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M Salvatore

Publications and source records attributed to M Salvatore.

At least 37 records · Page 2Linked to original sources

Follow-up of differentiated thyroid carcinoma.

Thyroid cancer is the most common endocrine malignancy. More than 90% of primary thyroid cancers are differentiated papillary or follicular types. The treatment of differentiated thyroid carcinoma (DTC) consists of total thyroidectomy and radioactive iodine ablation therapy, followed by L-thyroxine therapy. The extent of initial surgery, the indication for radioiodine ablation therapy and the degree of TSH-suppression are all issues that are still being debated cancers are in relation to the risk of recurrence. Total thyroidectomy reduces the risk of recurrence and facilitates (131)I ablation of thyroid remnants. The aim of radioiodine ablation is to destroy any normal or neoplastic residuals of thyroid tissue. These procedures also improve the sensitivity of thyroglobulin (Tg) as a marker of disease, and increase the sensitivity of (131)I total body scan (TBS) for the detection of persistent or recurrent disease. The aim of TSH-suppressive therapy is to restore euthyroidism and to decrease serum TSH levels, in order to reduce the growth and progression of thyroid cancer. After initial treatment, the objectives of the follow-up of DTC is to maintain adequate thyroxine therapy and to detect persistent or recurrent disease through the combined use of neck ultrasound (US) and serum Tg and (131)I TBS after TSH stimulation. The follow-up protocol should be adapted to the risk of recurrence. Recent advances in the follow-up of DTC are related to the use of recombinant human TSH (rhTSH) in order to stimulate Tg production and the ultrasensitive methods for Tg measurement. Undetectable serum Tg during TSH suppressive therapy with L-T4 does not exclude persistent disease, therefore serum Tg should be measured after TSH stimulation. The results of rhTSH administration and L-thyroxine therapy withdrawal are equivalent in detecting recurrent thyroid cancer, but the use of rhTSH helps to avoid the onset of hypothyroid symptoms and the negative effects of acute hypothyroidism on cardiovascular, hepatic, renal and neurological function. In low-risk DTC patients serum Tg after TSH stimulation, together with ultrasound of the neck, should be used to monitor persistent disease, avoiding diagnostic TBS which has a poor sensitivity. These recommendations do not apply when Tg antibodies are present in the serum, in patients with persistent or recurrent disease or limited thyroid surgery. Low-risk patients may be considered to be in remission when undetectable Tg after TSH stimulation and negative US evaluation of the neck are present. On the contrary, detectable Tg after TSH stimulation is an indicator in selecting patients who are candidates for further diagnostic procedures.

Biomarkers, Tumor↗

MIBI as prognostic factor in breast cancer.

Evaluation of treatment response is of primary importance in the management of patients with cancer. Both positron- and g-emitting compounds have been used to monitor changes in tumor metabolism or viability after therapy. The use of (99m)Tc-labeled lipophilic cations raised the possibility to predict the tumor response to treatment and to identify patients who will become refractory to subsequent therapy. In particular, many studies have shown the prognostic value of (99m)Tc-MIBI scan in different types of malignancy including breast and lung cancer, lymphoma and sarcoma. The ability of (99m)Tc-MIBI to interact with P-glycoprotein, allowing the functional assessment of the multidrug resistant phenotype, is one of the mechanisms underlying its prognostic value. Additional mechanisms of cell resistance, mainly involving alterations of apoptosis, may affect (99m)Tc-MIBI uptake in tumors. Therefore, either an enhanced tracer clearance or a reduced early uptake of (99m)Tc-MIBI indicate a poor response to therapy. In both cases, (99m)Tc-MIBI scan may ensure that the further management strategy will be effective in individual cancer patients.

Breast Neoplasms↗

Radiolabeling approaches for cholecystokinin B receptor imaging.

