Is 2-deoxy-2-[(18)F]fluoro-D-glucose PET/CT acquisition from the upper thigh to the vertex of skull useful in oncological patients?

AIM: To assess whether performing routinely 2-deoxy-2-[(18)F]fluoro-D-glucose PET/CT ((18)FDG PET/CT) scan from the upper thigh to the vertex of skull is clinically relevant. MATERIALS AND METHODS: 3502 (1634 female; mean-age 60+16) consecutive patients undergoing (18)FDG PET/CT were retrospectively analyzed. Patients were divided in 10 groups according to primary malignancy. Chi-square analysis was used to assess differences among proportions. A p value < 0.05 was considered significant. RESULTS: (18)FDG PET/CT was positive in head district in 130/3502 (3,7%) patients. In all patients lesions were unknown before PET/CT examination. PET/CT showed 158 positive brain/head uptake in the 130 patients. The 158 lesions were localized in: brain (43/158; 27%), bone (52/158; 33%), lymph node (1/158; 0,6%), soft tissue (55/158; 35%) and other sites (7/158; 4,4%). According to each group, patients were positive in the head district in 1.0% for Gastrointestinal Cancer (7/690), 3.0 % for Genitourinary Cancer (3/101), 3.7 % for Haemathologic Cancer (59/1590), 2.7 % for Gynaecologic Cancer (3/112), 7.8% for Head-Neck-Thyroid and Parathyroid Cancer (26/331), 3.5% for Breast Cancer (7/200), 2.6% for Lung Cancer (7/271), 3.4% for Melanoma (2/59), 7.4% for Sarcoma (2/27), 11.6% for Unknown Primary Tumour (14/121). CONCLUSION: Our data show a relatively high incidence of brain/head lesion in patients with Unknown Primary Tumour.

Clinical and research applications of simultaneous positron emission tomography and MRI.

Evaluation of the molecular processes responsible for disease pathogenesis and progression represents the new frontier of clinical radiology. Multimodality imaging lies at the cutting edge, combining the power of MRI for tissue characterization, microstructural appraisal and functional assessment together with new positron emission tomography (PET) tracers designed to target specific metabolic processes. The recent commercial availability of an integrated clinical whole-body PET-MRI provides a hybrid platform for exploring and exploiting the synergies of multimodal imaging. First experiences on the clinical and research application of hybrid PET-MRI are emerging. This article reviews the rapidly evolving field and speculates on the potential future direction.

Whole-tumour CT-perfusion of unresectable lung cancer for the monitoring of anti-angiogenetic chemotherapy effects.

OBJECTIVE: To determine whether CT-perfusion (CT-p) can be used to evaluate the effects of chemotherapy and anti-angiogenic treatment in patients with non-small-cell lung carcinoma (NSCLC) and whether CT-p and standard therapeutic response assessment (RECIST) data obtained before and after therapy correlate. METHODS: 55 patients with unresectable NSCLC underwent CT-p before the beginning of therapy and 50 of them repeated CT-p 90 days after it. Therapeutic protocol included platinum-based doublets plus bevacizumab for non-squamous carcinoma and platinum-based doublets for squamous carcinoma. RECIST measurements and calculations of blood flow (BF), blood volume (BV), time to peak (TTP) and permeability surface (PS) were performed, and baseline and post-treatment measurements were tested for statistically significant differences. Baseline and follow-up perfusion parameters were also compared based on histopathological subclassification (2004 World Health Organization Classification of Tumours) and therapy response assessed by RECIST. RESULTS: Tumour histology was consistent with large cell carcinoma in 14/50 (28%) cases, adenocarcinoma in 22/50 (44%) cases and squamous cell carcinoma in the remaining 14/50 (28%) cases. BF and PS differences for all tumours between baseline and post-therapy measurements were significant (p=0.001); no significant changes were found for BV (p=0.3) and TTP (p=0.1). The highest increase of BV was demonstrated in adenocarcinoma (5.2±34.1%), whereas the highest increase of TTP was shown in large cell carcinoma (6.9±22.4%), and the highest decrease of PS was shown in squamous cell carcinoma (-21.5±18.5%). A significant difference between the three histological subtypes was demonstrated only for BV (p<0.007). On the basis of RECIST criteria, 8 (16%) patients were classified as partial response (PR), 2 (4%) as progressive disease (PD) and the remaining 40 (80%) as stable disease (SD). Among PR, a decrease of both BF (18±9.6%) and BV (12.6±9.2%) were observed; TTP increased in 3 (37.5%) cases, and PS decreased in 6 (75%) cases. SD patients showed an increase of BF, BV, TTP and PS in 6 (15%), 21 (52.5%), 23 (57.5%) and 2 (5%) cases, respectively. PD patients demonstrated an increase of BF (26±0.2%), BV (2.7±0.1%) and TTP (3.1±0.8%) while only PS decreased (23±0.2%). CONCLUSION: CT-p can adequately evaluate therapy-induced alterations in NSCLC, and perfusion parameters correlate with therapy response assessment performed with RECIST criteria. ADVANCES IN KNOWLEDGE: Evaluating perfusional parameters, CT-p can demonstrate therapy-induced changes in patients with different types of lung cancer and identify response to treatment with excellent agreement to RECIST measurements.

