Abdominal arterial lesions associated with antiphospholipid antibodies: a comparative cross-sectional magnetic resonance angiography study.

OBJECTIVE: Case reports and small case series suggest that stenotic lesions of the renal, coeliac and mesenteric arteries may occur in the antiphospholipid syndrome (APS) resulting in clinical consequences such as hypertension and abdominal angina. The objective was to determine the prevalence of stenotic lesions in arteries arising from the middle aorta in patients with antiphospholipid antibodies (aPL) compared with healthy, hypertensive and atherosclerotic controls. METHODS: In a cross-sectional comparative radiological study using magnetic resonance angiography (MRA), we assessed five groups of subjects for the prevalence of stenotic lesions in arteries arising from the middle aorta: APS/aPL positive, healthy renal donors, patients with hypertension, patients with atherosclerosis defined radiologically and patients with systemic lupus erythematosus and vasculitis who were negative for aPL. All subjects underwent MRA in suspended respiration and images were assessed by two senior radiologists blinded to the clinical details. RESULTS: In the atherosclerosis group, vascular stenotic lesions were more prevalent (71%) than in any other group (P ≤0.000002). The prevalence of all stenotic lesions in aPL positive patients (33%) was significantly higher than in the renal donors (18%) and hypertensive patients (19%) (P ≤0.009). Renal artery stenosis was significantly more prevalent in aPL positive patients than in renal donors (P ≤0.0006) but similar to the prevalence in hypertensive patients. Coeliac and/or mesenteric lesions were significantly more common in aPL positive patients vs hypertensive patients (P ≤0.001). Stenoses did not correlate with traditional risk factors. CONCLUSION: Arterial stenotic lesions in arteries arising from the middle aorta were highly prevalent in atherosclerotic subjects and were more common in aPL-positive patients than in hypertensive patients and healthy renal donors.

Role of fluorodeoxyglucose positron emission tomography (FDG PET)-computed tomography (CT) in the staging of bladder cancer.

OBJECTIVE: To determine whether to use (18) F-fluorodeoxyglucose positron emission tomography (FDG PET) scans in the preoperative staging of bladder cancer (BC). PATIENTS AND METHODS: In all, 233 patients with muscle-invasive BC (MIBC) or high-risk non-MIBC being considered for radical cystectomy (RC) between 2005 and 2011 had FDG-PET and computed tomography (CT) of the chest, abdomen and pelvis to assess for pelvic lymph node (LN) involvement or distant metastases. Sensitivity and specificity for detecting pelvic LN involvement was determined by comparing the results of the scans to the histopathology reports in patients undergoing RC. These parameters for distant metastases were determined from biopsy results or follow-up imaging. In patients who did not undergo RC, follow-up imaging was used to evaluate the sensitivity and specificity. Patients were excluded from analysis if they either had neoadjuvant chemotherapy or had <10 LNs removed at lymphadenectomy. RESULTS: The PET scan was able to detect metastatic disease outside of the pelvis with a sensitivity of 54% compared with 41% for the staging CT (N = 207). Both scans had similar specificities of 97% and 98%. There were 13 PET avid lesions not visualised on the corresponding staging CT scans. These proved to be metastatic BC (six patients), a synchronous primary colonic cancer (one), colonic adenomas (one), basal cell tumour of the parotid gland (one) and inflammatory lesions (four). The sensitivity and specificity of the CT scans for pelvic LN involvement was 45% and 98%, respectively (N = 93). Using a combination of the PET and CT scan, the sensitivity for detecting metastatic disease in LNs increased to 69% with a 3% reduction in specificity to 95%. CONCLUSIONS: PET when used in conjunction with a standard CT scan provides a small improvement in preoperative staging of BC. However, this advantage is not significant enough to justify the additional cost. Hence we recommend use of dual imaging only in highly selected patients.

Observer variation in FDG PET-CT for staging of non-small-cell lung carcinoma.

