Does 99mTc-tilmanocept, as next generation radiotracer, meet with the requirements for improved sentinel node imaging?

INTRODUCTION AND OBJECTIVES: To evaluate the migration of 99mTc-tilmanocept from the injection site (IS) as well as the uptake in sentinel nodes (SNs) and non-SNs for lymphatic mapping in patients with breast cancer and melanoma, scheduled for SN biopsy after interstitial tracer administration. MATERIALS AND METHODS: For 29 primary tumours in 28 patients (mean age: 62y, range: 45-81y) scheduled for SN biopsy planar images were acquired 10 and 120min after administration of 74MBq 99mTc-tilmanocept, in order to evaluate lymphatic drainage as well as uptake ratios between injection site (IS), SN and non-SN. SPECT-CT was performed immediately after delayed planar images to enable anatomical lymph node localization. RESULTS: SNs were visualized in all patients (100%) with drainage to 34 basins. Uptake in non-SNs was perceived in 16 basins (47%). Number of SNs was concordant between early and delayed images in all basins excepting five (86%). In 24 patients tracer migrated to one lymph node basin (LNB), in three to 2 and in one to 4. When IS was included (N=29) on image, IS/SN ratio could be measured per LNB. The IS/SN ratio at 2h compared to 15min decreased with an average of 66% (range: 15-96%). SN/non-SN 2h ratio in LNBs with visible non-SNs averaged 6.6 (range: 2.3-15.6). In 9 patients with two SNs SN1/SN2 ratio averaged 1.9 on delayed images. At histopathology, SNs were found to be tumour positive in 7 basins (20%). CONCLUSION: 99mTc-tilmanocept appears to meet the requirements for improved SN imaging in breast cancer and melanoma on the basis of early and persistent SN visualization frequently accompanied by no or markedly less non-SN uptake. This is associated to rapid migration from the injection site together with increasing SN uptake and retention as expressed by decreasing IS/SN and persistently high SN/non-SN ratios. Further head-to-head comparison of 99mTc-tilmanocept with standard SN radiotracers in larger series of patients is necessary.

Value of one additional injection at the root of the limb in the lymphoscintigraphic evaluation and management of primary and secondary lower-limb lymphedemas.

INTRODUCTION: The classical lymphoscintigraphic investigations of lower-limb lymphatic edema [LLLE] sometimes reveal either no or few lymph nodes [LNs] at the root of the limb[s] and/or in the abdomen. The aim of the present paper is to report the results of performing one additional injection at the root of the edematous limb[s] to force the visualization of the LNs and/or to demonstrate the collateral lymphatic pathways in such patients. METHODS AND FINDINGS: We retrospectively reviewed our database and found 99 patients [44 primary LLLE with 47 limbs injected and 55 with LLLE secondary to treatments for cancer with 64 limbs injected] where such an additional injection had been performed. In the 43 LLLE patients where no LNs were seen at the end of the classical exam [15 primary LLLE and 28 secondary LLLE], the extra injection showed lymphatic drainage toward LN[s] in all except 3 and when at least one LN was seen, the injection showed lymphatic drainage in every case toward the same ipsilateral [inguinal and/or iliac] LNs [as shown by the classical injection] and/or toward additional LNs. In 40.7% of patients, we observed one or more additional lymphatic pathways: prepubic superficial lymphatic vessels [LV] crossing the midline anteriorly toward contralateral inguinal LNs in 21 [18.9%], "posterior" LV [toward contralateral inguinal LNs and/or ipsi- or contralateral lumbo-aortic and/or para-renal LNs] in 14 [12.6%], but deep LV toward the ipsilateral common iliac LNs passing between the gluteal muscles in 32 [28.8%]. CONCLUSION: Our work pinpoints one limitation of classical bipedal radionuclide lymphangiography. In patients with primary and secondary LLLE where inguinal and/or iliac LNs cannot be seen on bipedal radionuclide lymphangiography, this additional injection reveals the true lympho-nodal status and shows unexpected collateral lymphatic pathways in 40% of cases. Such information is of the utmost importance in LLLE management and its acquisition is consequently recommended in these patients.

Tc-99m GSA scintigraphy within the first 3 days after admission as an early predictor of outcome in severe acute liver injury.