Chest MR imaging in the follow-up of pulmonary alterations in paediatric patients with middle lobe syndrome: comparison with chest X-ray.

PURPOSE: The authors evaluated the role of magnetic resonance (MR) imaging of the chest in comparison with chest X-ray in the follow-up of pulmonary abnormalities detected by computed tomography (CT) in paediatric patients with middle lobe syndrome. MATERIALS AND METHODS: Seventeen patients with middle lobe syndrome (mean age 6.2 years) underwent chest CT at the time of diagnosis (100 kV, CARE dose with quality reference of 70 mAs; collimation 24×1.2 mm; rotation time 0.33 s; scan time 5 s); at follow-up after a mean of 15.3 months, all patients were evaluated with chest MR imaging with a respiratory-triggered T2-weighted BLADE sequence (TR 2,000; TE 27 ms; FOV 400 mm; flip angle 150°; slice thickness 5 mm) and chest X-ray. Images from each modality were assessed for the presence of pulmonary consolidations, bronchiectases, bronchial wall thickening and mucous plugging. Hilar and mediastinal lymphadenopathies were assessed on CT and MR images. RESULTS: Baseline CT detected consolidations in 100% of patients, bronchiectases in 35%, bronchial wall thickening in 53% and mucous plugging in 35%. MR imaging and chest X-ray identified consolidations in 65% and 35%, bronchiectases in 35% and 29%, bronchial wall thickening in 59% and 6% and mucous plugging in 25% and 0%, respectively. Lymphadenopathy was seen in 64% of patients at CT and in 47% at MR imaging. CONCLUSIONS: Patients with middle lobe syndrome show a wide range of parenchymal and bronchial abnormalities at diagnosis. Compared with MR imaging, chest X-ray seems to underestimate these changes. Chest MR imaging might represent a feasible and radiation-free option for an overall assessment of the lung in the follow-up of patients with middle lobe syndrome.

Clinical application of dual-source CT in the evaluation of patients with lung cancer: correlation with perfusion scintigraphy and pulmonary function tests.

PURPOSE: This study was done to assess the diagnostic potential of dual-source computed tomography (DSCT) in the functional evaluation of lung cancer patients undergoing surgical resection. The CT data were compared with pulmonary perfusion scintigraphy and pulmonary function tests (PFTs). MATERIALS AND METHODS: All patients were evaluated with DSCT, scintigraphy and PFTs. The DSCT scan protocol was as follows: two tubes (80 and 140 kV; Care Dose protocol); 70 cc of contrast material (5 cc/s); 5- to 6-s scan time; 0.6 mm collimation. After the automatic calculation of lung perfusion with DSCT and quantification of air volumes and emphysema with dedicated software applications, the perfusional CT studies were compared with scintigraphy using a visual score for perfusion defects; CT air volumes and emphysema were compared with PFTs. RESULTS: The values of accuracy, sensitivity, specificity and positive (PPV) and negative (NPV) predictive values of DSCT compared with perfusion scintigraphy as the reference standard were: 0.88, 0.84, 0.90, 0.93 and 0.88, respectively. The McNemar test did not identify significant differences either between the two imaging techniques (p=0.07) or between CT and PFTs (p=0.09). CONCLUSIONS: DSCT is a robust and promising technique that provides important and accurate information on lung function.

