Assessing value of contrast-enhanced ultrasound vs. conventional transthoracic ultrasound in improving diagnostic yield of percutaneous needle biopsy of peripheral lung lesions.

OBJECTIVE: The aim of the present study was to systematically assess the value of contrast-enhanced ultrasound (CEUS) vs. conventional transthoracic ultrasound (TUS) in improving diagnostic accuracy of percutaneous needle biopsy (PTNB) for subpleural lung lesions. PATIENTS AND METHODS: 232 patients with subpleural lesions were 1:1 randomly assigned to a group were CEUS was performed (n=116, mean age=65.5±5.6, M=69) or not (n=116, mean age=66.0±5.3, M=70). For CEUS study was used an injection of 4.8 mL of SonoVue (Bracco, Italy). For PTNB was employed a Menghini-modified technique with a semi-automatic 18-gauge needle. RESULTS: The mean diameter of subpleural lesions was 2.85±0.7 cm in the CEUS+ group and 2.95±0.6cm in the CEUS- group. Only 3 lesions, 1 in the CEUS+ group and 2 in the CEUS- group measured >5 cm. CEUS showed no superiority in terms of diagnostic accuracy compared to conventional TUS (p=0.34). Similar results were obtained in the sub-analysis of lesions sized between 1-2 cm (p=1.00) and 2-5 cm (p=0.08). As the lesion size increased, the detection rate of necrosis in lesions increased by CEUS (from 8% to 31%). CEUS showed no superiority in terms of diagnostic accuracy in the sub-analysis of necrotic lesions at CECT (p=0.38). AUC values for both the groups assessed an excellent diagnostic yield for TUS-PTNB (≥0.80). CONCLUSIONS: CEUS study does not improve the diagnostic accuracy of TUS-guided PTNB for peripheral lung lesions <5 cm of diameter. Further studies evaluating CEUS guidance for larger (>5 cm) and necrotic lesions are needed prior that its potential can be clarified.

Ultrasound-guided fine needle aspiration biopsy (FNAB) demonstrating upper distal extremity metastasis of lung adenocarcinoma: a case report and review of the literature.

Due to early metastasis and delayed diagnosis, lung cancer is the leading cause of cancer-related deaths. Although the most common metastasis sites are brain, bone, lung, adrenal glands, liver, and extra-thoracic lymph node, soft tissues, such as skeletal muscles, skin, and subcutaneous tissues, can also be undermined. This article aims to report the first case of an asymptomatic radial extensor muscle metastasis generating from a lung adenocarcinoma that was diagnosed by ultrasound-guided fine-needle aspiration biopsy (FNAB).

Ultrasound signs of pulmonary fibrosis in systemic sclerosis as timely indicators for chest computed tomography.

OBJECTIVES: Systemic sclerosis (SSc) patients in the early stages of pulmonary fibrosis (PF) often have few or no symptoms, normal to borderline pulmonary function tests, and negative chest X-ray (CXR); high-resolution computed tomography (HRCT) is the only reliable means of detecting the early signs of PF. However, thoracic ultrasound (TUS) enables detection of pleural thickening, pleural/subpleural nodules, and other subpleural lung abnormalities across 70% of the subpleural surface. We reassessed concordance between TUS abnormalities and HRCT findings in SSc patients, to see whether TUS pleural line thickness (normally <3.0 mm) could be used to earmark those with asymptomatic PF for timely HRCT assessment. METHOD: In total, 175 SSc patients (nine males, 166 females), aged 46.46±15.33 years, were given CXR, TUS, HRCT, echocardiography, and pulmonary function tests. RESULTS: In the 26 patients without HRCT signs of PF, pleural line thickness was ≤3.0 mm. In diffuse SSc, 97/137 patients showed pleural line thickening (between 3.0 and 5 mm) and subpleural nodules in 32/97; and 35/137 showed major pleural line thickening (≥5.0 mm) with nodules, with good concordance with HRCT patterns indicating lung fibrosis severity. HRCT was normal in 5/137, with pleural line thickness≤3.0 mm. CONCLUSIONS: TUS imaging of pleural/subpleural structures can detect ultrasonographic signs of initial PF prior to the onset of respiratory symptoms and function test abnormalities and, together with current criteria, could thereby enable exclusion of PF in SSc patients. Indicating some patients for selective referral to HRCT can thereby delay unwarranted procedures, provided that pulmonary function and TUS images are stable.

Alteration of circadian rhythmicity of CD3+CD4+ lymphocyte subpopulation in healthy aging.

