Contrast-enhanced ultrasound (CEUS) for the evaluation of focal liver lesions - a prospective multicenter study of its usefulness in clinical practice.

PURPOSE: To assess the value of contrast-enhanced ultrasound (CEUS) for differentiating malignant from benign focal liver lesions (FLLs) and for diagnosing different FLL types. MATERIAL AND METHODS: CEUS performed in 14 Romanian centers was prospectively collected between February 2011 and June 2012. The inclusion criteria were: age > 18 years; patients diagnosed with 1 - 3 de novo FLLs on B-mode ultrasound; reference method (computed tomography (CT), magnetic resonance imaging (MRI) or biopsy) available; patient's informed consent. FLL lesions were characterized during CEUS according to the European Federation of Societies for Ultrasound in Medicine and Biology guidelines. For statistical analysis, indeterminate FLLs at CEUS were rated as false classifications. RESULTS: A total number of 536 cases were included in the final analysis, 344 malignant lesions (64.2 %) and 192 benign lesions (35.8 %). The reference method was: CT/MRI - 379 cases (70.7 %), pathological exam - 150 cases (27.9 %) and aspiration of liver abscesses - 7 cases (1.4 %). CEUS was conclusive in 89.3 % and inconclusive in 10.7 % of cases. To differentiate between malignant and benign FLLs, CEUS had 85.7 % sensitivity, 85.9 % specificity, 91.6 % positive predictive value, 77.1 % negative predictive value and 85.8 % accuracy. The CEUS accuracy for differentiation between malignant and benign liver lesions was similar in tumors with diameter ≤ 2 cm and those with diameter > 2 cm. CONCLUSION: CEUS represents a useful method in clinical practice for differentiating between malignant and benign FLLs detected on standard ultrasonography, and the results of this study are in concordance with previous multicenter studies: DEGUM (Germany) and STIC (France).

Multi-layer haemocompatible diamond-like carbon coatings obtained by combined radio frequency plasma enhanced chemical vapor deposition and magnetron sputtering.

Radio-frequency Plasma Enhanced Chemical Vapour Deposition (in different methane dilutions) was used to synthesize adherent and haemocompatible diamond-like carbon (DLC) films on medical grade titanium substrates. The improvement of the adherence has been achieved by interposing a functional buffer layer with graded composition TixTiC1-x (x = 0-1) synthesized by magnetron co-sputtering. Bonding strength values of up to ~67 MPa have been measured by pull-out tests. Films with different sp(3)/sp(2) ratio have been obtained by changing the methane concentration in the deposition chamber. Raman spectroscopy, X-ray photoelectron spectroscopy and X-ray diffraction were employed for the physical-chemical characterization of the samples. The highest concentration of sp(3)-C (~87 %), corresponding to a lower DLC surface energy (28.7 mJ/m(2) ), was deposited in a pure methane atmosphere. The biological response of the DLC films was assayed by a state-of-the-art biological analysis method (surface enhanced laser desorption/ionization-time of flight mass spectroscopy), in conjunction with other dedicated testing techniques: Western blot and partial thromboplastin time. The data support a cause-effect relationship between sp(3)-C content, surface energy and coagulation time, as well as between platelet-surface adherence properties and protein adsorption profiles.

Technical performance of colonoscopy -- multicenter study in university and non-university centers of Romania.

UNLABELLED: The aim of the paper was to evaluate the national availability of colonoscopy and the quality parameters of this procedure in our country. MATERIAL AND METHOD: During a 6 months period (01.07- 31.12.2009), we performed a prospective multicenter study in which 76 centers were invited to respond to a questionnaire regarding colonoscopy, 39 centers agreeing to participate. We assessed: the number of colonoscopies, the number of total colonoscopies and the causes of incomplete colonoscopies. RESULTS: During the study period, 16,083 colonoscopies were performed, 12,294 (76.4%) of them total colonoscopies. In 1,191 cases, stenosis was the cause of incomplete colonoscopy. If we consider this an objective reason for an incomplete colonoscopy, there were 12,294 total colonoscopies (82.4%). Comparing university centers with non-university ones, the proportion of total colonoscopies was 10,400/12,475 (83.4%) vs. 1,894/2,417 (78.4%) (p less then 0.0001). However, comparing the present study with previous ones, performed in 2003 and 2007, the proportion of total colonoscopies increased from 70.5% to 76.9% and 82.4% respectively (2003 vs. 2007 p less then 0.0001; 2007 vs. 2009 p less then 0.0001), while the quality difference between university and non-university hospitals persisted. CONCLUSIONS: the quality of colonoscopy in Romania increased in the last 5 years, while the quality difference between university and non-university hospitals persisted.

