99mTc-MDP bone scintigraphy in the diagnosis of stress fracture of the metatarsal bones mimicking oligoarthritis

Background. Stress fractures are the injuries of soft tissues and bones caused by intensive and repeated stress on a bone. Repeated submaximal stress disturbs the balance between the processes of bone production and resorption that results in fracture. Case report. We presented a case of a patient with stress fracture of metatarsal bone. The patient was diagnosed and treated as having reactive oligoarthritis caused by Chlamydia trachomatis and administered antibiotics. Initial plain radiography was negative for bone fracture. Tc-99m bone scintigraphy suggested stress fracture of the second metatarsal. Plain radiography was became positive three weeks later, showing callus formation in the proximal part of the second metatarsal. Conclusion. Bone scintigraphy is a diagnostic test of choice in early diagnosis of stress fracture, and it is important to apply it timely in order to include the entire therapy and prevent complications, as well as to let a patient return to previous daily activites

Korelacija lokalne i sistemske ekspresije survivina sa patohistološkim parametrima melanoma kože

Background/Aim. Survivin is a multifunctional protein abundantly expressed in tumors of various types, including melanoma. There are still sparse data regarding relationship of melanoma cell survivin expression with accepted histopathological characteristics as well as serum concentration. The aim of this study was to investigate the association of local tumor survivin expression (primary tumor and metastatic lesions) and serum concentration with clinical and histopathological parameters in melanoma patients. Methods. The level of survivin expression was determined immunocytochemically in tumor tissue and with ELISA test in the serum of 84 melanoma patients diagnosed from 2009 to 2013 at the Institute for Pathology and Forensic Medicine and Institute for Medical Research at Military Medical Academy, Belgrade, Serbia. Results. The intensity of survivin expression was significantly higher in the patients whose tumor had ulceration, higher mitotic index, higher Clark and Breslow stage, that made vascular invasion or spread through lymphatic vessels in primary tumor, and was significantly higher in the patients with metastatic disease. Survivin expression and the number of survivin positive cells in metastatic lesions were significantly associated with the duration of disease free interval (DFI). The patients with high expression score had almost double shorter DFI comparing to those with weak local survivin expression and a small number of surviving + cells (9 ± 7 vs 19 ± 13 months, respectively). The degree of tumor infiltrating lymphocytes presence in tumor tissue was significantly associated with serum survivin concentration, with lowest average level detected in samples of patients with the highest degree of infiltration. Serum survivin concentrations were highest in samples of melanoma patients with IA American Joint Commission on Cancer (AJCC) clinical stage, pT1a histological stage, patients whose tumors were still in horizontal growth phase, without signs of lympho-hematological disease spreading, with the highest number of mitoses and the smallest Clark index. Conclusion. Survivin expression in tumor tissue and its serum concetration significantly correlate with clinical and histopathological parameters. Serum levels could be important in initial follow-up as indicators of those patients that would have aggressive local tumor growth and spreading. Survivin determination in tumor tissue is of great significance in estimation of DFI.Uvod/Cilj. Survivin je multifunkcionalni protein bogato ispoljen u tumorima različite vrste, uključujući i melanom. Retki su radovi koji opisuju odnos ispoljavanja survivina u melanomskim ćelijama sa njegovom serumskom koncentracijom kao i sa histopatološkim karakteristikama melanoma. Cilj rada bio je da se ispita udruženost lokalne ekspresije survivina u tumoru (primarni tumor i metastatske promene) i serumske koncentracije sa kliničkim i histopatološkim parametrima kod bolesnika sa melanomom. Metode. Nivo ekspresije survivina određivan je imunocitohistohemijski utumorskom tkivu i ELISA testom u serumu 84 bolesnika sa melanomom, dijagnostikovanih u periodu od 2009. do 2013. na Institutu za patologiju i sudsku medicínu i Institutu za medicinska istraživanja na Vojnomedicinskoj akademiji, Beograd, Srbija. Rezultati. Intezitet ekspresije survivina bio je značajno veći kod bolesnika čiji su tumori bili ulcerisani, sa visokim mitotskim indeksom, visokim Clark i Breslow indeksom, sa prisutnom vaskularnom i limfnom invazijom, kao i kod onih sa metastatskom bolesti. Ispoljavanje survivina i broj survivin pozitivnih ćelija u metastatskim lezijama bio je značajno udružen sa trajanjem intervala bez bolesti (disease free interval - DFI). Bolesnici sa visokim skorom ekspresije imali su skoro dvostruko kraći DFI u odnosu na one sa sla­bom lokalnom ekspresijom survivina i malim brojem survivin pozitivnih ćelija (9 ± 7 vs 19 ± 13 meseci). Stepen prisustva tumor infltrišućih limfocita u tumorskom tkivu bio je značajno udružen sa koncetracijom survivina u serumu, sa najnižim prosečnim vrednostima detektovanim u uzorcima bolesnika sa najvećim stepenom infiltracije. Serumske koncentracije survivina bile su najveće u uzorcima bolesnika sa melanomom IA kliničkog stadijuma American Joint Commission on Cancer (AJCC), pT1a histološkog stadijuma, bolesnika čiji su tumori bili u horizontalnoj fazi rasta, bez znakova širenja limfohematogenim putem, sa najvećim brojem mitoza i koji su imali najmanji Clark indeks. Zaključak. Ekspresija survivina u tumorskom tkivu i njegova serumska koncentracija značajno korelišu sa kliničkim i histopatološkim parametrima melanoma. Serumski nivo može biti važan kao inicijalni indikator kod onih bolesnika koji bi mogli imati agresivan lokalni tumorski rast i širenje. Određivanje survivina u tumorskom tkivu, kako u primarnom tumoru tako i u metastazama, od velikog je značaja u utvrđivanju trajanja DFI

