Islet transplantation is an attractive treatment for selected patients with brittle type 1 diabetes. In the clinical setting, intraportal transplantation predominates. However, due to extensive early islet cell death, the quantity of islets needed to restore glucose homeostasis requires in general a minimum of two donors. Moreover, the deterioration of islet function over time results in few insulin-independent patients after five-year followup. Specific obstacles to the success of islet transplantation include site-specific concerns for the liver such as the instant blood mediated inflammatory reaction, islet lipotoxicity, low oxygen tension, and poor revascularization, impediments that have led to the developing interest for alternative implantation sites over recent years. Within preclinical settings, several alternative sites have now been investigated and proven favorable in various aspects. Muscle is considered a very promising site and has physiologically properties and technical advantages that could make it optimal for islet transplantation.

A high percentage of unrecognized myocardial infarctions (UMIs) seen at delayed-enhanced magnetic resonance imaging (DE-MRI) are not detected by ECG. DE-MRI-detected UMIs are independent predictors of cardiovascular events in patients with coronary artery disease. In an elderly population, subjects with DE-MRI-detected UMIs do not have increased Framingham risk score or increased prevalence of artery stenosis in whole-body MR angiography as patients with recognized myocardial infarctions (RMI). Further investigation on the pathogenesis of DE-MRI-detected UMIs focus on the need to decide the management of these subjects.

From the Prospective Investigation of the Vasculature in Uppsala Seniors, 248 subjects underwent cardiac MRI at age 70 and from these, 185 underwent a 5-year follow-up MR. DE-MRI-detected UMIs had lower signal intensity than RMIs probably reflecting different composition of their tissues. Subjects with UMI scar had increased levels of NT-proBNP, a predictor of increased risk of cardiovascular events. After 5 years, UMI scars were in their majority seen on the same location and with the same size, and their prevalence increased. Subjects with an UMI did not differ from subjects without a scar in terms of coronary stenosis assessed by computed tomography angiography or signs of ischemia on exercise test.

In conclusion, DE-MRI-detected UMI scars are a frequent finding in an elderly population and its prevalence increases with age. The increased levels of NT-proBNP indicate that subjects with an UMI might have an increased rate of future cardiovascular events but the findings that these scars might have a different contrast distribution volume on MRI and that they are not related to CAD are indicators that they probably have a different etiology from RMIs. The prognosis of DE-MRI detected UMI scars in the general population is still unknown and therefore the clinical management of these individuals is yet to be defined.

Background:

We have previously discovered an unexpected high prevalence of unrecognized myocardial infarction (UMI) scars by delayed-enhanced magnetic resonance imaging (DE-MRI) in the general elderly population. We now investigated if those UMIs were associated with coronary artery disease (CAD).

Methods:

Eighty-eight subjects from the PIVUS study (age 75-years) who had been investigated with DE-MRI (45 with UMI and 43 without DE-MRI-detected scars) underwent coronary computed tomography angiography (CTA) to assess Agatston calcium score and coronary artery stenosis. Of those, 65 also performed an exercise ECG test.

Results:

No differences were found between the subjects with UMI and the group without DE-MRI-detected scars regarding the number of coronary artery segments with significant stenosis, Agatston calcium score, or degree of ST-depression at the exercise test.

Conclusion:

DE-MRI-detected UMI scars do not have an increased prevalence of coronary artery stenosis or signs of myocardial ischemia at exercise test when compared to a control group. These findings indicate that UMI scars in general are not related to CAD.

Endovascular implantation of stent grafts is currently considered the preferred treatment for many aortic pathologies. In Sweden, approximately 900 patients are treated with an aortic stent graft. Stent grafts consists of a metal stent which is manufactured in stainless steel or nitinol covered by a prosthetic graft material. The possibility to perform successful magnetic resonance imaging (MRI) of a patient depends on the metal composition of and the localisation of the stent graft. This article presents the most common types of stent grafts and how they affect patients’ possibility to undergo an MRI examination successfully.

Introduction

Perfusion magnetic resonance imaging (MRI) can be used in the pre-operative assessment of brain tumours. The aim of this prospective study was to identify the perfusion parameters from dynamic contrast-enhanced (DCE) and dynamic susceptibility contrast (DSC) perfusion imaging that could best discriminate between grade II and III gliomas.

Methods

MRI (3 T) including morphological ((T2 fluid attenuated inversion recovery (FLAIR) and T1-weighted (T1W)+Gd)) and perfusion (DCE and DSC) sequences was performed in 39 patients with newly diagnosed suspected low-grade glioma after written informed consent in this review board-approved study. Regions of interests (ROIs) in tumour area were delineated on FLAIR images co-registered to DCE and DSC, respectively, in 25 patients with histopathological grade II (n = 18) and III (n  = 7) gliomas. Statistical analysis of differences between grade II and grade III gliomas in histogram perfusion parameters was performed, and the areas under the curves (AUC) from the ROC analyses were evaluated.

Results

In DCE, the skewness of transfer constant (k _trans) was found superior for differentiating grade II from grade III in all gliomas (AUC 0.76). In DSC, the standard deviation of relative cerebral blood flow (rCBF) was found superior for differentiating grade II from grade III gliomas (AUC 0.80).

Conclusions

Histogram parameters from k _trans (DCE) and rCBF (DSC) could most efficiently discriminate between grade II and grade III gliomas.

BACKGROUND:

Adrenocortical carcinoma is a rare cancer that has a poor response to cytotoxic treatment.

METHODS:

We randomly assigned 304 patients with advanced adrenocortical carcinoma to receive mitotane plus either a combination of etoposide (100 mg per square meter of body-surface area on days 2 to 4), doxorubicin (40 mg per square meter on day 1), and cisplatin (40 mg per square meter on days 3 and 4) (EDP) every 4 weeks or streptozocin (streptozotocin) (1 g on days 1 to 5 in cycle 1; 2 g on day 1 in subsequent cycles) every 3 weeks. Patients with disease progression received the alternative regimen as second-line therapy. The primary end point was overall survival.

RESULTS:

For first-line therapy, patients in the EDP-mitotane group had a significantly higher response rate than those in the streptozocin-mitotane group (23.2% vs. 9.2%, P<0.001) and longer median progression-free survival (5.0 months vs. 2.1 months; hazard ratio, 0.55; 95% confidence interval [CI], 0.43 to 0.69; P<0.001); there was no significant between-group difference in overall survival (14.8 months and 12.0 months, respectively; hazard ratio, 0.79; 95% CI, 0.61 to 1.02; P=0.07). Among the 185 patients who received the alternative regimen as second-line therapy, the median duration of progression-free survival was 5.6 months in the EDP-mitotane group and 2.2 months in the streptozocin-mitotane group. Patients who did not receive the alternative second-line therapy had better overall survival with first-line EDP plus mitotane (17.1 month) than with streptozocin plus mitotane (4.7 months). Rates of serious adverse events did not differ significantly between treatments.