Clinical aggression of prolactinomas: correlations with invasion and recurrence.

Some hypophyseal adenomas are discrete, well-marked lesions, which can be curatively removed by surgical resection, while others seem aggressive, invasive, recidive-prone, most often progressing in spite of any pharmacological, surgical or radiotherapeutical interventions. There is also a great variability within the incidence of aggression and invasion among the various types of hypophyseal immunotypes. Despite their well-differentiated nature and their "benign" constitution, an important number of hypophyseal tumors will be surely invasive within the sclerous, osseous and neural structures. Because the aggressive behavior of invasive adenomas is generally resolved by surgical treatment, this aspect of their biology does not perfectly reflect within their histopathological aspect. In fact, the invasive tumors with local extreme aggression are most often deceiving due to their relatively harmless histopathological aspect. The usual morphological signs of tumor aggression, namely pleomorphism, nuclear atypia, hemorrhage, high cellular and mitotic activity, poorly correlate with the invasive potential of pituitary tumors, with their proliferation capacity, their tendency of post-surgical recurrence or with their global biological behavior.

The role of capsule endoscopy in the detection of small bowel disease.

Videocapsule endoscopy (VCE) can identify lesions in the small bowel which would otherwise be hard to detect. We have selected 53 patients with digestive symptoms in which upper and lower endoscopy had provided no findings. Patients were classified into three groups, based on their main indication for VCE exploration: group one--obscure gastrointestinal bleeding (OGIB); group two--unspecific abdominal symptoms; group 3--monitoring of a prior known pathology. We found that VCE has high predictive values, sensibility and specificity in the diagnosis of OGIB. VCE was also useful in the detection and extent evaluation of lesions in Crohn's and celiac disease. VCE is also able to detect tumors of the small bowel with sufficient accuracy, and can be used to monitor patients with hereditary pre-malignant diseases such as FAP. There were few light adverse effects and no major complications. We conclude that VCE is a safe and effective procedure for the detection of small bowel lesions.

Utility of endoscopic ultrasound multimodal examination with fine needle aspiration for the diagnosis of pancreatic insulinoma - a case report.

Insulinomas are benign insulin-secreting neuroendocrine tumors originating in the pancreatic beta cells. Symptoms are caused by hypoglycemia and clinical diagnosis is based on establishing their relationship to fasting, usually via a fasting test. The most conclusive imaging tests are endoscopic ultrasound (EUS) and CT. Surgery is the treatment of choice. A 33 year old male presented with a 2-year history of hunger which had intensified in the previous 6 months with added accompanying symptoms, culminating with an acute episode - loss of consciousness and seizures - which resolved after administering i.v. glucose. A fasting test was performed, with results suggestive for an insulinoma. Dual-phase CT showed a mass in the tail of the pancreas but no contrast enhancement. EUS was used for further assessment: B-mode showed a hypoechoic focal mass with a cystic component, on contrast enhancement the pattern was hypovascular, and elastography showed soft tissue. EUS fine needle aspiration (FNA) was performed and the immunohistochemistry (IHC) assay was conclusive for a neuroendocrine tumor of the pancreas. Treatment consisted of caudal pancreatectomy, with no recurrence after 1-year follow-up. Although this case started with a classic clinical presentation of an insulinoma, imaging studies related to tumor vascularization raised doubts about the actual diagnosis. Nevertheless, multimodal EUS assessment with FNA was considered to be the most appropriate diagnostic technique for detection, characterization and staging of the mass. EUS findings together with the IHC assay were able to offer the definite diagnosis of a benign neuroendocrine tumor and allowed us to refer the patient for appropriate treatment.

