Pier Francesco Rambaldi

Scintimammography with technetium-99m tetrofosmin in the diagnosis of breast cancer and lymph node metastases

The aim of the study was to evaluate the possible role of scintimammography (SMM) with technetium-99m tetrofosmin in breast cancer. Thirty-three patients with breast disease and ten normal controls were included in the study. Planar scintigraphic images in supine anterior, prone lateral and lateral views, with the patient lying in lateral recumbency, were acquired. A qualitative analysis evaluating both breasts and lymph nodes was performed. All breast lesions were verified after surgery and/or by fine-needle aspiration. In 8 of the 33 patients, mammography was inconclusive because of mastectomy or dense breasts. For mammography, a sensitivity of 95.6%, a specificity of 66.7% and an accuracy of 89.6% were obtained. At SMM, 26 out of 28 malignant lesions (average size 2.8 cm, range 0.4–12 cm), including two recurrences, were detected with a 92.8% sensitivity, a 100% specificity and a 95.1% accuracy. The smallest detectable carcinoma measured 0.6 cm. Two false-negative results on SMM were found in a 0.4-cm intraductal carcinoma and in the only mucinous papillary carcinoma in our series. With regard to lymph node analysis, 11 out of 12 axillary metastases (sensitivity=91.6%) were detected. A false-positive result, yielding a specificity of 92.3% was also obtained. A metastatic involvement of the internal mammary chain was observed. No uptake was seen in 11 benign mammary lesions or at the level of the breast and axilla when neoplastic involvement was absent. In conclusion, SMM with99mTc-tetrofosmin is an effective technique for the evaluation of primary breast carcinomas, recurrences and lymph node metastases.

ROBO2 Gene Variants Are Associated with Familial Vesicoureteral Reflux

The SLIT2 receptor ROBO2 plays a key role in the formation of the ureteric bud, and its inactivation in mice leads to supernumerary ureteric bud development, lack of ureter remodeling, and improper insertion of the ureters into the bladder. Recently, two heterozygous ROBO2 missense mutations were identified in two families with primary vesicoureteral reflux occurring in combination with congenital anomalies of the kidney and urinary tract (VUR/CAKUT). This study investigated a possible causal role of ROBO2 gene variants in 95 unrelated patients with primary VUR (n = 78) or VUR/CAKUT. Eighty-two percent of all patients had a family history of genitourinary anomalies. Twenty-four ROBO2 gene variants were identified by direct sequencing of all 26 exons and the exon-intron boundaries. Of these, four led to amino acid substitutions: Gly328Ser, Asn515Ile, Asp766Gly, and Arg797Gln. When the families were examined, the missense variants co-segregated with VUR (three families) or VUR/CAKUT (one family). These variants were not found in 190 control subjects, and the affected amino acids have been conserved through evolution. In conclusion, a relatively high frequency of ROBO2 variants (5.1%) was found in familial cases; however, functional studies and validation in other cohorts are warranted.

Breast Cancer Detection With Tc-99m Tetrofosmin

Myocardial SPECT imaging was performed with Tc-99m tetrofosmin. Intense focal uptake at the level of the left breast was observed. At mammography a breast carcinoma was suspected, which was confirmed after surgery. This may be the first report of neoplastic mammary uptake of Tc-99m tetrofosmin.

HIGH INCIDENCE OF A GENERALLY SMALL KIDNEY AND PRIMARY VESICOURETERAL REFLUX

PURPOSE We distinguished the scintigraphy pattern of congenital reflux nephropathy from that of acquired scarring in children with primary vesicoureteral reflux. MATERIALS AND METHODS We retrospectively evaluated the frequency and pattern of renal scintigraphy abnormalities in 41 patients with prenatally detected primary vesicoureteral reflux and in 322 with a mean age plus or minus standard deviation of 3.6 + or - 1 years in whom primary reflux was detected after urinary tract infection. Dimercapto-succinic acid scintigraphy was performed 4 to 6 and 1 to 4 months after reflux was diagnosed and/or the infection was cured in patients with urinary tract infection and prenatal detection, respectively. RESULTS We identified 3 patterns of renal damage, including overall decreased uptake of renal radionuclide that was 20% to 40% of relative uptake, focal defects in uptake and shrunken kidney with relative uptake less than 20%. Scintigraphy revealed renal damage in 12 prenatally detected cases of vesicoureteral reflux, including overall decreased uptake in 58% and shrunken kidney in 42%, and in 111 cases of reflux detected at urinary tract infection, including overall decreased uptake in 50%, uptake focal defects in 37% and shrunken kidney in 13%. In the urinary tract infection group overall decreased uptake was present in 25 of 90 boys and in 40 of 232 girls (p = 0.05). Of these children 15% of the girls had uptake focal defects and 17% had overall decreased uptake. Overall decreased uptake and uptake focal defects were significantly more common in kidney-ureter units with reflux grade 4 or greater than in those with grade 3 or less (p = 0. 00001 and 0.027, respectively). CONCLUSIONS When assuming that overall decreased radionuclide uptake indicates congenital reflux nephropathy and uptake focal defects indicate postnatal acquired scarring, congenital reflux nephropathy appears to be an important cause of renal damage in children with primary vesicoureteral reflux even beyond the neonatal age and even in girls. This finding is of interest because postnatally acquired scarring may but congenital reflux nephropathy may not be prevented.