Diagnostic validity of dynamic salivary gland scintigraphy with ascorbic acid stimulation in patients with Sjögren's syndrome: Comparation with unstimulated whole sialometry

Background/Aim. Beside many actual groups of classification criteria, uniform classification criteria for Sjögren’s syndrome (SS) are still missing. The ophtalmic component of SS is well defined. Criteria for classifying its oral component remain controversial. The fifth item of the European Union and the United States of America (EU-US) revised diagnostic classification criteria in 2002, is an objective evidence of xerostomia, diagnosed by one of the tests: unstimulated whole sialometry (UWS), parotid sialography, and dynamic salivary gland scintigraphy (DSGS). The aim of this study was to evaluate senstitivity, specificity, positive and negative predictive value and accuracy of DSGS with ascorbic acid stimulation in detecting xerostomia in SS patients and to compare DSGS findings with UWS values. Methods. Tests DSGS and UWS were done in 20 patients with SS and in 10 of the control subjects. The findings of DSGS were graded from 1 to 4 scintigraphie (SCT) grade 1 - normal finding; SCT grade 2 - moderate function damage; SCT grade 3 - serious function damage, SCT grade 4 - very serious function damage. UWS measured 1.5 hour after the breakfast lasted 15 minutes. UWS bellow 2.5 ml/15min min. considered pathological. Results. All SS patients had pathological SCT findings. Comparing SCT grade between the patients and the control group, high statistical significance was found (p < 0.001). The estimated sensitivity of DSGS was 100%, specificity 80%, positive predictive value 91%, negative predictive value 100% and accuracy 93%. The calculated sensitivity of UWS was 75%. Salivary function damage detected by scintigraphy was in positive correlation with UWS findings. Conclusion. DSGS is a diagnostic test with high sensitivity, specificity, accuracy and positive and negative predictive values in detecting salivary function damage in SS patients. DSGS and UWS are very sensitive diagnostic tests for objective evidence of xerostomia, and have to be ones of the earliest investigations which should be performed in subjects suspected of SS. Test DSGS is more sensitive, and seems to better reflect symptoms of dry mouth than UWS

123I-FP-CIT brain SPECT (DaTSCAN) imaging in the diagnosis of patients with movement disorders: First results

