Dorota Pach

Repeated cycles of peptide receptor radionuclide therapy (PRRT)--results and side-effects of the radioisotope 90Y-DOTA TATE, 177Lu-DOTA TATE or 90Y/177Lu-DOTA TATE therapy in patients with disseminated NET.

PURPOSE PRRT is a known tool in the management of patients with disseminated and inoperable NETs. The aim of study was to assess the effectiveness of the repeated cycles of PRRT in patients with disseminated and inoperable NETs. MATERIAL AND METHODS Eighty nine patients were included in the PRRT. Among them 16 patients (18%) were qualified for a repeated PRRT cycle due to progression of the disease. In one of the patients qualified for the repeated cycle, PRRT was used as neoadjuvant therapy. The results and side-effects of the repeated cycles of PRRT were analyzed. RESULTS Disease stabilization was observed in 10 patients 6 months after the repeated PRRT cycle and in 5 patients after 12 and 18 months. Ten of the patients who had received repeated PRRT cycles died. In the case of neoadjuvant therapy, further reduction of the tumor size was observed, enabling qualification for surgery. Clinically significant reduction in the mean values of morphological parameters was not observed. Only after 12 and 18 months the mean values of creatinine levels were higher than the normal range (only in 2 patients). CONCLUSIONS The repeated cycles of PRRT did not cause a clinically significant increase of the toxicity of PRRT. The changes in kidney and blood morphology parameters were transient. The repeated cycles of PRRT enabled stabilization of the disease.

Factors connected with the female sex seem to play an important role in differentiated thyroid cancer

Aim. The aim of the study was to analyze whether female sex hormones and other factors connected with the female sex could increase the risk of differentiated thyroid cancer (DTC). Material and methods. Ninety-nine patients with a mean age±SD of 40.5±5.9 years with DTC and 51 healthy women with a mean age of 36.52±8.3 years were examined. Gynecological and obstetric histories were taken and serum estradiol and progesterone levels were analyzed in all women. Results. Patients with DTC had more frequent menstrual cycle disturbances, used hormone-containing medicines more frequently, were mulitiparous more frequently, had spontaneous miscarriages more frequently, and their duration of lactation was significantly shorter than in controls. The mean serum estradiol level±SD in women with DTC was significantly higher than in the controls, in the follicular phase 193.74±66.31 vs. 157.63±42.88 pmol/l and in the luteal phase 519±176.9 vs. 369±71.49 pmol/l. The mean serum progesterone level±SD was higher in the controls than in patients with DTC, in the follicular phase: 2.11±0.70 vs. 1.38±0.56 nmol/l and in the luteal phase 20.95±17.46 vs. 17.31±12.28 nmol/l. Conclusions. The results of these studies imply that estrogens may at least modify the proliferation of thyroid cancer cells. The sex hormones probably intensify the actions of other carcinogens as well.

Prevention of type 2 diabetes by lifestyle intervention in primary health care setting in Poland: Diabetes in Europe Prevention using Lifestyle, physical Activity and Nutritional intervention (DE-PLAN) project:

Aim To find out whether diabetes prevention via a lifestyle intervention programme is feasible in a primary healthcare setting in Poland. Methods The intervention (Diabetes in Europe: Prevention using Lifestyle, physical Activity and Nutritional intervention; DE-PLAN project) was completed by 175 middle-aged, slightly obese participants in nine primary healthcare centres in Krakow, Poland. The inclusion criterion was diabetes risk (Finnish Diabetes Risk score (FRS) >14). The nurse-delivered intervention consisted of 10 group

Amiodarone and the thyroid.