Regulatory peptides and their analogs are being extensively investigated as radiopharmaceuticals for cancer imaging. In particular, cholecystokinin (CCK) receptors of the subtype B (CCK-BR) have been shown to be overexpressed in certain neuroendocrine tumors including medullary thyroid cancer. Our recent work has focused on new methods to radiolabel the CCK8 peptide with (111)In or (99m)Tc for the purpose of developing radiopharmaceuticals for in vivo CCK-B receptor imaging. Labeling of CCK8 with (111)In was achieved at the N-terminus of the peptide by adding, in solid phase, a glutamate coupled diethylenetriaminepentaacetic acid (DTPA) moiety through a glycine linker, yielding DTPA-Glu-G-CCK8. For labeling with (99m)Tc, the CCK8 peptide was modified at its N-terminus by introducing, in the following order--cysteine, glycine, and a diphenylphosphinopropionyl moiety--giving a 10-residue peptide derivative, Phos-GC-CCK8. A cell culture model was developed for the purpose of evaluating the binding properties of these two ligands. The human epidermoid carcinoma cell line, A431, was transfected with a plasmid containing the full coding sequence of the human CCK-BR under a strong viral promoter, obtaining a number of receptors in the range of 2-5 x 10(6) per cell. Control cells were transfected with vector alone. An animal tumor model utilizing these two cell lines was developed to evaluate the specificity of interaction with the CCK-BR and biodistribution properties of the compounds. CCK-BR positive and control cells were subcutaneously injected in opposite flanks of CD1 female nude mice in order to obtain xenografts differing only in their ability to express CCK-B receptors. High performance liquid chromatography (HPLC) and other chromatographic methods were utilized to assess stability of the radiolabeled compounds after injection. Both (111)In-DTPA-Glu-G-CCK8 and (99m)Tc-Phos-GC-CCK8 showed similar binding affinities for cultured CCK-BR expressing cells, with dissociation constants in the range of 20-40 nM. With the two xenograft approach, we were able to demonstrate specific interaction with the receptor of both CCK analogs in our animal model. The data obtained shows rapid specific localization of both compounds on the CCK-BR overexpressing xenografts. Both tracers show rapid plasma clearance of unbound peptide. Clearance of (111)In-DTPA-Glu-G-CCK8 appears to be preferentially through the kidneys, whereas (99m)Tc-Phos-GC-CCK8 clearance occurs both through kidneys and the hepatobiliary system. Both our labeling approaches appear adequate for clinical use of peptide based radiopharmaceuticals, although (99m)Tc-Phos-GC-CCK8 shows elevated accumulation in the gastrointestinal tract, which causes high background activity.

Animals↗

Acute myocardial infarction in a patient with unstable angina.

A 58-year-old-man with unstable angina developed a violent retrosternal and interscapular pain during coronary angiography with no associated ECG abnormalities. The patient was immediately submitted to transesophageal echocardiography, which revealed an echo-free space behind the ascending aorta thought to be consistent with an aortic dissection. To confirm this finding the patient underwent contrast-enhanced helical CT, which ruled out a dissection but revealed a small hypoattenuating, ill-defined area within the lateral wall of the left ventricle, consistent with an acute myocardial infarction. The finding was first confirmed by bedside echocardiography and later validated by laboratory tests. Review of the left coronary angiogram showed the culprit lesion at the origin of a major acute marginal branch of the circumflex artery.

Angina, Unstable↗

Coracoclavicular joint: osteologic study of 1020 human clavicles.