Thyroid stiffness assessment by acoustic radiation force impulse elastography (ARFI).

PURPOSE: To evaluate and compare the values of thyroid tissue elasticity in subjects without known thyroid pathology, in patients with Graves' disease and with chronic autoimmune thyroiditis (CAT). PATIENTS AND METHODS: We performed a prospective study that included 74 subjects, 23 without thyroid pathology, 29 with Graves' disease and 22 with CAT (diagnosed by specific tests). In all patients, 10 elastographic measurements were performed in the right thyroid lobe (RTL) and 10 in the left thyroid lobe (LTL) using a 2-6 MHz convex probe. Median values were calculated for each thyroid lobe, measured in meters/second (m/sec). We calculated a mean ARFI value from measurements made in the RTL and LTL. RESULTS: Thyroid stiffness was statistically significant lower in normal subjects vs. those with Graves' disease (2.07±0.44 m/sec vs. 2.82±0.47 m/sec, p<0.001) and with CAT (2.07±0.44 m/sec vs. 2.49±0.48 m/sec, p=0.004). We also found a statistically significant difference between subjects without thyroid pathology and those with autoimmune thyroid pathology (Graves' disease and CAT) (2.07±0.44 m/sec vs. 2.68±0.50 m/sec, p<0.001). CONCLUSION: ARFI seems to be a useful method for the evaluation of diffuse thyroid gland pathology and is able to predict with sufficient accuracy the presence of thyroid diffuse diseases (AUROC=0.80).

Acoustic radiation force impulse elastography as compared to transient elastography and liver biopsy in patients with chronic hepatopathies.

PURPOSE: To compare two methods of noninvasive assessment: transient elastography (TE) and acoustic radiation force impulse elastography (ARFI). PATIENTS AND METHODS: Our study included 114 subjects: 38 healthy volunteers, (considered to have no fibrosis - F 0) and 76 patients with chronic liver disease: 53 who had undergone liver biopsy (LB) (7 with F 1, 24 with F 2, 22 with F 3 Metavir) and 23 previously diagnosed with cirrhosis (F4 Metavir). In each patient we performed a liver stiffness measurement by means of TE and ARFI. ARFI (shear wave velocity quantification) was performed at 3 points: at 0 - 1 cm, at 1 - 2 cm and at 2 - 3 cm under the capsule. For each depth, 5 valid measurements were made, and a median value was calculated, measured in m/sec. RESULTS: A direct, strong, linear correlation (Spearman rho = 0.848) was found between TE and the stage of fibrosis (p < 0.001). A significant, direct correlation was found between ARFI measurements made 1 - 2 cm and 2 - 3 cm below the liver capsule and the severity of fibrosis (rho = 0.675 and 0.714 respectively). The subcapsularly measured ARFI values showed a poor correlation with fibrosis (rho = 0.469). The best test for predicting significant fibrosis (F ≥ 2) was TE, with the area under receiver-operating characteristic curve (AUROC) 0.908, significantly larger than the AUROCs for ARFI. If only ARFI is considered, measurements made 1 - 2 and 2 - 3 cm below the capsule have the best predictive value, with AUROCs not significantly different from each other (0.767 and 0.731, respectively). For predicting fibrosis (F > 0), TE had the best predictive value: optimized cut-off 5.65 kPa (AUROC -0.898). For ARFI, the cut-offs were: 1.4 m/sec, AUROC -0.747 (1 - 2 cm), and 1.26 m/sec AUROC -0.721 (2 - 3 cm). For predicting cirrhosis (F = 4 Metavir), the optimized cut-offs were: TE -12.9 kPa (AUROC -0.994); ARFI - 1.78 m/sec for measurements made 2 - 3 cm below the capsule, AUROC - 0.951. CONCLUSION: At present, liver elasticity evaluation by means of ARFI is not superior to TE for the assessment of liver fibrosis. For ARFI, the most reliable results are obtained if measurements are made 1 - 2 and 2 - 3 cm below the liver capsule. ARFI is an accurate test for the diagnosis of cirrhosis.