CAD (computed-aided detection) and CADx (computer aided diagnosis) systems in identifying and characterising lung nodules on chest CT: overview of research, developments and new prospects.

Computer-aided detection (CAD) systems allow the automatic identification of lung nodules on chest computed tomography (CT), providing a second opinion to the radiologist's judgement and a volumetric evaluation of lesions - a very important aspect in oncological patients. The natural evolution of these systems has led to the introduction of computer-aided diagnosis (CADx) systems, which are able not only to identify nodules but also to characterise them by determining a likelihood of malignancy or benignity. The aim of this article is to describe the main technical principles of CAD and CADx systems, their applicability and influence in clinical practice and new prospects for their future development.

MDCT assessment of lung volume in patients undergoing bronchial stenting for treatment of pulmonary emphysema: correlation with respiratory tests and personal experience.

PURPOSE: The aid of this study was to evaluate lung volume reduction with multidetector-row computed tomography (MDCT) in patients with emphysema who have undergone endobronchial valve placement. MATERIALS AND METHODS: Nine patients with emphysema were studied by low-dose chest MDCT (64-slice Somatom Sensation Cardiac, Siemens) with a collimation of 64 x 0.6 mm and a slice thickness of 1 mm. After treatment, MDCT scans were repeated at 7 and 30 days. A single observer calculated the volume of the treated lobe and of both lungs on a dedicated console. Volume calculations were then compared with the results of lung function tests. RESULTS: Four patients in whom MDCT showed severe emphysema of the right upper lobe (RUL) were selected for endobronchial valve insertion. Volume assessment at 30 days showed a 29% reduction in RUL volume in patient A, a 15% reduction in patient B, a <1% reduction in patient C and a 30% reduction in patient D. Correlation with lung function tests confirmed a major reduction of forced expiratory volume in 1 s (FEV(1)) and vital capacity (VC) and improved walking test results after 7 and 30 days. CONCLUSIONS: In patients undergoing endobronchial valve placement, MDCT with dedicated software allows for a better evaluation of volume reduction of a single lobe and of the whole lung.

[Usefulness of spiral CT in the prevention of pulmonary barotrauma: presentation of a case report in a hyperbaric operator]. / Utilità della TC-spirale nella prevenzione del barotrauma polmonare: presentazione di un "case report" in un'operatrice iperbarica.

A medical surveillance integrated system for health care workers, engaged in an hyperbaric environment exposure, was set upped and implemented in an university hospital, in accordance with doctrinal, legislative and methodological issues. In particular, a specific attention on anatomic and functional assessment of the respiratory system was applied, through an advanced technique of spiral-CT imaging, with the aim to carry out an early detection of conditions to be predispose "pulmonary barotrauma". Therefore, the present contribution proposes to illustrate clinical and instrumental data, and also to show chest spiral-CT acquired images results, in a 35-years-old nurse on assignment to an hyperbaric oxygen therapy unit. In this experience the described preventive protocol was operated in the context of a modern rational and justifiable, flexible and balanced health protection path.

Volumetric evaluation of therapy response in patients with lung metastases. Preliminary results with a computer system (CAD) and comparison with unidimensional measurements.

