC: (1) larger primary tumor at diagnosis; (2) metastatic pattern and features, namely: (a) greater prevalence of neck lymph node and distant metastases at diagnosis, (b) lungs almost the sole distant metastatic site, (c) pulmonary metastases nearly always functional; (3) closer-to-normal and more frequent sodium-iodide symporter (NIS) expression; and (4) higher recurrence rate but longer overall survival. These differences are especially distinct in prepubertal children. The goals of primary treatment of juvenile DTC are to eradicate disease and extend not only overall, but recurrence-free survival (RFS). Extending RFS is itself a desirable goal in children because it improves quality-of-life, alleviates anxiety during psychologically formative years, reduces medical resource consumption, and may increase overall survival. Primary treatment of DTC generally comprises a combination of surgery, radioiodine ((131)I) ablation, and thyroid hormone therapy applied at varying levels of intensity. Therapeutic decision-making must rely on retrospective adult and/or pediatric outcome studies and on treatment guidelines formulated mostly for adults. Differences between juvenile and adult DTC and physiology dictate distinct treatment strategies for children. We, and many others, advocate a routine intensive approach because of the more advanced disease at diagnosis, propensity for recurrence, and greater radioiodine responsiveness in children, as well as published evidence of significant survival benefits, especially regarding RFS. This intensive approach consists of total thyroidectomy and central lymphadenectomy in all cases, completed by modified lateral lymphadenectomy when necessary and followed by radioiodine administration. However, absence of prospective studies and of universal proof of overall cause-specific survival benefits of this approach have led some to propose more conservative strategies. Most European centers give radioiodine ablation to the vast majority of juvenile DTC patients. Ablation seeks to destroy any residual cancer, including microfoci, as well as healthy thyroid remnant. Large studies have documented the procedure to decrease cause-specific death rates and, in children, to significantly lessen locoregional recurrence rates (by factors of 2-11) independent of the extent of surgery. There is universal agreement on treating inoperable functional metastases with large radioiodine activities. Treatment is especially effective in small tumor foci up to 1 cm in diameter, and should be administered every 6-12 months until complete response, loss of functionality, or attainment of cumulative activities between 18.5-37 GBq (500-1000 mCi). Radioiodine therapy is generally safe. Short-term side effects include nausea and vomiting (more frequent in children than in adults), transient neck pain and edema, sialadenitis (<5% incidence), mild myelosuppression (approximately 25%), transient impairment of gonadal function both in females and males (sperm quality in boys), or nasolacrimal obstruction (approximately 3%), with most cases generally being asymptomatic-moderate, self-limiting, or easily prevented or treated. If pregnancy is ruled out before each (131)I administration, and conception avoided in the year afterward, radioiodine therapy appears not to impair fertility. However, therapeutic (131)I carries a small but definite increase in cancer risk, particularly in the salivary glands, colon, rectum, soft tissue and bone. To better guide primary treatment, different therapeutic combinations should be prospectively compared using RFS as the primary endpoint. Efforts also should be made to identify molecular signatures predicting recurrence, metastasis and mortality.

Estimation of risk of inherited medullary thyroid carcinoma in apparent sporadic patients.

PURPOSE: The study was undertaken to evaluate the frequency of inherited medullary thyroid carcinoma (MTC) among patients with apparent sporadic disease. A stepwise algorithm was used depending on clinical indices and the age of patient at MTC diagnosis. PATIENTS AND METHODS: One hundred sixteen patients with MTC verified by postoperative pathologic examination were subjected to genetic analysis of RET exons 10, 11, 13, 14, and 16 by means of polymerase chain reaction, restriction endonuclease digestion, and DNA sequencing. RESULTS: Among 116 apparent sporadic MTC patients, we identified eleven (9.5%) RET germline mutation carriers. Seven of these (6.0%) were found by routine analysis (exons 10 and 11). The frequency of inherited disease among patients younger than 45 years at diagnosis was 10.2% by analysis of typical mutations in exons 10 and 11. Extended genetic analysis (sequencing of exons 11, 13, 14, and 16) yielded 6.1% additional diagnoses, giving a risk of 16.3% in this age group. One previously unreported mutation in exon 11 affected codon 649 (TCG>TTG, Ser>Leu). In the true sporadic MTC patients younger than 30 years at diagnosis, frequencies of 36% and 4.5% in polymorphic variants L769L and S836S, respectively, were observed. The frequency for L769L was higher than in older patients (P <.05). CONCLUSION: The frequency of inherited disease among apparent sporadic medullary thyroid carcinoma patients is close to 10% in the Polish population of MTC patients. The extended analysis of all known RET proto-oncogene mutation sites is obligatory in patients younger than 45 years at diagnosis, but we also see the need to analyze the impact of rarer mutations in older patients.

Postnatal treatment of rats with the beta 2-adrenergic agonist salbutamol influences the volume of the sexually dimorphic nucleus in the preoptic area.

Sexual differentiation of the brain seems to be influenced by postnatal interaction of gonadal steroids with neurotransmitter systems, in particular the adrenergic system. Stimulation or inhibition of adrenergic receptors during early postnatal development had previously been shown to influence steroid-induced sexual differentiation of rat brain function. In the present study newborn male and female rats were treated daily for 5 days with salbutamol, a specific beta 2-receptor agonist, or with alprenolol, a beta-receptor antagonist and the volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA) was examined in adulthood. This nucleus, one of the most striking sex differences in brain anatomy, is several-fold larger in male than in female rats. Postnatal treatment with salbutamol increased SDN-POA volume in female and in male rats. The effect was particularly striking in males, because any previous pre- and/or postnatal treatment of male rats with large amounts of gonadal steroids had been unable to increase the volume of the SDN-POA above normal. The beta-receptor antagonist alprenolol had no effect on SDN-POA differentiation. The results indicate that beta 2-adrenergic stimulation influences development and differentiation of the SDN-POA.

