Allan O. Santos

18F-FDG PET/CT Delayed Images After Diuretic for Restaging Invasive Bladder Cancer

PET with 18F-FDG has been considered of limited value for detection of bladder cancer because of the urinary excretion of the tracer. The purpose of this study was to investigate the role of PET/CT in the detection and restaging of bladder cancer using furosemide and oral hydration to remove the excreted 18F-FDG from the bladder. Methods: Seventeen patients with bladder cancer (11 without cystectomy, 6 with total cystectomy and urinary diversion) underwent 18F-FDG PET/CT from head to the upper thighs 60 min after the intravenous injection of 370 MBq of 18F-FDG. Additional pelvic images were acquired 1 h after the intravenous injection of furosemide and oral hydration. PET/CT findings were confirmed by MRI, cystoscopy, or biopsy. Results: PET/CT was able to detect bladder lesions in 6 of 11 patients who had not undergone cystectomy. These images changed the PET/CT final reading in 7 patients: Recurrent bladder lesions were detected in 6 patients, pelvic lymph node metastases in 2 patients, and prostate metastasis in 1. This technique overcame the difficulties posed by the urinary excretion of 18F-FDG. Hypermetabolic lesions could be easily detected by PET and precisely localized in the bladder wall, pelvic lymph nodes, or prostate by CT. Seven of 17 patients (41%) were upstaged only after delayed pelvic images. Conclusion: Detection of locally recurrent or residual bladder tumors can be dramatically improved using 18F-FDG PET/CT with delayed images after a diuretic and oral hydration.

68Ga-DOTATATE PET/CT, 99mTc-HYNIC-Octreotide SPECT/CT, and Whole-Body MR Imaging in Detection of Neuroendocrine Tumors: A Prospective Trial

There are different metabolic imaging methods, various tracers, and emerging anatomic modalities to stage neuroendocrine tumor (NET). We aimed to compare NET lesion detectability among 99mTc-hydrazinonicotinamide (HYNIC)-octreotide (somatostatin receptor scintigraphy [SSRS]) SPECT/CT, 68Ga-DOTATATE PET/CT, and whole-body diffusion-weighted MR imaging (WB DWI). Methods: Nineteen consecutive patients (34–77 y old; mean, 54.3 ± 10.4 y old; 10 men and 9 women) underwent SSRS SPECT/CT, 68Ga-DOTATATE PET/CT, and WB DWI. Images were acquired with a maximum interval of 3 mo between them and were analyzed with masking by separate teams. Planar whole-body imaging and SPECT/CT were performed from thorax to pelvis using a double-head 16-slice SPECT/CT scanner 4 h after injection of 111–185 MBq of 99mTc-HYNIC-octreotide. 68Ga-DOTATATE PET/CT was performed from head to feet using a 16-slice PET/CT scanner 45 min after injection of 185 MBq of tracer. WB DWI was performed in the coronal plane using a 1.5-T scanner and a body coil. The standard method of reference for evaluation of image performance was undertaken: consensus among investigators at the end of the study, clinical and imaging follow-up, and biopsy of suggestive lesions. Results: McNemar testing was applied to evaluate the detectability of lesions using 68Ga-DOTATATE PET/CT in comparison to SSRS SPECT/CT and WB DWI: a significant difference in detectability was noted for pancreas (P = 0.0455 and P = 0.0455, respectively), gastrointestinal tract (P = 0.0455 and P = 0.0455), and bones (P = 0.0082 and P = 0.0082). Two unknown primary lesions were identified solely by 68Ga-DOTATATE PET/CT. 68Ga-DOTATATE PET/CT, SSRS SPECT/CT, and WB DWI demonstrated, respectively, sensitivities of 0.96, 0.60, and 0.72; specificities of 0.97, 0.99, and 1.00; positive predictive values of 0.94, 0.96, and 1.00; negative predictive values of 0.98, 0.83, and 0.88; and accuracies of 0.97, 0.86, and 0.91. Conclusion: 68Ga PET/CT seems to be more sensitive for detection of well-differentiated NET lesions, especially for bone and unknown primary lesions. NET can be staged with 68Ga-DOTATATE PET/CT. WB DWI is an efficient new method with high accuracy and without ionizing radiation exposure. SSRS SPECT/CT should be used only when 68Ga-DOTATATE PET/CT and WB DWI are not available.