PURPOSE: The aim of this study was to assess the efficacy of a Computer-Aided Detection (CAD) system in the identification of lung metastases and to compare the volumetric CAD measurements with unidimensional observer measurements in the evaluation of treatment response in oncology patients. MATERIALS AND METHODS: Two observers (A and B) evaluated nine patients undergoing lung computed tomography (CT) just before and immediately after treatment with chemotherapy. Multislice CT scans were performed before and after the injection of contrast material with a high-resolution protocol (collimation 4x1 mm, 100 mAs, 120 kV). Response Evaluation Criteria in Solid Tumours (RECIST) criteria were used to consider the disease as stable, increased or decreased. Subsequently, target lesions (most significant lesions identified before and after chemotherapy) were evaluated with a computerised system (CAD) to establish volumetric measurements. Observers' unidimensional measurements and CAD volumetric measurements were analysed for comparison. RESULTS: Twenty-four nodules (diameter: 5-18 mm in the first study and 4-20 mm in the follow-up study) were included. Observers agreed in the assessment of therapy response in 21 nodules: eight were considered to have increased in size, and 13 were judged stable. Observer and CAD measurements disagreed in three nodules: two were considered stable by radiologists and increased by CAD; one was considered increased by radiologists and stable by CAD.As regards patient response, radiologists disagreed in two cases. CAD and observers did not agree in one case. CONCLUSIONS: Our preliminary data suggest that volumetric measurements can modify the diagnostic and therapeutic evaluation of oncology patients under chemotherapy.CAD volumetric measurements allow an easy and objective evaluation, reducing interobserver variability in the evaluation of chemotherapy response.

Multidetector-row CT angiography of renal artery stenosis in 50 consecutive patients: prospective interobserver comparison with DSA.

PURPOSE: The purpose of this study was to establish the diagnostic value of multidetector-row computed tomography (MDCT) angiography compared with digital subtraction angiography (DSA) for detection and quantification of both main and accessory renal artery stenosis in patients with secondary hypertension. MATERIALS AND METHODS: Fifty consecutive patients scheduled for DSA were considered candidates for MDCT angiography. In all patients, MDCT angiography of the abdominal aorta was performed before DSA. For the purpose of interpretation, the arteries were separately interpreted either with DSA or MDCT angiography in order to provide qualitative and quantitative information. For qualitative evaluation, one experienced reader graded the opacification of renal arteries as excellent, good or poor; for quantitative evaluation, MDCT and DSA were independently evaluated for the number of renal arteries and the presence, location and degree of stenosis in random order by three readers. On the basis of consensus readings, calculations of sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) for detection of degree of stenosis were made by using DSA findings as the standard of reference. Interobserver variability was also assessed. RESULTS: With regard to qualitative analysis, arterial enhancement was considered excellent in 39 patients and good in 11. For quantitative analysis, 73 arteries were classified as normal with DSA. Although 72 of these were also classified as normal with CT angiography, one was overestimated by one grade; at DSA, 16 arteries were classified as moderately stenotic; in two arteries, there was an overestimation of one grade. Perfect correlation was achieved for the diagnosis of occlusion. In two patients, all three readers detected multiple severe stenoses on both modalities, with a "string-of-beads" appearance typical of fibromuscular dysplasia. Accessory arteries were correctly identified as such by all three readers on either DSA or MDCT. Levels of sensitivity, specificity and accuracy regarding degree of stenosis were 100%, 98.6% and 96.9%, respectively, with PPV and NPV of 97.6% and 100%, respectively. When we considered significant arterial stenosis (50%-100% luminal narrowing), sensitivity, specificity and accuracy were 100%, 97.3% and 97.8%, respectively, with a PPV and NPV of 98.2% and 97.8%, respectively. For all observers, interobserver agreement was almost perfect (k=0.81-1) for both MDCT and DSA, with a k value between 0.82 and 0.95. CONCLUSIONS: MDCT angiography is very accurate and robust, even for the assessment of renal artery stenosis, and has the potential to become a viable substitute, in most cases, for diagnostic catheter-based DSA.

Evaluation of effectiveness of a computer system (CAD) in the identification of lung nodules with low-dose MSCT: scanning technique and preliminary results.

