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Introduction: The national focus on cancer has propelled the use of PET/CT for cancer imaging in Denmark. We believe that first-year experiences from a large PET centre may be of interest to new users., Material and Methods: Data from all scans made in the period from February 28 2006 to March 1 2007 with a single PET/CT scanner and 18F-fluoro-deoxyglucose (FDG) were collected prospectively along with information on action diagnosis, study purpose, etc. Referring departments indicated if PET/CT had changed or confirmed diagnosis, staging and treatment plan., Results: A total of 970 scans were made in 826 patients, 14% had 2-5 scans performed. Diagnostic CT was performed in 53%. In all, 792 referrals came from Odense University Hospital. Nearly 85% were from the specialities of oncology (31%), haematology (24%), surgery (14%), internal medicine (9%) and gynaecology (6%). PET/CT for primary diagnosis was mainly used in lung cancer and in cases with unknown primary tumour. In malignant lymphomas and colorectal cancer, the technique was mainly employed for response evaluation. Use of PET/CT for staging and recurrence was more evenly distributed across specialities. PET/CT changed the primary diagnosis in 16% and induced a change in staging and treatment plan in 28% to 32% of cases, respectively., Conclusion: FDG PET/CT was mainly used for diagnosis in lung cancer and in cases with an unknown primary tumour, and for response evaluation in lymphomas and colorectal cancer. PET/CT caused a change of staging and treatment plan in 25-33% of cases.

Objectives: To evaluate prospectively [(18)F]-fluorocholine positron-emission/computed tomography (FCH PET/CT) for lymph node staging of prostate cancer before intended curative therapy, and to determine whether imaging 15 or 60 min after radiotracer injection is preferable., Patients and Methods: In all, 25 consecutive patients with newly diagnosed prostate cancer (Gleason score >6, and/or a prostate-specific antigen level of >10 ng/mL, and/or T3 cancer) were scanned before lymphadenectomy. Each patient was assessed twice with imaging, at 15 and 60 min after the injection with FCH. Images were compared with the results of histopathological examination of the surgically removed lymph nodes. Maximum standardized uptake values (SUV(max) ) at 15 and 60 min were also compared., Results: Histopathologically, metastases were present in removed lymph nodes from three patients. FCH PET/CT showed a high radiotracer uptake in four patients, the former three and a fourth. The sensitivity, specificity, positive and negative predictive value of FCH PET/CT for patient based lymph node staging of prostate cancer were 100%, 95%, 75% and 100%, respectively; the corresponding 95% confidence intervals were 29.2-100%, 77.2-99.9%, 19.4-99.4% and 83.9-100%, respectively. Values of SUV(max) at early and late imaging were not significantly different., Conclusions: This small series supports the use of FCH PET/CT as a tool for lymph node staging of patients with prostate cancer. Values of SUV(max) at early and late imaging did not differ. However, larger prospective studies are needed to validate these findings., (© 2010 THE AUTHORS. JOURNAL COMPILATION © 2010 BJU INTERNATIONAL.)

Aims/hypothesis: The leading cause of death in type 2 diabetes is cardiovascular disease (CVD). We examined the prevalence of myocardial ischaemia in type 2 diabetes patients and tried to establish an algorithm to identify patients with a high risk of ischaemic heart disease., Methods: Type 2 diabetes patients who had no known or suspected CVD, and had been referred consecutively to a diabetes clinic for the first time (n=305; age 58.6+/-11.3 years; diabetes duration 4.5+/-5.3 years) were screened for myocardial ischaemia using myocardial perfusion scintigraphy (MPS)., Results: The univariate predictors of myocardial ischaemia were: atypical or typical angina pectoris, two or more traditional risk factors for CVD, BMI >32 kg/m2, systolic blood pressure >140 mmHg, HbA1c >8.5%, high-sensitivity C-reactive protein >4.0 mg/l, N-terminal pro-brain natriuretic peptide >300 pg/ml, left atrial volume index >32 ml/m2, left ventricular ejection fraction <50%, and carotid and peripheral arterial disease. The algorithm identified low (n=96), intermediate (n=65) and high risk groups (n=115), in which the prevalence of myocardial ischaemia was 15%,23% and 43%, respectively. Overall the algorithm reduced the number of patients referred to MPS from 305 to 144.However, the sensitivity and specificity of the algorithm was just 68% and 62%, respectively., Conclusions/interpretation: Our algorithm was able to stratify which patients had a low, intermediate or high risk of myocardial ischaemia based on MPS. However, the algorithm had low sensitivity and specificity, combined with high cost and time requirements., Trial Registration: clinicaltrials.gov NCT00298844 FUNDING: The study was funded by the Danish Cardio vascular Research Academy (DaCRA), The Danish Diabetes Association and The Danish Heart Foundation.

