Contribution of PET/CT imaging to differential diagnosis of fever of unknown origin.

BACKGROUND: Vasculitis is a collective title for a heterogeneous group of diseases with common signs of inflammation, leukocytic infiltration and necrosis of the vessel wall leading to regional perfusion disturbances. There are many ways to classify vasculitis. Into the group of large-vessel vasculitis we include Takayasu´s arteritis as well as temporal arteritis (giant-cell arteritis) affecting also the aorta and its major branches. METHODS: FDG PET/CT is a hybrid imaging method combining spatial imaging of metabolic activity obtained by the detection of 18-fluorodeoxyglucose (FDG) with positron emission tomography (PET) and X-ray computed tomography (CT). While carried out together with PET imaging in the same session, CT imaging is helpful in identifying precisely the anatomical identification of hypermetabolic lesions detected via PET. RESULTS: In this case report we refer to the key contribution of PET/CT imaging to concluding successfully a diagnostic process lasting for a few months and leading to a revelation of large-vessel vasculitis manifesting itself only with systemic inflammation symptoms, i.e. without any clinical signs of specific organ damage. CONCLUSION: In conclusion, FDG PET/CT scan is a combined imaging technique which has a remarkable potential in the diagnosis of large-vessel vasculitis. This potential is particularly valued in cases when symptoms of vasculitis are clinically nonspecific and when other non-invasive methods are failing (Fig. 2, Ref. 20).

Metabolic syndrome and its effect on aortic stiffness in premenopausal women.

BACKGROUND: Metabolic syndrome (MS) is a cluster of proatherogenic risk factors (RF) (abdominal obesity, atherogenic dyslipidemia, impaired fasting glucose or type 2 diabetes mellitus, higher blood pressure or antihypertensive therapy) that move patients into a higher risk for development of cardiovascular disease (CVD) and type 2 diabetes. The preclinical (subclinical) target organ diseases (SOD) are early signs of atherosclerosis. An increased aortic stiffness characterised by an increased pulse wave velocity in aorta (PWV Ao) is one of SOD.The aim of the present study was to assess the impact of metabolic syndrome (MS) on aortic wall stiffness and the risk profile in premenopausal women. METHODS: The aortic stiffness was measured using Arteriograph-Tensiomed, based on oscillometric measurement and analysis of the shape of brachial pulse wave, giving the PWV Ao. The results of measurements characterise a global aortic stiffness. RESULTS: We examined 81 premenopausal women (without history of CVD). The MS (according to the 2009 "harmonizing" definition) was present in 31 women (mean age 41.5 y), in the control group, there were 50 women (39 y). The most frequent components of MS were abdominal obesity (93 % vs 42%), arterial hypertension (68 % vs 10 %) and dyslipidemia (29 % vs 8 %). The PWV Ao was significantly higher in women with MS (9.26 m/s) compared to the control group (7.44 m/s). CONCLUSION: The aortic stiffness in women with MS compared to controls was significantly higher despite a presumed general protective hormonal effect on cardiovascular system in women with child-bearing potential (Tab. 4, Ref. 25).

[Arterial hypertension in gravidity - a risk factor for cardiovascular diseases]. / Artériová hypertenzia v gravidite - rizikový faktor kardiovaskulárnych ochorení

Gravidity is a dynamic process and complications may occur at any stage and anytime during a thus far physiological gravidity. Such gravidity puts the mother, the foetus and, later, the newborn at a greater risk. The incidence of arterial hypertension is between 7 and 15% and is one of the 4 main causes of maternal and perinatal mortality. Cardiovascular stress test, such as gravidity, might help to identify women at a greater risk of cardiovascular diseases or with a subclinical vascular disease. Women with a history of preeclampsia are more likely to develop chronic arterial hypertension in the future either alone or associated with a cardiovascular disease. Arterial hypertension during gravidity should be considered as a risk factor for cardiovascular diseases during later stages of maternal life. Prevention of cardiovascular diseases should be a life-long aspiration.

From preoperative to intraoperative detection of hyperfunctioning parathyroid glands using tetrofosmin (99mTc) in primary hyperparathyroidism.