PURPOSE: Evaluation of the effectiveness of computer-aided diagnosis (CAD) in the identification of pulmonary nodules. MATERIALS AND METHODS: Two observers (A1, A2) with different levels of experience independently evaluated 20 chest MSCT studies with and without the aid of a CAD system (LungCheck, R2 Technology, Inc). The study parameters were as follows: 140 kVs, 40 mAs, collimation 4 x 1 mm, slice thickness 1.25 mm, reconstruction interval 1.0 mm. The observers analysed the images with and without CAD and evaluated: 1) nodule size (longer axis); 2) number and location of nodules; 3) reading time for each observer. The gold standard was represented by the evaluation of both readers in consensus with the aid of the CAD system. RESULTS: Without CAD support the two readers identified 77 (A1) and 79 (A2) nodules and with CAD 81 (A1) and 82 (A2) nodules. Working in consensus the two observers identified 81 nodules without the aid of the CAD and 84 nodules with the aid of CAD. Total number of nodules identified by CAD was 104, 25 of which were false positive and 5 false negative. The average reading time with the aid of the CAD decreased by as much as 40% for both the observers. CONCLUSIONS: The preliminary results of our study suggest that the CAD technique is an accurate automatic support tool in the identification of pulmonary nodules. It reduces reading time and automatically supplies the size, volume, density and number of nodules, thus being useful both in screening programmes and in the follow-up of cancer patients, in whom comparison of the images is particularly difficult.

High-resolution multidetector CT in the preoperative evaluation of patients with renal cell carcinoma.

OBJECTIVE: The purpose of our study was to evaluate the accuracy of multidetector CT (MDCT) using a high-resolution protocol in the preoperative assessment of patients with renal cell carcinoma who are possible candidates for nephron-sparing surgery. MATERIALS AND METHODS: Forty patients with suspected renal cell carcinoma underwent MDCT. Contrast-enhanced acquisitions were obtained during arterial, nephrographic, and urographic phases using a thin-slice protocol. One-millimeter-thick source images were evaluated by two observers on a dedicated workstation for the identification and characterization of the tumor, presence of a pseudocapsule or invasion of perirenal fat, involvement of adrenal glands or surrounding tissues, presence of satellite lesions within Gerota's fascia, infiltration of renal vein and inferior vena cava, involvement of lymph nodes, and presence of distant metastases. Imaging findings were compared with surgical specimens using criteria from the Robson and TNM classification systems. RESULTS: The presence and size of all lesions were correctly shown in all patients. In evaluating Robson stage I of renal cell carcinoma, we were able to diagnose fat infiltration on 1-mm scans with 96% sensitivity, 93% specificity, and 95% accuracy; the positive and negative predictive values were, respectively, 100% and 93%. One hundred percent accuracy was achieved in staging high-grade lesions. CONCLUSION: High-resolution MDCT is accurate in the preoperative evaluation of patients with renal cell carcinoma.

High-resolution CT angiography of the abdomen.

Multislice computed tomographic angiography (MSCTA) is a versatile technique that combines speed, excellent contrast, superb spatial resolution, and extreme simplicity. It has a wide range of applications in the abdomen including all vascular pathologies, occlusive or dilative, with excellent demonstration of atherosclerotic plaques in large or smaller branches. MSCTA is the method of choice in the follow-up of patients undergoing endovascular procedures for aneurysms. It provides excellent results in assessing vascular involvement by neoplasms arising from the liver, biliary tract, pancreas, kidneys, and all other abdominal organs. MSCTA can be used successfully in potential living donors and in the follow-up of recipients. Although MSCTA is a brand new technique, several developments are under investigation, which should allow further advancements in speed and spatial resolution.

Cl(-)-dependent secretory mechanisms in isolated rat bile duct epithelial units.

