Semi-quantitative analysis of salivary gland scintigraphy in Sjögren's syndrome diagnosis: a first-line tool.

OBJECTIVE: The aim of this study was the assessment of semi-quantified salivary gland dynamic scintigraphy (SGdS) parameters independently and in an integrated way in order to predict primary Sjögren's syndrome (pSS). MATERIALS AND METHODS: Forty-six consecutive patients (41 females; age 61 ± 11 years) with sicca syndrome were studied by SGdS after injection of 200 MBq of pertechnetate. In sixteen patients, pSS was diagnosed, according to American-European Consensus Group criteria (AECGc). Semi-quantitative parameters (uptake (UP) and excretion fraction (EF)) were obtained for each gland. ROC curves were used to determine the best cut-off value. The area under the curve (AUC) was used to estimate the accuracy of each semi-quantitative analysis. To assess the correlation between scintigraphic results and disease severity, semi-quantitative parameters were plotted versus Sjögren's syndrome disease activity index (ESSDAI). A nomogram was built to perform an integrated evaluation of all the scintigraphic semi-quantitative data. RESULTS: Both UP and EF of salivary glands were significantly lower in pSS patients compared to those in non-pSS (p < 0.001). ROC curve showed significantly large AUC for both the parameters (p < 0.05). Parotid UP and submandibular EF, assessed by univariated and multivariate logistic regression, showed a significant and independent correlation with pSS diagnosis (p value <0.05). No correlation was found between SGdS semi-quantitative parameters and ESSDAI. The proposed nomogram accuracy was 87%. CONCLUSION: SGdS is an accurate and reproducible tool for the diagnosis of pSS. ESSDAI was not shown to be correlated with SGdS data. CLINICAL RELEVANCE: SGdS should be the first-line imaging technique in patients with suspected pSS.

Evaluation of functional outcomes after laparoscopic partial nephrectomy using renal scintigraphy: clamped vs clampless technique.

OBJECTIVES: To examine differences in postoperative renal functional outcomes when comparing clampless with conventional laparoscopic partial nephrectomy (LPN) by using renal scintigraphy, and to identify the predictors of poorer postoperative renal functional outcomes after clampless LPN. PATIENTS AND METHODS: Between September 2010 and September 2012, 87 patients with renal masses suitable for LPN were prospectively enrolled in the study. From September 2010 to September 2011, LPN with renal artery clamping was performed and from September 2011 to September 2012 clampless LPN (no clamping of renal artery) was performed. Patients who underwent clampless LPN were unselected and consecutive, and the procedure was performed at the end of surgeon's learning curve. Patients were divided into two groups according to warm ischaemia time (WIT): group A, conventional LPN and group B, clampless-LPN (WIT = 0 min). Demographic and peri-operative data were collected and analysed and functional outcomes were evaluated using biochemical markers and renal scintigraphy at baseline and at 3 months after surgery. The percentage loss of renal function, evaluated according to renal scintigraphy, was calculated. Chi-squared and Student's t-tests were carried out and regression analysis was performed. RESULTS: Group A was found to be similar to group B in all variables measured except for WIT and blood loss (P < 0.001). The percentage reduction in renal scintigraphy values was not significantly different between the groups (reductions of 5% in group A and 6% in group B for split renal function [SRF] and 12% in group A and 17% in group B for estimated renal plasmatic flow [ERPF]; P = 0.587 and P = 0.083, respectively). Multivariate analysis in group B showed that the lower the baseline values of SRF and ERPF, the poorer the postoperative functional outcome of the treated kidney. CONCLUSIONS: In our experience, even clampless LPN was not found to be functionally harmless. The patients who benefitted most from a clampless approach were those with the poorest baseline renal function.

The effects of warm ischaemia time on renal function after laparoscopic partial nephrectomy in patients with normal contralateral kidney.