PURPOSE: Error and variation in reporting remains one of the weakest features of clinical imaging despite enormous technological advances in nuclear medicine and radiology. The aim of this study was to evaluate agreement amongst experienced readers in staging non-small-cell lung cancer (NSCLC) with PET-CT. METHODS: A series of (18)F-FDG PET-CT scans from 100 consecutive patients were reviewed independently by three experienced readers, with two readers reviewing each scan series a second time. Individual mediastinal lymph node stations were assessed as benign/inflammatory, equivocal or malignant, and AJCC N and M stage were also assigned. Kappa (kappa) was used to compare ratings from two categories and weighted kappa (kappa(w)) for three or more categories, and kappa values were interpreted according to the Landis-Koch benchmarks. RESULTS: Both intra- and interobserver agreement for N and M staging were high. For M staging there was almost perfect intra- and interobserver agreement (kappa = 0.90-0.93). For N staging, agreement was either almost perfect or substantial (intraobserver kappa(w) = 0.79, 0.91; interobserver kappa(w) = 0.75-0.81). Importantly, there was almost perfect agreement for N0/1 vs N2/3 disease (kappa = 0.80-0.97). Agreement for inferior and superior mediastinal nodes (stations 1, 2, 3, 7, 8, 9) was either almost perfect or substantial (kappa(w) = 0.71-0.88), but lower for hilar nodes (10; kappa(w) = 0.56-0.71). Interreporter variability was greatest for aortopulmonary nodes (5, 6; kappa(w) = 0.48-0.55). CONCLUSION: Amongst experienced reporters in a single centre, there was a very high level of agreement for both mediastinal nodal stage and detection of distant metastases with PET-CT. This supports the use of PET-CT as a robust imaging modality for staging NSCLC.

Imaging features of von Hippel-Lindau disease.

von Hippel-Lindau (VHL) disease is a rare, autosomal dominantly inherited multisystem disorder characterized by development of a variety of benign and malignant tumors. The spectrum of clinical manifestations of the disease is broad and includes retinal and central nervous system hemangioblastomas, endolymphatic sac tumors, renal cysts and tumors, pancreatic cysts and tumors, pheochromocytomas, and epididymal cystadenomas. The most common causes of death in VHL disease patients are renal cell carcinoma and neurologic complications from cerebellar hemangioblastomas. The various manifestations can be demonstrated with different imaging modalities such as ultrasonography, computed tomography, magnetic resonance imaging, and nuclear medicine. Although genetic testing is available, the manifestations of the syndrome are protean; therefore, imaging plays a key role in identification of abnormalities and subsequent follow-up of lesions. It is also used for screening of asymptomatic gene carriers and their long-term surveillance. Screening is important because the lesions in VHL disease are treatable; thus, early detection allows use of more conservative therapy and may enhance the patient's length and quality of life. A multidisciplinary team approach is important in screening for VHL disease.

Relative threshold of detection of active arterial bleeding: in vitro comparison of MDCT and digital subtraction angiography.

OBJECTIVE: The objective of our study was to determine the relative sensitivity and the lowest threshold of bleeding detectable with digital subtraction angiography (DSA) and with MDCT using an in vitro physiologic system. MATERIALS AND METHODS: A closed pulsatile cardiopulmonary bypass circuit was connected to tubes traversing a water bath to simulate the abdominal aorta and inferior vena cava. Three smaller interconnecting acrylic plastic tubes were connected as branches to the aortic tubing to simulate branch vessels. One of the three tubes, the control, had no holes in it, one had a 100-microm hole, and one had a 280-microm hole. The leakage rates were predetermined with a cardiac output of 2 and 4 L/min and with a mean arterial pressure (MAP) ranging from 30 to 100 mm Hg for each hole size. The following studies were performed for each of the predetermined leakage rates. For study 1, 16-MDCT was performed using bolus tracking after 35 mL of contrast medium had been injected into a simulated peripheral vein. For study 2, DSA was performed using a 4-French straight catheter placed 10 cm proximal to the holes (selective first aortic branch cannulation). For study 3, DSA was performed with a catheter placed in the small branch at the site of the hole (highly superselective). For study 4, 16-MDCT was performed with a catheter placed as in study 2, 10 cm proximal to the holes, for the detection of lower leakage rates. Cine loops of MDCT and DSA images were examined by two blinded observers to detect extravasation from the holes in the tubes (i.e., the branch arteries). Interobserver agreement was studied using Cohen's kappa statistic. RESULTS: The threshold to detect bleeding was as follows for each study: For IV contrast-enhanced MDCT (study 1), it was 0.35 mL/min; DSA with a catheter 10 cm proximal to the holes (study 2), 0.96 mL/min; DSA with a catheter at the holes (study 3), 0.05 mL/min [corrected] or lower; and intraarterial selective MDCT (study 4), 0.05 mL/min [corrected] or lower. The ease of detection improved with increasing MAPs and larger volumes of leakage. Interobserver correlation was excellent. CONCLUSION: In vitro, i.v. contrast-enhanced MDCT is more sensitive than first-order aortic branch-selective DSA in detecting active hemorrhage unless the catheter position is highly superselective and is close to the bleeding artery. These results suggest that MDCT can be used as the initial imaging technique in the diagnosis of active hemorrhage if the clinical condition of the patient allows.