CONCLUSIONS:

Rates of response and progression-free survival were significantly better with EDP plus mitotane than with streptozocin plus mitotane as first-line therapy, with similar rates of toxic events, although there was no significant difference in overall survival.

Susac syndrome is an autoimmune microangiopathy affecting the brain, retina and inner ear (cochlea and semicircular canals), leading to encephalopathy, branch retinal artery occlusions (BRAOs) and asymmetric neurosensory hearing loss, respectively. The natural history and long-term prognosis are variable as the disease has been shown to be monophasic and self-limiting, polycyclic or chronic continuous. We describe a 35-year-old woman who presented with a sudden hearing loss in the left ear in the 37th week of her second pregnancy. She subsequently developed BRAO in the right eye 2.5 months after having given birth. MRI findings included round lesions in the corpus callosum which are pathognomonic for Susac syndrome. Previous patient records documented encephalopathy, sudden deafness of the right ear and visual field defects in the left eye at the age of 12, followed by permanent hearing and visual defects. We expand on the variability in the course of Susac syndrome as recurrence may occur after as long as 23 years. Cases of monophasic self-limiting Susac syndrome may in fact turn polycyclic with an interval of more than 2 decades between the bouts of the disease. In these cases, suspecting the development of exacerbation early is important in order to start the treatment promptly.

BACKGROUND:

Atrophy in the medial temporal lobe, frontal lobe and posterior cortex can be measured with visual rating scales such as the medial temporal atrophy (MTA), global cortical atrophy - frontal subscale (GCA-F) and posterior atrophy (PA) scales, respectively. However, practical cut-offs are urgently needed, especially now that different presentations of Alzheimer's disease (AD) are included in the revised diagnostic criteria.

AIMS:

The aim of this study was to generate a list of practical cut-offs for the MTA, GCA-F and PA scales, both for diagnosis of AD and determining prognosis in mild cognitive impairment (MCI), and to evaluate the influence of key demographic and clinical factors on these cut-offs.

METHODS:

AddNeuroMed and ADNI cohorts were combined giving a total of 1147 participants (322 AD patients, 480 MCI patients and 345 control subjects). The MTA, GCA-F and PA scales were applied and a broad range of cut-offs was evaluated.

RESULTS:

The MTA scale showed better diagnostic and predictive performances than the GCA-F and PA scales. Age, apolipoprotein E (ApoE) ε4 status and age at disease onset influenced all three scales. For the age ranges 45-64, 65-74, 75-84 and 85-94 years, the following cut-offs should be used. MTA: ≥1.5, ≥1.5, ≥2 and ≥2.5; GCA-F, ≥1, ≥1, ≥1 and ≥1; and PA, ≥1, ≥1, ≥1 and ≥1, respectively, with an adjustment for early-onset ApoE ε4 non-carrier AD patients (MTA: ≥2, ≥2, ≥3 and ≥3; and GCA-F: ≥1, ≥1, ≥2 and ≥2, respectively).

CONCLUSIONS:

If successfully validated in clinical settings, the list of practical cut-offs proposed here might be useful in clinical practice. Their use might also (i) promote research on atrophy subtypes, (ii) increase the understanding of different presentations of AD, (iii) improve diagnosis and prognosis and (iv) aid population selection and enrichment for clinical trials. This article is protected by copyright. All rights reserved.

Adult-onset ADLD with autonomic symptoms is a rare disease with a clinical course somewhat similar to chronic progressive MS but with different imaging findings consisting of extensive white matter changes in the cerebrum and cerebellar peduncles. Patients usually present in the fourth to sixth decade with autonomic symptoms, manifesting later symptoms from the pyramidal tracts and ataxia. Here, we present magnetic resonance spectroscopy (MRS) findings in this disease. Fourteen subjects, from two non-related families, with genetic linkage to the disease were studied with magnetic resonance imaging and single-voxel MRS. Clinically, they ranged from asymptomatic to wheelchair-using. Their results were compared to those of age- and sex-matched healthy controls. One MRS was excluded due to suboptimal quality. The remaining 13 subjects manifested characteristic evidence of pathology on MRI, 11 of them exhibited extensive changes. The metabolite concentrations of total Cr, total Cho, and total NAA measured in millimolars, using internal water as a reference, were significantly lower in these 11 subjects compared to controls, and we found linear correlations between all these metabolite levels. When total Cr was used as a reference, we found no difference between subjects and controls. No lactate was detected. The decreased metabolite concentrations measured using internal water as a reference are most likely due to increased water content in the tissues, diluting all metabolites to a similar degree. This is also in agreement with the high signal intensity exhibited in the white matter on T2-weighted MR images and with the reported histopathological findings of vacuolated myelin.

Somatostatin analogs and alpha-interferon induce good responses as single drugs in the treatment of endocrine pancreatic tumors. We examined the efficacy and tolerability of the combination of alpha-interferon and somatostatin analogs in 16 patients with metastatic endocrine pancreatic tumors. All patients except one had received prior treatment and were in a progressive state. Doses of alpha-interferon and somatostatin analogs were individually titrated. The alpha-interferon doses varied between 9 and 25 million units per week and were combined with 100-1500 microg of octreotide or 6000 microg of lanreotide daily. Radiological response was seen in 3 of 16 (19%) patients (median duration 23 mo). Biochemical response was seen in 10 of 16 (62.5%) patients (median duration 22 mo). All three patients previously progressing on both alpha-interferon and somatostatin analog as single drugs achieved a stabilization of the disease when treated with the combination (median duration 10 mo). Seven of eight (88%) patients previously progressing on alpha-interferon treatment benefited from the combination with biochemical partial response or stabilization. All six patients previously progressing during somatostatin analog treatment achieved biochemical partial response or stabilization. More than 80% of patients who progressed during previous treatment with either drug benefited from the combined treatment, which also was well tolerated. Thus, a combination of alpha-interferon and somatostatin analogs may be considered for patients previously progressing on treatment with alpha-interferon or somatostatin analogs. However, in this study, the value of sequential treatment has not been evaluated.