The impact of preoperative scintigraphy on the management of patients with primary hyperparathyroidism has been largely documented for more than two decades. More recently, preoperative scintigraphy has also been used to select patients for intraoperative detection of hyperfunctioning parathyroid glands thanks to a gamma-probe. This procedure is now widely used, with MIBI as the main radiopharmaceutical for both preoperative scintigraphy and intraoperative detection. However MIBI was not available in Slovakia until very recently and tetrofosmin (TF), the alternative 99mTc labelled radiopharmaceutical for myocardial imaging has some advantages over MIBI and a close biological behaviour. Thus we have been using TF also for parathyroid preoperative scintigraphy and for intraoperative detection, a systematic indication which has never been reported by others. This article aims to demonstrate the feasibility and to present our protocol for TF parathyroid imaging and intraoperative detection, closely associating surgeons, nuclear medicine specialists, pathologists and also biologists as intraoperative assay of intact PTH is necessary. The results of literature are subsequently reported and discussed (Tab. 2, Fig. 4, Ref. 35). Full Text in free PDF www.bmj.sk.

Diastolic blood pressure as a major determinant of tissue perfusion: potential clinical consequences.

Blood pressure measuring represents a routine investigation in general medicine. In the last decades large studies have determined average blood pressure values all around the world. Large clinical trials have shown that blood pressure reduction irrespective of the used type of therapeutic intervention reduces mortality. Based on the outcomes of these trials current guidelines for hypertension encourage more "aggressive" hypertension treatment compared to recommendations from the past. In clinical practice blood pressure is sometimes reduced even below normotensive values (at least in comparison with pre-treatment levels). However there is evidence that achieving too low levels of diastolic blood pressure during antihypertensive treatment has undesirable effects. Especially in the elderly a diastolic blood pressure reduction below 70 mm Hg should be avoided, because it is associated with increased mortality. A possible explanation of this phenomenon could be that antihypertensive treatment disequilibriates the balance between sufficient perfusion pressure and arteriolar vasodilation, both of which are required for adequate tissue perfusion. Impaired microcirculation, especially in the coronary bed may account for the increased mortality in hypertensive patients with low diastolic blood pressure levels. Thus we support the idea of cautious blood pressure reduction in the elderly. Furthermore, we suggest, that monitoring the level of tissue perfusion in treated hypertensive patients might help to provide individually tailored therapy (Fig. 1, Ref. 9). Full Text (Free, PDF) www.bmj.sk.

[Gastroenteropatic neuroendocrine tumors: multidisciplinary approach in therapy]. / Multidiscipliniárny prístup k liecbe gastroenteropankreatických neuroendokrinných tumorov.

INTRODUCTION: Gastroenteropancreatic neuroendocrine tumors (GEP-NET) are classified on the basis of hormonal activity of tumor cells to functional and non-functional tumors. Therapy of well differentiated NETs includes surgical procedures, debulking of tumor mass, biotherapy and peptid receptor radionuclid therapy. AIM OF THE STUDY: Analysis of therapeutic modalities in group of patients with well differentiated GEP-NETs. RESULTS: In time period from 1. 1. 2005 to 1. 1. 2010 we followed up 50 pts (19 men/31 women) with well differentiated GEP neuroendocrine tumors. Primary localisation was: stomach--6 times, pancreas--9 times, duodenum--1 times, jejunum-- 4 times, appendix--3 times, ileum--23 times, rectum--4 times. Metastatic disease was affirmed in time of diagnosis in 36 patients. Carcinoid syndroma had 20 pts, 4 pts with pancreatic tumor had functional tumors (2 times overproduction of calcitonine, 1 times of gastrin, 1 times of insuline). Surgical treatment was performed in 40 pts--resection of primary tumor and debulking of metastases, in 5 pts with pancreatic tumor resection was not possible due to invasion to sorrounding tissue and vessels. Biological treatment with long acting somatostatin analogues was indicated in 20 pts with carcinoid syndroma and in 4 pts with functional pancreatic tumors. In 5 pts with non resectable neuroendocrine carcinoma of pancreas peptid radionuclide receptor therapy (PRRT) was indicated: in 4 of them with 90Ytrium-DOTA-octreotid and in 1 patient with MIBG. In all pts a reduction of tumor volume was noticed. Biotherapy with somatostatin analogues reduced symptoms of hormonal activities and brought on stabilisation of disease in most of patients. In period of follow up 5 patients died. CONCLUSION: Complex therapy in patients with well differentiated neuroendocrine tumors markedly contributes to prolongation of survival of patients and also to enhancement quality of their life.