Amiodarone, a benzofuranic iodine-rich antiarrhythmic drug, causes thyroid dysfunction in 15-20% of cases. Amiodarone can cause both hypothyroidism (AIH, amiodarone-induced hypothyroidism) and thyrotoxicosis (AIT, amiodarone-induced thyrotoxicosis). AIH is treated by L-thyroxin replacement and does not need amiodarone discontinuation. There are two main forms of AIT: type 1, a form of true iodine-induced hyperthyroidism; and type 2, a drug-induced destructive thyroiditis. However, mixed/indefinite forms exist, contributed to by both pathogenic mechanisms. Type 1 AIT usually occurs in diseased thyroid glands, whereas type 2 AIT develops in substantially normal thyroid glands. Thioamides represent the first-line treatment for type 1 AIT, but iodine-replete glands are poorly responsive; sodium/potassium perchlorate, by inhibiting thyroidal iodine uptake, may increase the response to thioamides. Type 2 AIT is best treated by oral glucocorticoids. Response depends on thyroid volume and severity of thyrotoxicosis. Mixed/indefinite forms may require a combination of thioamides, potassium perchlorate, and steroids. Radioiodine treatment is usually not feasible because amiodarone-related iodine load decreases thyroidal radioiodine uptake. Thyroidectomy represents an important and helpful option in cases resistant to medical therapy. Surgery performed by a skilled surgeon may represent an emergent treatment in patients who have severe cardiac dysfunction.

Are RECIST criteria sufficient to assess response to therapy in neuroendocrine tumors

MATERIAL AND METHODS Within the group of 47 patients treated with peptide receptor radionuclide therapy (PRRT), four patients were chosen: three with inoperable tumors without liver metastases and one with two lesions in the pancreas and metastases. RESULTS In all patients, after PRRT, the changes in the sum of the longest diameters of tumors were between -1% and -21%, resulting in stable disease reported [strict Response Evaluation Criteria in Solid Tumors (RECIST)]. But the measurements of tumor volume and attenuation in computed tomography and the tumor to nontumor ratio in somatostatin receptor scintigraphy resulted in different response assessments. CONCLUSIONS The RECIST standard may be not sufficient to properly assess the therapy response in patients with neuroendocrine tumors.

Incretins Yesterday, Pleiotropic Gastrointestinal Hormones Today:Glucagon-Like Peptide-1 (GLP-1) and Glucose-ependent Insulinotropic Polypeptide (GIP)

Incretins, which are insulinotropic gastrointestinal hormones, are produced mainly in K and L cells of the small intestine under the influence of nutritional stimuli. The best known incretins are glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). These hormones perform several functions: they stimulate insulin secretion in the pancreatic beta cells; they inhibit glucagon release from the alpha cells of the pancreas (GIP not in humans); they slow down gastric emptying and may directly suppress appetite; and, moreover, they indirectly increase peripheral glucose tolerance/insulin sensitivity. The insulinotropic and glucagonostatic effects of GLP-1 are glucose dependent. The incretins also have numerous other properties which are still being discovered and introduced in different branches of medicine. The patents mentioned in this work concern the use of incretins in diabetology, cardiology, gastroenterology and nuclear medicine. The pleiotropic effects of incretins offer therapeutic possibilities in numerous fields of medicine.

Can treatment using radiolabelled somatostatin analogue increase the survival rate in patients with non-functioning neuroendocrine pancreatic tumours?

BACKGROUND The aim of the study was to assess the effectiveness of peptide receptor radionuclide therapy (PRRT) in patients with non-functioning neuroendocrine pancreatic tumours (NFPNTs) and to compare survival rates in patients with NFPNTs and in patients with other neuroendocrine tumours (NETs) treated using radiolabelled somatostatin analogue in our Department. We would like to analyze factors potentially determining the effectiveness of the therapy and also to assess the myelo- and nephrotoxicity. MATERIAL AND METHODS Fourteen patients with disseminated disease and/or inoperable NFPNT were qualified to PRRT based on positive SRS (somatostatin receptor scintigraphy). There were 5 men and 9 women, with Karnofskys index>70%. RESULTS In the whole group of patients, partial response was observed in 21.4%, stabilization of the disease in 42.9%, and progression of the disease in 35.7% of patients. Mean observation time was 19±13 months, mean time to progression was 12±9 months, and mean time to death was 16±9 months. Six patients died--four of them due to progression of the disease, two due to myocardial infarction. After PRRT we did not observe clinically significant haemotoxicity and/or nephrotoxicity. CONCLUSIONS 1. Peptide receptor radionuclide therapy may be a safe and effective treatment option in patients with NFPNTs, leading to stabilization or regression of the disease in the majority of patients. 2. There is no statistically significant difference in survival rate between patients with NFPNTs and NETs of other localization treated with PRRT.