Interethnic variability of warfarin maintenance requirement is explained by VKORC1 genotype in an Asian population.

BACKGROUND: Chinese and Malay subjects have been reported to require less maintenance warfarin than Indians that could not be accounted for by cytochrome P450 (CYP) 2C9 variants. Vitamin K epoxide reductase complex 1 (VKORC1) is the target enzyme of warfarin, and VKORC1 intronic variants and haplotypes have recently been shown to influence VKORC1 activity and warfarin requirements. METHODS: We sequenced the coding regions of CYP2C9 and VKORC1 and inferred VKORC1 haplotype from 10 intronic variants in 147 Chinese, 85 Malay, and 43 Indian patients receiving maintenance warfarin. RESULTS: The mean weight-normalized warfarin dose was lower for Chinese and Malays than for Indians (0.058 +/- 0.025 mg/kg, 0.059 +/- 0.023 mg/kg, and 0.089 +/- 0.036 mg/kg, respectively; P < .001 for comparisons between Chinese and Malays with Indians). CYP2C9*2 and VKORC1 coding region variants were rare (<2%), whereas CYP2C9*3 associated with lower warfarin requirements was less common in Chinese and Malays (7% and 9%, respectively) than in Indians (18%) and could not account for their lower warfarin requirements. VKORC1 H1 and H7/H8/H9 haplotypes were associated with lower and higher warfarin requirements, respectively (0.050 +/- 0.019 mg/kg and 0.092 +/- 0.057 mg/kg, respectively; P < .001). VKORC1 H1 haplotype (requiring low warfarin doses) was common in Chinese (87%) and Malays (65%) but uncommon in Indians (12%), whereas H7, H8, and H9 haplotypes (requiring high warfarin doses) were rare in Chinese (9%), intermediate in Malays (30%), and common in Indians (82%). The interethnic difference in warfarin requirements became nonsignificant when adjusted for VKORC1 haplotype. CONCLUSIONS: Interethnic difference in VKORC1 haplotypes accounts for the difference in warfarin requirements between Chinese, Malays, and Indians, providing interesting insights into genetic variation between ethnogeographically distinct Asian groups.

A test of performance of breast MRI interpretation in a multicentre screening study.

OBJECTIVES: The aim of this study was to assess the consistency and performance of radiologists interpreting breast magnetic resonance imaging (MRI) examinations. MATERIALS AND METHODS: Two test sets of eight cases comprising cancers, benign disease, technical problems and parenchymal enhancement were prepared from two manufacturers' equipment (X and Y) and reported by 15 radiologists using the recording form and scoring system of the UK MRI breast screening study [(MAgnetic Resonance Imaging in Breast Screening (MARIBS)]. Variations in assessments of morphology, kinetic scores and diagnosis were measured by assessing intraobserver and interobserver variability and agreement. The sensitivity and specificity of reporting performances was determined using receiver operating characteristic (ROC) curve analysis. RESULTS: Intraobserver variation was seen in 13 (27.7%) of 47 of the radiologists' conclusions (four technical and seven pathological differences). Substantial interobserver variation was observed in the scores recorded for morphology, pattern of enhancement, quantification of enhancement and washout pattern. The overall sensitivity of breast MRI was high [88.6%, 95% confidence interval (CI) 77.4-94.7%], combined with a specificity of 69.2% (95% CI 60.5-76.7%). The sensitivities were similar for the two test sets (P=.3), but the specificity was significantly higher for the Manufacturer X dataset (P<.001). ROC curve analysis gave an area under the curve of 0.85 (95% CI 0.79-0.92) CONCLUSIONS: Substantial variation in all elements of the scoring system and in the overall diagnostic conclusions was observed between radiologists participating in MARIBS. High overall sensitivity was achieved with moderate specificity. Manufacturer-related differences in specificities possibly occurred because the numerical thresholds set for the scoring system were not optimised for both equipment manufacturers. Scoring systems developed on one equipment software may not be transferable to other manufacturers.