We examined 1020 dry clavicles from cadavers of Italian origin to determine the prevalence of the coracoclavicular joint (ccj), a diarthrotic synovial joint occasionally present between the conoid tubercle of the clavicle and the superior surface of the horizontal part of the coracoid process. Five hundred and nine clavicles from individuals of different ages were submitted to X-ray examination. Using radiography, we measured the entire length and the index of sinuosity of the anterior lateral curve, on which the distance between the conoid tubercle and the coracoid process depends. We also used radiography to record the differences in prevalence of arthritis in two neighbouring joints, the acromioclavicular and sternoclavicular joints. Of the 1020 clavicles, eight (0.8%) displayed the articular facet of the ccj. No statistical correlation was found between clavicular length and the index of sinuosity of the anterior lateral curve. The prevalence of arthritis in clavicles with ccj was higher than that revealed in clavicles without ccj. The prevalence of ccj in the studied clavicles is lower than that observed in Asian cohorts. Furthermore, ccj is not conditioned by either length or sinuosity of the anterior lateral curve of the clavicle. Finally, the assumption that ccj is a predisposing factor for degenerative changes of neighbouring joints is statistically justified.

Acromioclavicular Joint↗

Diagnostic accuracy of radionuclide imaging using 131I nor-cholesterol or meta-iodobenzylguanidine in patients with hypersecreting or non-hypersecreting adrenal tumours.

The aim of this retrospective study was to evaluate the diagnostic accuracy of nor-cholesterol and meta-iodobenzylguanidine radionuclide imaging in two separate groups of patients with adrenal tumours to characterize lesions as adenoma or pheochromocytoma. We studied 75 patients (22 male and 53 female, mean age 47 +/- 15 years) with hypersecreting (n = 32) or non-hypersecreting (n = 43) unilateral adrenal tumours detected by computerized tomography or magnetic resonance scans. 131I nor-cholesterol adrenal scintigraphy was performed in 41 patients. Meta-[131I]iodobenzylguanidine (131I-MIBG) imaging was acquired in the other 34 patients. Pathology examinations (n = 58) or computerized tomography follow-up studies (n = 17) were obtained. Adrenal lesions were represented by 44 adenomas, four cysts, one myelolipoma, one pseudotumour, one ganglioneuroma, 16 pheochromocytomas, three carcinomas, four metastases and one sarcoma. Radionuclide studies were qualitatively evaluated and the corresponding results were classified as true positive, true negative, false positive and false negative. Diagnostic sensitivity, specificity and accuracy as well as positive and negative predictive values were calculated. The diagnostic values of nor-cholesterol scintigraphy in identifying adrenal adenomas were sensitivity 100%, specificity 71%, accuracy 95%, positive predictive value 94% and negative predictive value 100%; of note, two false positive cases were observed represented by a pheochromocytoma and a myelolipoma. The diagnostic values of MIBG scintigraphy in recognizing pheochromocytoma were sensitivity 100%, specificity 95%, accuracy 97%, positive predictive value 94% and negative predictive value 100%; only one false positive case occurred consisting of a carcinoma. It is concluded that, in the large majority of cases, adrenal scintigraphy using nor-cholesterol or MIBG is able to characterize specific lesions such as adenoma and pheochromocytoma, respectively. These findings show relevant clinical impact, particularly in patients with non-hypersecreting adrenal lasions. Radiotracer selection depends on clinical patient history and department availability; since benign adenomas are the most common cause of non-hypersecreting tumours, nor-cholesterol should be the first choice followed by MIBG if nor-cholesterol shows normal images. However, rare as well as unusual findings may be observed; nor-cholesterol uptake may occasionally be also found in non-adenoma tumours such as myelolipoma and pheochromocytoma. Similarly, MIBG accumulation may occur not only in lesions arising from medullary chromaffin tissue, but also rarely in cortical adrenal carcinoma.

19-Iodocholesterol↗

Sentinel lymph node identification in breast cancer patients.