The CD4+ T helper/inducer and the CD8+ T suppressor/cytotoxic are major lymphocyte subsets that play a key role in cell-mediated immunity. Aging-related changes of immune function have been demonstrated. The purpose of this study is to analyze the dynamics of variation of these specific lymphocyte subsets in the elderly. In our study cortisol and melatonin serum levels were measured and lymphocyte subpopulation analyses were performed on blood samples collected every four hours for 24 hours from fifteen healthy young middle-aged subjects (age range 36-55 years) and fifteen healthy elderly male subjects (age range 67-79 years). A clear circadian rhythm was validated for the time-qualified changes of CD3+ and CD4+ cells with acrophase at night and for the time-qualified changes of CD8+ cells with acrophase at noon in young middle-aged subjects and for the time-qualified changes of CD3+ cells with acrophase at night and for the time-qualified changes of CD8+ cells with acrophase at noon in elderly subjects. No clear circadian rhythm was validated for the time-qualified changes of CD4+ cells in elderly subjects. No statistically significant correlation among lymphocyte subsets was found in elderly subjects. In elderly subjects CD3+ lymphocyte percentage was higher in the photoperiod and in the scotoperiod and cortisol serum level were higher in the scotoperiod in respect to young middle-aged subjects. In the elderly there is an alteration of circadian rhythmicity of T helper/inducer lymphocytes and this phenomenon might contribute to the aging-related changes of immune responses.

Neuro-endocrine correlations of hypothalamic-pituitary-thyroid axis in healthy humans.

Neuro-endocrine hormone secretion is characterized by circadian rhythmicity. Melatonin, GRH and GH are secreted during the night, CRH and ACTH secretion peak in the morning, determining the circadian rhythm of cortisol secretion, TRH and TSH show circadian variations with higher levels at night. Thyroxine levels do not change with clear circadian rhythmicity. In this paper we have considered a possible influence of cortisol and melatonin on hypothalamic-pituitary-thyroid axis function in humans. Melatonin, cortisol, TRH, TSH and FT4 serum levels were determined in blood samples obtained every four hours for 24 hours from ten healthy males, aged 36-51 years. We correlated hormone serum levels at each sampling time and evaluated the presence of circadian rhythmicity of hormone secretion. In the activity phase (06:00 h-10:00 h-14:00 h) cortisol correlated negatively with FT4, TSH correlated positively with TRH, TRH correlated positively with FT4 and melatonin correlated positively with TSH. In the resting phase (18:00 h-22:00 h-02:00 h) TRH correlated positively with FT4, melatonin correlated negatively with FT4, TSH correlated negatively with FT4, cortisol correlated positively with FT4 and TSH correlated positively with TRH. A clear circadian rhythm was validated for the time-qualified changes of melatonin and TSH secretion (with acrophase during the night), for cortisol serum levels (with acrophase in the morning), but not for TRH and FT4 serum level changes. In conclusion, the hypothalamic-pituitary-thyroid axis function may be modulated by cortisol and melatonin serum levels and by their circadian rhythmicity of variation.

Characterization of the normal pulmonary surface and pneumonectomy space by reflected ultrasound.

Interest has been increasing in the use of transthoracic ultrasound for the study of the pleuropulmonary disease. US imaging depends mainly on the physical interactions between ultrasound waves and the tissues being examined. In the thoracic region, the prescence of the chest wall and the air-containing pulmonary tissues cause various artifacts that strongly influence the resulting images. At the interface between tissues and air, the ultrasound beam is totally reflected and produces simple reverberation, comet-tail artifacts, and ring-down artifacts.We report the findings of transthoracic ultrasound in normal healthy subjects and in those who had undergone pneumonectomy.This experience shows that, in terms of the ultrasound artifacts mentioned above, the postpneumonectomy cavity is not significantly different from the healthy lung.

Mowat-Wilson syndrome: facial phenotype changing with age: study of 19 Italian patients and review of the literature.

Mowat-Wilson syndrome (MWS; OMIM #235730) is a genetic condition caused by heterozygous mutations or deletions of the ZEB2 gene, and characterized by typical face, moderate-to-severe mental retardation, epilepsy, Hirschsprung disease, and multiple congenital anomalies, including genital anomalies (particularly hypospadias in males), congenital heart defects, agenesis of the corpus callosum, and eye defects. Since the first delineation by Mowat et al. [Mowat et al. (1998); J Med Genet 35:617-623], approximately 179 patients with ZEB2 mutations, deletions or cytogenetic abnormalities have been reported primarily from Europe, Australia and the United States. Genetic defects include chromosome 2q21-q23 microdeletions (or different chromosome rearrangements) in few patients, and ZEB2 mutations in most. We report on clinical and genetic data from 19 Italian patients, diagnosed within the last 5 years, including six previously published, and compare them with patients already reported. The main purpose of this review is to underline a highly consistent phenotype and to highlight the phenotypic evolution occurring with age, particularly of the facial characteristics. The prevalence of MWS is likely to be underestimated. Knowledge of the phenotypic spectrum of MWS and of its changing phenotype with age can improve the detection rate of this condition.