BACKGROUND AND OBJECTIVE: The prevalence of childhood obesity has risen considerably on a global scale during the past decades, and the condition is associated with increased risk of morbidity. The objective is to describe the Uppsala Longitudinal Study of Childhood Obesity (ULSCO) cohort, including some baseline data, and outline addressed research areas that aim at identifying factors implicated in and contributing to development of obesity and obesity-related diseases, including type 2 diabetes. METHODS: Severely obese and lean control subjects are examined at enrollment and at subsequent annual visits by using detailed questionnaires, anthropometric measurements, indirect calorimetry, and functional tests such as oral glucose tolerance tests. Some subjects undergo additional characterization with MRI, subcutaneous fat biopsies, frequent blood sampling, and hyperglycemic clamps. Biological samples are obtained and stored in a biobank. RESULTS: Active recruitment started in 2010, and standard operating procedures have been established. A high participation rate and annual follow-ups have resulted in a cohort exceeding 200 subjects, including 45 lean controls (as of October 2013). Initial research focus has been on traits of the metabolic syndrome, hyperinsulinemia and identifying risk factors for type 2 diabetes. CONCLUSIONS: The ULSCO cohort serves as an important resource in defining and understanding factors contributing to childhood obesity and development of obesity-related diseases. Given the comprehensive characterization of the cohort, factors contributing to disease development and progression can be identified. Such factors are further evaluated for their mechanistic role and significance, and noncommunicable metabolic diseases are especially addressed and considered.

Today, the diagnosis of metastatic breast cancer is usually based on radiological findings, and therapeutic decisions are made by considering the pathological characteristics and predictive markers of the primary tumour. Accumulating evidence suggests that tumour characteristics, including estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2), are unstable through tumour progression. Several retrospective studies and, recently, two prospective studies have investigated the discrepancies in receptor status between primary tumours and the corresponding metastases in a total of 1773 patients (for ER) and 2845 patients (for HER2). Changes in ER and HER2 status in these studies range from 14.5% to 40% and from 0% to 37.5%, respectively. In the two prospective studies, a different diagnosis, usually non-malignant, was obtained in 3% and 9% of the cases, and the biopsy led to a treatment modification in about one out of seven patients. Here, we review and discuss the currently available data and provide our recommendations on when a metastatic biopsy should be obtained.

Social anxiety disorder (SAD) is associated with altered brain function and structure, but most structural studies include small samples and findings are mixed. This study compared regional gray matter volume between 48 SAD patients and 29 healthy controls (HC) as well as the relationship between volume and symptom severity. Structural magnetic resonance images from SAD patients and HC were evaluated using standard voxel-based morphometry (VBM) processing in the SPM8 software package. Social anxiety symptom severity was rated in SAD patients by a clinician using the Liebowitz Social Anxiety Scale (LSAS). SAD patients had greater regional gray matter volume in the lingual gyrus and lateral occipital cortex than the controls, and within the SAD group a positive correlation was found between symptom severity and regional gray matter volume in the lingual gyrus and the retrosplenial cortex. These findings replicate and extend earlier reports of enlarged visual processing areas in SAD. Increased gray matter volume in regions involved in visual processing and self-consciousness could underlie, or be the result of, abnormal emotional information processing and self-focused attention previously demonstrated in patients with SAD.

Background Previous studies have demonstrated that magnetic resonance imaging may be a method of choice to visualize transplanted pancreatic islets. However, contrast agents may interfere with microcirculation and affect graft function. Purpose To evaluate the effects manganese-containing contrast media on regional blood flow and glucose tolerance. Material and Methods Anesthetized rats were injected intravenously with MnCl2 (10 mu M/kg body weight) or Mn-DPDP (Teslascan; 5 mu M/kg body weight). Blood flow measurements were made with a microsphere technique 10min later. In separate animals vascular arteriolar reactivity in isolated, perfused islets was examined. Furthermore, an intraperitoneal glucose tolerance test was performed in separate rats. Results Glucose tolerance was unaffected by both agents. No changes in regional blood flow were seen after administration of Mn-DPDP, except for an increase in arterial liver blood flow. MnCl2 increased all blood flow values except that of the kidney. MnCl2, but not Mn-DPDP, caused a vasoconstriction in isolated rat islet arterioles but only at very high doses. Conclusion Mn-DPDP administration does not affect glucose tolerance or regional blood flow, besides an increase in arterial hepatic blood flow, and may therefore be suitable for visualization of islets.

Background: Chronic Achilles tendinosis is a common problem. When evaluating and comparing different therapies there is a need for reliable imaging methods. Our aim was to evaluate if chronic Achilles tendinosis affects the dynamic contrast-enhancement in the tendon and its surroundings and if short-term eccentric calf-muscle training normalizes the dynamic contrast-enhancement. Methods: 20 patients with chronic Achilles tendinopathy were included. Median duration of symptoms was 31 months (range 6 to 120 months). Both Achilles tendons were examined with dynamic contrast enhanced MRI before and after a 12-week exercise programme of eccentric calf-muscle training. The dynamic MRI was evaluated in tendon, vessel and in fat ventrally of tendon. Area under the curve (AUC), time to peak of signal, signal increase per second (SI/s) and increase in signal between start and peak as a percentage (SI%) was calculated. Pain and performance were evaluated using a questionnaire. Results: In the fat ventrally of the tendon, dynamic contrast enhancement was significantly higher in the symptomatic leg compared to the contralateral non-symptomatic leg before but not after treatment. Despite decreased pain and improved performance there was no significant change of dynamic contrast enhancement in symptomatic tendons after treatment. Conclusion: In Achilles tendinosis there is an increased contrast enhancement in the fat ventrally of the tendon. The lack of correlation with symptoms and the lack of significant changes in tendon contrast enhancement parameters do however indicate that dynamic enhanced MRI is currently not a useful method to evaluate chronic Achilles tendinosis.

Favourable outcomes of peptide receptor radiotherapy (PRRT) of neuroendocrine tumours have been reported during the last years. Still, there are uncertainties on the radionuclides to be used, the treatment planning, and the indication in patients with a high proliferation rate. This case report describes a patient with a high tumour burden of poorly differentiated neuroendocrine carcinoma of unknown primary with a proliferation rate in liver metastases up to 50%, undergoing fractionated treatment with 7 cycles of Lu-177-DOTA-octreotate (7.4 GBq each) after disease progression on two different chemotherapy regiments. Based on initial staging scintigraphy, somatostatin receptor expression was very high. Longitudinal dosimetry studies during therapy indicated ongoing increases in tumour-to-organ ratios that coincided with an objective response. We conclude that fractionated therapy with Lu-177-DOTA-octreotate should be considered a treatment option also for those patients with large tumours, high proliferation, and high receptor expression.

