Prognostic factors of overall and prostate-specific antigen-progression-free survival in metastatic castration-resistant prostate cancer patients treated with 177 Lu-PSMA-617. A single-center prospective observational study.

BACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) is characterized by heterogeneity among patients as well as therapy responses due to diverse genetic, epigenetic differences, and resistance mechanisms. At this stage of the disease, therapy modalities should be individualized in light of the patients' clinical state, symptoms, and genetic characteristics. In this prospective study, we aimed to evaluate the outcome of patients with mCRPC treated with 177 Lutetium labeled PSMA-617 therapy (PSMA-RLT), as well as baseline and therapy-related parameters associated with survival. METHODS: This prospective study included 52 patients who received two to six cycles of PSMA-RLT. Primary endpoints were overall survival (OS) and prostate-specific antigen (PSA)-progression-free survival (PFS). 18 F-Fluorodeoxyglucose (FDG) and 68 Ga-PSMA (PSMA) Positron Emission Tomography/Computer Tomography (PET/CT) scans were performed for a comprehensive assessment of tumor burden and heterogeneity. Biochemical, imaging, clinical, and therapy-related parameters were analyzed with the Kaplan-Meier, log-rank, and Cox regression analyses to predict OS and PFS. RESULTS: Median OS and PSA-PFS were 17.7 (95% confidence interval [CI]: 15.2-20.2) and 6.6 months (95% CI: 4.5-8.8), respectively. Primary resistance to PSMA-RLT (hazard ratio [HR]: 12.57, 95% CI: 2.4-65.2, p: 0.003), <30% PSA response rate after first cycle of PSMA-RLT (HR: 1.016, 95% CI: 1.006-1.03, p: 0.003), FDG > PSMA disease (HR: 4.9, 95% CI: 1.19-20.62, p: 0.03), PSA doubling time (PSA DT) of ≤2.4 months (HR: 15.7, 95% CI: 3.7-66.4, p: <0.0001), and low hemoglobin levels (HR: 0.59, 95% CI: 0.41-0.83, p: 0.003) were correlated with poor OS in the multivariate analysis. Bone scintigraphy > PSMA disease (HR: 5.6; 95% CI: 1.8-17, p: 0.002) and high C-reactive protein (HR: 1.4, 95% CI: 1.1-1.7, p: 0.001) were significant predictive biomarkers for PFS in the multivariate analysis. CONCLUSION: PSA response rate and pattern to PSMA-RLT are the most important predictors of survival in patients receiving PSMA-RLT. Being a strong predictive biomarker, combined FDG and PSMA PET can be helpful for the decision of PSMA-RLT eligibility.

Bone scintigraphy as a gatekeeper for the detection of bone metastases in patients with prostate cancer: comparison with Ga-68 PSMA PET/CT.

OBJECTIVES: Gallium-68-labeled prostate-specific membrane antigen (Ga-PSMA) positron emission tomography (PET)/computed tomography (CT) is a valuable diagnostic tool for the detection of bone metastases in patients with prostate cancer (PCa). However, bone scintigraphy (BS) with technetium-labeled diphosphonates is cheap and widely available for the same patient population. PSMA PET comes with a cost, and financial constraints in the present economic environment may require its more selective use. In this study, we aimed to compare the diagnostic performance of BS with Ga-PSMA PET/CT for the detection of bone metastases in patients with PCa and correlate the results with various clinical and biochemical variables. MATERIALS AND METHODS: Ninety-five patients who underwent Ga-PSMA PET/CT and BS within 3 months for newly diagnosed or recurrent PCa were extracted from our database. Lesion, region and patient-based analyses were performed. Clinical and imaging follow-up was used as the reference test. Results were compared with tumor grade, serum prostate-specific antigen (PSA), and alkaline phosphatase (ALP) values. RESULTS: On the patient-based analysis, 75% (42/56) and 98.2% (55/56) of the patients with bone metastases were correctly diagnosed by BS and Ga-PSMA PET, respectively. In 26/95 patients with equivocal lesions on BS, Ga-PSMA PET correctly reclassified skeletal involvement in 11 and excluded metastases in 15 patients BS missed bone metastases in 3 patients. The true-positive rate of BS in patients with serum ALP ≥ 120U/L and PSA ≥ 50 ng/ml was 95.8% and 87.5 respectively. CONCLUSION: Ga-PSMA is superior to BS for the evaluation of metastatic disease in patients with PCa. However, BS can also detect bone metastases in patients with PCa with a minimum sensitivity of 75%. Biochemical data are helpful to select patients with a high pretest probability who should undergo BS first as a part of the initial workup from an economic point of view. Due to its higher cost, Ga-PSMA PET should be performed in a selective group of patients when BS results are inconclusive or metastasis-directed therapy is planned.