General changes in hemostasis in gastric cancer.

Disorders of haemostasis and haemocoagulation are often seen in patients with cancer as a part of paraneoplastic syndrome. Thrombotic and/or haemorrhagic complications are the second most common cause of mortality in patients with cancer. The evaluation of the haemostatic parameters of 67 patients with gastric cancer have indicated tendency to thrombophilia and activation of intravascular coagulation, of which 31.3% showed tendency to hypercoagulation and 47.8% disseminated intravascular coagulation (DIC). Only 7.5% of subjects have yielded normal laboratory findings while 5.9% of patients had DIC with remarkable hypocoagulation. Thrombocytosis, platelet hyperaggregability and elevation of beta-thromboglobulin are the indicators of changes in primary haemostasis and elevation of thrombomodulin indicates vascular wall damage. Lower antithrombin III levels, C-protein and S-protein in plasma have indicated lower antithrombotic potential in patients with gastric cancer. It can be concluded that patients suffering from gastric cancer are at higher risk of thromboembolism as for haemorrhagic diathesis (20.1% thromboembolism, 11.94% fatal thromboembolic events vs 5.9 % haemorrhagic diathesis) (Tab. 5, Ref. 22). Full Text (Free, PDF) www.bmj.sk.

Local changes in hemostasis in patients with gastric cancer.

Disorders of haemostasis and haemocoagulation are often seen in cancer patients as a part of the paraneoplastic syndrome. This study describes a novel compound that activates coagulation and also inhibits fibrinolytic system and fibrin degradation products in the gastric juice of 33 patients with gastric cancer. Similar, but less pronounced changes have been found in gastric juice of patients with gastric precancerosis. Procoagulant activity, induced by pathologically changed cells or monocytes, macrophages from tumor stroma, indicates the activation of local coagulation with the production of fibrin. It can be concluded that the local changes of coagulation and fibrinolysis may precede coagulopathies in cancer patients (Tab. 2, Ref. 15). Full Text (Free, PDF) www.bmj.sk.

Does incorporation of gene for green fluorescent protein in BP6 fibrosarcoma tumor cells depress their intraperitoneal growth in rats? (In honour of Nobel Prize laureates 2008--Osamu Shimomura, Martin Chalfie, Roger Y. Tsien).

This manuscript was in honour of Nobel Prize in chemistry "for the discovery and development of the green fluorescent protein, GFP" to Osamu Shimomura, Martin Chalfie, and Roger Y. Tsien, simultaneously a brief information about experience with GFP in experimental tumorigenesis used this study is also presented. The experimental data have showed that BP6 cells incorporated with GFP gene have had smaller ability to induce both experimental intraperitoneal and subcutaneous tumor process. It was anticipated that incorporation of GFP gene might change physiological properties of cytoskeleton and worsen adhesive characteristics of tumor cells. It was also supposed that aftertime GFP will enable to monitor proliferation of cells not only within experimental work, but also in human medicine. GFP could help (supposedly) as reporter of proliferation, but also can serve as "target" for guide of tumorigenesis inhibiting substances. These ideas which are consequences of our experiments we append as congratulation to Nobel Prize in chemistry of the 2008 (Fig. 2, Ref. 44). Full Text (Free, PDF) www.bmj.sk.

[The complexity of interactions of the tumour growth process]. / Komplexita interakcií nádorového procesu.