PURPOSE: To assess the effects of warm ischaemia time (WIT) on renal function after laparoscopic partial nephrectomy (LPN) for renal masses in patients with a normal contralateral kidney. METHODS: From October 2006 to December 2008, 53 patients treated with LPN were enrolled in this prospective study. Effective renal plasma flow (ERPF) was estimated with 99mTc-mercaptoacetyltriglycine renal scintigraphy before the intervention and after 3 and 12 months. Multiple linear regression analysis was used to assess the effects of demographic and operative variables on postoperative renal function. Logistic regression analysis was used to evaluate the associations between the same variables and a ≥20% reduction in postoperative ERPF compared with baseline (defined as significant loss of renal function-LRF). ROC curve analysis was used to identify potential ischaemia time cut-off points. RESULTS: Fifty-one patients were eligible. The mean lesion size was 30 mm, and the mean WIT was 21.9 min. Longer WIT was associated with lower postoperative ERPF values (P < 0.001). A logistic regression model confirmed that longer WITs were significantly associated with ERPF decreases ≥20% (OR 1.454 and 1.741, for each 1-min increase, respectively). ROC analysis identified 25 min as a 'safe' cut-off for WIT (AUC 0.874, P < 0.001). Postoperative ERPF differences between the two groups (WIT ≤25 and >25 min) were significant. CONCLUSIONS: Longer WIT was associated with LRF, as estimated with renal scintigraphy. LRF occurred within 3 months and remains stable until the 12th month after LPN. Every effort should be made to minimise warm ischaemic intervals during LPN, and the limit of 25 min should be not exceeded.

A simple and accurate dosimetry protocol to estimate activity for hyperthyroidism treatment.

BACKGROUND: Aim of the study was to evaluate accuracy of different dosimetry protocols in estimating the required 131I activity to treat hyperthyroid patients. MATERIALS AND METHODS: Forty consecutive patients were analysed: twenty-eight Graves' disease; twelve autonomous thyroid nodule (ATN). Maximum-uptake, effective half-time and residence-time were estimated from Radioiodine Uptake Test. Residence-time was estimated using a bi-compartmental model. For 131I activity calculation, algorithms laid down in European Association of Nuclear Medicine (EANM) guidelines, ICRP 53 approach and a mono-exponential formula (ME), were compared with OLINDA/EXM results. RESULTS: Based on EANM guidelines, activities to be administered were 3% higher in Graves' disease (p = 0.001) and 3% higher in ATN (p = 0.046). Calculated activities using ICRP 53 approach were significantly lower compared to OLINDA/EXM: 33% in Graves' disease; 17% in ATN. Activities recommended by ME, were significantly higher: in Graves' disease 20%; 42% in ATN. CONCLUSIONS: Only EANM algorithm predict quite well, compared to OLINDA/EXM, the required activity to treat hyperthyroid patients.

Multicenter Semiquantitative Evaluation of (123)I-FP-CIT Brain SPECT.

AIMS: The aims of this study were: (1) to cross-compare data from semiquantitative, software-assisted, and phantom-corrected evaluations of (123)I-ioflupane [(123)I]N-ω-fluoropropyl-2ß-carbomethoxy-3ß-{4-iodophenyl}nortropane FP-CIT brain single-photon emission computed tomography (SPECT) acquired in three centers; (2) to assess the accuracy of semiquantitative evaluation; and (3) to identify the threshold with the best accuracy, sensitivity, and specificity in patients with suspected Parkinsonian Syndrome. MATERIAL AND METHODS: Two-hundred-twenty patients, acquired in three centers, were included. All of them underwent (123)I-FP-CIT brain SPECT. All examinations were analyzed with the freely available software, BasGan, and semiquantitative data were used to predict disease. Analysis was based on the values from the most deteriorated putamen and caudate, normalized for age, and corrected by anthropomorphic phantom data. Receiver operating characteristic (ROC) analysis was performed and areas under the curve (AUC) were estimated. RESULTS: Analysis showed high AUCs (.880, .866, .920, and .882 for each center and multicenter setting). Best thresholds were 1.53 and 1.56 for putamen and caudate, respectively. Thresholds of putamen data showed sensitivity and specificity of 86% and 89%, respectively, in the multicenter setting. Neither sensibility nor specificity showed significant differences among centers. CONCLUSION: A unique, accurate threshold for all centers, with high sensitivity and specificity was identified. Semiquantitative assessment of (123)I-FP-CIT brain SPECT among different centers resulted reliable, accurate, and potentially useful in clinical trials.