Patients with severe acute liver injury (SLI) usually recover spontaneously. However, some SLI patients progress to acute liver failure with varying degrees of hepatic encephalopathy. Acute liver failure is associated with high mortality and can be substantially reduced by liver transplantation. Therefore, distinguishing SLI patients who might progress to acute liver failure and are at a risk of death is important when evaluating patients needing liver transplantation. The present study aimed to determine whether technetium-99m-diethylenetriaminepentaacetic acid galactosyl human serum albumin (Tc-99m GSA) scintigraphy can predict the prognosis of patients with SLI. This prospective observational study included 69 SLI patients. The accuracy of Tc-99m GSA for predicting death or liver transplantation for 6 months was assessed. Between the two groups of patients stratified based on the cut-off values from the receiver operating characteristic curves, 6-month transplant-free survival was compared. Sixteen (23.2%) patients died or underwent liver transplantation from admission (poor outcome). The hepatic accumulation index was calculated by dividing the radioactivity of the liver region of interest by that of the liver-plus-heart region of interest at 15 min (i.e., LHL15). The LHL15 in the 16 patients (0.686) was significantly lower than that in survivors (0.836; P < 0.0001). The optimal LHL15 cut-off for distinguishing poor outcome and survival was 0.737 with a sensitivity of 81.3%, specificity of 88.7%, and area under the curve of 0.907 (95% CI, 0.832-0.981). When patients were divided into two groups based on the LHL15 cut-off value, the 6-month transplant-free survival was significantly lower in patients with an LHL15 level ≤ 0.737. Tc-99m GSA scintigraphy may help predict the prognosis of patients with SLI.

Visualización de un divertículo pielocalicial con [99mTc]Tc-DTPA y gammagrafía con [99mTc]Tc-DMSA / Visualization of a pyelocaliceal diverticulum with [99mTc]Tc-DTPA and [99mTc]Tc-DMSA scintigraphy

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Early Renal Function Alterations in Renal Branches vs. Renal Fenestrations - A Dynamic Scintigraphy Based Prospective Study.

OBJECTIVE: The objective of this prospective single centre study was to assess whether branches and fenestrations have different outcomes on renal function in the early phase. METHODS: From March 2018 to June 2019, 67 patients who underwent elective fenestrated and branched endovascular aneurysm repair (F/BEVAR) procedures were enrolled in this study. The patients were divided into two groups according to the renal bridging component configuration (fenestration vs. branch). All of them underwent dynamic renal scintigraphy with 99mTc diethylenetriaminepentaacetic acid (DTPA), two weeks pre-operatively, and three months and one year post-operatively. The primary end points were peri-procedural technical success, 30 day major adverse events, differences in glomerular filtration rate (GFR) between the branch and fenestration configurations, and variations between the pre-operative and the post-operative dynamic renal scintigraphy. RESULTS: Overall, 135 kidneys were analysed: 63 in the 32 patients treated with fenestrations, and 72 in the 35 patients treated with branches; the mean GFR on baseline scintigraphy was 58.4 ± 30.9 mL/min in the fenestration group, and 65.1 ± 29.2 mL/min in the branch group. Only kidneys associated with a patent fenestration/branch were included in the split GFR final analysis. The mean total GFR at three month scintigraphy decreased by 6.0 ± 2.9 mL/min in the fenestration group and by 23.4 ± 6.4 mL/min in the branch group. The split GFR decreased by 3.5 ± 0.6 mL/min in the fenestration group, and by 15.4 ± 5.4 mL/min in the branch group. The GFR decrease remained stable at one year. CONCLUSION: In this study, the use of branches for renal arteries during F/BEVAR resulted in a greater decrease in the GFR than in those patients who were treated with fenestrations alone. The scintigraphic alterations were evident at an early phase.

The Role of Tc-99m DTPA Renal Dynamic Scintigraphy in Retroperitoneal Liposarcoma.