It was believed for rather a long time that the only components of tumour tissue are transformed cells characterised by hyper-proliferation, invasivity and immortalisation. Therapeutic strategies thus focused on autonomous proliferation and tumour cell survival. These result from oncogene activation and inactivation of tumour-suppressor genes. Research studies showed that tumour growth itself is a complex process. In addition, studies confirmed involvement of heterotypical multicellular interactions in tumour tissue. Complexity as a characteristic is one of the processes that do not demonstrate attributes of linear systems. The process of tumour growth involves certain patterns that cannot be classified according to duration and sequence. Consequently, tumour growth can be viewed as a process with features typical for complexity. From this perspective, tumour environment consists of a range of cells, such as endothelial cells and their progenitor cells, pericytes, fibroblasts, tumour-associated fibroblasts, myofibroblasts, smooth muscle cells, mast cells, T- and B-lymphocytes, neutrophils, eosinophils, basophils, NK-cells and several different forms of macrophages. At present, well-founded assumptions exist that in-depth study of intra-tumour environment might lead to formulation of new principles in tumour biology as well as introduction of new therapeutic strategies. Research into details oftumour microenvironment is needed to expand scientific knowledge as well as to, subsequently, define tumour biomarkers. Monitoring of these biomarkers will facilitate molecular diagnostics. Biomarkers will be widely used to monitor tumour growth as well as to monitor the process of treatment. Monitoring of combinations of biomarkers will enable more detailed characterisation of tumour microenvironment. These might include, apart from receptors, signal molecules, growth factors and molecules accelerating apoptosis, specific molecules as well as their combinations or neoangiogenesis or tumour innervation parameters. Tumour complexity involves not just intracellular environment but also intracellular relationships and associations between cells and extracellular tumour components. Detection of circulating tumour cells represents another parameter to be monitored. Low-molecular weight fluorescent dyes will very likely be used for their detection. It can be assumed that circulating tumour cells will be used as markers of prognosis as well as indicators of malignity progression and treatment. Scientific advances in this area will facilitate individualised therapy of patients suffering from cancers. The aim of the present review study was to analyze scientific knowledge from the perspective of acceptance of complexity and heterogeneity of each tumour. We perceived processing of the vast amounts of literature as meaningful with respect to recognition of new knowledge and theoretical preparation for expected changes in diagnostics and treatment of tumours. We believe that the presented findings are a useful step towards achievement of comprehensive insight into tumour microenvironment.

Hemosuccus pancreaticus.

In this study, authors describe a rare case of a 40-year old patient with a history of chronic pancreatitis due to ethanol abuse, repeatedly hospitalized for intermittent bleeding into gastrointestinal tract (GIT). The sources of bleeding were pseudoaneurysms of the peripancreatic arteries (gastroduodenal artery, right hepatic artery) bleeding into GIT via pancreatic duct. This type of bleeding is referred as hemosuccus pancreaticus and belongs to a rare form of bleeding into upper GIT. Development of each pseudoaneurysm was monitored with a 6 month time interval. The diagnosis was established using endoscope, Doppler ultrasound and CT angiography. During the therapeutic process, while stopping bleeding, two different radiological interventions were used. In pseudoaneurysm of gastroduodenal artery, hemostasis was achieved using selective transcatheter arterial embolization (TAE) with steel coils. In the second intervention, a stent was inserted into vascular lesion. In the discussion, authors review the problems of hemosuccus pancreaticus, epidemiology, symptoms, diagnostic and possible therapeutic approaches (Fig. 3, Ref. 31). Full Text (Free, PDF) www.bmj.sk.

Brain natriuretic peptide (BNP) in differential diagnosis of dyspnea.

BACKGROUND: The differentiation of congestive heart failure from pulmonary cause of dyspnea is of extreme importance in patients presenting with acute shortness of breath. It seems that the use of B-type natriuretic peptide (BNP) can speed up the diagnostic process significantly. MATERIAL AND METHODS: 79 patients (46 men - 58.2%, average 71.9, range 43-92; 33 women - 41.8%, average 75.5, range 51-93). In each of them we measured BNP concentrations by means of rapid fluorescent immunoassay. RESULTS: We divided the patients according to BNP results into two groups: BNP positive and BNP negative. There were 28 BNP negative patients -35.40% (13 men, 15 women). BNP positive patients (51) were divided into NYHA I-IV groups in accordance with BNP results. CONCLUSION: The rapid, highly sensitive and specific measurement of BNP concentrations in the patients with dyspnea can significantly help to differentiate the cardiac and pulmonary causes of dyspnea (Tab. 1, Fig. 1, Ref. 24).

Carcinoid tumor.