Integration of 68Ga-PSMA-PET/CT in Radiotherapy Planning for Prostate Cancer Patients.

To assess the role of Gallium-labeled-prostate-specific membrane antigen PET/CT (Ga-PSMA-PET/CT) in risk group definition and radiotherapy planning in the initially planned definitive radiotherapy (RT) for prostate cancer patients. METHODS: The clinical data of 191 prostate cancer patients treated with definitive intensity-modulated RT were retrospectively analyzed. All patients were initially staged with thoracoabdominal CT and bone scintigraphy, and the second staging was performed using Ga-PSMA-PET/CT. Both stages were evaluated for the decision making of RT and any change in RT target volumes. RESULTS: After staging with Ga-PSMA-PET/CT, 26 patients (13.6%) had risk group changes, 16 patients (8.4%) had an increase in risk group, and 10 patients (5.2%) had a decrease in risk group. Down-staging occurred in 22 patients (11.5%), and upstaging was observed in 30 patients (15.7%). A total of 26 patients (13.6%) had nodal stage changes. After the Ga-PSMA-PET/CT scans, the number of metastatic patient increased to 17 (8.9%), with 4 of them moving from oligo- to polymetastatic disease. An additional irradiation of pelvic lymphatics and metastatic site was performed in 13 patients (6.8%) and 6 patients (3.2%), respectively. The RT was aborted in 4 patients (2.1%) because of parenchymal or distant site metastasis observed in the Ga-PSMA-PET/CT. CONCLUSIONS: We found that Ga-PSMA-PET/CT causes considerable migration in stage, risk group, and RT field arrangements, especially in high-risk patients regardless of the GS and baseline prostate-specific antigen values alone. Ga-PSMA-PET/CT seems to have a great influence on RT decision making in prostate cancer patients.

Thyroid volumes and serum VEGF levels in dyslipidemic patients: effects of statin treatment

Background/aim: Defective vascularization may be important in thyroid nodular disease. In this study, we aimed to investigate serum vascular endothelial growth factor (VEGF) levels in dyslipidemic patients with thyroid nodules, as well as the effects of statin therapy Materials and methods: The study included 37 dyslipidemic patients with thyroid nodules and 32 dyslipidemic patients without thyroid nodules. Anthropometry, serum VEGF levels, biochemical parameters, thyroid-stimulating hormone (TSH), free triiodothyronine (fT3) and free thyroxine (fT4) levels, and thyroid sonography were determined before and after 6 months of statin therapy. Results: Patients with and without thyroid nodules had similar metabolic parameters. Serum VEGF levels did not differ between the groups. In patients with nodules, VEGF levels remained unchanged (P = 0.931) after statin therapy. However, serum VEGF levels were lowered by statin treatment in patients without nodules (P = 0.030). Statin therapy resulted in a decrease in the dominant thyroid nodule volume. The changes in thyroid volume and dominant thyroid nodule volume were not correlated with changes in VEGF, body mass index, total cholesterol, low-density lipoprotein cholesterol, or homeostatic model assessment of insulin resistance (HOMA-IR). Conclusion: Although statin treatment decreases serum VEGF levels in dyslipidemic patients without thyroid nodules, it has no lowering effect on serum VEGF levels in patients with thyroid nodules. The decrease in thyroid nodule volume with statin treatment was associated with neither metabolic parameters nor serum VEGF levels.

68Ga-labelled PSMA ligand HBED-CC PET/CT imaging in patients with recurrent prostate cancer.

BACKGROUND: 68Ga-PSMA Positron Emission Tomography/Computerized Tomography (PET/CT) has shown promising results for the detection of recurrent prostate cancer (RPCa). However, the diagnostic value of this method is yet to be validated. The aim of this study was to determine the influence of clinical and biochemical variables on the detection rate of 68Ga-PSMA PET/CT in patients with RPCa. METHODS: This is a prospective study of 121 patients who underwent 68Ga-PSMA-PET/CT and conventional imaging (CI) for RPCa. Detection rates were analyzed and correlated with various clinical and biochemical variables such as Gleason score GS), androgen deprivation therapy (ADT), trigger PSA (tPSA), PSA doubling-time (PSAdt) and PSA velocity (PSAv). RESULTS: 68Ga-PSMA-PET/CT showed at least one focus of pathological 68Ga-PSMA uptake in 92/121 (76%) of patients. Nodal metastases (in 47% of patients) were the most common site of recurrent disease followed by bones (36%) and prostate (32%). Out of 121 patients, 57 (47%) had only positive findings on PSMA scan verified by biopsy or follow-up. The majority of these lesion were located in the lymph nodes (31/57, 54,5%), which were below the detection limit of CT. Univariate analysis showed higher detection rate of PET/CT with increasing tPSA, PSAv and short PSAdt. Best cutoff for tPSA, PSAv and PSAdt was 0.5 ng/ml, 2.25 ng/ml/year and 8.65 months, respectively. The detection rate of PSMA-PET/CT was higher in patients with high grade tumors (GS > 7, 23.7% vs 76.3%) and in patients who were on ADT during of PSMA scan (76.3% vs 96%). In multiple logistic regression analysis, PSAdt and concurrent ADT were identified as predictors of positive 68Ga-PSMA-PET/CT. CONCLUSION: 68Ga-PSMA-PET/CT is useful for re-staging patients with RPCa and has improved performance compared with CI for disease detection. Detection rates are improved in patients on ADT and with short PSAdt.