PURPOSE: Technetium-99m diethylene triamine pentaacetic acid (Tc-99m DTPA) renal dynamic scintigraphy is a widely used imaging technique that evaluates renal function of patients with extrarenal abnormalities, but its clinical value in potentially offering us information on proliferation of liposarcoma has not yet been reported. METHODS: We retrospectively reviewed 7 patients with histopathologically confirmed retroperitoneal liposarcoma who underwent Tc-99m DTPA renal dynamic scintigraphy. The clinical data, histopathological findings, Glomerular Filtration Rate (GFR), and Tc-99m DTPA uptake were recorded. RESULTS: Dedifferentiated liposarcoma and well-differentiated liposarcoma showed dissimilar degrees of Tc-99m DTPA uptake, an observation that correlated with Ki-67 expression (p < 0.01). 4 of the 7 patients were diagnosed with dedifferentiated liposarcoma, showing a moderate uptake of Tc-99m DTPA and greater than 20% Ki-67 expression on histological slides. Meanwhile, the remaining 3 patients, diagnosed with well-differentiated liposarcoma, showed no uptake of Tc-99m DTPA and Ki-67 expression of less than 5%. CONCLUSIONS: This study suggests that Tc-99m DTPA renal dynamic scintigraphy provides diagnostic value in patients with retroperitoneal liposarcoma, not only in evaluating renal function but also in visualizing lesion-related radionuclide uptake, which may potentially offer further clinical insights into tumor proliferation and provide prognostic value for clinical outcomes in patients with retroperitoneal liposarcoma.

In vivo deposition study of a new generation nebuliser utilising hybrid resonant acoustic (HYDRA) technology.

Conventional nebulisation has the disadvantages of low aerosol output rate and potential damage to macromolecules due to high shear (jet nebulisation) or cavitation (ultrasonic nebulisation). HYDRA (HYbriD Resonant Acoustics) technology has been shown to overcome these problems by using a hybrid combination of surface and bulk sound waves to generate the aerosol droplets. We report the first in vivo human lung deposition study on such droplets. Twelve healthy adult subjects inhaled saline aerosols radiolabelled with technetium-99 m complexed with diethylene triamine penta-acetic acid (99mTc-DTPA). The distribution of the aerosolised droplets in the lungs was imaged by single photon emission computed tomography combined with low dose computed tomography (SPECT/CT). The volume median diameter and geometric standard deviation of the droplets were 1.32 ± 0.027 µm and 2.06 ± 0.040, respectively. The mean delivery efficiency from the nebuliser into the body was 51.2%. About 89.1 ± 4.3% and 2.3 ± 1.4% of the inhaled radiolabelled dose deposited in the lungs and oropharynx, respectively. The deposition was symmetrical and diffusive between the two lungs, with a mean penetration index of 0.82. Thus, the prototype HYDRA nebuliser showed excellent in vivo aerosol deposition performance, demonstrating its potential to be further developed for clinical applications.

Full report on a survey of adverse reactions to radiopharmaceuticals from 1975 to 2017 in Japan.

OBJECTIVE: This pharmacovigilance-based survey was aimed at determining the prevalence of, and association between, radiopharmaceuticals and adverse reactions to radiopharmaceuticals from 1975 to 2017 in Japan. METHODS: The Subcommittee for Safety Issues of Radiopharmaceuticals of the Japan Radioisotope Association's Medical Science and Pharmaceutical Committee mailed a form for reporting adverse reactions to radiopharmaceuticals to all institutes performing nuclear medicine examinations in Japan. This investigation included adverse reactions to diagnostic radiopharmaceuticals labeled with both single-photon- and positron-emitting radionuclides and therapeutic sodium iodide labeled with 131I. Each institute returned the reporting form to the subcommittee each time an adverse reaction occurred. RESULTS: Replies were obtained from 75% of the institutions. In total, 1099 adverse reactions were reported from 46,645,580 radiopharmaceutical administrations, giving a prevalence of 2.4 adverse reactions per 100,000 administrations (95% confidence interval 2.2-2.5). Adverse reactions were most frequently observed for 131I-iodomethylnorcholesterol (230.1/105 administrations), followed by 131I-HSA (76.3/105 administrations), 131I-sodium iodohippurate (31.2/105 administrations), and 99mTc-DTPA (12.0/105 administrations). Comparison of adverse reactions between before and after 1997 revealed that prevalence dropped from 3.7/105 administrations (95% confidence interval 3.5-4.1) to 1.5/105 administrations (95% confidence interval 1.4-1.6). During the study period, vasovagal reactions accounted for 50.3% of adverse reactions, fever for 7.5%, allergic reactions for 25.7%, and other for 16.5%; 3.7% of all adverse reactions were considered severe but none were lethal. A definite, probable, possible, less likely, and uncertain causal relationship with radiopharmaceuticals was observed in 13.1%, 33.7%, 39.9%, 6.2%, and 7.1% of adverse reactions, respectively. CONCLUSIONS: These results suggest that nuclear medicine staff must be aware of the possibility of adverse reactions from radiopharmaceuticals, despite their rarity.