Influence of the corticotropin releasing hormone (CRH) on the brain-blood barrier permeability in cerebral ischemia in rats.

The increase in the blood-brain barrier (BBB) permeability and a developing cerebral oedema due to the ischemic infarction appear a few hours, and intensify during a few days, after closing the carotid arteries. It fails to be clear, however, what causes the increase in the microvessels damage, and whether the damage is a secondary result of the vasoactive substances released by the neurones and glia cells damaged by the ischemia. CRH, which plays an essential role in integrative the nervous, endocrine, and immunological systems, has a positive effect on the decrease in the permeability of the BBB damaged by various physical and chemical factors. Therefore, the examination of the CRH role in the cerebral ischemia may prove useful for explaining the processes taking place in the foci of the cerebral infarction and their environment. The experiment was carried out on rats which, 20 minutes before closing of both internal carotid arteries, was administered 10 microg CRH to cerebrospinal fluid via cisterna magna of the brain. The BBB permeability was measured 30 minutes, 3 hours, 3 days, and 7 days after closing the arteries. The experiment has shown the CRH protective effect on the BBB and its consequent effect on the decrease in the BBB permeability which appears in the 3 hours after closing the arteries (p<0.05), and is high significant during the chronic phase of the cerebral ischemia (p<0.03). It can be thus concluded that CRH, by affecting directly the endothelium of the cerebral vessels, decreases the endothelial damage in the acute phase of the ischemia. The decrease is noted to be more significant in the chronic phase of the ischemia; such an effect can be attributed to CRH stimulating the hypothalamic-adrenal axis, and to the secondary activation of the mechanisms decreasing the BBB permeability.

Corticotropin releasing hormone (CRH) increases beta-endorphin (beta-end like) concentration in cerebrospinal fluid of rats with vasospasm following subarachnoid hemorrhage.

The chronic stage of vasospasm occurring several days after subarachnoid hemorrhage (SAH) is characterized by the development of histopathologic changes in cerebral arteries causing cerebral ischemia. Numerous experimental data indicate the involvement of immune mechanisms in the angiopathy caused by SAH. Endogenous opioids play also an important role in the ischemic lesions of the brain. Corticotropin releasing hormone (CRH) induces the release of beta-endorphin (beta-END) from hypothalamic neurons and also from mononuclear white blood cells. The function of CRH and beta-END in vasospasm following SAH and the interrelationship between neuroendocrine and immune changes requires further elucidation. In the present study we investigated the influence of CRH injected into cerebral cisterna magna (CM) of rats on beta-END-like level in cerebrospinal fluid (CSF) in acute and chronic phase of cerebral vasospasm following artificial SAH. Acutely CRH induced a significant rise of beta-END-like in CSF both in SAH and sham SAH rats. However, in rats subjected to SAH, a single injection of CRH caused a prolonged rise of 5-END in CSF, which was also seen 2 days after SAH, during the chronic phase of vasospasm. The obtained results indicate that CRH increases neuroendocrine changes induced by SAH, probably by an activation of immune cells involved in the patomechanism of chronic vasospasm.

A comparison of the clinical usefulness of CA 19-9 and CA 50 in the diagnosis and monitoring of gastrointestinal cancers.

We compared serum levels of CA 19-9 and CA 50 in 108 patients with malignant neoplasms of the stomach, pancreas, liver, and colon with the serum levels in 60 patients with benign gastrointestinal diseases, and 10 healthy subjects. Increased serum levels of CA 19-9 and CA 50 were found in 51.8 and 62% of the cancer patients, respectively. The results of CA 19-9 and CA 50 assays in the nonneoplastic group showed less specificity. False positive results were noted in 11.7% of CA 19-9 tests and in 31.6% of CA 50 tests. We concluded that in gastrointestinal cancer, the CA 19-9 test should be performed initially. CA 50 determination can be useful, but the lower specificity of the test should be taken into consideration. CA 50 should be recommended only for postoperative monitoring, especially in patients with normal CA 19-9 serum levels.

Molecular changes in thyroid neoplasia.

All authors integrating the known facts into a model of thyroid carcinogenesis concur that two main histotypes of thyroid cancer exhibit different routes of molecular development. RET rearrangements are an initiating event in papillary carcinoma, and simultaneously the most characteristic mutation for this type of cancer. They are followed by further, not well recognized, mutations. RAS mutations are regarded as a crucial event in the development of follicular tumors already at the adenoma step, while in papillary cancer they belong to the spectrum of secondary mutations, enabling tumor progression. Aberrant DNA methylation, causing loss of P16 tumor supressor gene, may be a common event in both types of cancer. Aneuploidy is seen much more frequently in follicular than in papillary cancer, which also exhibits a low rate for loss of heterozygosity and microsatellite instability. Mutations of the P53 tumor supressor gene are a common feature of undifferentiated thyroid cancers and could be responsible for their aggressive phenotype. RET rearrangements have been proposed as identifying fingerprints for irradiation induced thyroid cancer in children. Our own data speak against this hypothesis. We noted a high frequency of RET/PTC3 mutations in a group of Polish children with papillary thyroid carcinoma, regarded as sporadic cancer.