Value of CT, FDG PET-CT and serum tumor markers in staging recurrent colorectal cancer.

BACKGROUND: Serum tumor markers and computed tomography (CT) are the most widely accepted monitoring tools for the follow-up patients with colorectal cancer (CRC). Positron emission tomography (PET) with 18[F]-fluorodeoxyglucose (FDG) is a promising modality for the evaluation of recurrent CRC. The purpose of this study was to (1) investigate the sensitivity and specificity of serum tumor marker assay, CT and FDG PET-CT, (2) determine the correlation of these markers with FDG PET-CT quantitative indices such as maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) in patients suspected to have recurrent CRC. PATIENTS: FDG PET-CT imaging was performed in 212 patients with possible CRC recurrence. A retrospective study was performed on patients with (1) a history of CRC with complete remission after treatment, (2) pathology of adenocarcinoma and (3) increase in cancer antigen 19-9 (CA 19-9) and/or carcinoembryonic antigen (CEA) or suspicious radiological evaluation during follow-up after complete remission. METHODS: All patients underwent integrated FDG PET-CT scan. Serum tumor markers were obtained within 3 months of PET-CT. All enrolled cases showed increase in a tumor marker over the reference value on at least two serial measurements or abnormal CT scan before PET-CT was performed. Results were compared with histopathological findings or clinical follow-up. RESULTS: Following exclusion of 57 patients with missing data or lost to follow-up, 155 patients (87 men, mean age: 61 years) remained for final analysis. Serum CEA and CA 19-9 had a sensitivity of 74 and 35% and specificity of 86 and 83% for the detection recurrent CRC, respectively. The sensitivities of CT and FDG PET-CT were 79 and 92% and specificities were 45 and 100%, respectively. At an adaptive threshold of 42%, the median SUVmax, SUVmean, MTV and TLG of these lesions were 8.8, 5.2, 11.3 cm[Formula: see text] and 55.4, respectively. All FDG PET-CT quantitative parameters correlated positively with serum CEA levels, and the correlation coefficients were 0.45, 0.44 and 0.49 for SUVmax, MTV and TLG [Formula: see text]. CONCLUSION: PET-CT scan, CEA and CA-19-9 results were correlated. However, both tumor markers had poor sensitivity to detect metastatic disease. PET-CT is more accurate than CT in detecting recurrent CRC in this study. Majority of the recurrences were in the liver and the sensitivity is affected by tumor histology. The correlation between semiquantitative FDG PET parameters and serum tumor marker levels is moderate.

Comparison of 800 and 3700 MBq iodine-131 for the postoperative ablation of thyroid remnant in patients with low-risk differentiated thyroid cancer.