Cholangiocytes absorb and secrete fluid, modifying primary canalicular bile. In several Cl(-)-secreting epithelia, Na(+)-K(+)-2Cl(-) cotransport is a basolateral Cl(-) uptake pathway facilitating apical Cl(-) secretion. To determine if cholangiocytes possess similar mechanisms independent of CO2/HCO, we assessed Cl(-)-dependent secretion in rat liver isolated polarized bile duct units (IBDUs) by using videomicroscopy. Without CO2/HCO, forskolin (FSK) stimulated secretion entirely dependent on Na(+) and Cl(-) and inhibited by Na(+)-K(+)-2Cl(-) inhibitor bumetanide. Carbonic anhydrase inhibitor ethoxyzolamide had no effect on FSK-stimulated secretion, indicating negligible endogenous CO2/HCO transport. In contrast, FSK-stimulated secretion was inhibited approximately 85% by K(+) channel inhibitor Ba(2+) and blocked completely by bumetanide plus Ba(2+). IBDU Na(+)-K(+)-2Cl(-) cotransport activity was assessed by recording intracellular pH during NH4Cl exposure. Bumetanide inhibited initial acidification rates due to NH entry in the presence and absence of CO2/HCO. In contrast, when stimulated by FSK, a 35% increase in Na(+)-K(+)-2Cl(-) cotransport activity occurred without CO2/HCO. These data suggest a cellular model of HCO-independent secretion in which Na(+)-K(+)-2Cl(-) cotransport maintains high intracellular Cl(-) concentration. Intracellular cAMP concentration increases activate basolateral K(+) conductance, raises apical Cl(-) permeability, and causes transcellular Cl(-) movement into the lumen. Polarized IBDU cholangiocytes are capable of vectorial Cl(-)-dependent fluid secretion independent of HCO. Bumetanide-sensitive Na(+)-K(+)-2Cl(-) cotransport, Cl(-)/HCO exchange, and Ba(2+)-sensitive K(+) channels are important components of stimulated fluid secretion in intrahepatic bile duct epithelium.

[Magnetic resonance angiography with contrast media in the study of carotid arteries]. / Angiografia con Risonanza Magnetica con mezzo di contrasto nello studio delle arterie carotidi.

PURPOSE: Purpose of our study was to determine the feasibility and accuracy of contrast enhanced Turbo-MRA (CE-MRA) in the evaluation of patients with carotid artery stenosis, using a dynamic technique with multiple acquisitions. MATERIAL AND METHODS: 37 patients with suspected carotid artery stenosis were studied with a 1.5 T magnet (Siemens Vision Plus) using, with a neck phased array coil, a dynamic tridimensional T1 weighted spoiled GRE (TR/TE/NEX: 3.8/1.4/1; Matrix = 110 x 160; FOV = 163 x 260 mm TA = 10 seconds for each sequence); 4 consecutive sequences were performed during the same breath hold, acquired after i.v. bolus injection with a power injector (Spectris, Medrad) of 15 ml of Gd-DTPA followed by 10 ml of saline solution (flow rate 2 ml/s). The beginning of the sequence coincided with the injection of Gd-DTPA. Images were reconstructed using a standard MIP algorithm, by selecting which of the sequences provided the highest enhancement. In all patients a DSA was also performed. Images were separately evaluated using conventional angiography as the gold standard and assessed for degree of stenosis by using NASCET criteria, and morphology of the plaque. RESULTS: CE-MRA correctly evaluated the degree of stenosis in 71 of the 74 patients, while overestimated the remaining 3 cases correctly evaluated by DSA. In 12 cases ulcerations were adequately demonstrated by one of the radiologist, while 11 on 12 were depicted by the other one. CE MRA allowed to detect tandem lesions of the internal carotid arteries (by both radiologists) in 13 of 74 carotids studied. Stenosis at the origin of the common carotid arteries were correctly detected in 9 cases. Sensitivity, specificity and accuracy were respectively of 98, 97 and 99%. DISCUSSION AND CONCLUSIONS: In order to perform an optimal CE-MRA a dynamic technique must be performed to avoid venous filling. The possibility to use ultrafast imaging allows to selectively image the carotid arteries without jugular filling. The well known tendency to overestimate the degree of stenosis has not been found in this group of patients. CE-MRA is a rapid, reliable method to evaluate patients with suspected carotid artery stenosis. These results allow to consider dynamic CE-MRA as a valid method for direct imaging of the carotid arteries.

[Inflammatory markers after laparoscopy versus laparotomy cholecystectomy]. / Markers infiammatori post colecistectomia laparoscopica versus laparotomica.