Combined lung resection and transdiaphragmatic adrenalectomy in patients with non-small cell lung cancer and homolateral solitary adrenal metastasis.

Surgery may offer a long-term survival benefit to a small proportion of patients with operable non-small cell lung cancer (NSCLC) and solitary adrenal metastasis. Several approaches to lung resection with a separate open or laparoscopic adrenalectomy have been advocated. We describe a technique that allows a single incision, single operation through a transdiaphragmatic approach to the ipsilateral adrenal gland following a standard lung resection through a postero-lateral thoracotomy. By using this approach, along with the harmonic scalpel to aid adrenal dissection, both lobectomy and adrenalectomy can be carried out safely and effectively with minimal perioperative and postoperative morbidity.

Novel CYP2C9 genetic variants in Asian subjects and their influence on maintenance warfarin dose.

BACKGROUND: Commonly occurring genetic variants in CYP2C9 are known to reduce catalytic activity and are associated with enhanced patient sensitivity to warfarin. Interethnic differences in warfarin dose requirement have been described in the Asian population, and we postulate that this could be related to genetic variants of CYP2C9 that are unique to ethnic groups. METHODS: We prospectively genotyped 125 patients who were receiving a stable daily warfarin dose to maintain international normalized ratio values between 2 and 3 through comprehensive sequencing of the promoter and coding regions of the CYP2C9 gene. RESULTS: The mean weight-adjusted warfarin maintenance dose was significantly lower for Malay and Chinese subjects than Indian subjects ( P <.001 and.014, respectively). Warfarin dose negatively correlated with age (r = -0.4, P <.001) but not with sex. Multiple variants were detected in the promoter, exonic, intronic, and 3'-untranslated regions of CYP2C9, of which 16 were novel, including 7 nonsynonymous exonic variants ( 208G>C, 374G>A, 485C>A, 895A>G, 1144C>T, 1190A>C, and 1362G>C ). CYP2C9*3, but not CYP2C9*2, was found in Chinese and Malay patients, and carriers of the CYP2C9*3 variant in Chinese ( P <.01) and Indian ( P <.01) patients, but not Malay patients ( P =.77), required less warfarin. The influence of the novel exonic variants on warfarin dose requirement was unclear, because they were rare, but the lower warfarin dose requirement for Chinese and Malay patients existed despite omission of individuals with any coding region variants from analysis. CONCLUSIONS: Interethnic differences in warfarin dosing in Asian subjects may result from other genetic, dietary, or environmental influences; however, these novel variants in the gene warrant further characterization through functional studies.

Differential uptake of 18F-FDG in patients with synchronous lung cancers.

(18)F-fluoro-2-deoxy-D: -glucose positron emission tomography ((18)F-FDG PET/CT) has developed into the standard of care for investigating patients with non-small cell lung cancer (NSCLC) to determine the optimal treatment. However, although the majority of patients with NSCLC do have intense uptake of tracer, false negatives do occur and should be considered. We report cases of patients that have synchronous NSCLCs. In both cases, there was intense uptake of FDG in one tumour type, with very low grade uptake in the separate tumour. Histology confirmed separate lung malignancies, demonstrating that differential FDG uptake may not always be inflammatory and should be considered to have a separate malignant aetiology.

Role of integrated 18-fluorodeoxyglucose position emission tomography-computed tomography in patients surveillance after multimodality therapy of malignant pleural mesothelioma.