INTRODUCTION: The initial treatment of differentiated thyroid cancer is thyroidectomy, followed by remnant ablation with iodine-131 (I-131) in some patients. However, controversy exists concerning the appropriate radioiodine dose. The aim of the study is to compare the success rate of low and high activities of I-131 for postoperative remnant ablation. PATIENTS AND METHODS: A total of 108 nonmetastatic low-risk patients (mean age: 46, 85% women) with papillary and follicular carcinoma had I-131 ablation for the postoperative thyroid remnant. Fifty-three patients received a low dose (L) (800 MBq) and 55 patients received a high dose (H) (3700 MBq) of I-131. After total thyroidectomy, thyroid bed I-131 uptake (RAIU) and neck ultrasonography (USG) were performed to determine the remnant volume and the iodine avidity, which were used to calculate the dose delivered to the remnant tissue. The success rate of I-131 ablation was assessed with four different criteria based on serum thyroglobulin (Tg) and USG with and without the utilization of I-131 diagnostic whole-body scintigraphy (DxWBS). Ablation was considered to be successful if patients fulfilled all of the following criteria. (a) Strict criteria based on three tests: (i) USG negative, (ii) no tracer uptake or less than twice the background activity in the thyroid bed on DxWBS and/or up to 0.2% RAIU, and (iii) Tg < 0.2 ng/ml; (b) lax criteria based on three tests: (i) USG negative, (ii) no tracer uptake or less than twice the background activity in the thyroid bed on DxWBS and/or ≤ 0.2% RAIU, and (iii) Tg < 2 ng/ml; (c) strict criteria based on two tests: (i) USG negative and (ii) Tg < 0.2 ng/ml; (d) lax criteria based on two test: (i) USG negative and (ii) Tg < 2 ng/ml. RESULTS: When three tests were used to define successful ablation, in group L, 32 out of 53 (60%) and 43 out of 53 (81%) patients were successfully treated versus 35 out of 55 (64%) and 42 out of 55 (76%) for group H on the basis of strict and lax criteria, respectively (P=NS). The differences were not statistically significant between the two groups when only two tests were used to define ablation success (62 vs. 69% with strict and 89 vs. 87% with lax criteria, respectively). CONCLUSION: Our findings suggest that remnant thyroid tissue in patients with low-risk, well-differentiated thyroid cancer after total thyroidectomy can be ablated with 800 MBq of I-131. The success rate is not different from that obtained with 3700 MBq I-131.

Is the predicted postoperative FEV1 estimated by planar lung perfusion scintigraphy accurate in patients undergoing pulmonary resection? Comparison of two processing methods.

BACKGROUND: Estimation of postoperative forced expiratory volume in 1 s (FEV1) with radionuclide lung scintigraphy is frequently used to define functional operability in patients undergoing lung resection. We conducted a study to outline the reliability of planar quantitative lung perfusion scintigraphy (QLPS) with two different processing methods to estimate the postoperative lung function in patients with resectable lung disease. METHODS: Forty-one patients with a mean age of 57 +/- 12 years who underwent either a pneumonectomy (n = 14) or a lobectomy (n = 27) were included in the study. QLPS with Tc-99m macroaggregated albumin was performed. Both three equal zones were generated for each lung [zone method (ZM)] and more precise regions of interest were drawn according to their anatomical shape in the anterior and posterior projections [lobe mapping method (LMM)] for each patient. The predicted postoperative (ppo) FEV1 values were compared with actual FEV1 values measured on postoperative day 1 (pod1 FEV1) and day 7 (pod 7 FEV1). RESULTS: The mean of preoperative FEV1 and ppoFEV1 values was 2.10 +/- 0.57 and 1.57 +/- 0.44 L, respectively. The mean of Pod1FEV1 (1.04 +/- 0.30 L) was lower than ppoFEV1 (p < 0.0001) but increased on day 7 (1.31 +/- 0.32 L) (p < 0.0001); however, it never reached the predicted values. Zone and LMMs estimated mean ppoFEV1 as 1.56 +/- 0.45 and 1.57 +/- 0.44 L, respectively. Both methods overestimated the actual value by 50% (ZM), 51% (LMM) and 19% (ZM), 20% (LMM) for pod 1 and pod 7, respectively. This overestimation was more pronounced in patients with chronic lung disease and hilar tumors. No significant differences were observed between ppoFEV1 values estimated by ZM or by LMM (p > 0.05). CONCLUSIONS: PpoFEV1 values predicted by both the zone and LMMs overestimated the actual measured lung volumes in patients undergoing pulmonary resection in the early postoperative period. LMM is not superior to ZM.

Differential renal function estimation by dynamic renal scintigraphy: influence of background definition and radiopharmaceutical.

OBJECTIVES: Differential renal function (DRF) calculation with 99mTc-diethylenetriamine-pentaacetic acid (DTPA) or mercaptoacetyltriglycine (MAG3) is gaining clinical importance in the evaluation of patients with ureteropelvic junction obstruction with hydronephrosis (HN). Although many decisions regarding surgery are based on the functional changes detected by serial diuretic renography, the reliability of DRF estimation has been questioned. Factors such as the correction of nonrenal activity included in the renal region of interest (background subtraction) and immature function resulting in poor renal extraction may cause unusual elevation in the differential function. The aim of this study is to evaluate the impact of the radiopharmaceutical and positioning of the background on the DRF. PATIENTS AND METHODS: A prospective study was undertaken in 83 patients (48 male, 35 female, median age 5 years) with unilateral or bilateral ureteropelvic junction obstruction with or without HN. Forty-five and 38 renograms were performed with 99mTc-DTPA and 99mTc-MAG3, respectively. DRF was calculated using two different regions of interest (subrenal and perirenal) for background subtraction. Of the 83 patients, 37 also had dimercaptosuccinic acid scans. The difference between DRF based on background selection, age, radiopharmaceutical, and correlation with dimercaptosuccinic acid uptake was analyzed. The difference in DRF between two background (BG) drawings (sebrenal and perirenal) and 95% confidence intervals were calculated. RESULTS: For 83 renograms, the mean difference was 4.82 (range -7 to +25, SD 5.26). The 95% confidence intervals were -3.67 to 5.97. Analysis of the data revealed that greater spread of DRF between the techniques was seen in patients with right HN (mean 7.96, P<0.001). In patients with right HN, when lower pole background activity was used, the right renal function was overestimated by an average of 4.67%. When MAG3 was used, all patients had statistically significant DRF for the different BG subtraction techniques, whereas the DRF values were only statistically different in those with right HN when DTPA was used. DISCUSSION: The current study supports the existence of BG-related variation in the DRF calculations. We found that the average counts in the perirenal BG more precisely represent nonrenal activity and recommend the use of semilunar-perirenal background region of interest to reduce the overlapping hepatic activity.