PURPOSE: To evaluate the predictive value of sentinel lymph node biopsy versus axillary node dissection on lymph node status in patients with T1-T2 breast cancer. MATERIAL AND METHODS: Twenty-nine patients with T1 and 12 with T2 breast carcinoma and clinically N0 axillary lymph nodes, underwent lymphoscintigraphy following the administration of 99mTc-human albumin nanocolloids. The tracer was injected subdermally, over the tumor mass, in the 34 patients with palpable lesions and peritumorally (n=3) or intratumorally (n=4), under stereotactic or ultrasound guidance, in the 7 patients with non-palpable lesions. Anterior and lateral planar images were acquired 15 min after the injection of the tracer and repeated every 30 min up to 3 hr until identification of sentinel lymph node. At the end of the scintigraphic study, sentinel node skin projection was marked using a dermographic pen. Eighteen hours after lymphoscintigraphy, sentinel lymph node was identified and removed during surgery by hand-held gamma probe, then, the remaining axillary lymph nodes were dissected. All surgical specimens underwent histologic examination. Sentinel lymph nodes free of metastasis at histology, underwent additional examination with immunohistochemistry using monoclonal antibodies against cytokeratin and EMA to search for micrometastases. RESULTS: Sentinel lymph node was identified in the 34 patients injected subdermally and in the 3 patients injected peritumorally, while it remained undetected in the 4 patients injected intratumorally except for one case in which it was isolated by radioguided surgery but not scintigraphically. Sentinel nodes resulted free of metastases both at histology and immunohistochemistry in 32 cases and metastatic in 6. In the 32 patients with non-metastatic sentinel lymph nodes the other axillary nodes were also free of metastases. Among the 6 metastatic sentinel lymph nodes, in 3 cases they were the only metastatic nodes of the axilla while in the other 3 cases metastases were spread to other axillary nodes. CONCLUSIONS: In agreement with previous studies, our results showed that sentinel lymph node radioguided biopsy is a simple and reliable method for predicting axillary lymph nodes status and for avoiding axillary dissection in early breast cancer patients with sentinel node free of metastases.

Adult↗

Sequence of the 1918 pandemic influenza virus nonstructural gene (NS) segment and characterization of recombinant viruses bearing the 1918 NS genes.

The influenza A virus pandemic of 1918-1919 resulted in an estimated 20-40 million deaths worldwide. The hemagglutinin and neuraminidase sequences of the 1918 virus were previously determined. We here report the sequence of the A/Brevig Mission/1/18 (H1N1) virus nonstructural (NS) segment encoding two proteins, NS1 and nuclear export protein. Phylogenetically, these genes appear to be close to the common ancestor of subsequent human and classical swine strain NS genes. Recently, the influenza A virus NS1 protein was shown to be a type I IFN antagonist that plays an important role in viral pathogenesis. By using the recently developed technique of generating influenza A viruses entirely from cloned cDNAs, the hypothesis that the 1918 virus NS1 gene played a role in virulence was tested in a mouse model. In a BSL3+ laboratory, viruses were generated that possessed either the 1918 NS1 gene alone or the entire 1918 NS segment in a background of influenza A/WSN/33 (H1N1), a mouse-adapted virus derived from a human influenza strain first isolated in 1933. These 1918 NS viruses replicated well in tissue culture but were attenuated in mice as compared with the isogenic control viruses. This attenuation in mice may be related to the human origin of the 1918 NS1 gene. These results suggest that interaction of the NS1 protein with host-cell factors plays a significant role in viral pathogenesis.

Amino Acid Sequence↗

Scintimammography with 99mTc-MIBI versus dynamic MRI for non-invasive characterization of breast masses.

