Nagabhushan Seshadri

Extracellular fluid volume and glomerular filtration rate in 1878 healthy potential renal transplant donors: effects of age, gender, obesity and scaling

UNLABELLED Aim. The aim of this study was to investigate the influence of age, gender, obesity and scaling on glomerular filtration rate (GFR) and extracellular fluid volume (ECV) in healthy subjects. METHODS This is a retrospective multi-centre study of 1878 healthy prospective kidney transplant donors (819 men) from 15 centres. Age and body mass index (BMI) were not significantly different between men and women. Slope-intercept GFR was measured (using Cr-51-EDTA in 14 centres; Tc-99m-DTPA in one) and scaled to body surface area (BSA) and lean body mass (LBM), both estimated from height and weight. GFR was also expressed as the slope rate constant, with one-compartment correction (GFR/ECV). ECV was measured as the ratio, GFR to GFR/ECV. RESULTS ECV was age independent but GFR declined with age, at a significantly faster rate in women than men. GFR/BSA was higher in men but GFR/ECV and GFR/LBM were higher in women. Young women (<30 years) had higher GFR than young men but the reverse was recorded in the elderly (>65 years). There was no difference in GFR between obese (BMI>30 kg/m2) and non-obese men. Obese women, however, had lower GFR than non-obese women and negative correlations were observed between GFR and both BMI and %fat. The decline in GFR with age was no faster in obese versus non-obese subjects. ECV/BSA was higher in men but ECV/LBM was higher in women. ECV/weight was almost gender independent, suggesting that fat-free mass in women contains more extracellular water. BSA is therefore a misleading scaling variable. CONCLUSION There are several significant differences in GFR and ECV between healthy men and women.

Utility of 111In-labelled leucocyte scintigraphy in patients with fever of unknown origin in an era of changing disease spectrum and investigational techniques.

Background111In-labelled leucocyte, imaging is often used to investigate patients with fever of unknown origin (FUO). Its diagnostic performance, however, has been variable and a broad range of sensitivities and specificities have been reported. The purpose of this investigation was to evaluate the usefulness of 111In-labelled leucocytes scintigraphy in the detection of a cause of FUO in the light of a changing spectrum of diseases causing it and advances in investigational techniques. Materials and methodsSixty-one patients with a clinical diagnosis of FUO underwent whole-body 111In-troponolate-labelled leucocyte scintigraphy in our department over a 2 year period between February 2004 and February 2006. Of these, 54 patients were retrospectively reviewed to identify a cause of FUO. Other parameters such as C-reactive protein (CRP), leucocyte count and radiological findings were also evaluated. ResultsLeucocyte scintigraphy was found to be true positive in 12 patients, true negative in 24 patients, false positive in 10 patients and false negative in eight patients. The overall sensitivity of scintigraphy was 60%, specificity 71%, positive predictive value 55%, and negative predictive value 75%. There was no difference in the scintigraphic sensitivity between patients with spontaneous FUO and those with post-operative FUO although the latter showed a higher specificity and PPV. CRP and leucocyte count did not differ significantly between patients with true positive and true negative scintigrams. Overall, 83% of patients with abnormal radiological examinations had positive findings on scintigraphy and 87% of patients with negative findings on radiology had normal scintigraphy. ConclusionDespite changes in disease spectrum and advances in investigational techniques, our results suggest that 111In-leucocyte scintigraphy is still a useful technique in establishing the cause of FUO. A higher PPV of this test in post-operative situations makes it especially applicable in this category of patients. Equally, the higher NPV in patients with spontaneous FUO virtually excludes infection/inflammation. Finally, a higher pre-test probability based on the radiological tests seems to be important in the optimal use of leucocyte imaging.

The reliability of glomerular filtration rate measured from plasma clearance: a multi-centre study of 1,878 healthy potential renal transplant donors

