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Purpose: To compare the diagnostic yields of a radiologist and trained technologists in the detection of advanced neoplasia within a population-based computed tomographic (CT) colonography screening program., Materials and Methods: Ethical approval was obtained from the Dutch Health Council, and written informed consent was obtained from all participants. Nine hundred eighty-two participants (507 men, 475 women) underwent low-dose CT colonography after noncathartic bowel preparation (iodine tagging) between July 13, 2009, and January 21, 2011. Each scan was evaluated by one of three experienced radiologists (≥800 examinations) by using primary two-dimensional (2D) reading followed by secondary computer-aided detection (CAD) and by two of four trained technologists (≥200 examinations, with colonoscopic verification) by using primary 2D reading followed by three-dimensional analysis and CAD. Immediate colonoscopy was recommended for participants with lesions measuring at least 10 mm, and surveillance was recommended for participants with lesions measuring 6-9 mm. Consensus between technologists was achieved in case of discordant recommendations. Detection of advanced neoplasia (classified by a pathologist) was defined as a true-positive (TP) finding. Relative TP and false-positive (FP) fractions were calculated along with 95% confidence intervals (CIs)., Results: Overall, 96 of the 982 participants were referred for colonoscopy and 104 were scheduled for surveillance. Sixty of 84 participants (71%) referred for colonoscopy by the radiologist had advanced neoplasia, compared with 55 of 64 participants (86%) referred by two technologists. Both the radiologist and technologists detected all colorectal cancers (n = 5). The relative TP fraction (for technologists vs radiologist) for advanced neoplasia was 0.92 (95% CI: 0.78, 1.07), and the relative FP fraction was 0.38 (95% CI: 0.21, 0.67)., Conclusion: Two technologists serving as a primary reader of CT colonographic images can achieve a comparable sensitivity to that of a radiologist for the detection of advanced neoplasia, with far fewer FP referrals for colonoscopy., (© RSNA, 2012)

Sarcoidosis is a multisystem disorder of unknown cause with a highly variable course. Corticosteroids are considered the standard agent for treatment, however there is no consensus about when and in whom therapy should be initiated, what dose should be given and for how long. There seems to be a limited benefit on chest radiographic findings, forced vital capacity and diffusing capacity. The evidence supporting the disease-modulating effect is limited. Cytotoxic agents are often used as steroid-sparing in patients requiring chronic therapy, however there are only little randomized controlled trials to support their use and side effects are common. Tumour necrosis factor-a is thought to be crucial in the development of the typical granulomas in sarcoidosis. Many case reports and case series suggest that specific therapy targeted against this cytokine is very effective. Despite these promising results, only limited evidence is found in multicenter randomized controlled trials.

Background: Screening for colorectal cancer is widely recommended, but the preferred strategy remains unidentified. We aimed to compare participation and diagnostic yield between screening with colonoscopy and with non-cathartic CT colonography., Methods: Members of the general population, aged 50-75 years, and living in the regions of Amsterdam or Rotterdam, identified via the registries of the regional municipal administration, were randomly allocated (2:1) to be invited for primary screening for colorectal cancer by colonoscopy or by CT colonography. Randomisation was done per household with a minimisation algorithm based on age, sex, and socioeconomic status. Invitations were sent between June 8, 2009, and Aug 16, 2010. Participants assigned to CT colonography who were found to have one or more large lesions (≥10 mm) were offered colonoscopy; those with 6-9 mm lesions were offered surveillance CT colonography. The primary outcome was the participation rate, defined as number of invitees undergoing the examination relative to the total number of invitees. Diagnostic yield was calculated as number of participants with advanced neoplasia relative to the total number of invitees. Invitees and screening centre employees were not masked to allocation. This trial is registered in the Dutch trial register, number NTR1829., Findings: 1276 (22%) of 5924 colonoscopy invitees participated, compared with 982 (34%) of 2920 CT colonography invitees (relative risk [RR] 1·56, 95% CI 1·46-1·68; p<0·0001). Of the participants in the colonoscopy group, 111 (9%) had advanced neoplasia of whom seven (<1%) had a carcinoma. Of CT colonography participants, 84 (9%) were offered colonoscopy, of whom 60 (6%) had advanced neoplasia of whom five (<1%) had a carcinoma; 82 (8%) were offered surveillance. The diagnostic yield for all advanced neoplasia was 8·7 per 100 participants for colonoscopy versus 6·1 per 100 for CT colonography (RR 1·46, 95% CI 1·06-2·03; p=0·02) and 1·9 per 100 invitees for colonoscopy and 2·1 per 100 invitees for CT colonography (RR 0·91, 0·66-2·03; p=0·56). The diagnostic yield for advanced neoplasia of 10 mm or more was 1·5 per 100 invitees for colonoscopy and 2·0 per 100 invitees for CT colonography, respectively (RR 0·74, 95% CI 0·53-1·03; p=0·07). Serious adverse events related to the screening procedure were post-polypectomy bleedings: two in the colonoscopy group and three in the CT colonography group., Interpretation: Participation in colorectal cancer screening with CT colonography was significantly better than with colonoscopy, but colonoscopy identified significantly more advanced neoplasia per 100 participants than did CT colonography. The diagnostic yield for advanced neoplasia per 100 invitees was similar for both strategies, indicating that both techniques can be used for population-based screening for colorectal cancer. Other factors such as cost-effectiveness and perceived burden should be taken into account when deciding which technique is preferable., Funding: Netherlands Organisation for Health Research and Development, Centre for Translational Molecular Medicine, and the Nuts Ohra Foundation., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Rationale: Forced vital capacity (FVC) is an established measure of pulmonary function in idiopathic pulmonary fibrosis (IPF). Evidence regarding its measurement properties and minimal clinically important difference (MCID) in this population is limited., Objectives: To assess the reliability, validity, and responsiveness of FVC and estimate the MCID in patients with IPF., Methods: The study population included all 1,156 randomized patients in two clinical trials of IFN-γ1b. FVC and other measures of functional status were measured at screening or baseline and 24-week intervals thereafter. Reliability was assessed based on two proximal measures of FVC, validity was assessed based on correlations between FVC and other measures of functional status, and responsiveness was assessed based on the relationship between 24-week changes in FVC and other measures of functional status. Distribution-based and anchor-based methods were used to estimate the MCID., Measurements and Main Results: Correlation of percent-predicted FVC between measurements (mean interval, 18 d) was high (r = 0.93; P < 0.001). Correlations between FVC and other parameters were generally weak, with the strongest observed correlation between FVC and carbon monoxide diffusing capacity (r = 0.38; P < 0.001). Correlations between change in FVC and changes in other parameters were slightly stronger (range, r = 0.16-0.37; P < 0.001). Importantly, 1-year risk of death was more than twofold higher (P < 0.001) in patients with a 24-week decline in FVC between 5% and 10%. The estimated MCID was 2-6%., Conclusions: FVC is a reliable, valid, and responsive measure of clinical status in patients with IPF, and a decline of 2-6%, although small, represents a clinically important difference.