Low bone mass density is associated with hemolysis in brazilian patients with sickle cell disease

OBJECTIVES: To determine whether kidney disease and hemolysis are associated with bone mass density in a population of adult Brazilian patients with sickle cell disease. INTRODUCTION: Bone involvement is a frequent clinical manifestation of sickle cell disease, and it has multiple causes; however, there are few consistent clinical associations between bone involvement and sickle cell disease. METHODS: Patients over 20 years of age with sickle cell disease who were regularly followed at the Hematology and Hemotherapy Center of Campinas, Brazil, were sorted into three groups, including those with normal bone mass density, those with osteopenia, and those with osteoporosis, according to the World Health Organization criteria. The clinical data of the patients were compared using statistical analyses. RESULTS: In total, 65 patients were included in this study: 12 (18.5%) with normal bone mass density, 37 (57%) with osteopenia and 16 (24.5%) with osteoporosis. Overall, 53 patients (81.5%) had bone mass densities below normal standards. Osteopenia and osteoporosis patients had increased lactate dehydrogenase levels and reticulocyte counts compared to patients with normal bone mass density (p<0.05). Osteoporosis patients also had decreased hemoglobin levels (p<0.05). Hemolysis was significantly increased in patients with osteoporosis compared with patients with osteopenia, as indicated by increased lactate dehydrogenase levels and reticulocyte counts as well as decreased hemoglobin levels. Osteoporosis patients were older, with lower glomerular filtration rates than patients with osteopenia. There was no significant difference between the groups with regard to gender, body mass index, serum creatinine levels, estimated creatinine clearance, or microalbuminuria. CONCLUSION: A high prevalence of reduced bone mass density that was associated with hemolysis was found in this population, as indicated by the high lactate dehydrogenase levels, increased reticulocyte counts and low hemoglobin levels.

Scintigraphic follow-up of the effects of therapy with hydroxyurea on splenic function in patients with sickle cell disease

Abstract. Patients with sickle cell disease (SCD) may develop functional asplenia as a chronic complication, secondary to repeated episodes of polymerisation of haemoglobin S. It is known that increased plasma concentrations of fetal haemoglobin (HbF) reduce the polymerisation of haemoglobin S. Hydroxyurea is a chemotherapeutic agent capable of increasing HbF levels in the red blood cells and its use has recently been proposed in the treatment of SCD. The objective of this study was to evaluate the effects of long-term therapy with hydroxyurea on recovery of splenic function. Twenty-one patients (aged 3–22 years; 14 with SS haemoglobinopathy, 7 with Sβ0 haemoglobinopathy) were studied with liver/spleen scintigraphy before and after 6 and 12 months of treatment. All studies were submitted to visual inspection and semi-quantitative analyses using spleen/liver ratios. Imaging prior to treatment demonstrated functional asplenia in nine SS patients and one Sβ0 patient and impaired splenic function in five SS patients and six Sβ0 patients. After treatment, splenic function improved in ten patients, remained unchanged in eight and worsened in three . Using liver/spleen imaging, it was possible to demonstrate that hydroxyurea is capable of improving splenic function in some SCD patients. Improvement is not always possible and frequently does not lead to a normal splenic function even after 1 year of treatment.