Permanent renal parenchymal defects after febrile UTI are closely associated with vesicoureteric reflux

The finding of scintigraphic renal defects in children with febrile urinary tract infection (UTI) even in the absence of vesicoureteric reflux (VUR) has led to the conclusion that VUR is a weak predictor of renal defects in these patients. We used isotopic cystography (IC) for diagnosis of VUR in children with febrile UTI. Dimercaptosuccinic acid renal scintigraphy was performed 6 months after cure of the last UTI. Renal defects were defined by the finding of focal defects of radionuclide uptake and/or by a split renal function <43%. The study included 206 children with primary VUR and 77 without VUR. Among the subjects with and without VUR, respectively, renal defects were found in 40 and 6% (p=0.0001), focal uptake defects in 33 and 5% (p=0.0001) and split renal function <43% in 26 and 5% (p=0.0001). Permanent renal defects in children with febrile UTI are closely associated with VUR. The possibility that a child will have permanent renal defects can reasonably be ruled out on the basis of the absence of VUR by IC.

Enhanced detection of vesicoureteric reflux with isotopic cystography

Abstract We compared the accuracy of isotope cystography (IC) and fluoroscopic cystourethrography (FC) in detecting vesicoureteric reflux (VUR) in children. FC and IC were performed in 124 children, 56 boys and 68 girls, aged 1 month to 9.2 years (mean 2.1 years), admitted consecutively for suspected VUR over a 10-month period. VUR was diagnosed by one or both studies in 51 of 124 (41%) patients. The two methods were concordant for the detection of VUR in 84% of kidney-ureter units and in 93% for the detection or exclusion of severe VUR. IC detected VUR more accurately than FC, both when all grades of VUR were considered together (P=0.00001) and when only severe reflux was considered (P=0.004). VUR was missed by FC in 23 of 51 (45%) subjects. Of those 23, 12 had severe VUR detected on one side at least by IC. VUR was missed by IC in 3 subjects. IC is significantly more accurate than FC in the initial diagnosis of VUR, even of severe grade. IC is the method of choice for the first diagnosis of VUR. Boys with VUR diagnosed by IC also need FC to investigate for posterior urethral valves.

A genome search for primary vesicoureteral reflux shows further evidence for genetic heterogeneity.

Vesicoureteral reflux (VUR) is the most common disease of the urinary tract in children. In order to identify gene(s) involved in this complex disorder, we performed a genome-wide search in a selected sample of 31 patients with primary VUR from eight families originating from southern Italy. Sixteen additional families with 41 patients were included in a second stage. Nonparametric, affected-only linkage analysis identified four genomic areas on chromosomes 1, 3, and 4 (p < 0.05); the best result corresponded to the D3S3681-D3S1569 interval on chromosome 3 (nonparametric linkage score, NPL = 2.75, p = 0.008). This region was then saturated with 26 additional markers, tested in the complete group of 72 patients from 24 families (NPL = 2.01, p = 0.01). We identified a genomic area on 3q22.2–23, where 26 patients from six multiplex families shared overlapping haplotypes. However, we did not find evidence for a common ancestral haplotype. The region on chromosome 1 was delimited to 1p36.2–34.3 (D1S228-D1S255, max. NPL = 1.70, p = 0.03), after additional fine typing. Furthermore, on chromosome 22q11.22–12.3, patients from a single family showed excess allele sharing (NPL = 3.35, p = 0.015). Only the chromosome 3q region has been previously reported in the single genome-wide screening available for primary VUR. Our results suggest the presence of several novel loci for primary VUR, giving further evidence for the genetic heterogeneity of this disorder.

Effects of α-lipoic acid therapy on sympathetic heart innervation in patients with previous experience of transient takotsubo cardiomyopathy.

BACKGROUND Takotsubo syndrome is a stress cardiomyopathy, characterized by reversible left ventricle (LV) apical ballooning in the absence of significant angiographic coronary artery stenosis. The frequent association with emotional stress suggests in this disease an autonomic nervous system involvement. We could think that a therapeutic treatment targeting heart sympathetic dysfunction could be of crucial importance. METHODS From January 2010 to June 2012, 886 patients were consecutively evaluated at Cardarelli Hospital, Naples, Italy. Among these, 48 patients met takotsubo cardiomyopathy (TCM) criteria. Each patient was assessed with history and physical examination, 12-lead electrocardiogram, serum troponin, coronary arteriography, and left ventricular angiogram, perfusion myocardial scintigraphy with technetium 99m, with echocardiography and 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy. At discharge, the surviving patients were randomly assigned to α-lipoic acid (ALA) treatment (600mg once daily) or placebo. Following discharge, after the initial TCM event, patients returned to our outpatient clinic at Internal Medicine of the Second University Naples for the follow-up evaluation quarterly until 12 months. Routine analysis, myocardial damage serum markers, oxidative stress serum markers, pro-inflammatory cytokines, and sympathetic tone activity were evaluated in all patients. RESULTS ALA administration improved MIBG defect size at 12 months compared to placebo. CONCLUSIONS Adrenergic cardiac innervation dysfunction in TCM patients persists after previous experience of transient stress-induced cardiac dysfunction. ALA treatment improves the adrenergic cardiac innervation. This study evaluates whether sympatho-vagal alterations are TCM event-related.