Although mammography remains the technique of choice for the early detection of breast cancer, several imaging techniques, including scintimammography and magnetic resonance imaging (MRI), have recently been proposed as adjuncts for this purpose and included in many diagnostic protocols. This study was undertaken to assess the clinical accuracy of scintimammography with technetium-99m methoxyisobutylisonitrile (MIBI) and contrast-enhanced MRI in the detection of primary breast carcinoma in patients with equivocal mammographic findings. Forty-nine patients with a suspicious breast mass detected either by physical examination or by mammography and ultrasound (US) were studied. All patients underwent scintimammography and dynamic contrast-enhanced MRI 1 week apart. The results of the two techniques were compared and correlated to the final diagnoses. Two independent readers reported the scans using a four-point confidence scale. The areas under the receiver operator characteristic (ROC) curves were obtained. Scintimammography showed an accuracy for tumour detection of 84%, with a sensitivity of 80% and a specificity of 88%. MRI showed an accuracy of 86%, with a sensitivity and specificity of 96% and 75%, respectively. Comparison of the two areas under the ROC curves showed no significant differences between MRI, 0.91+/-0.05 (mean+/-SD), and scintimammography, 0.88+/-0.05 (P=0.9). It is concluded that dynamic MRI and scintimammography possess comparable accuracy in the diagnosis of primary breast carcinoma in patients with equivocal mammographic or US findings.

Biopsy↗

Bone marrow uptake of 99mTc-MIBI in patients with multiple myeloma.

In a previous study, we showed the ability of technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) scan to identify active disease in patients with multiple myeloma (Eur J Nucl Med 1998; 25: 714-720). In particular, a semiquantitative score of the extension and intensity of bone marrow uptake was derived and correlated with both the clinical status of the disease and plasma cell bone marrow infiltration. In order to estimate quantitatively 99mTc-MIBI bone marrow uptake and to verify the intracellular localization of the tracer, bone marrow samples obtained from 24 multiple myeloma patients, three patients with monoclonal gammopathy of undetermined significance (MGUS) and two healthy donors were studied for in vitro uptake. After centrifugation over Ficoll-Hypaque gradient, cell suspensions were incubated with 99mTc-MIBI and the uptake was expressed as the percentage of radioactivity specifically retained within the cells. The cellular localization of the tracer was assessed by micro-autoradiography. Twenty-two out of 27 patients underwent 99mTc-MIBI scan within a week of bone marrow sampling. Whole-body images were obtained 10 min after intravenous injection of 555 MBq of the tracer; the extension and intensity of 99mTc-MIBI uptake were graded using the semiquantitative score. A statistically significant correlation was found between in vitro uptake of 99mTc-MIBI and both plasma cell infiltration (Pearson's coefficient of correlation r=0.69, P<0.0001) and in vivo score (Spearman rank correlation coefficient r=0.60, P<0.01). No specific tracer uptake was found in bone marrow samples obtained from the two healthy donors. Micro-autoradiography showed localization of 99mTc-MIBI inside the plasma cells infiltrating the bone marrow. Therefore, our findings show that the degree of tracer uptake both in vitro and in vivo is related to the percentage of infiltrating plasma cells which accumulate the tracer in their inner compartments.

Aged↗

Predictive value of technetium-99m sestamibi in patients with multiple myeloma and potential role in the follow-up.

Technetium-99m 2-methoxyisobutylisonitrile (99mTc-MIBI or setamibi) has recently been proposed for use in the evaluation of multiple myeloma (MM). The aims of this study were to investigate its potential predictive value in patients with MM and its possible role in the follow-up. Thirty patients with MM who had undergone two 99mTc-MIBI scintigraphic studies at least 2 months apart constituted the study group; 22 of them received chemotherapy in the interval between the two scans. The scans were classified as showing pattern N when only physiological uptake was present, pattern D when diffuse bone marrow uptake was observed, pattern F when areas of focal uptake of the tracer were evident, and pattern F + D when both D and F patterns were observed. Comparative 99mTc-MIBI scintigraphy was considered indicative of disease progression when there was a worsening of the pattern (i.e. from N to D, or from N or D to F or to F + D) or an increase in the pattern D semiquantitative score. It was considered indicative of disease improvement when the opposite trend was observed; otherwise, it was considered to document a stable condition. A significant association was observed between the baseline scintigraphic pattern and clinical status at follow-up in the group of patients evaluated after chemotherapy (chi 2 = 16.7, P < 0.05). A negative baseline 99mTc-MIBI scintigram showed a high predictive accuracy (100%) for remission, while the presence of pattern F or F + D was often associated with a less favourable outcome. A multivariate analysis showed that 99mTc-MIBI uptake pattern has an added value in relation to known prognostic variables such as C-reactive protein. 99mTc-MIBI scintigraphy patterns at follow-up were significantly associated with the clinical status evaluated after chemotherapy (chi 2 = 32.6, P < 0.0001). Considering pattern N as indicating remission, pattern D stable condition, and pattern F or F + D progressive disease, a high concordance between scintigraphic findings and clinical status was found in the 22 patients undergoing chemotherapy (91%). Variation in 99mTc-MIBI findings comparing baseline and follow-up evaluations was significantly associated with clinical status both in patients undergoing chemotherapy (chi 2 = 26.5, P < 0.0005) and in those not undergoing chemotherapy (chi 2 = 8.0, P < 0.005). In conclusion, the results of this study suggest a prognostic value of 99mTc-MIBI scintigraphy in patients with MM and a potential role during the follow-up.