PurposeThe objective of the study was to undertake a clinical audit of departmental performance in the measurement of glomerular filtration rate (GFR) using the coefficient of variation (CV) of extracellular fluid volume (ECFV) as the benchmark. ECFV is held within narrow limits in healthy subjects, narrower than GFR, and should therefore have a low CV.MethodsFifteen departments participated in this retrospective study of healthy renal transplant donors. Data were analysed separately for men (n ranged from 28 to 115 per centre; total = 819) and women (n = 28–146; 1,059). All centres used the slope-intercept method with blood sample numbers ranging from two to five. Subjects did not fast prior to GFR measurement. GFR was scaled to body surface area (BSA) and corrected for the single compartment assumption. GFR scaled to ECFV was calculated as the terminal slope rate constant and corrected for the single compartment assumption. ECFV/BSA was calculated as the ratio of GFR/BSA to GFR/ECFV.ResultsThe departmental CVs of ECFV/BSA and GFR/BSA ranged from 8.3 to 25.8% and 12.8 to 21.9%, respectively, in men, and from 9.6 to 21.1% and 14.8 to 23.7%, respectively, in women. Both CVs correlated strongly between men and women from the same centre, suggesting department-specific systematic errors. GFR/BSA was higher in men in 14 of 15 centres, whereas GFR/ECFV was higher in women in 14 of 15 centres. Both correlated strongly between men and women, suggesting regional variation in GFR.ConclusionThe CV of ECFV/BSA in normal subjects is a useful indicator of the technical robustness with which GFR is measured and, in this study, indicated a wide variation in departmental performance.

Clinical significance of scintigraphic rapid gastric emptying.

ObjectivesTo analyse our results of gastric-emptying scintigraphy in relation to presenting symptoms, and examine in detail the clinical significance of rapid gastric emptying (RGE). Materials and methodsResults of 642 consecutive patients who underwent a solid gastric-emptying scintigraphy in our department over an 11-year period were retrospectively reviewed with particular emphasis to the presenting symptoms and the clinical profile of patients, especially of those who showed an accelerated pattern of emptying. ResultsSeventy (11%) patients were clinically suspected to have a RGE and 572 (89%) patients had presumed gastroparesis. Gastric emptying was found to be normal in 290 (45%), rapid in 182 (28%) and delayed in170 (27%) patients. Normal, rapid and delayed gastric emptying were seen, respectively, in 17 (24%), 48 (69%) and five (7%) patients with the clinical suspicion of dumping and 273 (48%), 134 (23%) and 165 (29%) patients with suspected gastroparesis. The positive predictive value of clinical suspicion for RGE was 62%, whereas the positive predictive value of delayed gastric emptying was 29%. Of the 182 patients with RGE, 144 (79%) were found to have no obvious explanation for this result; reactive hypoglycaemia was present in a quarter of these patients, but diarrhoea was seen only in 3%. ConclusionUpper gastrointestinal symptoms have a poor clinical specificity to the actual rate of gastric emptying on scintigraphy. Diarrhoea as a symptom does not appear to be associated frequently with RGE, but our results confirm its relationship with hypoglycaemia. The majority of patients with a rapid emptying on gastric-emptying scintigraphy have no identifiable cause for an accelerated motility. Scintigraphic gastric-emptying studies provide a reliable and noninvasive method of investigation in patients where conventional investigations have failed to establish the cause of upper gastrointestinal dysfunction.

Bilateral adrenal metastases from malignant melanoma: concordant findings on 18F-FDG and 18F-FDOPA PET

Adrenal masses often pose a diagnostic challenge. The majority represent functional adrenal adenomas, but primary or secondary malignancy must be considered. Therefore functional characterisation of the lesion is important in determining the type of treatment. The adrenal gland is the fourth most common site of metastasis after the lungs, liver and bone [1]. Malignant melanoma is one of the most common primary tumours that metastasise to the adrenal gland apart from lung, breast, kidney, thyroid and colon cancers [1]. In the literature the incidence of adrenal metastases from malignant melanoma is about 50%. The prognosis and treatment are linked to the early detection of metastatic disease in malignant melanoma [2, 3]. Ffluorodeoxyglucose positron emission tomography (FFDG PET) is a well-accepted method for the detection of metastatic disease in malignant melanoma [4]. However, some benign lesions may be classified as malignant

WHAT IS THE SIGNIFICANCE OF SOLITARY BONY ABNORMALITIES ON BONE SCINTIGRAMS OF CHILDREN WITH MALIGNANCY

This investigation was undertaken to evaluate the significance of solitary bony abnormalities on bone scintigrams of children with known or suspected malignancy. A total of 215 bone scans were performed in 183 children in order to look for possible metastasis over a 10-year period. Forty-nine scans (22.8%) were found to have single lesions, of which 18 were due to uptake at the primary site and were excluded from further consideration. Of the remaining 31 lesions, 13 (41.9%) were confirmed as metastases, 17 lesions were proved to be benign, and 1 indeterminate. Solitary hot spots in children with known or suspected malignancy are common and therefore have to be taken seriously due to their higher malignant potential.