Background: Although type 2 diabetes mellitus is a risk factor for developing congestive heart failure, the mechanism leading to heart failure is unclear. We examined the prevalence of left ventricular (LV) systolic and diastolic dysfunction in patients with type 2 diabetes mellitus in relation to vascular function and myocardial perfusion., Methods and Results: A prospective observational study of 305 patients with type 2 diabetes mellitus (diabetes duration, 4.5+/-5.3 years) referred consecutively to a diabetes clinic were screened for LV systolic and diastolic function by echocardiography. Vascular function was estimated using noninvasive estimation of pulse pressure, carotid arterial compliance, total arterial compliance, and valvulo-arterial impedance. The prevalences of LV diastolic dysfunction and left atrial (LA) volume index >32 mL/m(2) were 40% and 32%, respectively. The prevalence of myocardial ischemia on myocardial perfusion scintigraphy was more frequent in patients with grade 2 diastolic dysfunction and LA volume index >32 mL/m(2) compared with those having normal or grade 1 diastolic dysfunction (P=0.002) or LA volume index < or =32 mL/m(2) (P<0.001), respectively. Predictors of grade 2 diastolic dysfunction and LA dilation were summed stress score on myocardial perfusion scintigraphy, total arterial compliance, and valvulo-arterial impedance, whereas pulse pressure and carotid arterial compliance were not, after adjusting for age, sex, and diabetes duration. On multivariable modeling, summed stress score (P<0.001) and valvulo-arterial impedance (P=0.027) remained predictors of grade 2 diastolic dysfunction, and only summed stress score (P<0.001) was a predictor of LA dilation., Conclusions: Abnormal LV filling is closely associated with abnormal myocardial perfusion on myocardial perfusion scintigraphy, whereas the association of LV filling with vascular function is less prominent.

Purpose: For certain cancer indications, the current patient evaluation strategy is a perfect but locally restricted gold standard procedure. If positron emission tomography/computed tomography (PET/CT) can be shown to be reliable within the gold standard region and if it can be argued that PET/CT also performs well in adjacent areas, then sample sizes in accuracy studies can be reduced., Procedures: Traditional standard power calculations for demonstrating sensitivities of both 80% and 90% are shown. The argument is then described in general terms and demonstrated by an ongoing study of metastasized prostate cancer., Results: An added value in accuracy of PET/CT in adjacent areas can outweigh a downsized target level of accuracy in the gold standard region, justifying smaller sample sizes., Conclusions: If PET/CT provides an accuracy benefit in adjacent regions, then sample sizes can be reduced and the conduct of trials accelerated, leading to earlier decisions on the use of PET/CT while exposing fewer patients and reducing overall costs.