Targeted Lung Deposition From Nebulization Is Not Improved in the Lateral Decubitus Position in Healthy Volunteers.

BACKGROUND: Clinical benefits of inhaled therapies are related to the amount of drug deposited in the targeted area of the lung. Body positions that influence the distribution of lung ventilation should impact lung deposition of the nebulized drug. The aim of this study was to analyze the immediate effect of body position while the subject lies on his side (lateral decubitus) during nebulization on 3-dimensional total and regional lung deposition. METHODS: A randomized crossover trial was performed on healthy male volunteers without cardiovascular or pulmonary disease. A technetium-99m diethylenetriaminepentaacetic acid (99mTc-DTPA) solution (4 mL) was nebulized using an individual-controlled inhalation system in left lateral decubitus and sitting positions with a 96-h washout period (43 inspirations of 4 s [ie, drug delivered until second 3] with a tidal volume of 0.8 L and a low inspiratory flow (200 mL/s). Drug deposition was followed with the use of planar images and single-photon-emission computed tomography combined with low-resolution computed tomography. Total and regional depositions were the main outcomes. Penetration index was also considered. RESULTS: Six participants (26.8 ± 6.9 y old) were included. Total lung deposition tended to be higher in a sitting position than in a lateral decubitus position: 10.2 ± 0.9% of nominal dose (95% CI 9.1-11.3) vs 8.6 ± 1.4% of nominal dose (95% CI 6.8-10.4) (P = .09). The deposition was significantly reduced in the dependent (left) lung in the lateral decubitus position: 3.5 ± 0.7% of nominal dose (95% CI 2.6-4.3) vs 4.7 ± 0.3% of nominal dose (95% CI 4.3-5.0) (P = .03). Penetration index was only influenced by body position for the dependent (left) lung (P = .043). CONCLUSIONS: The total amount of drug delivered to the lungs during nebulization with an individual-controlled inhalation system tended to decrease when performed in the left lateral decubitus position. Moreover, contrary to the initial hypothesis, the deposition of particles in the dependent lung was not improved by the lateral decubitus position in this configuration. (ClinicalTrials.gov registration NCT02451501.).

Validation of the full-age spectrum equation in the approximation of glomerular filtration rate in Chinese patients with chronic kidney disease.

Introduction: To investigate the validity of the full age spectrum (FAS) equation in determining the glomerular filtration rate (GFR) in Chinese patients with chronic kidney disease (CKD) and to compare the performance of FAS equation and the technetium-99m-diethylene triamine pentaacetic acid (Tc-99m-DTPA) renal dynamic imaging method. Methods: The GFR was determined by three methods in the same day: (a) Tc-99m-DTPA dual plasma sample clearance method (mGFR); (b) FAS equation (eGFR1); (c) Tc-99m-DTPA renal dynamic imaging method (eGFR2). The mGFR was used as the reference standard. The Bland-Altman method, concordance correlation coefficient and regression equation were applied to evaluate the validity of the estimated glomerular filtration rate (eGFR). The bias, precision and accuracy were analyzed to compare the performances of eGFR1 and eGFR2. Results: A total of 162 subjects were enrolled in this study. The eGFR1 was correlated well with mGFR (concordance correlation coefficient was 0.896, p < 0.0001) and the regression equation was mGFR = -0.374 + 1.029eGFR1 (p < 0001). The Bland-Altman analysis proved good agreement between the eGFR1 and mGFR. In comparison with eGFR2, the eGFR1 showed better performance on bias (-1.22 vs. 8.92, p < 0001), precision (15.69 vs. 18.36, p = 0.047) and 30% accuracy (75.31% vs. 59.26%, p = 0.0009) in all participants. Conclusions: The FAS equation is valid in determining the glomerular filtration rate in Chinese patients with chronic kidney disease. The Tc-99m-DTPA renal dynamic imaging method is less accurate than the FAS equation and cannot be employed as the reference method in assessing the performance of FAS equation.

Validation of Glomerular Filtration Rate Measurement with Blood Sampling from the Injection Site.