Higher extracellular fluid volume in women is concealed by scaling to body surface area

Abstract Objective. The objective was to assess body surface area (BSA) for scaling extracellular fluid volume (ECV) in comparison with estimated lean body mass (LBM) and total body water (TBW) across a range of body mass indices (BMI). Methods. This was a multi-centre study from 15 centres that submitted raw data from routine measurement of GFR in potential kidney transplant donors. There were 819 men and 1059 women in total. ECV was calculated from slope-intercept and slope-only measurements of GFR. ECV was scaled using two methods: Firstly, division of ECV by the scaling variable (ratio method), and secondly the regression method of Turner and Reilly. Subjects were placed into five BMI groups: < 20, 20–24.9, 25–29.9, 30–34.9, and 35 + kg/m2. LBM and TBW were estimated from previously published, gender-specific prediction equations. Results. Ratio and regression scaling gave almost identical results. ECV scaled to BSA by either method was higher in men in all BMI groups but ECV scaled to LBM and TBW was higher in women. There was, however, little difference between men and women in respect to ECV per unit weight in any BMI group, even though women have 10% more adipose tissue. The relations between TBW and BSA and between LBM and BSA, but not between LBM and TBW, were different between men and women. Conclusion. Lean tissue in women contains more extracellular water than in men, a difference that is obscured by scaling to BSA. The likely problem with BSA is its insensitivity to body composition.

68Ga-DOTANOC Focal Pulmonary Activity With No Corresponding CT Abnormality.

A 28-year-old woman with medullary thyroid cancer treated with total thyroidectomy and bilateral central and right lateral neck nodal resection postoperatively had increasing calcitonin and carcinoembryonic antigen values. A Ga-DOTANOC PET/CT study performed showed tracer-avid disease in the neck, mediastinal, and hilar lymph nodes. However, there were 3 tracer-avid foci in the lungs bilaterally, suggestive of lung metastases but with no corresponding abnormalities on low-dose CT. A negative contrast-enhanced CT of the lungs along with clinical and radiological follow-up confirmed that the lung activity was artifactual, demonstrating the possibility of Ga-DOTANOC-avid iatrogenic pulmonary microembolism.

Renal manifestation of Birt–Hogg–Dubé syndrome depicted by 18F-fludeoxyglucose positron emission tomography/computed tomography in a patient with hurtle cell thyroid malignancy

Birt–Hogg–Dubé (BHD) syndrome is an autosomal dominant genetic disorder characterized by small papular skin lesions (fibrofolliculomas) causing susceptibility to kidney cancer, renal and pulmonary cysts, spontaneous pneumothoraces, and several noncutaneous tumors. We report a case of a 67-year-old woman, with a previous history of right hemithyroidectomy for adenomatous lesion. She presented with a swelling in the right thyroid bed that on subsequent biopsy revealed features of metastatic carcinoma. 18F-fludeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) performed for the detection of primary malignancy showed increased high-grade metabolic activity in the right supraclavicular soft tissue mass extending into the superior mediastinum. Moreover, on low-dose CT, there have been bilateral renal interpolar cortical lesions with mild metabolic activity. Given the fact that the right neck mass was highly unlikely to represent renal metastases in the absence of widespread metastatic disease, surgical excision of the right neck mass was performed. The histology of the mass was in keeping with hurtle cell thyroid carcinoma. In regard to renal lesions, bilateral partial nephrectomy was performed, which was consistent with chromophobe renal cell carcinoma, raising the suspicion of BHD that was confirmed by the subsequent genetic evaluation. It is well established that 18F-FDG PET/CT study is not an optimal modality for evaluation of renal lesions. However, careful assessment of the CT features in conjunction with the associated metabolic activity of the 18F-FDG PET component increases the diagnostic accuracy of PET/CT.

Skeletal Metastases and Benign Mimics on NaF PET/CT: A Pictorial Review

OBJECTIVE The aim of this article is to present examples in which sodium fluoride labelled with 18F (NaF) bone PET/CT would be a useful adjunct to guide complex clinical decisions about the staging, restaging, and treatment approach for patients with skeletal metastases and benign causes of NaF activity that can be mistaken for bone metastases. We present a pictorial review of selected cases of this cohort of patients. CONCLUSION NaF PET/CT hybrid fusion imaging is extremely useful in identifying potential causes of pain in patients with malignancies that have an affinity for skeletal metastases. This technique can help detect bone metastases, in problem solving, and to direct appropriate management.