Mutant HFE genotype leads to significant iron overload in patients with liver diseases from western Romania.

The present study aimed at assessing the frequency of HFE mutations (C282Y, H63D and S65C) in western Romanian patients with liver disease of diverse aetiologies suspected of iron overload. A total of 21 patients, all Romanian residents hospitalized with clinical suspicion of iron overload and liver disease, were assayed for C282Y, H63D and S65C mutations, serum ferritin and viral hepatitis markers. Overall, 9 out of the 21 patients (42.86%) were found to harbour mutations in the HFE gene: 4 homozygotes C282Y (19.0%), 1 compound heterozygote C282Y/H63D (4.8%), 1 single heterozygote C282Y (4.8%), 2 single heterozygotes H63D (9.5%), 1 single heterozygote S65C (4.8%), and 12 wild-type cases (57.1%). Among the subgroup of 10 patients with the most prominent signs of iron overload (hyperferritinaemia and/or hepatocyte iron score > or = 1), without hepatocellular carcinoma, the HFE genotypes were conclusive in 5 cases (50%). They had significantly increased ferritin levels compared to wild-type cases (P = 0.029). The inclusion of iron studies during routine clinical visits, coupled with the availability of HFE genotyping for family and population studies, should facilitate the early detection of hereditary haemochromatosis in Romania.

Changes in prescribed doses for the Seattle neutron therapy system.

From the beginning of the neutron therapy program at the University of Washington Medical Center, the neutron dose distribution in tissue has been calculated using an in-house treatment planning system called PRISM. In order to increase the accuracy of the absorbed dose calculations, two main improvements were made to the PRISM treatment planning system: (a) the algorithm was changed by the addition of an analytical expression of the central axis wedge factor dependence with field size and depth developed at UWMC. Older versions of the treatment-planning algorithm used a constant central axis wedge factor; (b) a complete newly commissioned set of measured data was introduced in the latest version of PRISM. The new version of the PRISM algorithm allowed for the use of the wedge profiles measured at different depths instead of one wedge profile measured at one depth. The comparison of the absorbed dose calculations using the old and the improved algorithm showed discrepancies mainly due to the missing central axis wedge factor dependence with field size and depth and due to the absence of the wedge profiles at depths different from 10 cm. This study concludes that the previously reported prescribed doses for neutron therapy should be changed.

Left atrial remodelling early after mitral valve repair for degenerative mitral regurgitation.

OBJECTIVE: Left atrial (LA) size is an important predictor of outcome after mitral valve replacement in patients with symptomatic chronic mitral regurgitation (MR). Data on LA remodelling after mitral valve repair (MVr) for chronic non-ischaemic MR are scarce. The aim of this study was to assess changes in LA size early after MVr for chronic severe degenerative MR and to identify clinical and echocardiographic correlates of those changes. METHODS: The study analysed 225 consecutive patients who underwent MVr and were echocardiographically evaluated in our hospital within 1 month before and 1-6 months after surgery. Patients with MR aetiology other than degenerative, associated aortic valve replacement, or congenital heart disease were excluded. The remaining 79 patients (aged 60 (SD 12) years, 55 men) with isolated chronic severe degenerative MR formed the study group. LA reverse remodelling was defined as a decrease in LA volume index (LAVi) > or = 15%. RESULTS: LA dimensions significantly decreased after MVr (p<0.001). Mean LAVi reduction was 29% (SD 18%). LA reverse remodelling was observed in 63 patients (80%). Correlates of LAVi reduction were preoperative LAVi (p = 0.008), systolic and diastolic blood pressure (p = 0.032, p = 0.009), postoperative transmitral mean pressure gradient (p = 0.001) and residual MR (p = 0.043). LAVi reduction was lower in patients > 45 years (p = 0.008) and in hypertensive patients (p = 0.031). CONCLUSION: LA reverse remodelling is common early after MVr for chronic severe degenerative MR. Preoperative LAVi, blood pressure, postoperative transmitral mean pressure gradient, residual MR and age > 45 are related to LAVi reduction. The prognostic value of LA reduction in this setting needs further study.