OBJECTIVE: The study is carried out to determine whether the level of IL-6 is altered and in what way after surgery as well as if such a change could be an indicator of increased morbidity after surgical treatment. MATERIALS OF THE STUDY: Chemiluminesence immunoeassay system was used in order to establish IL-6 level in blood samples of 71 patients that underwent abdominal surgery, 36 Laparoscopic Cholecystectomy (LC) and 35 Open Cholecystectomy (OC) at time 0 (before the operation), 1 h, 2 h, 3 h, 6 h, 24 h and 48 h after the operation. RESULTS: Plasma IL-6 levels are significantly increased after OC; we observed 3 cases of post-operative infections, in which IL-6 returned to normal levels 6 days after surgery. Analogous variation to the IL-6 levels was noted for the C-reactive protein levels. DISCUSSION: Laparoscopic cholecystectomy, a so called mini-invasive surgical procedure, is associated to a small increase of IL-6 serum levels and provides better post-operative conditions to the patients by reducing surgical stress and the infectious complications correlated to the surgical procedure. CONCLUSIONS: During OC there is a significant higher elevation of IL-6 serum levels than after laparoscopic cholecystectomy. Variation of C-reactive protein serum levels after surgery is analogous to variation of IL-6 levels.

Molecular identification and functional characterization of Mdr1a in rat cholangiocytes.

BACKGROUND & AIMS: The multidrug resistance P-glycoprotein 170 gene products (mdr1a and 1b) are glycosylated plasma membrane proteins that function as adenosine triphosphate-dependent transmembrane export pumps for lipophilic xenobiotics of widely different structure. We assessed whether these P-glycoproteins are functionally expressed in cholangiocytes. METHODS: A reverse-transcription polymerase chain reaction was performed on RNA from a normal rat cholangiocyte cell line using mdr1-specific primers. Northern and Western blot analyses were performed on cholangiocytes immunoisolated from 2-week bile duct-ligated rats and cholangiocytes and isolated cholangiocyte membrane subfractions, respectively. Functional assays were performed in isolated bile duct units from bile duct-ligated rats and incubated with rhodamine 123, a P-glycoprotein substrate, with or without the P-glycoprotein inhibitors verapamil or GF120918. RESULTS: A 400-base pair fragment with 99% homology to the cytosolic domain of rat intestinal mdr1a (5' 1953-2350 3') was identified that hybridized to a 5.2-kilobase RNA transcript in a normal rat cholangiocyte cell line, isolated rat cholangiocytes, and ileum. Western analysis localized mdr1 to the apical membrane of cholangiocytes. Confocal microscopy showed active secretion of rhodamine 123 into the lumen of isolated bile duct units that was abolished by vanadate and P-glycoprotein competitive antagonists, verapamil and GF120918, in a dose-dependent manner. CONCLUSIONS: These findings provide the first molecular and functional evidence for the expression of mdr1a on the luminal membrane of cholangiocytes, where it may have a protective role.

Localization of pancreatic insulinomas with MR imaging at 0.5 T.

OBJECTIVE: To determine the role of MR imaging in the localization of pancreatic insulinomas in patients with clinical and laboratory diagnosis of insulin-producing tumor. MATERIAL AND METHODS: Thirty-one patients presenting with signs and symptoms of pancreatic insulinomas were prospectively included in our study. Twenty-six patients underwent surgery, and pathologic specimens were examined: 5 patients, in whom the initial diagnosis of insulinoma was excluded, were also studied and then followed up. All patients were studied with a high gradient power 0.5 T magnet. Images were evaluated by 2 radiologists blinded to previous investigations, tests and results. RESULTS: MR imaging correctly localized 24 of the 26 insulinomas (2 were false-negative and 1 false-positive) and was correctly negative in the 5 control patients. The interobserver agreement had a kappa value of 0.89. CONCLUSION: MR imaging was accurate in localizing pancreatic insulinomas and as a consequence, patients in our institution are now submitted to surgery directly after the MR examination. Invasive methods are considered only in cases in which, despite clear biochemical results, MR imaging has not demonstrated a pancreatic focal lesion.