INTRODUCTION: To investigate the role of 18-fluorodeoxyglucose positron emission tomography-computed tomography (18-FDG-PET-CT) in the surveillance of patients after multimodality treatment of malignant pleural mesothelioma. METHODS: Retrospective study of patients who had chemotherapy, radical surgery, extrapleural pneumonectomy or pleurectomy/decortication, and radiotherapy for mesothelioma in our unit. PET-CT was performed after multimodality therapy to evaluate response to treatment or when disease recurrence was suspected. 18-FDG-PET scans were acquired from skull base to upper thigh with low-dose CT scans for attenuation correction and image fusion. RESULTS: Forty-four patients had extrapleural pneumonectomy (21) or pleurectomy/decortication (23) between January 2004 and July 2008. Twenty-five patients had PET-CT performed after multimodality therapy. This was performed in 11 patients in whom disease recurrence was suspected at a median of 9 (range, 6-16) months after treatment. PET-CT correctly diagnosed recurrent disease in eight patients and missed microscopic recurrence in one. Surveillance PET-CT was performed in 14 asymptomatic patients at a median of 11 (range, 7-13) months after treatment. It showed unsuspected recurrences in four patients. The standard uptake value max of recurrent mesothelioma was 8.9 +/- 4.0 (4-18.4). PET-CT had a sensitivity of 94%, a specificity of 100%, and the positive and negative predictive values of 100 and 88%, respectively. CONCLUSIONS: 18-FDG-PET-CT is useful in diagnosing disease recurrence after multimodality therapy for malignant pleural mesothelioma. We propose a prospective study to fully assess its value in this group of patients.

Assessing the feasibility of a one-stop approach to diagnosis for urological patients.

INTRODUCTION: Conventional publicly funded out-patient services in many specialties are characterised by delays, fragmented diagnostic processes, and overloaded clinics. This is bad for patients as it is clinically dangerous; bad for managers who spend hours managing the failure; bad for doctors who respond by overloading clinics; and bad for purchasers who have to fund the multiple out-patient visits needed. Sound clinical and financial reasons exist for introducing more efficient diagnostic processes. PATIENTS AND METHODS: A total of 330 consecutive patients referred to the urology department of Guy's and St Thomas' NHS Foundation Trust were invited to attend one of nine one-stop clinics staffed by consultant urologists with specialist registrars, nurses, and clerical staff. Pre-clinic blood and urine tests were ordered based on the referral letter. Clinics had facilities to perform cystoscopy, ultrasound, and urinary flow studies. Correspondence was generated in real time, and a copy given to the patient. RESULTS: Overall, 257 patients attended the clinics. Twenty-three patients cancelled appointments and 50 patients did not attend. Pre-clinic tests were requested in 133 patients and were completed by 86% of the patients who attended. Of patients, 42% were diagnosed and discharged; 28% were listed for surgery, extracorporeal shock wave lithotripsy (ESWL), or referred to another specialty. About 30% of patients needed further out-patient review; in approximately two-thirds to complete a diagnosis and one-third to review the results of therapy initiated. An estimated 350 appointments and 550 patient visits to hospital were saved. CONCLUSIONS: A one-stop method of consultation is efficient across a range of urological presenting complaints, and dramatically reduces the need for follow-up consultations. It has potential to: (i) reduce delays to being seen in out-patients; (ii) lead to more cost-effective care; and (iii) increase safety and patient satisfaction. It should become the standard of care in urology, and is probably applicable in many other disciplines.

Observer variation in interpreting 18F-FDG PET/CT findings for lymphoma staging.

UNLABELLED: Many studies demonstrate a high accuracy for PET in staging lymphoma, but few assess observer variation. This study quantified agreement for staging lymphoma with PET/CT. METHODS: The PET/CT images of 100 patients with lymphoma who had been referred for staging were reviewed by 3 experienced observers, with 2 observers reviewing each series a second time. Ann Arbor stage and individual nodal and extranodal regions were assessed. Weighted kappa (kappa(w)) and intraclass correlation coefficient were used to compare ratings. RESULTS: Intra- and interobserver agreement was high for Ann Arbor stage (kappa(w) = 0.79-0.91), number of nodal regions involved (intraclass correlation coefficient, 0.83-0.93), and presence of extranodal disease (kappa = 0.74-0.86). High agreement was also observed for all nodal regions (kappa(w) > 0.60) except hilar (kappa(w) = 0.56-0.82) and infraclavicular (kappa(w) = 0.14-0.55). Lower agreement was observed for bowel involvement (kappa(w) = 0.37-0.71). CONCLUSION: Experienced observers had a high level of agreement using PET/CT for lymphoma staging, supporting its use as a robust noninvasive staging tool. Further research is needed to evaluate observer variability for restaging during and after chemotherapy.