Background/Aim. 123I-FP-CIT brain single-photon emission computed tomography (SPECT), DaTSCAN imaging, offers a possibility to study structural and biochemical integrity of presinaptic dopaminergic neurotransmitter system. The aim of this study was to evaluate the usefulness of 123I-FP-CIT brain SPECT scintigraphy in patients with extrapyramidal diseases. Methods. Fifteen patients (8 males and 7 females), aged 26-81 years, presenting with extrapyramidal symptoms entered the study. Out of them, 7 patients were diagnosed with definite clinical form of idiopathic Parkinson’s disease (PD) or clinical probable for PD clinical stage 2-4 using the Hoehn&Yahr scale (H&Y); 6 patients were with atypical parkinsonism (AP), 1 patient with essential, and 1 with psychogenic tremor. SPECT was performed 180 min after injection of 185 MBq 123IFP- CIT using a dual head Gamma camera. Sixty four one minutes’ frames were acquired using a noncircular rotation mode into a 128 × 128 image matrix. Transverse slices were reconstructed using a 0.6 order Butterworth filter. Visual interpretation was based on striatal uptake, left to right asymmetry and substructures most affected. The ratio of binding for the entire striatum, caudate and putamen to nonspecific binding in occipital cortex was calculated. SPECT findings were categorized as normal and abnormal (incipient, moderate and severe presinaptic deficit). Results. 123I-FP-CIT uptake was reduced in the striatum of 6/7 patients with PD and 5/6 patients with AP. Two patients with PD and AP showed a negative finding. The remaining 2 negative results were obtained in the patients diagnosed with essential tremor and psychogenic tremor. The mean striato-occipital ratio (SDR) of the most affected side was lower in the patients with PD. Conclusion. Our first results confirm the usefulness of 123I-FPCIT brain SPECT in differential diagnosis of extrapyramidal diseases

Renal scintigraphy in infants with antenatally diagnosed renal pelvis dilatation

Background/Aim. Ureteropelvic junction obstruction and vesicoureteral reflux are the most frequent entities identified on the basis of antenatal hydronephrosis. The aim of this study was to determine the incidence and pattern of abnormal renal scintigraphy findings in postnatal investigation of children with antenatal hydronephrosis. Methods. Twenty four infants (19 boys and five girls) presented with antenatal hydronephrosis and mild to moderate hydronephrosis on ultrasound in newborn period were referred for renal scintigraphy. Ten patients with vesicoureteral reflux documented on micturating cystoureterography underwent 99mTc-DMSA renal scintigraphy and 14 patients were subjected to 99mTc-DTPA scintigraphy. Results. Anteroposterior pelvic diameter on ultrasound ranged from 11 to 24 mm. Renal DMSA scans identified congenital scars in two boys with bilateral reflux of grade V and unilateral reflux of grade III. Relative kidney uptake (RKU) less than 40% was found in three, and poor kidney function (RKU less than 10%) in two patients. Significant obstruction was shown on DTPA diuretic renal scintigraphy in 6/14 patients. Some slowing in dranaige (T1/2 greater than 10 minutes) with no reduction in differential renal function was identified in three patients. Differential renal function less than 10% was obtained in one case. Conclusion. A high percent of abnormal renal scintigraphy findings was obtained. Renal scintigraphy was useful in determination of underlying cause of antenatally detected hydronephrosis

Diuretic 99mTc DTPA renography in assessment of renal function and drainage in infants with antenatally detected hydronephrosis

Background/Aim. The controversy over the postnatal management of infants with antenataly detected hydronephrosis (ANH) still exists. We presented the results of diuretic 99mTc diethylenetriamine pentaacetic acid (DTPA) renography in 30 infants with the antenatal diagnosis of unilateral renal pelvic dilatation. The aim of this study was to assess the renal function determined by the pattern of drainage and split renal function (SRF) on diuretic renography and to correlate these findings with anteroposterior pelvic diameter (APD) estimated by ultrasonography. Methods. A total of 30 infants with 60 renal units (RU) (25 boys and 5 girls, median age 6.0 months, range 2-24) presented with unilateral hydronephrosis on ultrasound in the newborn period, underwent DTPA diuretic renal scintigraphy (F+15 protocol). The median APD evaluated on perinatal ultrasound was 15 mm (range 5-30). The postnatal associated clinical diagnosis were pelviureteric junction obstruction (PUJ), simple hydronephrosis, megaureter, vesicoureteral reflux (VUR) and posterior urethral valves in 11, 10, 6, 2 and 1 infant, respectively. Images and Tmax/2 after diuretic stimulation on the background subtracted renographic curves were used as the criteria for classifying the drainage as good, partial, and poor or no drainage. The SRF was calculated with the integral method. Results. Good drainage was shown in 36/60, partial drainage in 13/60 and poor or no drainage in 11/60 RU. The SRF >40% was observed in 55/60 RU, with no RU showing SRF lower than 23.5%. In infants with severe ANH the obstruction was not excluded in 94.1%. Conclusion. Diuretic renography in antenatally detected hydronephrosis should be a useful tool in postnatal follow up, especially in differentiating nonobstructive hydronephrosis from obstructive. It is also importanat to assess and monitor the SRF. Our results suggest that even in the presence of partial or no drainage, SRF may not be significantly impaired