Background: Cardiovascular disease (CVD) is the leading cause of death in type 2 diabetes mellitus (T2DM) patients. We examined the relationship between CVD in different vascular territories., Methods: T2DM patients without known or suspected CVD (n = 305) referred consecutively to a diabetes clinic for the first time and age-matched nondiabetic reference subjects (n = 40) were screened for myocardial ischemia, carotid, and peripheral arterial disease by means of myocardial perfusion scintigraphy, carotid artery ultrasonography, and peripheral ankle and toe systolic blood pressure measurements., Results: In the T2DM patients, the prevalence of myocardial ischemia, carotid, and peripheral arterial disease was 30%, 42%, and 15%, respectively, almost three times higher than in the reference subjects (P = 0.007, P = 0.001, and P = 0.09, respectively). T2DM patients with myocardial ischemia, carotid, or peripheral arterial disease had a significantly increased risk of CVD in other vascular territories as well (OR: 1.99, 2.09, and 3.09, respectively). However, 40%, 52%, and 22% of the T2DM patients with myocardial ischemia, carotid, or peripheral arterial disease demonstrated exclusively this particular type of CVD manifestation., Conclusions: In T2DM patients, signs of CVD in one vascular territory carry a significantly increased risk of CVD in other territories, although many patients only presented one manifestation.

Background: Fast and accurate staging is essential for choosing treatment for non-small-cell lung cancer (NSCLC). The purpose of this randomized study was to evaluate the clinical effect of combined positron-emission tomography and computed tomography (PET-CT) on preoperative staging of NSCLC., Methods: We randomly assigned patients who were referred for preoperative staging of NSCLC to either conventional staging plus PET-CT or conventional staging alone. Patients were followed until death or for at least 12 months. The primary end point was the number of futile thoracotomies, defined as any one of the following: a thoracotomy with the finding of pathologically confirmed mediastinal lymph-node involvement (stage IIIA [N2]), stage IIIB or stage IV disease, or a benign lung lesion; an exploratory thoracotomy; or a thoracotomy in a patient who had recurrent disease or death from any cause within 1 year after randomization., Results: From January 2002 through February 2007, we randomly assigned 98 patients to the PET-CT group and 91 to the conventional-staging group. Mediastinoscopy was performed in 94% of the patients. After PET-CT, 38 patients were classified as having inoperable NSCLC, and after conventional staging, 18 patients were classified thus. Sixty patients in the PET-CT group and 73 in the conventional-staging group underwent thoracotomy (P=0.004). Among these thoracotomies, 21 in the PET-CT group and 38 in the conventional-staging group were futile (P=0.05). The number of justified thoracotomies and survival were similar in the two groups., Conclusions: The use of PET-CT for preoperative staging of NSCLC reduced both the total number of thoracotomies and the number of futile thoracotomies but did not affect overall mortality. (ClinicalTrials.gov number, NCT00867412.), (2009 Massachusetts Medical Society)

Objectives: Coronary computed tomography angiography (CTA) has proven clinically useful for non-invasive assessment of coronary pathology. However, coronary calcium can reduce its diagnostic value. The objective of this study was to define a calcium score above which CTA appears less reliable., Design: We prospectively investigated 109 patients referred for elective coronary angiography (CA). With a 64-slice CT-scanner, coronary calcium was determined and expressed in Agatston unit (AU). A significant coronary stenosis was defined as > or =50% luminal diameter reduction. Following blinded interpretation, diagnostic values of CTA at different levels of AU were calculated using quantitative CA as reference., Results: A strong association with stent and the severity of coronary calcium was observed. In patients without stents (n = 91) sensitivity, specificity and positive and negative predictive value for presence of significant stenosis were: 100%, 91%, 74%, and 100% in patients with a calcium score < or =400 AU versus 100%, 17%, 75%, and 100% in patients with a score >400 AU., Conclusions: The diagnostic accuracy of CTA in patients with no or little coronary calcium is excellent. However, in patients with an Agatston score >400 specificity declines and therefore, these patients should not go on to CTA, but be referred to CA instead.