In vitro and in vivo study of solid lipid nanoparticles loaded with superparamagnetic iron oxide.

Solid Lipid Nanoparticles (SLN) are already under investigation as a pharmaceutical tool able to change the pharmacokinetic and biodistribution of carried molecules. SLN are able to target drugs to lymph after duodenal administration and to overcome the Blood Brain Barrier (BBB). In this study, superparamagnetic SLN have been prepared, have colloidal size, in vitro analysis showed relaxometric properties similar to Endorem. In vivo Magnetic Resonance Imaging (MRI) of the central nervous system (CNS) with both SLN and Endorem showed that superparamagnetic SLN have slower blood clearance than Endorem. MRI data are consistent with CNS uptake of SLN lasting up to the end of the experiment (135 min). These findings confirm the ability of SLN to overcome the BBB; SLN might be used as a CNS MRI contrast agent.

Duodenal administration of solid lipid nanoparticles loaded with different percentages of tobramycin.

Three types of solid lipid nanoparticles (SLN) containing three different percentages of tobramycin (1.25, 2.50, 5.00%) were prepared (Tobra-SLN), and the in vitro tobramycin diffusion through a hydrophilic/lipophilic membrane was determined. A variable quantity of each of the three SLN types was placed in the donor compartment to achieve the same amount of tobramycin in each case. Tobramycin diffusion varied with the percentage of drug incorporated in SLN: the higher the percentage of tobramycin incorporated, the greater the amount of the drug diffused. In vivo uptake and transport were determined after administering a fixed dose of tobramycin (5 mg/kg) in each of the three types of SLN intraduodenally to rats. At fixed times, blood was sampled from the jugular vein and lymph from the thoracic duct. Lymph and blood were examined by transmission electron microscopy (TEM) analysis to detect the presence, sizes, and shape of SLN. The pharmacokinetic parameters varied considerably with the type of Tobra-SLN: the area under the curve of plasma concentration versus time (AUC) of 1.25% Tobra-SLN was more than five times higher than that of 5.00% Tobra-SLN; the longest residence time was obtained with 1.25% Tobra-SLN; and the clearance of 5.00% Tobra-SLN was fivefold than that of 1.25% Tobra-SLN. This behavior may be related to the differences among the three types of SLN; namely, the number of SLN administered and the mean diameter, the total surface area, and the drug content in each nanoparticle. TEM analysis showed that Tobra-SLNs were targeted to the lymph. Tobra-SLN may act as a reservoir of the drug in the lymphatic system, thereby favoring its sustained release.

Long-term functional evaluation of the treated kidney in a prospective series of patients who underwent laparoscopic partial nephrectomy for small renal tumors.

BACKGROUND: Renal scintigraphy may allow long-term monitoring of ischemic damage after partial nephrectomy (PN). OBJECTIVE: Evaluate use of renal scintigraphy for evaluating long-term effects of warm ischemia on renal function in patients with a normal contralateral kidney. DESIGN, SETTING, AND PARTICIPANTS: We prospectively examined kidney function of 54 patients who underwent laparoscopic PN (LPN). Minimum follow-up time was 4 yr. INTERVENTION: LPN was performed with warm ischemia by transperitoneal or retroperitoneal approach. MEASUREMENTS: Demographic, perioperative, and pathologic data and postoperative complications were registered. Split renal function (SRF) and effective renal plasma flow (ERPF) were evaluated by renal scintigraphy preoperatively, at 3 and 12 mo postoperatively, then yearly. Baseline weighted differentials (b-WDs) of both SRF and ERPF in the affected kidney were calculated between baseline condition and every time point. Multivariate linear regression was used to find independent variables for increased b-WDs at 3 and 48 mo. P values<0.05 were considered significant. RESULTS AND LIMITATIONS: The SRF and ERPF of kidneys treated by LPN decreased significantly at month 3 and subsequently remained stable through the duration of follow-up. Conversely, neither serum creatinine nor estimated glomerular filtration rate changed significantly during follow-up. The regression model showed statistical significance at month 3 for warm ischemia time (WIT) and age, whereas at 48 mo, statistical significance was reached by WIT alone. No new onset of cardiovascular disease was registered. No evidence of local recurrence was recorded with computed tomography scan. Our study may be underpowered due to small sample size; however, this is one of the largest long-term prospective series using renal scintigraphy to evaluate the renal function after LPN. CONCLUSIONS: WIT contributes to irreversible kidney damage observed at month 3 that does not appear to worsen.