Fractionated (177)Lu-DOTA-octreotate therapy has been reported to be an effective treatment option for patients with generalized neuroendocrine tumors. In our clinic, full individual dosimetry is performed during the first therapy cycle, while dosimetry at later cycles is based on the 24 h uptake measurement assuming an unchanged effective half-life. Our aim was to evaluate this assumption and the variation in the 24 h uptake during therapy. Patients. Thirty patients, 13 women and 17 men, were included in the study. Methods. During the first therapy cycle the (177)Lu-concentration was measured with SPECT/CT over the abdomen at 24 h, 96 h and 168 h after infusion. The effective half-life was determined for the kidneys, liver and spleen. The procedure was repeated at cycle 4 or 5. Results. The median ratio between the effective half-lives of the latter and the first cycle was 0.97 and 1.01 for the right and left kidney, with a range of 0.89-1.01 (1st-3rd quartile) and 0.93-1.05, respectively. Discussion. The mean value of the ratios was slightly lower than one, indicating a tendency towards increased activity elimination during therapy. In individual patients, significant changes were found for all organs, often when a large tumor burden reduction occurred during treatment. Possible contributing factors appeared to be larger amounts of non-tumor bound tracer, improved organ function (kidneys), decrease of vessel obstruction (spleen), less scatter from large tumors and reduction of small metastases (liver and spleen). Conclusion. With most patients it is safe to estimate absorbed doses to kidneys, liver and spleen from 24 h activity concentration assuming an unchanged effective half-life during therapy. Patients with risk factors for kidney dysfunction need to be monitored in more detail. Simplified dosimetry based on the assumption of unchanged effective half-life can function as guidance to the number of therapy cycles an individual patient can tolerate.

Neuroendocrine tumors (NET) are malignant solid tumors that arise in hormone-secreting tissue of the diffuse neuroendocrine system or endocrine glands. Although traditionally understood to be a rare disease, the incidence and prevalence of NET have increased greatly in the past 3 decades. However, during this time, progress in diagnosis and outcome of NET has generally been modest. In order to achieve improved outcome in NET, a better understanding of NET biology combined with more reliable serum markers and better techniques to identify tumor localization and small lesions are needed. Although some NET biomarkers exist, sensitive and specific markers that predict tumor growth and behavior are generally lacking. In addition, the integration of new molecular imaging technologies in patient diagnosis and follow-up has the potential to enhance care. To discuss developments and issues required to improve diagnostics and management of NET patients, with specific focus on the latest advances in molecular imaging and biomarker science, 17 global leaders in the fields of NET, molecular imaging and biomarker technology gathered to participate in a 2-day meeting hosted by Prof. Kjell Oberg at the University of Uppsala in Sweden. During this time, findings were presented regarding methods with potential prognostic and treatment applications in NET or other types of cancers. This paper describes the symposium presentations and resulting discussions.

Purpose

To test the hypothesis that a whole-body fat–water MRI (FWMRI) protocol acquired at 3 Tesla combined with semi-automated image analysis techniques enables precise volume and mass quantification of adipose, lean, and bone tissue depots that agree with static scale mass and scale mass changes in the context of a longitudinal study of large-breed dogs placed on an obesogenic high-fat, high-fructose diet.

Materials and Methods

Six healthy adult male dogs were scanned twice, at weeks 0 (baseline) and 4, of the dietary regiment. FWMRI-derived volumes of adipose tissue (total, visceral, and subcutaneous), lean tissue, and cortical bone were quantified using a semi-automated approach. Volumes were converted to masses using published tissue densities.

Results

FWMRI-derived total mass corresponds with scale mass with a concordance correlation coefficient of 0.931 (95% confidence interval = [0.813, 0.975]), and slope and intercept values of 1.12 and −2.23 kg, respectively. Visceral, subcutaneous and total adipose tissue masses increased significantly from weeks 0 to 4, while neither cortical bone nor lean tissue masses changed significantly. This is evidenced by a mean percent change of 70.2% for visceral, 67.0% for subcutaneous, and 67.1% for total adipose tissue.

Conclusion

FWMRI can precisely quantify and map body composition with respect to adipose, lean, and bone tissue depots. The described approach provides a valuable tool to examine the role of distinct tissue depots in an established animal model of human metabolic disease.

BACKGROUND:

Premenstrual dysphoric disorder (PMDD), characterized by luteal phase-induced negative affect and loss of impulse control, often results in compromised social interactions. Although amygdala activation is generally linked to negative affect, increased amygdala reactivity to aversive stimuli in the luteal phase has not been consistently reported in PMDD. We tested the hypothesis that amygdala hyper-reactivity in PMDD is symptom specific, rather than generalized, and linked to socially relevant stimuli. Blood oxygenation level dependent signal changes during exposure to negative images with social and non-social content were evaluated in the mid-follicular and late luteal phase of the menstrual cycle. Fourteen women with PMDD and 13 healthy controls participated.

RESULTS:

When compared with healthy controls, women with PMDD in the luteal phase had enhanced reactivity to social stimuli compared to non-social stimuli in the amygdala and insula, but attenuated reactivity in the anterior cingulate cortex. Functional couplings between emotion processing and controlling areas were significantly different, being positive in women with PMDD and negative in healthy controls. Changes in progesterone levels in women with PMDD correlated positively with altered amygdala reactivity.

CONCLUSIONS:

Socially relevant aversive stimulation elicited enhanced activity in affective processing brain regions that were functionally coupled to compromised activity in cognitive control areas. Because increased reactivity correlated positively with alterations in ovarian steroid levels, data preliminary support the hypothesis that enhanced progesterone sensitivity in PMDD affects corticolimbic processing of social emotions.

Premenstrual disorder (PMDD) affects around 5% of women in childbearing ages. An increased sensitivity in emotion processing areas of the brain to variations in ovarian steroid levels has been suggested as part of the pathophysiology in PMDD, but prior neuroimaging studies of emotion processing are yet inconclusive. Previous behavioral studies of women with PMDD have, however, reported enhanced luteal phase startle responsivity during emotional anticipation. Here we used functional magnetic resonance imaging (fMRI) to investigate central neural circuitry activity during anticipation of, and exposure to, emotional stimuli across the menstrual cycle in women with and without PMDD. As compared to healthy controls, women with PMDD displayed significantly enhanced reactivity in the prefrontal cortex during anticipation of, but not exposure to, negative emotional stimuli during the luteal phase. In PMDD patients, BOLD reactivity during anticipation or viewing of negative emotional stimuli was not dependent on absolute levels of estradiol or progesterone. However, progesterone levels were positively correlated with emotion-induced reactivity in the dorsolateral prefrontal cortex to positive emotional stimuli. These findings suggest that cortical emotional circuitry reactivity during anticipation is altered in PMDD during the luteal phase, which might be part of the pathophysiology behind the emotional symptoms or lack of emotional control reported by women with PMDD.