Gated myocardial perfusion scintigraphy in children with myocarditis: can it be considered as an indicator of clinical outcome?

PURPOSE: Myocarditis is an inflammation of the heart muscle and represents a challenge for diagnosis and treatment. On account of the lack of sensitivity and specificity of routine cardiac tests, there is a need for accurate diagnostic imaging. The aim of this study is to review the role of gated 99Tc-methoxyisobutylisonitrile myocardial perfusion scintigraphy (G-MPS) in the diagnosis and follow-up of the patients with myocarditis in comparison with gallium scintigraphy. MATERIALS AND METHODS: Thirteen patients with a clinical diagnosis of myocarditis were included in the study. All underwent rest G-MPS and the images were then evaluated by quantitative perfusion single-photon emission computed tomography and quantitative gated single photon emission computed tomography software program. Visual evaluation of perfusion was performed as well as analysis of motion with thickening function [expressed as summed rest score, summed motion score, and summed thickening score (STS)] with calculation of ejection fraction (EF) and lung-to-heart (L/H) ratio. Eight patients underwent 67Ga scintigraphy. Clinical, echocardiography, and cardiac enzymes (creatinine kinase-MB, myoglobulin, troponin T, brain natriuretic peptide) data were gathered from the patients' charts. Clinical outcome was grouped according to prognosis. Spearman's correlation (SC) test was used for comparison analysis. RESULTS: Myocardial perfusion defects were observed in eight patients. Perfusion defects in the left ventricle involve a mean of 7.25% (range: 1-11%), whereas wall motion abnormality on G-MPS was more prominent, which showed to be a better marker for myocardial inflammation and necrosis. The 67Ga scintigraphy findings were normal in all, but two. The G-MPS EF (33+/-21%) was slightly lower than the echocardiography EF (40+/-15%), but with close correlation (SC coefficient: 0.635). Comparison of scintigraphic findings with clinical parameters showed that summed motion score with G-MPS EF and STS with L/H ratios were highly correlated (0.932 and 0.622, respectively). The maximum brain natriuretic peptide and L/H ratio with STS were highly correlated with the patients' outcomes (SC coefficient: -0.621, 0.821, and 0.579, respectively), as well. CONCLUSION: Tc-methoxyisobutylisonitrile G-MPS is therefore helpful in providing additional diagnostic and prognostic information in patients with myocarditis.

99mTc sestamibi myocardial perfusion scintigraphy with the novel use of metamizol for the detection of perfusion reversibility.

PURPOSE: This study aims to investigate whether induction with metamizol, an analgesic-antipyretic drug having spasmolitic activity, could be used to increase the detectability of ischemic/jeopardized myocardium during MPS (myocardial perfusion scintigraphy). MATERIALS AND METHODS: Metamizol-enhanced rest MPS (45 min after administration of 1 g metamizol orally, 740 MBq (99m)Tc sestamibi was injected, MPS was acquired 45 min later) was performed in 21 patients who had perfusion defects on their previous stress-rest (99m)Tc sestamibi MPS. Blood pressure was monitored at 15-min intervals. Stress, rest, metamizol-rest MPS images were interpreted on the model of 20 segments using a visual uptake score (VUS; 0 = normal, 1 = mild, 2 = moderate, 3 = significant decreases, 4 = no uptake). (99m)Tc sestamibi uptake ratios (MIBI-UR; mean counts in the region of the perfusion defect/mean counts in the region of the normal-perfused wall) were obtained on each MPS and compared with each other. Average MIBI-UR in each scintigraphic examination was calculated. MPS were compared with coronary angiography results. RESULTS: VUS and MIBI-UR results showed that metamizol-rest MPS displayed the defect reversibility better than rest MPS. Of the 14 segments with fixed perfusion defects on stress-rest MPS, 8 showed improvement of perfusion after metamizol induction. In 33 segments, lesion reversibility was better delineated on metamizol-rest MPS. Metamizol-induced sestamibi uptake was significantly higher (p < 0.001) than stress/baseline rest examinations as calculated by the MIBI-UR. Blood pressure remained unaltered. Coronary angiography results were in concordance with metamizol induced MPS. CONCLUSIONS: Metamizol-enhanced rest MPS increases detectability of ischemic/viable myocardium during MPS. Metamizol should be discontinued like nitrates before stress MPS since it may mask the visualization of ischemic perfusion defects.