Role of thoracic ultrasound in the assessment of pleural and pulmonary diseases.

Although numerous studies have been conducted on the use of ultrasonography (US) for the examination of thoracic structures, this procedure is not as widely accepted as abdominal US. The newer portable scanners can be used at the bedside to detect pleural malignancies and effusions, as well as peripheral lung nodules of the lung, even in seriously ill patients. Focal thickening of the pleura can be easily detected with US and further investigated with a US-guided biopsy. US guidance can also be used during percutaneous drainage of pleural effusion or transthoracic biopsy of peripheral lung lesions, thus reducing the incidence of procedure-related pneumothorax to almost zero. We review the current literature on thoracic US and present our clinical experience with the technique in large groups of patients with pleural and peripheral lung diseases.

Prolonged remission of neuro-Behcet disease following autologous transplantation.

Two young male patients with severe progressive Behcet's disease with neurological involvement (N-BD) were treated by high-dose immunosuppressive chemotherapy (HIC) followed by autologous CD34+ selected peripheral blood stem cell transplantation (APBSCT). Neurological impairment and disability were quantified by means of Expanded Disability Status Scale (EDSS). Neuroimaging included spine and brain MRI and brain SPECT by radiolabeling technetium (Tc99m) Ethyl Cisteynate Dimer (ECD). Disease progression halted after treatment in both patients. At 48 months of follow-up they were therapy-free and one showed neurological status and disability improvement. Brain MRI findings were unchanged in both patients, but SPECT-ECD showed an increase of blood flow in the hypoperfused cerebral areas in the ameliorated patient. Immune ablation followed by APBSCT can modify the course of severe N-BD. Because of the high risk and the transplant-related mortality, these cases have to be carefully selected.

Computed-tomographic-guided biopsy of thoracic nodules: a revision of 583 lesions.

OBJECTIVES: In pulmonary lesions, when bronchial or trans-bronchial biopsy is negative, thoracic Fine-Needle Aspiration Biopsy (FNAB) allows to obtain a cytological or histological diagnosis. The purpose of the current study is to investigate the usefulness of CT-guided FNAB to define the nature of pulmonary or thoracic lesions. MATERIALS AND METHODS: Between May 1995 and September 2005, 583 patients (453 males, 133 females), with thoracic lesions, without evident intrabronchial neoplasm, underwent CT-guided FNAB of thoracic nodules. FNAB was performed with 19-20-21 gauge needles, disposable soft tissue, automatic aspiration biopsy Menghini set, 10-15 cm long. RESULTS: In 292 patients (50%) lesions were < or = 3 cm diameter. Post biopsy pneumothorax occurred in 103 (18%) patients, with 29 patients requiring chest tube placement. Post biopsy haemoptysis occurred in 21 (4%) patients, but no patient required treatment for haemoptysis. There were 72 benign lesions (16 neoplasms) and 491 cancers (456 primary, 35 metastasis). Diagnostic accuracy was 93% and sensitivity for malignancy 93%. CONCLUSIONS: FNAB has excellent diagnostic rates and is a suitable technique for diagnosing thoracic lesions.

Hemangioma-like lesions in chronic liver disease: diagnostic evaluation in patients.

PURPOSE: To quantify the risk of misdiagnosis of focal hepatic lesions manifesting at ultrasonography (US) as typical hemangiomas in a population at high risk for hepatocellular carcinoma (HCC) and to identify the most effective approach to their diagnostic evaluation. MATERIALS AND METHODS: A total of 1,982 patients with newly diagnosed cirrhosis underwent US and serum alpha-fetoprotein determinations for early detection of HCC. Focal lesions with typical features of hemangioma were evaluated with confirmatory findings of contrast material-enhanced dynamic or spiral computed tomography (CT) and/or single photon emission CT with technetium 99m-labeled red blood cells and, in the absence of confirmatory imaging findings, US-guided fine-needle biopsy. Patients whose initial US scan depicted no lesions or hemangiomas were enrolled in a US follow-up program. All hemangioma-like lesions detected during follow-up were evaluated, or biopsy was performed. RESULTS: US depicted hemangioma-like lesions in 44 of 1,982 patients: 22 hemangiomas and 22 HCCs. Hemangioma-like lesions detected during follow-up in 1,648 patients were HCCs (n = 22) or dysplastic nodules (n = 4). Only 85 (22%) of 383 patients with HCC had alpha-fetoprotein levels suggestive of the diagnosis. The probability of a diagnosis of HCC (or preneoplastic lesion) is 100% for hemangioma-like lesions depicted on subsequent US scans. CONCLUSION: If initial US examination of a cirrhotic liver depicts a hemangioma, confirmatory findings of imaging studies are necessary since 50% of hemangiomas in this study were hyperechogenic HCCs. US-guided biopsy can be safely performed, and its findings can be used to confirm the diagnosis.