OBJECTIVE:

Most women on combined oral contraceptives (COC) report high levels of satisfaction, but 4-10% complain of adverse mood effects. The aim of this randomized, double-blinded, placebo-controlled trial was to investigate if COC use would induce more pronounced mood symptoms than placebo in women with previous history of COC-induced adverse mood. A second aim was to determine if COC use is associated with changes in brain reactivity in regions previously associated with emotion processing.

METHODS:

Thirty-four women with previous experience of mood deterioration during COC use were randomized to one treatment cycle with a levonorgestrel-containing COC or placebo. An emotional face matching task (vs. geometrical shapes) was administered during functional magnetic resonance imaging (fMRI) prior to and during the COC treatment cycle. Throughout the trial, women recorded daily symptom ratings on the Cyclicity Diagnoser (CD) scale.

RESULTS:

During the last week of the treatment cycle COC users had higher scores of depressed mood, mood swings, and fatigue than placebo users. COC users also had lower emotion-induced reactivity in the left insula, left middle frontal gyrus, and bilateral inferior frontal gyri as compared to placebo users. In comparison with their pretreatment cycle, the COC group had decreased emotion-induced reactivity in the bilateral inferior frontal gyri, whereas placebo users had decreased reactivity in the right amygdala.

CONCLUSION:

COC use in women who previously had experienced emotional side effects resulted in mood deterioration, and COC use was also accompanied by changes in emotional brain reactivity. These findings are of relevance for the understanding of how combined oral contraceptives may influence mood. Placebo-controlled fMRI studies in COC sensitive women could be of relevance for future testing of adverse mood effects in new oral contraceptives.

Premenstrual dysphoric disorder (PMDD) with luteal phase related anxiety and mood swings compromise quality of life in around 4% of reproductive women. While anxiety is related to amygdala function, prior studies on amygdala reactivity both in healthy controls and women with PMDD are inconsistent with respect to menstrual cycle effects. Here women with PMDD and healthy controls were exposed to emotional faces during the mid-follicular and late luteal phase, and mean blood-oxygen-level dependence (BOLD) signal changes in the amygdala were determined with functional magnetic resonance imaging (fMRI). Women with PMDD had enhanced bilateral amygdala reactivity in the follicular phase in comparison with healthy controls, but there was no difference between groups during the luteal phase. In contrast, healthy controls displayed higher left amygdala reactivity in the luteal than in their follicular phase. However, among women with PMDD follicular phase progesterone serum concentrations were positively correlated with bilateral amygdala reactivity while depression scores were positively correlated with right amygdala reactivity in the luteal phase. In addition, women with PMDD and high scores on trait anxiety had increased right amygdala reactivity in the luteal as compared to the follicular phase. Finally, amygdala reactivity was more prone to habituation in women with PMDD, as they had enhanced amygdala reactivity in comparison with controls at the first, but not the second scanning session. Thus, while the study failed to indicate increased luteal phase amygdala reactivity in women with PMDD, our findings suggest that anxiety proneness and progesterone levels modulate menstrual cycle related amygdala reactivity in women with PMDD.

Nude rats were injected with human colonic cancer cells (LS 174 T) in the superior mesenteric vein and the extent of hepatic metastases at sacrifice was estimated by visual inspection and computer-based area calculation. After 3 weeks, 5.0 x 10(6) cells caused hepatic metastases in 14/14 rats whereas 0.5 x 10(6) cells failed to produce liver metastases in 4/4 rats (P < 0.001). Injection of 1.0 x 10(7) cells caused portal vein occlusion in 3/5 rats. Extrahepatic tumour growth was rare; lung metastases were observed in four rats, and three rats had local tumour in the abdomen. The average extent of hepatic tumour replacement was 20.2 +/- 4.0%. Injection of embolies or single cells did not affect the incidence or extent of hepatic metastases. The incidence of hepatic metastases was similar in male and female rats, but the extent of hepatic tumour was larger in males (24.6%) than in females (3.2%) (P = 0.005). The pathophysiological similarities to human disease should make this model suitable for diagnostic and therapeutic studies with clinical application.

3.0Tesla magnetic resonance imaging (MRI) with diffusion-weighted imaging (DWI) was compared with combined 18F-fluorodeoxyglucose positron emission tomography and computed tomography (PET/CT) in patients with suspected bone metastases from breast cancer. A prospective clinical study was performed in 13 female breast cancer patients (mean age 61years; range 45-85 years). The spine was imaged in the sagittal plane with T1-weighted (T1), short tau inversion recovery (STIR), and T2-weighted fat-saturated (T2) sequences. The pelvis was imaged similarly in the coronal plane. Axial DWI was performed from the skull base to the mid-thigh. MRI and PET/CT were performed in all patients at a maximum interval of 10 working days and at least 14 days after chemotherapy. MRI was reviewed by two radiologists, and their consensus on potential metastases in 27 predefined locations was recorded. The predefined locations were the vertebral bodies (24), the left (1) and right (1) pelvic bones, and the sacral bone (1). The PET/CT was reviewed by a radiologists and a nuclear medicine physician. MRI detected 59 of the 60 active metastases found with our gold standard modality PET/CT. T1 had the highest sensitivity (98%) but rather low specificity (77%), but with the addition of STIR and DWI, the specificity increased to 95%. The additional metastases detected with MRI most likely represented postherapeutic residual scars without active tumour. In conclusion, 3.0Tesla MRI with T1, STIR, and DWI is useful for the clinical evaluation of bone metastases from breast cancer and compares well to PET/CT.

Aim: 

The aim of this study was to investigate whether patients with diverticulitis can be prioritised with higher urgency for a subsequent full colonic examination based upon the emergency abdominal computerised tomography (CT) at the time of presentation.

Method: 

All patients with a diagnosis of diverticulitis hospitalized during 2006 having CT on admission and a subsequent 'clean colon' examination were reviewed. The CT was reviewed by two independent and blinded senior radiologists (A and B) for signs inconsistent with diverticulitis and suggestive of malignancy. The patients were classified on CT into group 1 (normal findings, non-tumour pathology or benign polyps < 1 cm) and group 2 (benign polyps ≥ 1 cm and cancer).

Results: 

93 patients were reviewed with 83 in group 1and 10 in group 2. Radiologist A suggested high priority colonic examination in 18% and 50% of groups 1 and 2, and Radiologist B in 63% and 90%. There was a statically significant inter-observer difference and also lower accuracy of Radiologist B than Radiologist A in predicting a subsequent 'clean colon' examination.