Carcinoid tumors are slow growing malignancies which occur most frequently in the gastrointestinal tract (about 74%). They can also be found in the bronchus, ovary, lung, thymus, kidney or thyroid gland. Carcinoid tumors are usually identified histologically by their affinity to silver salts, or more specifically by immunocytochemistry using antibodies against their specific cellular products. Survival rates depend on the location of primary tumor, extent of locoregional and metastatic disease, functional status of the tumor and the feasibility of complete surgical extirpation. Clinical manifestations are often vague or absent. Nevertheless, tumours secrete bioactive mediators which may in approximately of 10% of patients engender various elements of characteristics of carcinoid syndrome. Patients with advanced carcinoid disease should be treated with aggressive medical and surgical therapies. (Ref. 103.)

[Autoimmune thyroid disease in patients with type 1 diabetes mellitus]. / Výskyt autoimunitnej tyreopatie u pacientov s diabetes mellitus I. typu.

Insulin dependent diabetes mellitus type I. (IDDM) is often connected with other autoimmune diseases. The most frequently concomitant disease is autoimmune thyroiditis. The authors present the results of the observation of 33 patients. The age of patients at the beginning of the study was 39.5 (24-65) years (median + confidential intervals). In all these patients, there were performed the assessment of thyroid stimulating hormone (TSH), free thyroxine (fT4), thyroid peroxidase antibodies (AbTPO) and TSH receptor antibodies (TRAK). An ultrasound examination and percutaneous aspiratory biopsy were performed in all patients. The control examination was realised 5 years later. In 1991, primary hypothyroidism due to lymphoid thyroiditis in 12.1% and autoimmune hyperthyroidism in 3% of all patients were found. During the observation period 2 patients died. In 1996 the diagnosis of primary hypothyroidism in 9.6% and M. Graves-Basedow in 3% of all patients were confirmed. Thyroid peroxidase antibodies have been positive in 33.4% of all patients with primary hypothyroidism and they correlated with ultrasound and cytology findings. (Tab. 3, Ref. 13.)

[Therapy of metastasizing carcinoid tumor]. / Terapia metastazujúceho karcinoidu.

Carcinoids are tumors producing excessive amounts of serotonin. The authors briefly characterize the possibilities of diagnosis. The case of a 43-year-old patient with a multifold carcinoid of the ileum with metastases in the liver is used for the description of the therapy strategy. They summarize the current opinions on the therapy of this disease. (Tab, 1, Fig. 4, Ref. 14.)

Carcinoid tumors--somatostatine in the diagnosis and therapy.

BACKGROUND: Carcinoid tumors have a neuroendocrine origin and endocrine activity is typical for them. OBJECTIVES: The main objective of the present study was to determine differences in the levels of an endogenous somatostatin, a neuron specific enolase in serum and excretion of 5-HIAA in the urine in patients with carcinoid tumors and also to determine the changes of these parameters during the treatment with long acting somatostatin analogue--lanreotide. SUBJECTS AND METHODS: 30 pts with carcinoid tumors (20 pts with metastatic disease, 10 pts after resection of the primary tumor without known metastases at the time of the investigation) and 12 healthy probands were included in the study. Circadian rhythm of endogenous somatostatin in all groups was performed. Levels of neuron specific enolase in the serum and the excretion of 5-HIAA in the urine in pts with carcinoid tumors were done. The estimation of these parameters were repeated in the group of pts with advanced metastatic disease during the treatment with the lanreotide. RESULTS: We confirmed the existence of the circadian rhythm of endogenous somatostatin in all groups. Chronogram of somatostatin in pts without known metastases shows the same characteristics as the chronogram of healthy volunteers. The chronogram of pts with metastatic carcinoid disease shows a statistically significant differences in comparison with healthy volunteers--higher mesor and later acrophase of 24-hour rhythm (p < 0.05). During the therapy with lanreotide lower mesor was observed (p < 0.05). The amount of the 5-hydroxyindolacetate acid in urine in pts with metastatic carcinoid was statistically significant higher than in the pts without metastases (p < 0.001). During therapy with the lanreotide the decrease in the 5-HIAA in the urine (p < 0.05) was observed. Neuron specific enolase in the serum was higher in group with the metastatic disease (p < 0.001). CONCLUSION: Abnormalities in the somatostatin secretion and the concentration of the neuron specific enolase in serum are useful markers for the differential diagnosis and might distinguish the carcinoid patients with and without metastases. Urine excretion of 5-HIAA is a good marker of endocrine activity of the carcinoid tumor. (Fig. 4, Tab. 3, Ref. 22.)