Measurement of glomerular filtration rate (GFR) from the plasma clearance of a radionuclide-labeled tracer is reliable and accurate. However, to avoid contamination of the blood samples with radioactivity remaining at the injection site, venepuncture at 2 or more sites is required: one for tracer administration and the others for blood sampling. This requirement is uncomfortable for patients, particularly when venous access is difficult. The objective of this study was to validate the use of a single site of venous access in combination with injection site imaging, for GFR measurement. Methods: Twenty-two adults (≥18 y) who were referred for GFR determination were included prospectively. GFR was measured from the plasma clearance of 99mTc-diethylenetriaminepentaacetic acid according to international guidelines. After administration of the tracer through an intravenous cannula, a 60-s static image of the injection site was acquired. A second intravenous cannula was inserted into the contralateral arm. Venous blood samples were collected at 2, 3, and 4 h after administration of the radiotracer from both the injection site (experimental) and the contralateral arm (conventional). GFR was calculated using slope-intercept and single-sample methods. The median conventional and experimental plasma counts (decay- and background-corrected) were compared for the 2-, 3-, and 4-h venous samples. Conventional and experimental GFRs were then compared, with a more than 10% difference between conventional and experimental GFRs being regarded as significant. Results: Four individuals had visible residual activity at the injection site. The median 2-h counts differed significantly between the conventional and experimental sampling sites (P = 0.007), whereas no significant difference was found at 3 or 4 h. When there was a clear injection site image, the difference between the experimental and conventional GFRs was more than 10% in 1 case for single-sample GFR but less than 8% in all cases for slope-intercept GFR. Conclusion: In cases with clear injection site images, slope-intercept GFR calculated after injection site blood sampling showed no clinically significant difference from conventional contralateral-arm sampling.

Evaluation of BBB permeable nucleolipid (NLDPU): A di-C15-ketalised palmitone appended uridine as neuro-tracer for SPECT.

Despite being in routine for onco-diagnostics for years, the applicability of nucleosidic molecular imaging probes is severely restricted in neurological applications due to their low permeability across blood-brain-barrier (BBB). For extending nucleoside tracers utility for neuro-onco early diagnostics, suitable modification which enhances their BBB permeation needs investigation. Among various modifications, lipidization of nucleosides has been reported to enhance cellular permeability. Extending the concept, the aim was to exemplify the possibility of lipidized nucleosides as potential brain tracer with capability to cross intact BBB and evaluate as metal based neuro-imaging SPECT agent. Uridine based non-lipidic (NSDAU) and di-C15-ketal appended lipidic (NLDPU) ligands were conjugated to chelator, DTPA (DTPA-NSDAU and DTPA-NLDPU) using multi-step chemistry. The ligands were evaluated in parallel for comparative physical and biological parameters. Additionally, effects of enhanced lipophilicity on UV-absorption, acid strength, fluorescence and non-specific protein binding were evaluated. Fluorescence quenching of BSA indicated appreciable interaction of DTPA-NLDPU with protein only above 10 mM without inducing conformational changes. In addition, DTPA-NLDPU was found to be haematocompatible and cytocompatible with low dose-dependent toxicity in HEK-cells. The chelator DTPA was used for 99mTc-complexation for SPECT imaging. Optimized 99mTc-radiolabeling parameters resulted in quantitative (≥97%) labeling with good stability parameters in in-vitro serum and cysteine challenge studies. We demonstrate that the nucleolipid radiotracer (99mTc-DTPA-NLDPU) was successfully able to permeate the BBB with brain uptake of 0.2% ID/g in normal mice as compared to 0.06% ID/g uptake of 99mTc-DTPA-NSDAU at 5 min. Blood kinetics indicate biphasic profile and t1/2(distribution) 46 min for 99mTc-DTPA-NLDPU. The preferential accumulation of 99mTc-DTPA-NLDPU in brain tumor intracranial xenograft indicate the targeting capability of the nucleoside. We conclude that as first-of-its-kind, this work presents the potential of the biocompatible nucleolipidic system for brain targeting and early diagnostics.

A prospective study to compare the measured glomerular filtration rate compared to estimated glomerular filtration rate in patients undergoing definitive chemoradiation, with platinum agents for various malignancies.