Conclusion: 

Using an emergency acute CT scan at the time of diagnosis of diverticulitis to predict a clean colon examination for neoplasia is not reliable since there is considerable degree of inter-observer difference between rediologista.

INTRODUCTION: Parastomal hernia in patients with a permanent colostomy is common. The aim of this study was to evaluate the reliability of the diagnosis based on clinical examination and to compare this examination with the result of a specially designed questionnaire and computerised tomography (CT) scan. METHODS: Forty-one patients operated upon with an abdominoperineal resection due to rectal cancer at three hospitals between 1996 and 2002 were included. At minimum of 4 years after the operation, they underwent clinical examination by two or three independent surgeons, answered a colostomy questionnaire and were offered a CT scan of the abdominal wall. RESULT: At Hospital I, 17 patients were examined by three surgeons, with inter-observer kappa values between 0.35 and 0.64. At Hospital II, 13 patients were examined by three surgeons, the kappa values ranged between 0.29 and 0.43. At Hospital III, 11 patients were examined by two surgeons, with kappa value of 0.73. The kappa value between CT scan and the colostomy questionnaire was 0.45. CONCLUSION: The inter-observer reliability was low, indicating that parastomal hernia is difficult to diagnose by patient history and clinical examination. Some herniae may not be detected by CT scan, and the correlation to patient-reported complaints is low. A more sensitive radiological method to detect parastomal hernia is needed.

OBJECTIVE:

To compare endoanal ultrasound (EUS) with a 10-MHz probe vs. bodycoil magnetic resonance imaging (MRI) in the preoperative evaluation of anal fistula.

SUBJECTS AND METHODS:

23 patients with fistula in the anal region underwent preoperative 0.5 T bodycoil MRI and 10 MHz EUS which included probing in 6 patients. The results of the EUS and MRI were compared against the surgical findings as a reference method.

RESULTS:

In classification of the primary tract there was agreement between EUS and surgical findings in 14 (61%) and between MRI and surgery in 11 (48%). Concerning the presence of an internal opening the corresponding figures were 17 (74%) and 10 (43%) and in judging the presence of an extension or an abscess 15 (65%) vs. 11 (48%), respectively. In three out of eight patients with nonhealing or recurrence after surgery preoperative imaging had shown an extension and/or an abscess that was not identified by the surgeon.

CONCLUSION:

EUS, sometimes complemented with probing, is well comparable to bodycoil MRI in classifying and describing the topography of an anal fistula.

Histopathologic analysis of an anterior mediastinal mass of unknown origin is essential for treatment decision. Mediastinoscopy is the most common procedure performed to obtain biopsies, but general anaesthesia and hospitalization are necessary. The aim of this study was to evaluate whether transsternal core biopsies, an easy outpatient biopsy technique, could be an alternative to mediastinoscopy. A biopsy instrument that makes it possible to reach tumours hidden behind bone was used for transsternal CT-guided core biopsies in 21 patients with a newly diagnosed anterior mediastinal mass. No severe side effects were observed. In 19/21 (90%) patients the biopsies were diagnostic. In 2/21 patients additional biopsy techniques had to be used. In these two patients Hodgkin's disease was suspected in the first biopsy procedures. The diagnosis was confirmed by new core biopsies, from other parts of the tumour, not using a transsternal approach (transclavicular and parasternal, respectively). In addition, one mediastinoscopy was performed in a patient who was diagnosed with a non-Hodgkin's lymphoma but where more material was needed for lymphoma subclassification. It is concluded that CT-guided transsternal core biopsy is a clinically valuable method in patients with a newly diagnosed anterior mediastinal mass.

Context:

In diseases with increased PTH such as hyperparathyroidism and chronic renal failure, dementia is common. Little is known of PTH and dementia in the community.

Objective:

We sought to investigate relations between PTH, clinical dementia and cerebral micro-vascular disease.

Setting and Design:

The Uppsala Longitudinal Study Of Adult Men (ULSAM) was prospective, baseline, 1991-1995; followup, 15.8 years. The Prospective Investigation Of The Vasculature In Uppsala Seniors (PIVUS) was cross-sectional, baseline, 2001. Both settings were community based.

Participants and Main Outcome Measure:

In the ULSAM study of 998 men (age 71) the association between PTH and dementia was investigated. In the PIVUS study of 406 men and women (age 70) the relation between PTH and magnetic resonance imaging signs of cerebral small vascular disease was investigated.

Results:

During followup, 56 individuals were diagnosed with vascular, 91 with Alzheimer's, and 59 with other dementias. In Cox-regression analyses, higher PTH was associated with vascular dementia (hazard ratio per 1 SD increase of PTH, 1.41; P < .01), but not with other dementias. The top tertile of PTH accounted for 18.5% of the population-attributable risk for vascular dementia, exceeding all other risk factors. In linear regression analysis in PIVUS, PTH was associated with increasing white matter hyperintensities (WMHI), reflecting increasing burden of cerebral small vessel disease (1 SD PTH increase, 0.31 higher category of WMHI; P = .016). All models were adjusted for vascular risk factors and mineral metabolism.

Conclusions:

In two community-based samples, PTH predicted clinically diagnosed and neuroimaging indices of vascular dementia and cerebral small vessel disease. Our data suggest a role for PTH in the development of vascular dementia.

OBJECTIVE: Cardiovascular risk factors have different impact on different arterial territories. Diseases with elevated circulating parathyroid hormone (PTH) such as primary hyperparathyroidism and chronic renal failure have been shown to be associated with an increased risk of cardiovascular disease, predominantly heart or cerebrovascular diseases. However, data on the associations between circulating PTH and peripheral atherosclerosis are limited.

APPROACH AND RESULTS: Two prospective, community-based studies were used. In 306 men and women, who were 70 years old, from the Prospective investigation of the vasculature in Uppsala seniors (PIVUS) study, cross-sectional relations between PTH and atherosclerotic burden assessed by whole-body magnetic resonance angiography were investigated. In 998 men, who were 71 years old, from the Uppsala longitudinal study of adult men (ULSAM) study, the association between PTH concentration and risk of subsequent nonfatal atherosclerotic disease (excluding coronary or cerebrovascular disease) was investigated. Adjusting for established vascular risk factors, PTH was associated with burden of atherosclerosis (increase in total atherosclerotic score per SD PTH increase: 0.04, 0.003-0.08; P=0.03) in the PIVUS study. During follow-up in the ULSAM study (median 16.7 years), 89 men were diagnosed with nonfatal atherosclerotic disease. In Cox-regression analyses adjusting for established vascular risk factors and mineral metabolism, higher PTH was associated with an increased risk of nonfatal atherosclerotic disease (hazard ratio for 1 SD increase of PTH: 1.55, 1.33-1.88; P<0.0001). Results were similar when including fatal atherosclerotic disease in the outcome.