99mTc-MIBI Imaging in the presurgical characterization of thyroid follicular neoplasms: relationship to multidrug resistance protein expression.

UNLABELLED: Recently, thyroid (99m)Tc-methoxyisobutylisonitrile ((99m)Tc-MIBI) scintiscanning has been proposed in an attempt to preoperatively identify thyroid malignancies, but discrepant results have been reported for oncocytic lesions. The aim of this study was to investigate the usefulness of visual and semiquantitative analyses of (99m)Tc-MIBI scintigraphy for preoperatively characterizing thyroid nodules with indeterminate cytologic diagnoses, segregating in advance nononcocytic variants from those that are oncocytic. This study also aimed to analyze the relationship between (99m)Tc-MIBI images and P-glycoprotein (P-gp)/multidrug resistance-associated protein-1 (MRP1) immunohistochemical expression. METHODS: Fifty-one consecutive patients with cold thyroid nodules cytologically diagnosed as nononcocytic or oncocytic follicular neoplasm were prospectively studied. Visual and semiquantitative (99m)Tc-MIBI scanning was performed and the diagnoses of the lesions were histologically proven by subsequent thyroidectomy. Immunohistochemical evaluation of P-gp and MRP1 was also performed on surgical samples. RESULTS: Visual and semiquantitative (99m)Tc-MIBI scintiscans showed a low specificity in preoperatively discriminating malignant oncocytic lesions. In nononcocytic nodules, the semiquantitative method was more accurate than the visual (94.44% and 77.78%, respectively). P-gp protein expression was negative in all thyroid lesions, whereas apical plasma membrane MRP1 expression was found in 78% of the lesions with a negative (99m)Tc-MIBI retention index, compared with 11% of lesions with a positive retention index, correlating most strongly with a negative (99m)Tc-MIBI RI in those cases with strong MRP1 apical expression. CONCLUSION: Semiquantitative (99m)Tc-MIBI scintigraphy is an adjunctive method to predict preoperatively the malignant behavior of nononcocytic follicular thyroid nodules indeterminate at fine-needle aspiration biopsy, with a potential impact on the definition of their clinical management. Moreover, the good correlation found between immunohistochemical apical expression of MRP1 and the scintigraphic findings supports the (99m)Tc-MIBI results and provides tissue information on the molecular mechanisms responsible for (99m)Tc-MIBI images in thyroid lesions.

Is renal warm ischemia over 30 minutes during laparoscopic partial nephrectomy possible? One-year results of a prospective study.

OBJECTIVE: To evaluate renal damage and impairment of renal function 1 yr after laparoscopic partial nephrectomy (LPN) with warm ischemia >30 min. METHODS: From July 2004 to June 2005, 18 patients underwent LPN with warm ischemia time >30 min. Kidney damage markers (daily proteinuria and tubular enzymes) and renal function (serum creatinine, cystatin C, and creatinine clearances) were assessed on postoperative days 1 and 5 and at 12 mo. Glomerular filtration rate (GFR) was evaluated before surgery and at 3 mo. Renal scintigraphy was performed before the procedure, at 5 d and at 3 and 12 mo postoperatively. Statistical analysis was performed using the Student t test and logistic regression analysis. RESULTS: In terms of kidney damage and renal function markers, the statistical analysis demonstrated that at 1 yr there was complete return to the normal range and no statistical difference between the values at the various time points. The GFR was not significantly different before and 3 mo after surgery. In terms of scintigraphy of the operated kidney, the values were 48.35+/-3.82% (40-50%) before the procedure, 36.88+/-8.42 (16-50%) on postoperative day 5 (p=0.0001), 40.56+/-8.96 (20-50%) at 3 mo (p=0.003), and 42.8+/-7.2% (20-50%) 1 yr after surgery (p=0.001). CONCLUSION: Our results demonstrate that kidney damage occurs during LPN when warm ischemia is >30 min. This damage is only partially reversible and efforts should be made to keep warm ischemia within 30 min.