Peri-procedural tight glycemic control during early percutaneous coronary intervention up-regulates endothelial progenitor cell level and differentiation during acute ST-elevation myocardial infarction: effects on myocardial salvage.

BACKGROUND We examined the effects of peri-procedural intensive glycemic control during early percutaneous coronary intervention (PCI) on the number and differentiation of endothelial progenitor cells (EPCs) and myocardial salvage (MS) in hyperglycemic patients with first ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS We conducted a randomized, prospective, open label study on 194 patients with STEMI undergoing PCI: 88 normoglycemic patients (glucose < 140 mg/dl) served as the control group. Hyperglycemic patients (glucose ≥140 mg/dl) were randomized to intensive glycemic control (IGC) for almost 24 h after PCI (n = 54; 80-140 mg/dl) or conventional glycemic control (CGC, n = 52; 180-200 mg/dl). EPC number, differentiation, and SIRT1expression were assessed immediately before, 24 h, 7, 30 and 180 days after PCI. The primary end point of the study was salvage index, measured as the proportion of initial perfusion defect (acute technetium-99m sestamibi scintigraphy, performed 5 to 7 days after STEMI) and myocardium salvaged by therapy (6 months after STEMI). Hyperglycemic patients had lower EPC number and differentiation and lower SIRT1 levels than normoglycemic patients (P < 0.01). After the insulin infusion, mean plasma glucose during peri-procedural period was greater in CGC group than in IGC group (P < 0.001). The EPC number, their capability to differentiate, and SIRT1 levels were significantly higher in IGC group than in CGC, peaking after 24 h (P < 0.01). In the IGC group, the salvage index was greater than in patients treated with CGC (P < 0.001). CONCLUSIONS Optimal peri-procedural glycemic control, by increasing EPC number and their capability to differentiate, may improve the myocardial salvage.

The role of technetium-99m hexakis-2-methoxyisobutyl isonitrile in the detection of neoplastic lung lesions

OBJECTIVE Our goal was to determine the role of technetium-99m hexakis-2-methoxyisobutyl isonitrile ((99m)Tc-MIBI) in the detection of neoplastic lung lesions. MATERIALS AND METHODS We prospectively studied 79 consecutive patients with indeterminate lung lesion between January 2006 and September 2007. All patients were submitted to (99m)Tc-MIBI single-photon emission chest tomography (SPECT) before invasive diagnostic procedure. Qualitative analysis was performed to evaluate SPECT images in order to localize abnormal activity in the radiologically demonstrated lesion. In addition, semiquantitative analysis was made by calculating tumor/contralateral normal lung ratio (T/N). Finally, the scintigraphic findings were correlated to the histopathological diagnosis obtained by invasive procedure or confirmation of instrumental exams. RESULTS Sixty patients had a malignant lesion: 44 squamous cell carcinoma, 7 adenocarcinomas, 4 large cell carcinoma, 1 small cell lung cancer, and 4 metastases. The mean size+/-standard deviation of malignant nodules was 3.9+/-1.61 cm (range 1.5-5.5 cm). Nineteen patients had a benign disease. The mean size+/-standard deviation of benign nodules was 3.3+/-1.71 cm (range 2-6 cm). (99m)Tc-MIBI SPECT delineated focal lesions with an increase in tracer accumulation in 55/60 malignant lesions; in 5/60 malignant lesions was negative. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 91%, 73%, 91%, and 73%, respectively. In patients with neoplastic lesion, the mean T/N ratio value+/-standard deviation was 1.72+/-0.35 whereas in patients with benign lesions was 1.14+/-0.25. Semiquantitative analysis showed that for a T/N value >1.23, the value of sensitivity, specificity, PPV, and PNV were 91%, 84%, 94%, and 76%, respectively (ROC curve). Metastatic mediastinal lymph nodes were found in 3/57 patients. (99m)Tc-MIBI SPECT showed a specificity and PPV of 100% in the detection of mediastinal lymph nodes with sensitivity, and PNV of 66% and 97%, respectively. Age, sex, histological type, and size of lesion did not affect the SPECT results. CONCLUSION Our experiences seem to confirm that (99m)Tc-MIBI SPECT is a reliable diagnostic tool in the finding of lung cancer particularly cases in which radiological evaluation is indeterminate.