Aged↗

Diagnostic accuracy of low-dose dobutamine echocardiography in predicting post-revascularisation recovery of function in patients with chronic coronary artery disease: relationship to thallium-201 uptake.

It is known that contractile reserve may be blunted if perfusion and coronary flow reserve are reduced. Thus, it is conceivable that the predictive accuracy of dobutamine echocardiography may differ according to perfusion tracer uptake. The aim of this study was therefore to assess the relationship between the level of thallium-201 uptake and the accuracy of dobutamine echocardiography in identifying reversible dysfunction. Sixty-nine patients (age 59+/-8 years, ejection fraction 40%+/-11%) with chronic coronary artery disease scheduled for coronary revascularisation were studied. All patients underwent rest 201Tl single-photon emission tomography and two-dimensional echocardiography at rest and during low-dose dobutamine infusion on the same day before revascularisation and repeated echocardiography at least 30 days thereafter. At follow-up, recovery of function was observed in 49% of 339 dysfunctional segments. The percentage of segments with post-revascularisation recovery of function and the percentage with contractile reserve increased in parallel with 201Tl uptake both in the total group of segments (chi2=35.5, P<0.0001 and chi2=35.9, P<0.0001, respectively) and among the 183 akinetic segments (chi2=44.4, P<0.0001 and chi2=14.6, P<0.05, respectively). The dysfunctional segments were divided into three groups according to 201Tl uptake: (a) uptake <65%, (b) uptake between 65% and 79%, (c) uptake >80%. The positive predictive value increased significantly with the level of 201Tl uptake, and was suboptimal (46%) in akinetic segments with severely reduced 201Tl uptake. The negative predictive value decreased significantly with 201Tl uptake, and it was less than suboptimal (29%) in akinetic segments with normal tracer uptake. Sensitivity was lower in the subset of akinetic segments (42%-63%) than in all dyssynergic segments (63%-76%), whereas specificity was very high in akinetic segments (80%-84%). It is concluded that the accuracy of low-dose dobutamine echocardiography in predicting reversibility of regional dysfunction varies considerably according to 201Tl uptake at rest and to the severity of regional dysfunction.

Adult↗

Synchronous primary adenocarcinoma and adenosquamous carcinoma of the esophagus.

Multiple malignant esophageal tumors of the same cell type are described. In the esophageal mucosa, widespread carcinomatous transformation may be observed and multicentric invasive squamous cell carcinomas may develop. The concomitance of two independent esophageal malignant neoplasms of different epithelial histogenesis is uncommon. Synchronous adenocarcinoma and squamous cell carcinoma of the esophagus is reported. Adenosquamous carcinoma of the esophagus is a rare tumor. Adenocarcinoma of the esophagus represents 10% of esophageal cancer. We report a case of a synchronous primary invasive adenosquamous carcinoma and adenocarcinoma of the esophagus. Both tumors were demonstrated radiographically. The peculiarity of this neoplastic association and the importance of complete radiographic esophageal evaluation in patients with one obvious obstructing tumor of the esophagus are emphasized.