Amniotic fluid ferritin as a marker of intestinal damage in gastroschisis: a time course experimental study.

BACKGROUND/PURPOSE: Intestinal damage (ID) is closely related to morbidity and mortality in gastroschisis. This study was performed to determine the intraamniotic substances that may correlate ID and also to verify their time course levels that would be useful for determining when ID starts in gastroschisis. METHODS: In this study, 13-day-old fertilized chick eggs were used. The amnioallantoic membrane was perforated to create amnioallantoic cavity in all embryos. Gastroschisis was created in gastroschisis group to simulate human gastroschisis. Amnioallantoic fluid samples were collected from the embryos on the 13th to 19th gestational days, and the intestines of each group were harvested for evaluation. Amnioallantoic levels of interleukin-8, ferritin, alkaline phosphatase, and amylase were measured. Serosal thickness of the intestines in each group was evaluated. RESULTS: Increasing amnioallantoic fluid levels of interleukin-8, alkaline phosphatase, and amylase were found in both groups. In contrast to control group, ferritin levels, as a sign of inflammation, were found increased only in gastroschisis group. Histopathologic examination of intestines in the gastroschisis group showed a significant increase in the serosal thickness especially after the 16th day. CONCLUSION: Increases in amnioallantoic fluid levels of ferritin show promise as a marker for determining ID encountered in gastroschisis but warrant further investigation.

Inter- and intraobserver variability of (99m)Tc-DMSA renal scintigraphy: impact of oblique views.

UNLABELLED: (99m)Tc-Dimercaptosuccinic acid (DMSA) scintigraphy is a frequently used diagnostic test to assess the presence and severity of cortical damage. The aim of this study is to investigate the variability in the interpretation of (99m)Tc-DMSA scans, evaluate the usefulness of oblique images, and assess their impact on scan interpretation. METHODS: Two experienced nuclear medicine physicians independently interpreted 100 (99m)Tc-DMSA scans (197 kidneys) 4 times. Interpretation was twice based on posterior projection images and twice based on posterior and posterior oblique projection images. For each kidney, the observers had to choose between the following results: normal, abnormal, and indeterminate. The indices of variability used were the percentage of agreement, kappa-statistic, and marginal homogeneity. RESULTS: Intraobserver and interobserver reproducibility (kappa-values) varied between 0.683 and 0.708 and between 0.609 and 0.671, respectively, for posterior images. Disagreement in (99m)Tc-DMSA scan interpretation occurred in 18% of kidneys within observers and in 21% of kidneys between observers when only posterior images were used. Oblique views changed the interpretation in 14% and 11.5% of kidneys for the first and second observers, respectively. The use of oblique views increased the agreement rate within and between observers (kappa-values, 0.725-0.812 and 0.768-0.732, respectively; mean agreement, 86.5 and 87.25, respectively). CONCLUSION: Oblique views were found useful in approximately 13% of kidneys and affected inter- and intraobserver variability. Our results suggest that oblique views should be used routinely in children with clinically suspected urinary tract infection to reliably interpret images.

Primary sternal osteomyelitis in a healthy child due to community-acquired methicillin-resistant Staphylococcus aureus and literature review.

Primary sternal osteomyelitis is a rare condition. Most of the recent cases have been reported in intravenous drug abusers. A 4-y-old male case of primary sternal osteomyelitis due to community-acquired methicillin-resistant Staphylococcus aureus with no apparent risk factors is reported. The diagnosis should be suspected in a young patient presenting with acute inflammatory swelling over the sternum. While bacteriological culture results are pending, antibiotic therapy with Staphylococcus aureus coverage should be initiated empirically and the possibility of community-acquired methicillin-resistant S. aureus must be borne in mind. In this report we also review the literature of paediatric primary sternal osteomyelitis.

Urinary trypsin inhibitor present in fetal urine prevents intraamniotic meconium-induced intestinal damage in gastroschisis.