CONCLUSIONS: In 2 independent community-based cohorts, PTH was associated to the degree of atherosclerosis and risk of clinically overt atherosclerotic disease, respectively. Our data confirm and extend previous studies supporting a role for PTH in the development of atherosclerotic disease.

Due to broader use of conventional imaging techniques, adrenal tumors are detected with increasing frequency comprising a wide variety of different tumor entities. Despite improved conventional imaging techniques, a significant number of adrenal lesions remain that cannot be easily determined. A particular diagnostic challenge are lesions in patients with known extra-adrenal malignancy because these patients frequently harbor adrenal metastases. Furthermore, adrenal masses with low fat content and no detectable hormone excess are difficult to diagnose properly. Fine needle biopsy is invasive, often unsuccessful, and puts patients at risk, e. g., in cases of pheochromocytoma or adrenal cancer. Noninvasive characterization using radiotracers has therefore been established in recent years. ¹⁸F-FDG PET helps to differentiate benign from malignant lesions. However, it does not distinguish between adrenocortical or nonadrenocortical lesions (e.g., metastases or adrenocortical carcinoma). More recently, enzyme inhibitors have been developed as tracers for adrenal imaging. Metomidate is most widely used. It binds with high specificity and affinity to CYP11B enzymes of the adrenal cortex. As these enzymes are exclusively expressed in adrenocortical cells, uptake of labeled metomidate tracers has been shown to be highly specific for adrenocortical neoplasia. ¹¹C-metomidate PET and ¹²³I-iodometomidate SPECT imaging has been introduced into clinical use. Both tracers not only distinguish between adrenocortical and nonadrenocortical lesions but are also able to visualize metastases of adrenocortical carcinoma. The very specific uptake has recently led to first application of ¹³¹I-iodometomidate for radiotherapy in ACC. In conclusion, metomidate-based imaging is an important complementary tool to diagnose adrenal lesions that cannot be determined by other methods.

Introduction

Knee stiffness after total knee arthroplasty (TKA) impairs patient satisfaction and can necessitate mobilisation under anaesthesia (MUA). We investigated what factors predispose towards the need for MUA after TKA.

Patients and methods

The study population was extracted from our local arthroplasty register. Within the setting of a retrospective case/control study, we compared patients who underwent MUA after TKA (n = 35) with a randomly selected control group that did not need MUA after TKA (n = 122) using binary logistic regression analysis.

Results

We found that the risk of MUA due to flexion below 90° was increased in patients suffering from chronic obstructive pulmonary disease (COPD) with a risk ratio (RR) of 12 (95 % confidence interval [CI] 1.7–84, p = 0.01). Increasing age decreased the risk of developing stiffness with a RR of 0.88 (CI 0.81–0.95, p < 0.001) per year. Greater preoperative flexion decreased the risk of stiffness with a RR of 0.97 (CI 0.94–1.0, p  = 0.03) per degree of flexion. Gender, body mass index, medical and psychiatric comorbidities, rheumatoid arthritis, the Insall–Salvati index, and the increase in sagittal femoral diameter induced by prosthesis insertion did not significantly affect the risk of stiffness. A certain type of knee prosthesis (Natural Knee 2) was overrepresented among patients requiring MUA.

Discussion and conclusion

We conclude that stiffness after TKA is more frequent in younger patients and in those with limited preoperative flexion. It is also suggested that postoperative stiffness may be associated with COPD and with the choice of certain implants.  

BACKGROUND

Pseudotumors and immunologic alterations are reported in patients with elevated metal ion levels after resurfacing arthroplasty of the hip. A direct association of increased cobalt and chromium concentrations with the development of pseudotumors has not been established.

QUESTIONS/PURPOSE

 We hypothesized that (1) patients with higher blood cobalt and chromium concentrations are more likely to have pseudotumors develop, (2) elevated cobalt and chromium concentrations correlate with increased activation of defined T cell populations, and (3) elevated metal ion levels, small implant size, cup inclination angle, and patient age are risk factors for the development of pseudotumors.

METHODS

A single-surgeon cohort of 78 patients with 84 Articular Surface Replacement(®) implants was retrospectively investigated. Between 2006 and 2010, we performed 84 THAs using the Articular Surface Replacement(®) implant; this represented 2% (84/4950) of all primary hip replacements performed during that period. Of the procedures performed using this implant, we screened 77 patients (99%) at a mean of 43 months after surgery (range, 24-60 months). Seventy-one patients were investigated using ultrasound scanning, and cobalt and chromium concentrations in whole blood were determined by high-resolution inductively coupled plasma mass spectrometry. Differential analysis of lymphocyte subsets was performed by flow cytometry in 53 patients. Results of immunologic analyses were investigated separately for patients with and without pseudotumors. Pseudotumors were found in 25 hips (35%) and were more common in women than in men (p = 0.02). Multivariable regression analysis was performed to identify risk factors for the development of pseudotumors.

RESULTS

Cobalt and chromium concentrations were greater in patients with pseudotumors than in those without (cobalt, median 8.3 versus median 1.0 μg/L, p < 0.001; chromium, median 5.9 versus median 1.3 μg/L, p < 0.001). The percentage of HLA-DR(+)CD4(+) T cells was greater in patients with pseudotumors than in those without (p = 0.03), and the proportion of this lymphocyte subtype was positively correlated with cobalt concentrations (r = 0.3, p = 0.02). Multivariable regression analysis indicated that increasing cobalt levels were associated with the development of pseudotumors (p < 0.001), and that patients with larger implants were less likely to have them develop (p = 0.04); age and cup inclination were not risk factors.

CONCLUSIONS

We found a distinct association of elevated metal ion concentrations with the presence of pseudotumors and a correlation of increased cobalt concentrations with the proportion of activated T helper/regulator cells. Thus, the development of soft tissue masses after metal-on-metal arthroplasty could be accompanied by activation of T cells, indicating that this complication may be partly immunologically mediated. Further investigations of immunologic parameters in larger cohorts of patients with metal-on-metal arthroplasties are warranted.

LEVEL OF EVIDENCE

Level III, therapeutic study. See the Instructions for Authors for a complete description of levels of evidence.