Treatment of bone pain secondary to metastases using samarium-153-EDTMP

CONTEXT More than 50% of patients with prostate, breast or lung cancer will develop painful bone metastases. The purpose of treating bone metastases is to relieve pain, reduce the use of steroids and to maintain motion. OBJECTIVE To evaluate the use of samarium-153-EDTMP (153Sm-EDTMP) for the treatment of bone pain secondary to metastases that is refractory to clinical management. TYPE OF STUDY Retrospective. SETTING Division of Nuclear Medicine, Universidade Estadual de Campinas (Unicamp). METHODS Fifty-eight patients were studied (34 males) with mean age 62 years; 31 patients had prostate cancer, 20 had breast cancer, three had lung cancer, one had lung hemangioendothelioma, one had parathyroid adenocarcinoma, one had osteosarcoma and one had an unknown primary tumor. All patients had multiple bone metastases demonstrated by bone scintigraphy using 99mTc-MDP,and were treated with 153Sm-EDTMP. Response to treatment was graded as good (pain reduction of 50-100%), intermediate (25-49%) and poor (0-24%). RESULTS All patients showed good uptake of 153Sm-EDTMP by bone metastases. Among the patients with prostate cancer, intermediate or good response to therapy occurred in 80.6% (25 patients) and poor response in 19.4% (6). Among the patients with breast cancer, 85% (17) showed intermediate or good response to therapy while 15% (3) showed poor response. All three patients with lung cancer showed poor response to treatment. The lung hemangioendothelioma and unknown primary lesion patients showed intermediate response to treatment; the osteosarcoma and parathyroid adenocarcinoma patients showed good response to treatment. No significant myelotoxicity occurred. DISCUSSION Pain control is important for improving the quality of life of patients with advanced cancers. The mechanism by which pain is relieved with the use of radionuclides is still not yet completely understood, however, the treatment is simple and provides a low risk of mielotoxicity. CONCLUSION Treatment with 153Sm-EDTMP can control the pain secondary to bone metastases effectively in most patients with breast and prostate cancer without significant side effects.

Impact of [F-18] FDG-PET/CT in the restaging and management of patients with malignant melanoma.

PurposeTo assess the impact of [F-18] FDG-PET/CT on the restaging and changing management of patients with malignant melanoma. MethodsSeventy-eight patients (32 female, 27–83 years) were reviewed. Treatment planning before and after [F-18] FDG-PET/CT scan was evaluated for changes in the management of the disease. Restaging was classified according to the disease extent as follows: local recurrence, locoregional recurrence or distant recurrence. Initial restaging of patients was as follows: local recurrence in 11 patients, locoregional recurrence in 23 patients and distant recurrence in 44 of 78 patients. All the patients were injected with 370 MBq of [F-18] FDG and imaged from the head to feet after 60 min. All the patients fasted for 4–6 h before imaging and blood glucose levels were below 140 mg/dl. Images were taken using a PET/CT scanner (Siemens Biograph). Two nuclear medicine physicians and a radiologist (all experienced in oncology) interpreted the images. ResultsIn 27% of the patients the management was changed after the [F-18] FDG-PET/CT studies. Upstaging from locoregional recurrence to distant recurrence occurred in a striking 5 of 23 (22%) patients. The sensitivity, specificity and positive and negative predictive values for lesion detection were 95%, and accuracy was 94.9%. There were two false-positive and two false-negative studies. Conclusion[F-18] FDG-PET/CT seems to be a valuable diagnostic tool in restaging and management of patients with malignant melanoma suspected of recurrence especially in patients with locoregional recurrence and distant recurrence.