PET/CT for staging and monitoring non small cell lung cancer.

Correct staging of non small cell lung cancer (NSCLC) is vital for appropriate management. Initial staging is usually performed with computerised tomography (CT), but increasingly functional imaging using integrated positron emission tomography and CT (PET/CT) is being used to provide more accurate staging, guide biopsies, assess response to therapy and identify recurrent disease.

How best to manage the space after pneumonectomy? Theory and experience but no evidence.

OBJECTIVE: We set out to find a policy for the management of the pneumonectomy space which would minimise risk and be acceptable to all the surgeons. We believe this will reduce opportunities for error, be welcomed by nursing staff, and improve adherence to protocols. METHODS: We sought evidence in the scientific and educational literature. Finding no sure guidance, we audited our own experience of two policies, with the emphasis on minimising risk. RESULTS: There was no evidence from randomised trials. There was no cohesive advice in the text books. Our data indicated that it was improbable that randomised controlled trial (RCT) would have the power to find the evidence. Unable to establish the best strategy, we chose what appeared to be the lowest risk management policy. CONCLUSIONS: It is instructive that such a fundamental question should be unanswered. We have adopted a low risk and well established strategy--an unclamped underwater seal drain--but have no evidence base other than clinical experience. This is illustrative of much of what we do in clinical surgical practice. Avoiding major risk is often more important than proving small differences in benefit.

PET in face and neck tumours.

FDG-PET is a useful tool in the imaging of head and neck tumours. It can be used to stage the primary tumour, to assess response to therapy and most importantly for the detection of recurrent tumour. The advantages and limitations of this technique are discussed in this article.

Magnetic resonance renal angiography and venography: an analysis of 111 consecutive scans before donor nephrectomy.

OBJECTIVE: To determine the accuracy of magnetic resonance imaging (MRI) renal angiography in predicting vascular anatomy before donor nephrectomy, to determine the significance of missed vessels and to ascertain whether vessels are missed because of technical limitations or errors in interpretation. PATIENTS AND METHODS: In all, 111 consecutive living donations were assessed; the anatomy on MRI before donation was compared with that at nephrectomy. The significance of additional arteries and veins was recorded at the time of donation, with extra vessels either anastomosed or sacrificed. Finally, the scans in which extra vessels had not been identified were re-examined to establish whether these could be identified retrospectively. RESULTS: In all, 93 kidneys had a single renal artery and 18 had two. All lower pole arteries were anastomosed and all upper pole arteries were sacrificed. Nine arteries were identified before surgery (five were to the lower pole), and nine were missed (four to the lower pole). There were 13 kidneys with more than one vein. Four of these were seen on MRI. However, an extra vein was anastomosed in only one case. On review of the imaging, three arteries were missed because of human error and six due to technical limitations. Of the nine missed veins, only three were easily identified retrospectively. Overall, using MRI as a preoperative investigation for the 111 consecutive cases, the surgeon encountered a previously unidentified accessory artery in nine (8%), and this required anastomosis in four (4%). CONCLUSION: MR angiography has the advantage over computed tomography (CT) of having virtually no side-effects, and if the small possibility is accepted of missing extra vessels because of technical limitation or interpretation, it is a good investigation. However, in light of the failure to visualize all arteries transplanted, we have started to use multi-slice (16-channel) CT to see if its improved spatial resolution alters the results.

Assessment of response to therapy using conventional imaging.

The response of lymphoma to treatment is usually documented using cross-sectional imaging. The definitions of response and the changes seen on CT and MRI in the chest and abdomen are well recognised. However, the appearances of residual masses are more variable and features that may help in diagnosis will be included in this review.