Context: IGF-I and IGF binding protein-3 (IGFBP-3) are essential for growth and maturation of the developing brain. Objective: The aim of this study was to evaluate the association between postnatal serum concentrations of IGF-I and IGFBP-3 and brain volumes at term in very preterm infants. Design: Fifty-one infants with a mean (sd) gestational age (GA) of 26.4 (1.9) wk and birth weight (BW) of 888 (288) g were studied, with weekly blood sampling of IGF-I and IGFBP-3 from birth until 35 gestational weeks (GW) and daily calculation of protein and caloric intake. Magnetic resonance images obtained at 40 GW were segmented into total brain, cerebellar, cerebrospinal fluid, gray matter, and unmyelinated white matter volumes. Main Outcome Measures: We evaluated brain growth by measuring brain volumes using magnetic resonance imaging. Results: Mean IGF-I concentrations from birth to 35 GW correlated with total brain volume, unmyelinated white matter volume, gray matter volume, and cerebellar volume [r = 0.55 (P < 0.001); r = 0.55 (P < 0.001); r = 0.44 (P = 0.002); and r = 0.58 (P < 0.001), respectively]. Similar correlations were observed for IGFBP-3 concentrations. Correlations remained after adjustment for GA, mean protein and caloric intakes, gender, severe brain damage, and steroid treatment. Protein and caloric intakes were not related to brain volumes. Infants with BW small for GA had lower mean concentrations of IGF-I (P = 0.006) and smaller brain volumes (P = 0.001-0.013) than infants with BW appropriate for GA. Conclusion: Postnatal IGF-I and IGFBP-3 concentrations are positively associated with brain volumes at 40 GW in very preterm infants. Normalization of the IGF-I axis, directly or indirectly, may support normal brain development in very preterm infants.

Diagnosis of new bone growth in patients with compound tibia fractures or deformities treated using a Taylor spatial frame is difficult with conventional radiography because the frame obstructs the images and creates artifacts. The use of Na¹⁸F PET studies may help to eliminate this difficulty.

Methods:

Patients were positioned on the pallet of a clinical PET/CT scanner and made as comfortable as possible with their legs immobilized. One bed position covering the site of the fracture, including the Taylor spatial frame, was chosen for the study. A topogram was performed, as well as diagnostic and attenuation correction CT. The patients were given 2 MBq of Na¹⁸F per kilogram of body weight. A 45-min list-mode acquisition was performed starting at the time of injection, followed by a 5-min static acquisition 60 min after injection. The patients were examined 6 wk after the Taylor spatial frame had been applied and again at 3 mo to assess new bone growth.

Results:

A list-mode reconstruction sequence of 1 × 1,800 and 1 × 2,700 s, as well as the 5-min static scan, allowed visualization of regional bone turnover.

Conclusion:

With Na¹⁸F PET/CT, it was possible to confirm regional bone turnover as a means of visualizing bone remodeling without the interference of artifacts from the Taylor spatial frame. Furthermore, dynamic list-mode acquisition allowed different sequences to be performed, enabling, for example, visualization of tracer transport from blood to the fracture site.

Anthracyclines and taxanes are active cytotoxic drugs in the treatment of early metastatic breast cancer. It is yet unclear whether addition of capecitabine to the combination of these drugs improves the treatment outcome. Patients with advanced breast cancer were randomized to first-line chemotherapy with a combination of epirubicin (Farmorubicin(A (R))) and paclitaxel (Taxol(A (R))) alone (ET) or in combination with capecitabine (Xeloda(A (R)), TEX). Starting doses for ET were epirubicin 75 mg/m(2) plus paclitaxel 175 mg/m(2), and for TEX epirubicin 75 mg/m(2), paclitaxel 155 mg/m(2), and capecitabine 825 mg/m(2) BID for 14 days. Subsequently, doses were tailored related to side effects. Primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), time to treatment failure (TTF), objective response (OR), safety and quality of life (QoL). 287 patients were randomized, 143 to ET and 144 to TEX. Median PFS was 10.8 months for patients treated with ET, and 12.4 months for those treated with TEX (HR 0.84, 95% CI 0.65-1.07, P = 0.16); median OS was 26.0 months for women in the ET versus 29.7 months in the TEX arm (HR 0.84, 95% CI 0.63-1.11, P = 0.22). OR was achieved in 44.8% (ET) and 54.2% (TEX), respectively (chi(2) 3.66, P = 0.16). TTF was significantly longer for patients treated with TEX, 6.0 months, versus 5.2 months following ET (HR 0.73, 95% CI 0.58-0.93, P = 0.009). Severe hematological side effects related to epirubicin and paclitaxel were evenly distributed between the treatment arms, mucositis, diarrhea, and Hand-Foot syndrome were significantly more frequent in the TEX arm. Toxicity-adjusted treatment with ET and TEX showed similar efficacy in terms of PFS, OS, and OR. In this trial with limited power, the addition of capecitabine to epirubicin and paclitaxel as first-line treatment did not translate into clinically relevant improvement of the outcome.

Bladder tumor is the most common tumor detected in patients presenting with gross hematuria. Early detection and treatment is crucial for good prognosis, however, delay in diagnosis and treatment is common. Routine work-up of gross hematuria includes cystoscopy and Computed Tomography Urography (CTU). If CTU has a high detection rate of bladder tumor, it can be used to direct further investigation of the patient, hopefully reducing delay to diagnosis and treatment. There is no consensus on which phase the bladder should be assessed at CTU. Assessment of the bladder in an early contrast-enhancing phase requires contrast material enhancement in bladder tumors and a bladder that is properly distended with urine. For patients younger than 50 years, the routine CTU protocol used for examining gross hematuria patients included unenhanced (UE), corticomedullary phase (CMP), and excretory phase (EP), with the start of the scan being enhancement triggered: patients aged 50 years or older followed the same protocol plus a nephrographic phase (NP).

The CTU protocol was compared with flexible cystoscopy for detecting bladder tumors. Sensitivity for bladder cancer detection was equal for CTU and cystoscopy (0.87).

Patients diagnosed with bladder cancer (n=50) were examined during UE, CMP, and EP, and 21 patients were additionally examined in NP. The highest mean tumor contrast enhancement was seen in CMP (37 HU).

The CMP, NP, and EP in 106 patients were randomized into an evaluation order (n=318 different phases) and blindly reviewed by two uroradiologists. In CMP, sensitivity (0.95) and negative predictive value (0.99) were higher than in NP and EP.

Four different preparation protocols for achieving bladder distension were compared. The protocol that included drinking 1 l of fluid during a two-hour period prior to examination without voiding during that period, gave satisfactory bladder distension without causing unacceptable patient discomfort and having the lowest compliance.

Gross hematuria patients should be primarily examined with CTU including UE, CMP and EP to direct further investigation of the patients. The patients should follow a preparation protocol including drinking 1 l of fluid during a two-hour period before examination and not voiding during that period.