Laparoscopic hand-assisted adrenalectomy for a 20 cm benign tumor.

Since its introduction in 1992, laparoscopic adrenalectomy (LA) has become the technique of choice in the surgical treatment of both secreting or non-secreting benign adrenal pathology. Although traditionally, laparoscopic approach was recommended only for tumor sizes less than 6-8 cm--as larger tumors were known to have an increased risk of malignancy--the currently growing experience and improvement of surgical techniques has allowed for an extension of the therapeutic indication, as shown by the recent case report of LA use for a benign 22 cm tumor (1). We report the case of a young patient operated in our Department for a benign 20 cm adrenal tumor for which laparoscopic "hand-assisted" adrenalectomy yielded a good postoperative outcome and minimal complications.

Multinuclear magnetic resonance studies of Escherichia coli adenylate kinase in free and bound forms. Resonance assignment, secondary structure and ligand binding.

The crystal structure of Escherichia coli adenylate kinase (AKe) revealed three main components: a CORE domain, composed of a five-stranded parallel beta-sheet surrounded by alpha-helices, and two peripheral domains involved in covering the ATP in the active site (LID) and binding of the AMP (NMPbind). We initiated a long-term NMR study aiming to characterize the solution structure, binding mechanism and internal dynamics of the various domains. Using single (15N) and double-labeled (13C and 15N) samples and double- and triple-resonance NMR experiments we assigned 97% of the 1H, 13C and 15N backbone resonances, and proton and 13Cbeta resonances for more than 40% of the side chains in the free protein. Analysis of a 15N-labeled enzyme in complex with the bi-substrate analogue [P1,P5-bis(5'-adenosine)-pentaphosphate] (Ap5A) resulted in the assignment of 90% of the backbone 1H and 15N resonances and 42% of the side chain resonances. Based on short-range NOEs and 1H and 13C secondary chemical shifts, we identified the elements of secondary structure and the topology of the beta-strands in the unliganded form. The alpha-helices and the beta-strands of the parallel beta-sheet in solution have the same limits (+/- 1 residue) as those observed in the crystal. The first helix (alpha1) appears to have a frayed N-terminal side. Significant differences relative to the crystal were noticed in the LID domain, which in solution exhibits four antiparallel beta-strands. The secondary structure of the nucleoside-bound form, as deduced from intramolecular NOEs and the 1Halpha chemical shifts, is similar to that of the free enzyme. The largest chemical shift differences allowed us to map the regions of protein-ligand contacts. 1H/2H exchange experiments performed on free and Ap5A-bound enzymes showed a general decrease of the structural flexibility in the complex which is accompanied by a local increased flexibility on the N-side of the parallel beta-sheet.

Wedge factor dependence with depth, field size, and nominal distance--a general computational rule.

We have investigated the dependence of the wedge factors with field size, depth, nominal, and extended distances for 4, 6, 18, and 24 MV photon beams. Analysis of the experimental data suggests a general linear dependence of the wedge factors with field size and depth. The study shows that changes in wedge factors are insignificant (< or = +/-1.0%) with respect to measurements at nominal SSD, SAD, or extended SSD. This independence of the wedge factors on source-to-surface distance was studied for different photon energies (4-24 MV) and for different attenuating wedges (external and internal wedges). For clinical applications, an algorithm is presented to calculate the wedge factor dependence with field size and depth. The new algorithm has been successfully implemented to replace wedge look-up tables for dose and MU calculations in PRISM 1.2 treatment planning system used in our department.

[The vitreoretinal complications of cataract surgery]. / Complicatii vitreoretiniene ale chirurgiei cataractei.