Obesity and Cytokines in Childhood-Onset Systemic Lupus Erythematosus

Background. In systemic lupus erythematosus (SLE), atherosclerosis is attributed to traditional and lupus related risk factors, including metabolic syndrome (MetS), obesity, and inflammation. Objective. To evaluate the association between obesity, measures of body fat content, serum tumor necrosis factor alpha (TNF-α), and interleukin (IL)-6 and -10 levels in childhood-onset SLE (cSLE). Methods. We screened consecutive cSLE patients followed up in the Pediatric Rheumatology Outpatient Clinic of the State University of Campinas. cSLE patients were assessed for disease and damage. Obesity was definite as body mass index (BMI) ≥30 kg/m2. Serum TNF-α, IL-6, and IL-10 levels were measured by ELISA. Dual-energy X-ray absorptiometry was used to determine total fat mass, lean mass, and percent of body fat. Results. We included 52 cSLE patients and 52 controls. cSLE patients had higher serum TNF-α  (P = 0.004), IL-6 (P = 0.002), and IL-10 (P < 0.001) levels compared to controls. We observed higher serum TNF-α  (P = 0.036) levels in cSLE patients with obesity. An association between serum TNF-α levels and body fat percent (P = 0.046) and total fat mass on trunk region (P = 0.035) was observed. Conclusion. Serum TNF-α levels were associated with obesity and body fat content in cSLE. Our finding suggests that obesity may contribute to the increase of serum TNF-α levels in cSLE.

Body weight and composition in users of levonorgestrel-releasing intrauterine system

BACKGROUND There is little information about body weight and body composition (BC) among users of the levonorgestrel-releasing intrauterine system (LNG-IUS). The aim of this study was to evaluate body weight and BC in LNG-IUS users compared to users of the TCu380A intrauterine device (IUD). STUDY DESIGN A prospective study was done with 76 new users of both contraceptive methods. Women were paired by age (±2 years) and body mass index (BMI, kg/m², ±2). Body weight and BC (% lean mass and % fat mass) were evaluated by a trained professional at baseline and at 1 year of contraceptive use. The BC measurements were obtained using Lunar DXA equipment. Weight and BC were evaluated in each woman at baseline and at 12 months and analyzed as the mean change within each woman. Then, the changes in weight and BC for each woman were calculated and then compared between LNG-IUS and TCu380A IUD users (paired data for each woman). The central-to-peripheral fat ratio was calculated by dividing trunk fat by the upper and lower limb fat. RESULTS There were no significant differences at time of IUD insertion between LNG-IUS and TCu380A IUD users regarding age (mean±SD) (34.4±7.5 vs. 33.9±8.0 years), BMI (25.3±4.1 vs. 25.9±4.1) and number of pregnancies (1.9±0.2 vs. 1.7±0.2), respectively. Mean body weight gain of 2.9 kg was observed among LNG-IUS users at 12 months (p=.0012), whereas the body weight of TCu380A IUD users only increased by 1.4 kg (p=.067). There was no significant difference in body weight change between the two groups of users at 12 months. The variation in the central-to-peripheral fat ratio was the same between the two groups (-1.6% vs. -0.2%; p=.364). LNG-IUS users showed a 2.5% gain in fat mass (p=.0009) and a 1.4% loss of lean mass, whereas TCu380A IUD users showed a loss of 1.3% of fat mass (p=.159) and gain of 1.0% of lean mass (p=.120). TCu380A IUD users gained more lean mass than LNG-IUS users (p=.0270), although there was no significant difference between the two groups after 12 months of use. CONCLUSIONS Although an increase in mean fat mass among LNG-IUS users at 12 months of use was observed, it should be noted that an increase of body weight was also observed in both groups after 1 year of insertion of the device. However, a study with a larger number of women and long-term evaluation is necessary to evaluate these body changes.

51Cr-EDTA measurements of the glomerular filtration rate in patients with sickle cell anaemia and minor renal damage.