Adenocarcinoma↗

Assessment of scanner performance and normalization of estimated relaxation rate values.

The purpose of this study was to develop and test a method for the assessment of Magnetic Resonance (MR) scanner performance suitable for routine brain MR studies and for normalization of calculated relaxation times. We hypothesized that regular monitoring of machine performance changes could provide a helpful normalization tool for calculating tissue MR parameters, thus contributing to support their use for longitudinal and comparative studies of both normal and diseased tissues. The method is based on the acquisition of phantom images during routine brain studies with standard spin-echo sequences. MR phantom and brain tissue parameters were used to assess the influence of machine related changes on relaxation parameter estimates. Experimental results showed that scanner performance may affect relaxation rate estimates. Phantom and in vivo results indicate that the correction method yields a reduction in variability of estimated phantom R1 values up to 29% and of R1 for different brain structures up to 17%. These findings support the validity of using brain coil phantoms for routine system monitoring and correction of tissue relaxation rates.

Brain↗

Role of US-guided fine-needle aspiration with on-site cytopathologic evaluation in management of nonpalpable breast lesions.

RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate the accuracy of ultrasound (US)-guided fine-needle aspiration (FNA), with radiographic follow-up or surgical excision, in conjunction with on-site cytopathologic support in the management of nonpalpable breast lesions. MATERIALS AND METHODS: The findings of 266 consecutive mammographically or sonographically identified, nonpalpable lesions (228 patients) that underwent US-guided FNA were examined retrospectively. Clustered microcalcifications did not undergo biopsy with this method. Patients who underwent follow-up excisional biopsy or mammography with a duration of at least 24 months were included in the study. RESULTS: In all, 117 lesions met criteria for inclusion, of which 85 (73%) were diagnosed as benign at cytopathologic evaluation and underwent mammographic follow-up of at least 24 months (range, 24-67 months; mean, 36 months). Thirty-two lesions (27%) had either malignant or atypical cytopathologic findings, for which surgery was recommended. Eleven (9%) of the 32 had malignant cytopathologic findings from initial US-guided FNA, which were confirmed at surgical excision. The remaining 21 lesions (18%) were diagnosed as atypical on the basis of US-guided FNA results. Of these, 18 lesions underwent excisional biopsy: Two were diagnosed as carcinoma (not otherwise specified), and 16 were diagnosed with a variety of benign disorders. The remaining three patients with atypical lesions chose mammographic follow-up rather than surgical diagnosis, and their conditions have remained stable for more than 24 months. Of the 85 benign cases, one changed during follow-up (12 months) and underwent repeat biopsy, with malignancy noted. The sensitivity of US-guided FNA in identifying malignant lesions was 93% (13 of 14), and the specificity of a benign finding was 100% (102 of 102). The positive and negative predictive values of US-guided FNA supported by on-site cytopathologic evaluation were 100% (13 of 13) and 99% (102 of 103), respectively. CONCLUSION: Supported by appropriately trained on-site cytopathologists and in conjunction with follow-up mammography, US-guided FNA appears to be efficacious in the management of patients with abnormal radiographic findings. It is quick, relatively inexpensive, and minimally invasive, and, in the presence of competent cytopathologists, should be the modality of choice.

Biopsy, Needle↗

Is the acromegalic cardiomyopathy reversible? Effect of 5-year normalization of growth hormone and insulin-like growth factor I levels on cardiac performance.