Determination of metamizole metabolites in surface water and groundwater

Lekovi predstavljaju najznačajniju grupu novih zagađujućih supstanci koje se nalaze u prirodnim vodama [1]. Otpadne vode, poreklom iz domaćinstava, industrije i životinjskih farmi predstavljaju osnovne izvore zagađenja životne sredine. U prirodnim vodama, lekovi mogu biti prisutni u svojoj osnovnoj formi ili u formi metabolita. Koncentracije metabolita lekova koje su prisutne u životnoj sredini često su veće od koncentracija osnovnog leka. Metamizol je veoma popularan antipiretik i analgetik koji se koristi u mnogim zemljama preko 70 godina. Iako je, zbog sumnje da može da izazove agranulocitozu kod pacijenata, zabranjen u mnogim zemljama, u većini evropskih zemalja i dalje se koristi zbog svog analgetičkog dejstva. Posle apsorpcije metamizola u gastro-intestinalnom traktu, on potpuno hidrolizuje u 4-metil-aminoantipirin (4-MAA), koji u jetri metabolizuje u 4-aminoantipirin (4-AA), pa se dalje acetilizuje do 4-acetilaminoantipirina (4-AAA) i 4-formil-aminoantipirina (4-FAA) [2]. Krajnji metaboliti 4-AAA i 4-FAA su dosta stabilni u životnoj sredini i nađeni su u dosta visokim koncentracijama u otpadnim i prirodnim vodama [3]. U ovom radu je optimizovana, validirana i primenjena analitička metoda za određivanje metamizola i njegovih metabolita 4-AAA i 4-FAA u podzemnim i površinskim vodama

Validity of ultrasound-guided aspiration needle biopsy in the diagnosis of micrometastases in sentinel lymph nodes in patients with cutaneous melanoma

Background/Aim. Cutaneous melanoma is one of the most aggressive solid cancers, that develops local, regional and distant metastases. The presence of metastases in lymph nodes is in correlation with Breslow tumor thickness. According to various researches, in melanoma with more than 4 mm Breslow thickness, lymph node micrometastases can be found in 60-70% of cases. Sentinel lymph nodes biopsy is a diagnostic procedure for lymph node micrometastasis detection, which is necessary for disease staging. In recent studies, ultrasound-guided fine needle aspiration with cytology (US FNAC) of the sentinel lymph node was used as less invasive procedure, but is not accepted as the standard procedure. The goal of this work was to define sensitivity, specification and precision of the ultrasound-guided fine needle aspiration method in comparison with standard sentinel lymph node biopsy. Methods. After obtaining the Ethics Committee’s permission, from 2012 to 2014 a total of 60 patients with cutaneous melanoma were enrolled, and divided into three groups: group I with thin melanoma, group II with intermediate thickness melanoma and group III with thick melanoma. The presence of micrometastases in sentinel regional lymph nodes was analyzed by US FNAC. The results obtained were compared to sentinel lymph nodes biopsy (SLNB) results. The golden standard for calculating the specific, sensitive and precise characteristics of the method of US FNAC of sentinel lymph nodes was histopathologic lymph node examination of sentinel lymph nodes acquired through biopsy. Results. Detection rate of US FNAC was 0% in the group I, 5% in the group II and 30% in the group III. SLNB detection rates were: 10% in the group I, 15% in the group II, and 45% in the group III. In melanoma thicker than 4 mm, 15% of the patients were false negative by US FNAC. The sensitivity of US FNAC for all the patients was 50%: in the group I, 0%; in the group II, 33.3%; and in the group III, 66.6%. The method specificity for all examined patients was 100% and accuracy 88%: group I, 90%; group II, 90%; group III, 85%. The FNAC and SLNB micrometastasis detection rate was significantly higher in melanoma with Breslow thickness > 4 mm (group 3) in comparison to thin and intermediate thickness tumors. Conclusion. The method of ultrasound-guided fine needle aspiration of sentinel lymph nodes, according to its sensitivity, has a place in the diagnostics of micrometastasis in regional lymph nodes only in thick melanoma, but not in thin and intermediary thickness melanoma. The results must be confirmed in a larger number of patients. If this observation could be confirmed, it would rationalize treatment of patients with thick melanoma, decrease the number of operations and shorten the time to make the diagnosis