Arginine transport through system y(+)L in cultured human fibroblasts: normal phenotype of cells from LPI subjects.

In lysinuric protein intolerance (LPI), impaired transport of cationic amino acids in kidney and intestine is due to mutations of the SLC7A7 gene. To assess the functional consequences of the LPI defect in nonepithelial cells, we have characterized cationic amino acid (CAA) transport in human fibroblasts obtained from LPI patients and a normal subject. In both cell types the bidirectional fluxes of arginine are due to the additive contributions of two Na(+)-independent, transstimulated transport systems. One of these mechanisms, inhibited by N-ethylmaleimide (NEM) and sensitive to the membrane potential, is identifiable with system y(+). The NEM- and potential-insensitive component, suppressed by L-leucine only in the presence of Na(+), is mostly due to the activity of system y(+)L. The inward and outward activities of the two systems are comparable in control and LPI fibroblasts. Both cell types express SLC7A1 (CAT1) and SLC7A2 (CAT2B and CAT2A) as well as SLC7A6 (y+LAT2) and SLC7A7 (y+LAT1). We conclude that LPI fibroblasts exhibit normal CAA transport through system y(+)L, probably referable to the activity of SLC7A6/y+LAT2.

Relaxation of insulin-like growth factor 2 imprinting and discordant methylation at KvDMR1 in two first cousins affected by Beckwith-Wiedemann and Klippel-Trenaunay-Weber syndromes.

Beckwith-Wiedeman syndrome (BWS) and Klippel-Trenaunay-Weber syndrome (KTWS) are different human disorders characterized, among other features, by tissue overgrowth. Deregulation of one or more imprinted genes located at chromosome 11p15.5, of which insulin-like growth factor 2 (IGF2) is the most likely candidate, is believed to cause BWS, whereas the etiology of KTWS is completely obscure. We report a case of BWS and a case of KTWS in a single family. The probands, sons of two sisters, showed relaxation of the maternal IGF2 imprinting, although they inherited different 11p15.5 alleles from their mothers and did not show any chromosome rearrangement. The patient with BWS also displayed hypomethylation at KvDMR1, a maternally methylated CpG island within an intron of the KvLQT1 gene. The unaffected brother of the BWS proband shared the same maternal and paternal 11p15.5 haplotype with his brother, but the KvDMR1 locus was normally methylated. Methylation of the H19 gene was normal in both the BWS and KTWS probands. Linkage between the insulin-like growth factor 2 receptor (IGF2R) gene and the tissue overgrowth was also excluded. These results raise the possibility that a defective modifier or regulatory gene unlinked to 11p15.5 caused a spectrum of epigenetic alterations in the germ line or early development of both cousins, ranging from the relaxation of IGF2 imprinting in the KTWS proband to disruption of both the imprinted expression of IGF2 and the imprinted methylation of KvDMR1 in the BWS proband. Analysis of these data also indicates that loss of IGF2 imprinting is not necessarily linked to alteration of methylation at the KvDMR1 or H19 loci and supports the notion that IGF2 overexpression is involved in the etiology of the tissue hypertrophy observed in different overgrowth disorders, including KTWS.

Structure of the SLC7A7 gene and mutational analysis of patients affected by lysinuric protein intolerance.

Lysinuric protein intolerance (LPI) is a rare autosomal recessive defect of cationic amino acid transport caused by mutations in the SLC7A7 gene. We report the genomic structure of the gene and the results of the mutational analysis in Italian, Tunisian, and Japanese patients. The SLC7A7 gene consists of 10 exons; sequences of all of the exon-intron boundaries are reported here. All of the mutant alleles were characterized and eight novel mutations were detected, including two missense mutations, 242A-->C (M1L) and 1399C-->A (S386R); a nonsense mutation 967G-->A (W242X); two splice mutations IVS3 +1G-->A and IVS6 +1G-->T; a single-base insertion, 786insT; and two 4-bp deletions, 455delCTCT and 1425delTTCT. In addition, a previously reported mutation, 1625insATCA, was found in one patient. It is noteworthy that 242A-->C causes the change of Met1 to Leu, a rare mutational event previously found in a few inherited conditions. We failed to establish a genotype/phenotype correlation. In fact, both intrafamilial and interfamilial phenotypic variability were observed in homozygotes for the same mutation. The DNA-based tests are now easily accessible for molecular diagnosis, genetic counseling, and prenatal diagnosis of LPI.