BACKGROUND/PURPOSE: Contact with amniotic fluid causes intestinal damage in gastroschisis, and intraamniotic meconium has been shown to be responsible. Meconium has been shown to contain a significant amount of IL-8, which may be the responsible cytokine for harmful effects of meconium. Neonatal urine contains high amount of urinary trypsin inhibitor (UTI) compared with adult human urine. Urinary trypsin inhibitor has been shown to exert inhibitory effects on IL-8. Therefore, far from being destructive, presence of fetal urine in the amniotic fluid might be beneficial because human urine contains UTI. An experimental study has been performed to investigate whether presence of intraamniotic human urine (consequently UTI) besides meconium is beneficial on intestines of chick embryo with gastroschisis. METHODS: Five-day-old fertilized chick eggs were used. Gastroschisis was created through amniotic cavity without opening the allantoic cavity. Sterile urine and meconium were obtained from newborn humans. Study was conducted in 2 stages. In the first stage, gastroschisis was created, and meconium suspensions at minimal harmful meconium concentration were prepared using natural and denatured human neonatal urine and instilled into the amniotic cavity. In the second stage of study, various concentrations of UTI plus meconium suspension at minimal harmful meconium concentration was instilled into the amniotic cavity. RESULTS: Serosal thickening, inflammation, and focal fibrin deposits were observed in intestines of the groups with meconium and meconium in denatured urine. Histopathologic features of intestines of the group with meconium in natural urine did not differ from the intestines of the control group. Histopathologic examination of intestines of groups with meconium and meconium plus 50 U/mL UTI showed serosal thickening, inflammation, focal fibrin, and collagen deposits. Histopathologic features of intestines of the groups with 1:400 intraamniotic meconium plus 100 and 200 U/mL UTI did not differ from the intestines of control group. CONCLUSION: Urinary trypsin inhibitor 100 U/mL prevented the intestinal damage via inhibiting IL-8, which is contained by 1:400 concentration of meconium. Therefore, besides the existence of threshold level of meconium, the existence of UTI, which is capable of inhibiting IL-8 contained by threshold level of meconium, may be a factor in the occurrence of intestinal damage in gastroschisis.

Value of 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) gated SPECT for the detection of silent myocardial ischemia in hemodialysis patients: clinical variables associated with abnormal test results.

BACKGROUND: Although coronary artery disease is a major cause of mortality and morbidity in patients undergoing hemodialysis, there is no accurate diagnostic strategy for these patients. AIM: To assess the value of 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) gated single-photon emission computed tomography for the detection of silent myocardial ischemia in patients undergoing hemodialysis and to evaluate the clinical variables associated with abnormal test results. METHODS: Thirty-one asymptomatic patients undergoing hemodialysis (20 men, 11 women), with a mean age of 45 years (range, 25-75 years), were included in the study. Serum electrolytes, creatinine, homocysteine and adhesion molecules were measured prior to dialysis. Ambulatory blood pressure, carotid intima-media thickness measurements, echocardiography and stress 99mTc-MIBI imaging were performed in all patients, whereas coronary angiography was performed only in patients with abnormal myocardial perfusion scintigraphy and/or echocardiography. RESULTS: Gated myocardial perfusion scintigraphy results were abnormal in nine patients (29%) and coronary angiography was abnormal in six patients. After a median follow-up of 20 months (range, 14-28 months), nine patients experienced a cardiac event. Seven of the nine patients (78%) with abnormal myocardial perfusion scintigraphy suffered a cardiac event, compared with only two of 22 patients (9%) with normal myocardial perfusion scintigraphy (P<0.0001). Patients with abnormal perfusion scintigraphy had higher serum C-reactive protein, homocysteine and adhesion molecule levels and the duration of hemodialysis was significantly longer. CONCLUSION: In asymptomatic hemodialysis patients, gated myocardial perfusion scintigraphy is a safe and non-invasive screening technique for the detection of coronary artery disease and for predicting future cardiac events. The presence of ischemia correlates significantly with markers of inflammation. The discordant results (abnormal myocardial perfusion scintigraphy/normal coronary angiography) can be attributed to angiographically unrecognized occult atherosclerotic changes and abnormal vasodilatation capacity of the coronary circulation.

To use MIBI or not to use MIBI? That is the question when assessing tumour cells.

99mTc-sestamibi (MIBI) is a well-known tumour imaging agent. Its retention within tumour cell mitochondria is related to perfusion and to the magnitude of the electrical gradient, reflecting cell viability. Several internal cell factors modulate this uptake; for example, multidrug resistance membrane proteins (Pgp and MRP1) and anti-apoptotic BCl-2 protein of the outer mitochondrial membrane can limit retention of MIBI. At the early stage of cell apoptosis, the electrical driving forces of MIBI uptake are impaired, and influx and accumulation are reduced. It seems clear that MIBI can be used before treatment to detect drug resistance, assess anti-apoptotic status and predict treatment efficacy. Although it has been suggested that MIBI might be used to monitor tumour response to treatment, MIBI is unable to differentiate tumours with ongoing apoptosis from those developing drug resistance.