Background Creatinine clearance has been reported to be inaccurate for the estimation of glomerular filtration rate (GFR) in patients with sickle cell anaemia (SCA). Inulin clearance, the reference method for GFR estimation, is impractical for routine use in these patients, and 51Cr-EDTA measurements of the GFR have been rarely reported in this disease. Methods In order to obtain reference 51Cr-EDTA values in this disease, we studied 70 patients (40 females; 13–59 years of age, mean: 31.6 years) with homozygous SCA, normal serum creatinine and urinary albumin excretion <or=200 μg·min−1. All patients were submitted to single-injection 51Cr-EDTA GFR, urinary albumin and haematocrit measurements. 51Cr-EDTA clearances were calculated in different age groups (<20, 20–29, 30–39, 40–49 and>50 years). Results The mean GFR (±standard deviation) obtained for the 70 patients was 111.5±23.1 ml·min−1. Analysis of variance for evaluation of the possible interaction effect between 51Cr-EDTA clearance and sex, age, urinary albumin and haematocrit demonstrated patient age as the only factor influencing 51Cr-EDTA clearance (P<0.001). The Spearman correlation coefficient showed a significant relationship between 51Cr-EDTA clearance and patient age (r=−0.44, P=0.0001), but not between 51Cr-EDTA and urinary albumin (r=−0.17, P=0.1546) or haematocrit (r=0.079, P=0.5121). The group aged 20–29 years presented the highest 51Cr-EDTA clearance mean value (126.7±20.4 ml·min−1), with a progressive reduction in the older groups. Conclusion Young adults with homozygous SCA, normal serum creatinine and micro-albuminuria or normo-albuminuria present supranormal 51Cr-EDTA GFR values. These values rapidly decrease after 30 years of age. We did not find association between urinary albumin and GFR in these patients.

Activation of the growth plates on three-phase bone scintigraphy: the explanation for the overgrowth of fractured femurs

Abstract. Children with an uncomplicated femoral fracture, treated with superimposition of fragments and intentional shortening, usually develop overgrowth of the fractured femur and the ipsilateral tibia which may compensate for the initial shortening and enable the limb in question to reach a length similar to that on the normal side. The overgrowth is evaluated clinically and by scanography. The increased metabolic activity of the growth plates that support this overgrowth has not been documented by any laboratory method.In order to evaluate the metabolic activity of the growth plates, 18 patients (11 males, seven females; mean age 6.1 years) with fractures of the femur were studied at three different time intervals (2–5 months, 6–12 months and 18–24 months). Three-phase bone scintigraphy was performed in all patients. Ten children (five males, five females; mean age 7.5 years) who had had bone imaging for other reasons were used as the control group. Visual analysis of the flow and equilibrium phases was performed for the distal femoral and proximal tibial growth plates. Visual and semi-quantitative analyses of the delayed images were performed for the distal femoral and proximal and distal tibial growth plates. Semi-quantitative analyses yielded the following activity ratios: (a) the distal femoral growth plate of the fractured femur to the contralateral one (FR); (b) the proximal growth plate of the tibia on the side of the fractured femur to the contralateral one (TpR); (c) the distal growth plate of the tibia on the side of the fractured femur to the contralateral one (TdR); and (d) in the control group, the distal growth plates of both femora (FCG) and the proximal (TCGp) and distal (TCGd) growth plates of the tibiae. Visual analysis of the blood flow, equilibrium and delayed images showed increased activity in the distal femoral growth plates during the first and second time intervals, but not during the third. No significant activity changes were found in the proximal and distal tibial growth plates during any of the phases analysed. The mean and standard deviation for FR in the three time intervals were: FRI=1.22±0.27, FRII=1.17±0.16 and FRIII=1.09±0.20. FR values were significantly higher than in the control group (FCG=0.99±0.03) (P=0.033). The mean and standard deviation for TpR in the three time intervals were: TpRI=1.08±0.18, TpRII=0.94±0.09 and TpRIII=0.96±0.20. TpR values were not significantly different from those in the control group (TCGp=1.00±0.05). However, TpRI was significantly higher than TpRII (P=0.043). The mean and standard deviation for TdR in the three time intervals were: TdRI=1.10±0.41, TdRII=1.05±0.15 and TdRIII=1.13±0.36. TdR values were not significantly higher than in the control group (TCGd=1.00±0.04) (P=0.777). These results support the concept that three-phase bone imaging is able to quantify and determine that activation occurs in the distal femoral and proximal tibial growth plates of fractured femora. This phenomenon may explain the overgrowth observed in this injured bone structure.