Acromegalic patients are considered to be exposed to a doubled mortality rate, mostly for cardiovascular diseases. This open prospective study was designed to evaluate whether the impairment of cardiac performance could be reversed by the long-term suppression of GH and insulin-like growth factor I (IGF-I) levels. Eighteen patients with active acromegaly were studied before and 5 yr after surgery, followed by sc octreotide in 11 patients. Disease control (GH levels < or =1 microg/L after glucose load or < or =2.5 microg/L after fasting, respectively, together with normalized IGF-I levels for age) was achieved in seven patients after surgery and in six patients after 0.3--0.6 mg/day sc octreotide. Five patients were not controlled during the 5-yr follow-up. Cardiac performance at rest and at peak exercise was assessed by equilibrium radionuclide angiography at study entry and 5 yr after surgery alone or plus octreotide. Thirty-six sex- and age-matched healthy subjects served as controls. At study entry, patients had a lower left ventricular ejection fraction (LVEF) at peak exercise and LVEF exercise-induced changes, exercise duration, and capacity than controls (P < 0.001). After 5 yr of treatment, a significant decrease of resting heart rate (P = 0.03) and a significant increase of LVEF at peak exercise (P = 0.003) was found in patients achieving disease control. LVEF response at peak exercise worsened in none of the patients with controlled disease and in three patients with uncontrolled disease (60%) (chi(2) = 5.5; P = 0.02). Diastolic filling, exercise duration, and workload did not significantly change during the 5-yr follow-up. No difference was found between patients controlled by surgery alone or by surgery plus octreotide. This 5-yr prospective study demonstrated that the LVEF response at peak exercise improved in all patients achieving disease control, while it was worsened in 60% of uncontrolled ones. These results strengthen the need of a stable suppression of GH and IGF-I hypersecretion to restore a normal cardiac performance in acromegaly.

Acromegaly↗

Improved cardiovascular risk factors and cardiac performance after 12 months of growth hormone (GH) replacement in young adult patients with GH deficiency.

Adult GH deficiency (GHD) is associated with increased cardiovascular morbidity and mortality due to unfavorable lipid profile, hyperfibrinogenemia, and impairment of cardiac performance. This prospective controlled cohort study evaluated the effects of 12-month GH replacement on lipid profile, fibrinogen levels, cardiac mass by echocardiography, and performance by equilibrium radionuclide angiography. To this end we studied 20 patients (11 men and 9 women, aged 19-40 yr), 10 with childhood-onset (co-) and 10 with adult-onset (ao-) disease, and 20 sex- and age-matched healthy subjects. At study entry, insulin-like growth factor I (IGF-I; P < 0.0001) and high density lipoprotein (HDL) cholesterol (P < 0.0001) levels, left ventricular mass index (LVMi; P < 0.0001), ejection fraction (LVEF) at rest (P = 0.001) and at peak exercise (P < 0.0001), peak ejection rate (P = 0.005), and exercise duration (P < 0.0001) and capacity (P = 0.002) were lower, whereas total cholesterol (P = 0.02), triglycerides (P = 0.003), and fibrinogen (P = 0.005) levels were higher in patients than in controls. After 12 months, increases in IGF-I (P < 0.0001) and HDL cholesterol levels (P = 0.04), LVMi (P < 0.0001), LVEF at peak exercise (P < 0.0001), and exercise duration (P = 0.009) and capacity (P = 0.003) and decreases in total cholesterol (P < 0.0001), low density lipoprotein cholesterol (P < 0.0001), triglycerides (P < 0.0001), and fibrinogen (P = 0.01) levels were found in all patients, without any difference between co- and ao-GHD. At the end of treatment, however, total cholesterol, triglycerides, and fibrinogen levels were still higher, and HDL cholesterol levels, IGF-I levels, and LVEF at rest and at peak exercise were lower in patients than in controls. In conclusion, GH replacement for 12 months significantly improved lipid profile, decreased fibrinogen levels, and increased LVMi and LVEF in young adults with co- or ao-GHD. However, lipid profile, fibrinogen levels, and systolic function remained abnormal compared with those in age- and sex-matched controls, suggesting that a longer period of GH replacement is necessary to normalize cardiovascular parameters and reverse the cardiovascular risk of these patients.

Adolescent↗