[Primary pulmonary hypertension]. / Primárna plúcna hypertenzia.

Authors described a case of 26-year old patient with history of progressing dyspnea and repetitive syncopes. In history is intermittent hemoptysis and dyspnea from 1990. Diagnosis of thromboembolic disease was suspected. Clinical picture was dominated by dyspnea, central cyanosis, sinus tachycardia without pulmonary signs of hearth failure. On ecg there is right heart hypertrophy. Echocardiographic examination shows dilatation of right heart, systolic pressure in a. pulmonalis about 90 mmHg and tricuspidal regurgitation of the III. degree. Phlebothrombosis was not found. Complete hemocoagulation examination excluded a primary procoagulating hematologic disease. Pulmonary angiography did not confirm thromboembolic disease but found a high grade pulmonary hypertension--mean pulmonary arterial pressure of 93 mmHg. After complex pneumological examination, including HRCT, and other examinations the diagnosis of primary pulmonary hypertension was made. Patient is indicated to lung transplantation. (Fig. 4, Ref. 9.)

Malignant carcinoid in two brothers.

Familial occurrence of malignant carcinoid is rare (about 3%). Authors describe occurrence of the malignant carcinoid in two brothers. In the older one the diagnosis was estimated in 1991. He had multiple intestinal carcinoid tumor with multiple liver metastases histological type III by Soga classification. Patient is intermittently treated with somatostatin analogue--lanreotid and with interferon alfa. By this therapy the disease is stabile. In the younger of brothers the diagnosis was estimated in 1999. The disease had rapid progression and in ten months patient died despite of the therapy. Definitive diagnosis was a malignant neuroendocrine tumor of pancreas-mixed low differentiated carcinoid with calcitonin overproduction. (Fig. 4, Ref. 15.)

The occurrence of malignant carcinoid syndrome in patients with carcinoid tumors.

BACKGROUND: The carcinoid syndrome occurs in about 10% of patients with carcinoid tumors. OBJECTIVES: The main objective of the present study was to determine the presence of the carcinoid syndrome in a group of patients with carcinoid tumor. SUBJECTS AND METHODS: 35 pts with carcinoid tumors (group A--24 pts with metastatic disease, group B--11 pts after resection of the primary tumor with no metastases detected at the time of the investigation) were included into the study. The localisation and the diameter of the primary tumor were ascertained. Somatostatin receptor scintigraphy--Octreoscan and echocardiography were done. The urinary excretion of 5-HIAA was performed. We estimated the presence of the carcinoid syndrome in all patients. RESULTS: We confirmed the difference in the diameter of the primary carcinoid tumor in patients with metastases--group A 3.0 (2.5-4.2) cm by comparison with group B 0.7 (0.6-0.8) cm, (p < 0.001). Patients in the metastatic group are older 64 year (42-70) than pts without metastases--33 y (20-54) (p < 0.01). The amount of the 5-hydroxyindolacetate acid in urine in pts with metastatic carcinoid was statistically significantly higher than in the pts without metastases (p < 0.001). The carcinoid syndrome in the metastatic group was found in 6 patients (25%), with maximum (12.5%) localised in midgut. Out of the whole sample it counts up to 15.1%. During the follow up period, 8 patients from group A died. CONCLUSION: The large diameter of the primary carcinoid tumor and the higher age are the bad prognostic factors in patients with carcinoid tumors. (Tab. 4, Ref. 27.)

[The electrocardiogram in primary pulmonary hypertension]. / Elektrokardiogram u primárnej plúcnej hypertenzie.

Primary pulmonary hypertension is a rare disease characterized by a rise of arterial pressure in the pulmonary artery without a known cause. The authors define, based on a case-history, the etiopathogenesis of the disease, its diagnosis and approach to treatment. They analyze the contribution of ECG examination for detection of right ventricular hypertrophy and for monitoring the therapeutic success with the finding above all of repolarization changes in the right precordium. The patient had a transplantation of the lungs.