Dietary patterns as risk factors of differentiated thyroid carcinoma.

UNLABELLED Nutritional factors are known to be important in the development of different metabolic diseases. The history of nodular or diffuse goiter is closely related to risk of thyroid carcinoma. On account of the function of the thyroid gland, many studies focus on iodine intake. The aim of the study was to assess whether dietary patterns could be risk factors of differentiated thyroid carcinoma. MATERIAL/METHODS The case-control study was based on a questionnaire, which included information about dietary patterns and was carried out on 284 patients comprising 30 males (mean age 58.4±13.7 years), and 254 females (mean age 52.1±13.8 years), as well as 345 randomly selected controls: 58 males (mean age 60.2±12 years) and 287 females (mean age 53.4±14.3 years) randomly selected from the Population Register and adjusted by age and gender to the group of TC. The main groups of nutritional products, i.e. starchy foods, meat, dairy products, vegetables, fruits, and beverages, were analyzed. RESULTS Consumption of vegetables, fruits, saltwater fish and cottage cheese was significantly lower in patients with differentiated thyroid carcinoma than in controls, quite the contrary to starchy foods, especially white bread. CONCLUSIONS Dietary patterns appear to modify the risk of thyroid carcinoma. A diet rich in vegetables and fruit, as well as saltwater fish (a source of iodine) and low-fat meat, could be an important protective factor.

Current and Future Medical Therapy, and the Molecular Features of Adrenocortical Cancer

Adrenocortical carcinoma (ACC) is a rare neoplasm with very poor prognosis despite the recent development of aggressive antitumor therapies. The cause of adrenal cancer remains elusive, but some molecular mechanisms could be responsible for its development. Target-specific therapies have been developed for a number of human malignancies and have resulted in therapeutic benefits in some cancer patients. However, these therapies are only effective in cases in which the corresponding targets are expressed in tumor tissues. Molecular analysis has had a significant impact on the understanding of the pathogenetic mechanism of ACC development and the evaluation of prognostic and predictive markers, among which alterations of the IGF system, the Wnt pathway, p53 and molecules involved in cancer cell invasion properties and angiogenesis seem to be very promising. These molecular markers may not just play a role in the biology of these tumors and have prognostic implications, but can also be used as potential targets for treatment. The aim of this review is to summarize the genetic and molecular events implied in the pathogenesis of ACC and to highlight challenges to the development of anticancer agents in recent patents.

Reference Values for TSH and Free Thyroid Hormones in Healthy Pregnant Women in Poland: A Prospective, Multicenter Study

Objectives: The diagnosis and treatment of thyroid diseases in pregnant women remains a challenge. Various medical associations recommend establishing the reference intervals for thyroid hormones by a local laboratory. Considering differences within geophysical, socioeconomic conditions, and iodine prophylaxis in various populations, it is advisable to assess reference intervals for thyroid hormones specific to a region of residence. The objective was to assess trimester-specific reference intervals for TSH, fT3, and fT4 for pregnant women in the Polish population. Methods and Results: We conducted a prospective study in 4 centers representing different regions of Poland (Krakow, Warsaw, Poznan, and Bialystok). Our study included consecutive, healthy pregnant women (172 patients), with an age range of 27-47 years. All women had a negative history for thyroid diseases, normal thyroid peroxidase antibody levels, and proper iodine prophylaxis. All newborns had TSH levels in the appropriate reference range. Serum TSH, fT3, fT4, and thyroid-peroxidase antibodies were measured in each trimester. The reference intervals were calculated using the percentile method, as recommended by the International Federation of Clinical Chemistry. The reference values calculated were 0.009-3.177, 0.05-3.442, and 0.11-3.53 mIU/L for TSH; 3.63-6.55, 3.29-5.45, and 3.1-5.37 pmol/L for fT3; and 11.99-21.89, 10.46-16.67, and 8.96-17.23 pmol/L for fT4 in consecutive trimesters of pregnancy. Reference intervals for pregnant women when compared to the general population showed a lower concentration of TSH in every trimester of pregnancy and lower fT4 in the 2nd and 3rd trimesters. Conclusions: Using appropriate trimester-specific reference intervals may improve care of pregnant women by preventing misdiagnosis and inadequate treatment.