Combined bone scintigraphy with 99mTc-MDP and 99mTc-ciprofloxacin in differentiation of hip and knee prosthesis aseptic loosening and infection: A preliminary study

Background/Aim. Although the number of new primary implantation of hip and knee prostheses every year increases, the rate of failed arthroplasty is nearly the same. The main question is whether it is an aseptic instability or instability caused by infection. The aim of this preliminary study was an attempt with combined 99mTc-ciprofloxacin and 99mTc-methylene diphosphonate (MDP) bone scintigraphy to improve diagnostic accuracy in the differentiation of hip and knee prosthesis aseptic loosening and periprosthetic joint infection. Methods. Inclusion criteria of patients for this study were based on suspected periprosthetic joint infection: painful prosthetic joint, restricted joint movements and increased value of erythrocyte sedimentation rate or levels of C-reactive protein. We examined 20 patients with implanted 14 hip and 6 knee prosthesis. All patients also underwent plain radiography of suspected joint. In all patients, three-phase 99mTc-MDP bone scintigraphy was performed. Three to five days after the bone scan, we performed scintigraphy using 99mTc-ciprofloxacin with the calculation of accumulation index. Periprosthetic joint infection was confirmed on the basis of microbiological findings. Results. Periprosthetic joint infection was confirmed in fourteen of twenty observed joints, in five of them the aseptic loosening was present and in one patient’s symptoms were not related to the prosthesis (poor biomechanics of prosthetic joints caused by weaknesses of muscle). Estimated sensitivity/specificity for 99mTc-MDP bone scintigraphy alone were 100/17%; for 99mTc-ciprofloxacin scintigraphy were 85,7/100%. Sensitivity and specificity were 92,3% and 83,3%, respectively for results obtained with combined assessment by both methods. Our study confirmed the high negative predictive value of 99mTc-MDP bone scan. The negative result of bone scan virtually excludes the possibility of periprosthetic infection. On the other hand, positive findings of 99mTc-MDP scintigraphy cannot with certainty confirm the infection. Conclusion. Combined 99mTc-MDP scintigraphy with 99mTc-ciprofloxacin scintigraphy significantly increases the ability of differentiation of aseptic loosening from periprosthetic joint infection

Interferon alpha-induced reduction in the values of myeloid-derived suppressor cells in melanoma patients

Background/Aim. Interaction between tumor cells and host’s immunoregulatory cells in creation of microenvironment that supports tumor progression is the focus of numerous investigations in recent years. Myeloid-derived suppressor cells (MDSCs) are heterogeneous population of immature dendritic cells, macrophages and granulocytes. In cancer patients, these cells accumulate in tumor microenvironment, tumor-draining lymph nodes, peripheral blood and the liver and their numbers correlate with the stage of the disease and the metastatic disease. The aim of the study was to investigate the effect of interferon alpha on MDSCs percentage in peripheral blood of melanoma patients. Methods. The interferon treated melanoma patients were given subcutaneously interferon alpha, in optimal dose, for a period of at least 6 months before the analysis. Blood samples were collected from the melanoma patients (n = 91) and the age/sex matched healthy controls (n = 8). The following anti-human monoclonal antibodies were used for immunostaining: anti-CD15-FITC, anti-CD33-PE, anti-CD45-ECD, anti-HLA-DR PE/Cy5, anti-CD14-FITC, anti-CD16-PE and anti-CD11b-PE. Results. Comparison of myeloid-derived suppressor cells values in the stage 2 melanoma patients with and without interferon alpha therapy did not show a significant difference. When we compared the MDSCs values in the patients within stage 3 melanoma, we found a significant difference in granulocytic subset values between the interferon alpha-treated and the untreated group. Comparison of values of all suppressor cells populations between the interferon alpha-treated patients and healthy controls showed a significant increase in suppressor cells percentage in the melanoma patients. The granulocytic and total MDSCs values were significantly lower in the interferon alpha treated melanoma patients with progression in comparison with untreated patients with stable disease. Conclusion. We confirmed that interferon alpha effect in stage 3 melanoma patients was reduction in MDSCs percentage. We also found an unexpected bounce back of these suppressor cells levels, many months after the discontinuation of interferon alpha therapy