CONTEXT: Renal function assessment is of paramount importance before using the platinum agents especially cisplatin. Glomerular filtration rate (GFR) estimation by diethyl-triamine-penta-acetic acid (DTPA) scan (measured GFR [mGFR]) is considered gold standard. AIMS: The aim of this study is to know if we can replace the mGFR with the GFR estimation with Cockcroft-Gault formula (eGFR) in patients undergoing chemoradiation. SETTINGS AND DESIGN: This is a prospective, descriptive study. SUBJECTS AND METHODS: Patients who are planned for definitive chemoradiation will be eligible for the study. Renal function will be measured DTPA scan and Cockcroft-Gault (CG) formula. Subgroup analysis based on the weight, age, and sex will be done. STATISTICAL ANALYSIS USED: Demographic and renal function parameters were analyzed using summary measures. To test the significance of the difference between mGFR and cGFR, a paired t-test will be used; to look for an association between various estimates of renal function, the Pearson's correlation coefficient will be calculated using a two-tailed test. RESULTS: Median mGFR of patients was 82.7 (range: 65-125 ml/min, standard deviation [SD] =14.0 ml/min) while the median eGFR as per the CG formula was 83.9 ml/min (range: 37-137 ml/min, SD = 24.4 ml/min). The median mGFR was only 1.2 ml/min lesser when measures by the CG formula with no significance difference between them (P = 0.66, 95% confidence interval: -4.5-6.3). CONCLUSIONS: We concluded that in resource-limited setting eGFR using CG formula can replace mGFR, especially in patients with age <60 years. Although weight did not showed a significant difference by two methods, a study with large sample is needed to confirm the result.

Staging a great escape -Incidentally detected renal urothelial carcinoma with extensive squamous metaplasia presenting as pyonephrosis.

Incidentally, detected upper urinary tract urothelial carcinoma is a rare entity. We report the case of a 70-year-old female patient who presented with flank pain, pyuria, fever, and a unilateral nonfunctioning kidney with nephrolithiasis and pyonephrosis on pyelography. Routine imaging failed to identify a mass lesion. In an Indian setting, the clinical differential of tuberculosis was considered likely. A nephrectomy was performed in view of the poor perfusion and functional status of the right kidney. Histopathological examination of the kidney showed a tumor of urothelial origin arising at the renal pelvis displaying extensive squamous metaplasia. Such a near total metaplastic change is rare and has hitherto been undescribed in the renal pelvis. Activation of pleuripotent urothelial stem cells in the setting of chronic irritation and inflammation may be the pathogenetic process behind such an occurrence.

Development and validation of a more accurate estimating equation for glomerular filtration rate in a Chinese population.

Previously published equations to estimate glomerular filtration rate (GFR) have limited accuracy in Asian populations. We aimed to develop and validate a more accurate equation for estimated GFR (eGFR) in the Chinese population, using data from 8571 adults who were referred for direct measurement of GFR by renal dynamic imaging (mGFR) at 3 representative hospitals in China. Patients from the Third Xiangya Hospital were included in our development (n=1730) and internal validation sets (n=1042) and patients from the other hospitals comprised the external validation set (n=5799). We excluded patients who were prescribed medications known to influence the tubular secretion of creatinine, patients on dialysis, kidney transplant recipients, and patients with missing creatinine values or with creatinine >700 µmol/l. We derived a novel eGFR equation by linear regression analysis and compared the performance to 12 creatinine-based eGFR equations, including previously published equations for use in Chinese or Asian populations. In the development and internal validation sets, the novel Xiangya equation had high accuracy (accuracy within 30% [P30], 79.21% and 84.33%, respectively), low bias (mean difference between mGFR and eGFR, -1.97 and -1.85 ml/min per 1.73 m2, respectively), and high precision (interquartile range of the differences, 21.13 and 18.88 ml/min per 1.73 m2, respectively). In external validation, the Xiangya equation had the highest P30 among all eGFR equations, with P30 ≤ 75% for the other 12 equations. This novel equation provides more accurate GFR estimates in Chinese adults and could replace existing eGFR equations for use in the Chinese population.

Creatinine-based estimation of glomerular filtration rate in patients with a Fontan circulation.