Objective: To evaluate the indium-111 ((111)In)-transferrin method as a means of localization and quantification of gastrointestinal protein loss., Methods: Fourteen patients and 15 healthy subjects underwent an (111)In-transferrin study consisting of abdominal scintigraphy, whole-body counting measurement and determination of plasma activity of (111)In during the course of 5 days. Two of the patients went through a subsequent chromium-51-trichloride test with analysis of radioactivity in faeces in order to compare the results of the two methods., Results: The patients had a mean +/-SEM whole-body loss of (111)In of 10.9+/-2.9% for 96 h, while the healthy controls lost 1.8+/-1.3% (p=0.0045). The decay in plasma activity followed biexponential kinetics. The characteristic plasma transit time was 5.0+/-1.0 h in patients and 12.1+/-1.5 h in controls (p=0.0007). Scintigraphically, patients had obvious abdominal foci of activity, while the control subjects showed diffuse activity. Anatomic localization of the leaking spot seemed more uncertain. By comparison with the (51)CrCl(3) test, the loss of radio-labelled protein appeared to be in the same order of magnitude., Conclusions: Quantification of gastrointestinal protein loss can be done without collecting faeces. Normal subjects have a loss of a few per cent, making the (111)In-transferrin method comparable with the former standard using (51)CrCl(3). Plasma measurements of (111)In are not predictive of the magnitude of the loss. Scintigraphic localization of the site of the loss needs to be optimized, for instance by serial imaging or image fusion with an anatomical modality.

In phase I oncology trials conducted over the past few decades, the maximum tolerated dose (MTD) has usually been estimated by the traditional escalation rule (TER), which traces back to 1973. In the meantime, new methods have been proposed which hope to estimate the true MTD more precisely than the TER while using less patients. In this simulation study, TER is compared with the accelerated titration dose design (ATD), two up-and-down designs (biased coin design, r-in-a-row (RIAR)), the maximum likelihood version of the continual reassessment method (CRML), and a Bayesian method that is implemented in the software Bayesian ADEPT (assisted decision-making in early phase trials). Each design was applied to 50,000 simulated studies. The designs were then compared for accuracy in detecting the true MTD (which is known here), while taking into account the average number of patients and toxicities per run. In terms of accuracy, ADEPT outperformed the other methods in the scenario with medium toxicity and was close to the best methods in the low and high toxic scenarios. The average number of patients needed per run was the lowest for TER in the scenario with low toxicity and for ADEPT in the remaining scenarios. The longer the escalation path to the target region of the MTD, the more the difference in the average number of patients per run pronounced between TER and ADEPT. TER induced least toxicities in all scenarios. ADEPT turned out to be quick and accurate in determining the MTD, while TER was the safest but least accurate method. CRML was as accurate as TER, and the up-and-down designs did not excel. Bayesian ADEPT is considered a valuable tool for the conduct of phase I dose-escalation trials in oncology, but careful preparation is indispensable before its practical use.

Objectives: When the combined diagnostic imaging technique PET/CT is considered promising with respect to diagnosis/staging of a certain cancer type, a systematic investigation by means of clinical diagnostic studies in the target population is necessary to evaluate the usefulness of PET/CT compared to the current standard. It is often difficult to decide in advance whether it is appropriate to plan a superiority or non-inferiority study. We propose a statistical analysis strategy which is flexible enough to cope with both aims alike., Methods: In opposition to clinical studies on drugs, each patient can be subjected to both PET/CT and the current standard, leading to paired observations of binary data (e.g., cancer = yes/no, stage = 0/1+). The analysis strategy focuses on point estimates and confidence intervals for the difference (or relative increase) in accuracy measures., Results: Formulas for approximate 95% confidence intervals for the differences in sensitivity, specificity, positive and negative predictive values between PET/CT and the standard procedures are given, respectively. The strategy can also be applied if results obtained with a golden standard are not available in patients in whom both PET/CT and the standard procedure gave negative results. Sample sizes can and should be determined in an adaptive manner., Conclusions: Diagnostic studies to assess the merit of PET/CT in the diagnostic work-up of cancer patients can and should start with phase II studies focusing on 95% confidence intervals for differences in diagnostic measures. Even if the gold standard procedure is incomplete, the statistical analysis strategy given here may still be applicable.