Value of technetium scintigraphy and iodine uptake measurement during follow-up of differentiated thyroid cancer.

UNLABELLED: Measurement of serum thyroglobulin (Tg) levels and I-131 whole body scintigraphy (WBS) are used in the follow-up of patients with differentiated thyroid cancer (DTC). This study was designed to evaluate the significance of persistent I-131 uptake in the thyroid bed in patients with DTC following surgery and/or radioactive iodine ablation. Tc-99m thyroid scintigraphy (TS) and I-131 thyroid uptake (IU) were also performed to determine their clinical impact on patient management. PATIENTS AND METHODS: Sixty-two non-metastatic patients (14 men, 48 women) with a mean age of 44 years (range: 16-75) who had undergone surgical thyroidectomy for DTC were evaluated prospectively. All patients had undergone technetium and iodine scintigraphy (IS). Although serum Tg levels were measured in all patients, IU was available in 36. RESULTS: Tg values were in the range of 0.2-24 ng/ml (median: 0.2 ng/ml) when patients were in the hypothyroid state. I-131 WBS detected residual tissue in the neck in 30 patients (48%); however TS was positive in only 12 (19%). I-131 uptake in the thyroid bed ranged from 0 to 14% (median: 0.1%). Twelve of 13 patients with positive IS and negative TS had uptake values < or = 0.3% (p < 0.00001). When IU values were < or = 0.3%, 54% of our patients did not have any uptake in the thyroid bed on TS or IS, whereas when IU was > 0.3%, 80% of patients had neck uptake on both TS and IS (p < 0.00001). CONCLUSION: The results of this study demonstrate that the concordance of IS and TS depends on the IU level after suspension of replacement therapy. Measurements of IU and TS are of considerable value in evaluating patient response to therapy and will substantially reduce the need for repetitive radioiodine scans and unnecessary treatment doses in patients with undetectable Tg values.

Association between activated renin angiotensin system and bone formation in hemodialysis patients: is the bone mass genetically determined by ACE gene polymorphism?

BACKGROUND: Angiotensin II (ang II) receptor subtype I binding sites has been recently demonstrated on bone cell precursors. Ang II stimulates DNA and collagen synthesis in human adult bone cells. The aim of this study is to evaluate the role of renin angiotensin system in the bone metabolism and to address the genetic influence of angiotensin converting enzyme (ACE) gene polymorphism on bone mass in hemodialysis patients. METHODS: Forty-eight end-stage renal disease patients (28 male, 20 female mean age 42+/-13 years,) on maintenance hemodialysis were included in the study. Bone mineral density (BMD) was estimated at lumbar spine and T score worse than -1.5 were considered as osteopenia. Serum parathyroid hormone (iPTH) and osteocalcin (OC), bone alkaline phosphatase (bAP) and carboxy terminal propeptide type 1 collagen (PICP) levels were measured as markers of bone metabolism. Plasma renin activity (PRA), serum ACE activity and ACE gene polymorphism (II, ID, DD) were determined. RESULTS: Bone mineral density and T score of the hemodialysis patients were 0.92+/-0.17 g/cm2 and -1.36+/-1.50, respectively. Twenty-one patients (43,7%) were osteopenic (T score worse than -1.5) and mean T score of osteopenic patients was -2.72+/-0.72. T score of nonosteopenic group was -0.29+/-0.99. Serum calcium, serum, phosphorus, serum OC, serum bAP, serum PCIP, serum PTH levels were similar in osteopenics and nonosteopenics. No difference was observed in predialysis PRA and in both pre- and postdialysis serum ACE activity of patients in both groups. PRA after hemodialysis in nonosteopenic group was higher than osteopenics (p<0.05). Percent increment in PRA in hemodialysis patients was correlated with T score (R=0.48 p <0.05). Serum ACE activity was positively correlated with serum iPTH (R=0.29, p=0.02), serum OC (R=0.35, p=0.01), serum bAP (R=0.34, p=0.01), serum PCIP (R=0.36, p=0.01). T score (-0.7+/-1.5, vs -1.7+/-1.3 p <0.05) was higher in DD group (n=19) compared to II+ID group (n=29). CONCLUSIONS: Association of biochemical and radiological signs of increased bone formation with activated RAS in hemodialysis patients might be an evidence for the involvement of this system in the regulation of bone metabolism.