BACKGROUND: Patients with a Fontan circulation are at risk of renal dysfunction. We analyzed cross-sectional data in pediatric and adult Fontan patients in order to assess the accuracy of commonly used serum creatinine-based methods in estimating glomerular filtration rate (GFR). METHODS: A total of 124 Fontan patients (58 children, 66 adults) were enrolled across three study centers. Measurement of GFR (mGFR) using in vivo 99m Tc-DTPA clearance was performed. Various serum creatinine-based equations were used to calculate estimated GFR (eGFR). RESULTS: Mean mGFR was 108 ± 28 mL/min/1.73 m2 in children and 92 ± 20 mL/min/1.73 m2 in adults. Fourteen children (25%) and 28 adults (45%) had an mGFR <90 mL/min/1.73 m2 . There was no significant correlation between mGFR and eGFR (Schwartz) in children (r = 0.22, P = .1), which substantially overestimated mGFR (bias 50.8, 95%CI: 41.1-60.5 mL/min/1.73 m2 , P < .0001). The Bedside Schwartz equation also performed poorly in the children (r = 0.08, P = .5; bias 5.9, 95%CI: -2.9-14.6 mL/min/1.73 m2 , P < .0001). There was a strong correlation between mGFR and both eGFR (CKD-EPI) and eGFR (MDRD) in adults (r = 0.67, P < .0001 in both cases), however, both methods overestimated mGFR (eGFR(CKD-EPI):bias 23.8, 95%CI: 20-27.6 mL/min/1.73 m2 , P < .0001; eGFR (MDRD):bias 16.1, 95%CI: 11.8-20.4 mL/min/1.73 m2 , P < .0001). None of the children with an mGFR <90 mL/min/1.73 m2 had an eGFR (Schwartz) <90 mL/min/1.73 m2 . Sensitivity and specificity of eGFR (CKD-EPI) and eGFR (MDRD) for mGFR <90 mL/min/1.73 m2 in adults were 25% and 92% and 39% and 100%, respectively. CONCLUSIONS: This study identifies the unreliability of using creatinine-based equations to estimate GFR in children with a Fontan circulation. The accuracy of formulas incorporating cystatin C should be further investigated and may aid noninvasive surveillance of renal function in this population.

Consecutive Case Series of Melanoma Sentinel Node Biopsy for Lymphoseek Compared to Sulfur Colloids.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is an important adjunct in the staging of patients with melanoma. Preoperative lymphoscintigraphy with radiolabeled isotopes is essential to localize sentinel nodes for removal. Our study compared the effectiveness of Lymphoseek to standard sulfur colloids in patients with melanoma undergoing SLNB. METHODS: We queried our IRB-approved melanoma database to identify 370 consecutive patients who underwent SLNB from 2012 to 2016 with at least 1 y of follow-up. There were 185 patients in each group. Data points included characteristics of the primary melanoma lymphoscintigraphy and SLNB. Student's t-test and chi-square were used to analyze the data with a P value of <0.05 being considered significant. RESULTS: Patients were equally matched in regard to age, sex, and primary characteristics of their melanoma. In comparison to sulfur colloid, Lymphoseek required lower radiation dosages (P < 0.001), shorter mapping times (P = 0.008), and decreased number of sentinel nodes removed (P = 0.03). There was no difference in the number of patients with positive nodes (P = 0.5). In addition, there were no statistical differences between the two radioactive tracers in regard to the number of patients with false-negative SLNB. CONCLUSION: Lymphoseek has the potential to decrease radioactivity and mapping time in patients who need SLNB. With a decrease in the number of nodes removed without loss of sensitivity, there is a potential to avoid unnecessary node removal and thus complications such as lymphedema. Longer follow-up will help to determine if there is any increase in false-negative rates despite fewer nodes removed.

Predictive ability of renal cortex enhancement in dynamic computed tomography for residual renal function after nephroureterectomy: Comparison with 99m Tc-diethylenetriaminopentacetic acid renography and validation study.