The paper reports a retrospective study performed between January 1996 and January 1999 which comprised 423 patients who underwent eye cataract surgery. Vitreoretinal complications (retinal detachment, cystoid macular edema, choroidal detachment, endophthalmitis, luxation of the lens into the vitreous body) were related to age, sex, other general and local diseases and surgical complications, like disruption of the posterior capsule. The study presents also vitreoretinal complications after Nd:YAG laser posterior capsulotomy. The outcomes of the study show that 18 cases (4.25%) had retinal detachment, 11 (2.60%) had cystoid macular edema, 2 cases had endophthalmitis, while choroidal detachment and luxation of the lens into the vitreous body were reported each in 1 case. Retinal detachment following Neodymium:YAG laser capsulotomy (performed in 109 cases) was found in 2 cases. All of those vitreoretinal complications were reported with a higher incidence in patients with vascular diseases (diabetes mellitus, arterial hypertension, angiosclerosis) and also in patients who had axial lengths of 25 mm or greater.

[Cataract and the exfoliative syndrome]. / Cataracta si sindromul exfoliativ.

Exfoliation syndrome is more frequently in the older age and represents a risk factor for cataract surgery. This paper presents the results of a clinical trial made on 436 patients with troubles of transparency of the lens who were investigate in our clinic during January 1995-January 1997, and in whom, clinic and paraclinic exams have not revealed any associated ocular disease. In 14% of these patients who presented troubles of transparency of the lens were found uni- or bilateral exfoliation. The authors present the treatment applied both in patients in clinical follow-up (50% of patients with exfoliation syndrome develop secondary glaucoma) and patients who underwent surgical treatment. The patients with exfoliation syndrome and cataract have had a high risk to develop intra- and postoperative complications. The surgical treatment suggested by authors is extracapsular cataract extraction, either or without lens implantation and peripheral iridectomy which represents a compulsory step.

[The use of viscoelastic compounds in cataract surgery]. / Utilizarea compusilor vâscoelastici în chirurgia cataractei.

The viscoelastic substances are very useful generally in cataract surgery, but absolutely useful in phacoemulsification. In present is used for viscoelastic compounds two terms that assemble the rheologic and physics-chemical properties: is said about the viscoelastic substance that is cohesive and dispersive (respective cohesivity or dispersivity property). Thus both types of viscoelastic substances--cohesive and dispersive--is used, sequentially, in one system. This double technique provides a fluid, heterogeneous work environment, which differ from the other techniques that use only one viscoelastic substance and provide a fluid, homogeneous work environment.

Acute simulated ischaemia produces both inhibition and activation of K+ currents in isolated ventricular myocytes.

OBJECTIVE: The aim was to investigate the effects of acute ischaemia on cardiac repolarizing K+ currents. METHODS: We developed a model of acute ischaemia in isolated rat ventricular myocytes transiently surrounded with a mineral oil droplet. During ischaemic challenges, we recorded intracellular pH using the fluorescent probe seminaphthorhodafluor-1 (SNARF-1) and whole-cell K+ currents using the patch-clamp technique. RESULTS: Decrease in intracellular pH (pH1) during simulated ischaemia was dependent upon the extracellular proton buffer used (pH1 decreased from 7.44 +/- 0.02 to 7.16 +/- 0.04 in a Hepes-buffered medium and from 7.08 +/- 0.04 to 6.56 +/- 0.07 with bicarbonate buffer). In Hepes, action potential duration initially lengthened and then shortened under the effects of ischaemia. Initial action potential duration lengthening was concomitant with a block of the inward rectifier K+ current, whereas late shortening corresponded with the activation of the ATP-sensitive K+ current. Similar changes occurred in bicarbonate buffer although with different amplitudes and kinetics. Patch-clamp experiments also showed inhibition of the transient outward K+ current. Brief transient episodes of ischaemia activated ATP-sensitive K+ current in only 20% of control cells (n = 21) but in 100% of cells treated with 15 microM cromakalim (n = 9). CONCLUSIONS: (i) Simulated ischaemia produces complex effects on repolarizing K+ currents including both inhibition and activation; (ii) cromakalim accelerates activation of ATP-sensitive K+ current during simulated ischaemia.