OBJECTIVE: To estimate postoperative residual renal function after radical nephroureterectomy for upper tract urothelial carcinoma using the preoperative dynamic computed tomography renal cortex enhancement ratio in comparison with the split kidney glomerular filtration rate measured by 99m Tc-diethylenetriaminopentacetic acid renography. METHODS: A total of 47 patients who received radical nephroureterectomy and underwent both preoperative dynamic computed tomography and renography were the model-development cohort; and 109 patients who underwent dynamic computed tomography alone were the validation cohort. Postoperative renal function of the unremoved kidney was estimated using the following formulas: preoperative estimated glomerular filtration rate × the percentage of total renal cortex radiodensity for the intact kidney in Hounsfield units obtained from corticomedullary phase images in the computed tomography-based model, or the percentage of the total glomerular filtration rate measured by renography in the nuclear model. The correlation between observed and estimated postoperative renal function was determined. The computed tomography-based prediction model derived from linear regression analysis was validated externally. RESULTS: The correlation of computed tomography-based split renal function with the observed postoperative estimated glomerular filtration rate (r = 0.80) was equivalent to that of nuclear split renal function (r = 0.78). In the validation cohort, the computed tomography-based prediction model showed an equivalently strong correlation (r = 0.78). CONCLUSIONS: The present study showed that the percentage of total renal cortex radiodensity for the intact kidney is a useful tool for predicting unremoved kidney function in upper tract urothelial carcinoma patients, thereby allowing appropriate patient selection for perioperative cisplatin-based combination chemotherapy.

The effect of remote ischemic preconditioning on serum creatinine in patients undergoing partial nephrectomy: a study protocol for a randomized controlled trial.

BACKGROUND: Acute kidney injury (AKI) may develop during partial nephrectomy due to ischemic reperfusion injury induced by renal artery clamping or surgical insult. The effect of remote ischemic preconditioning (RIPC) on reducing the renal injury after partial nephrectomy has not been evaluated in terms of urinary biomarkers. METHODS/DESIGN: We will conduct a randomized controlled trial enrolling the patients who will undergo partial nephrectomy. In the study group, RIPC which consisted of four 5-min cycles of limb ischemia and reperfusion will be conducted after induction of anesthesia. Postoperative serum creatinine values, the incidence of AKI, and urinary biomarkers, including urinary creatinine, microalbumin, ß-2 microglobulin, and N-acetyl-beta-D-glucosaminidase, will be compared between groups during the postoperative 2 weeks. Regional oxygen saturation on the skin of the contralateral kidney will be measured to evaluate the association between intraoperative regional oxygen saturation values and renal injury of the operating side. DISCUSSION: We expect that our trial may demonstrate the effect of RIPC on mitigating the immediate postoperative renal injury and improving patient outcomes after partial nephrectomy. Moreover, our patients will undergo 99mTc-DTPA radionuclide scintigraphy to calculate glomerular filtration rate 6 and 12 months after surgery. This data should show the long-term effect of RIPC. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03273751 . Registered on 6 September 2017.

Molecular Imaging of endometrial sentinel lymph nodes utilizing fluorescent-labeled Tilmanocept during robotic-assisted surgery in a porcine model.

Molecular imaging with a fluorescent version of Tilmanocept may permit an accurate and facile detection of sentinel nodes of endometrial cancer. Tilmanocept accumulates in sentinel lymph nodes (SLN) by binding to a cell surface receptor unique to macrophages and dendritic cells. Four female Yorkshire pigs underwent cervical stromal injection of IRDye800-Tilmanocept, a molecular imaging agent tagged with near-infrared fluorescent dye and radiolabeled with gallium-68 and technetium-99m. PET/CT scans 1.5 hours post-injection provided pre-operative SLN mapping. Robotic-assisted lymphadenectomy was performed two days after injection, using the FireFly imaging system to identify nodes demonstrating fluorescent signal. After removal of fluorescent nodes, pelvic and periaortic node dissections were performed. Nodes were assayed for technetium-99m activity, and SLNs were established using the "10%-rule", requiring that the radioactivity of additional SLNs be greater than 10% of the "hottest" SLN. Thirty-four nodal samples were assayed ex vivo for radioactivity. All the SLNs satisfying the "10%-rule" were detected using the FireFly system. Five fluorescent nodes were detected, corresponding with preoperative PET/CT scan. Three pigs had one SLN and one pig had two SLNs, with 100% concordance between fluorescence and radioactivity. Fluorescent-labeled Tilmanocept permits real-time intraoperative detection of SLNs during robotic-assisted lymphadenectomy for endometrial cancer in a porcine model. When radiolabeled with gallium-68, Tilmanocept allows for preoperative localization of SLNs using PET/CT, and shows specificity to SLNs with persistent fluorescent signal, detectable using the FireFly system, for two days post-injection. In conclusion, these findings suggest that a phase I trial in human subjects is warranted, and that a long-term goal of an intra-operative administration of non-radioactive fluorescent-labeled Tilmanocept is possible.