Purpose: To assess the maximum tolerated dose (MTD)/dose-limiting toxicities (DLT), safety, pharmacokinetics, and pharmacodynamics of tivozanib, a potent and selective oral VEGF receptor (VEGFR) tyrosine kinase inhibitor., Experimental Design: Dose levels of 1.0, 1.5, and 2.0 mg/d tivozanib for 28 days followed by 14 days of medication were explored in patients with advanced solid tumors., Results: Forty-one patients were enrolled. Animal data incorrectly predicted toxicity, resulting in DLTs at the starting dose (2.0 mg) consisting of grade 3 proteinuria and hypertension and grade 3 ataxia. At 1.0 mg, no DLT was observed. At an intermediate dose (1.5 mg), 1 patient experienced DLT consisting of grade 3 hypertension. This dose was determined as the MTD. Of 10 additional patients treated at 1.5 mg, 1 patient each experienced grade 3 hypertension and grade 3 fatigue, and 2 patients experienced grade 3 and 4 transaminase elevation. In 12 additional patients treated at 1.0 mg, no DLT was observed. Pharmacokinetics displayed long absorption time, dose proportional exposure, and a half-life of 4.7 days. Plasma levels of VEGF-A and soluble VEGFR-2 showed dose-dependent increases and decreases, respectively. Dynamic contrast-enhanced MRI indicated reduction in tumor perfusion. Clinical activity was observed in renal cell cancer, colorectal cancer, and other tumors., Conclusion: Tivozanib was well tolerated with manageable side effects. The pharmacokinetics profile revealed that tivozanib was suitable for once-daily dosing. Encouraging and durable clinical activity was observed. The recommended daily dose of tivozanib in a 4-week-on and 2-week-off dosing regimen is 1.5 mg.

Purpose of Review: This review critically discusses recent advances in the treatment of idiopathic pulmonary fibrosis (IPF). Moreover, it also focuses on the practical approach of a patient diagnosed with IPF and uncovers challenges for the future., Recent Findings: Treatment can be divided into three major parts. Firstly, many new agents have been tested, but only the combination of N-acetylcysteine with corticosteroids, azathioprine and pirfenidone was able to show some significant effects. In the mean time, many second-generation agents are under development. Lung transplantation has made some major progress by introducing an appropriate allocation system. Finally, as part of best supportive care, several studies show that pulmonary rehabilitation might induce some important effects on quality of life., Summary: So, it is clear that major progress has been made in the treatment of IPF, but we are convinced that an orchestrated effort will lead to a better understanding and treatment of this devastating condition.

Rationale: Several predictors of mortality in patients with idiopathic pulmonary fibrosis have been described; however, there is a need for a practical and accurate method of quantifying the prognosis of individual patients., Objectives: Develop a practical mortality risk scoring system for patients with idiopathic pulmonary fibrosis., Methods: We used a Cox proportional hazards model and data from two clinical trials (n = 1,099) to identify independent predictors of 1-year mortality among patients with idiopathic pulmonary fibrosis. From the comprehensive model, an abbreviated clinical model comprised of only those predictors that are readily and reliably ascertained by clinicians was derived. Beta coefficients for each predictor were then used to develop a practical mortality risk scoring system., Measurements and Main Results: Independent predictors of mortality included age, respiratory hospitalization, percent predicted FVC, 24-week change in FVC, percent predicted carbon monoxide diffusing capacity, 24-week change in percent predicted carbon monoxide diffusing capacity, and 24-week change in health-related quality of life. An abbreviated clinical model comprising only four predictors (age, respiratory hospitalization, percent predicted FVC, and 24-wk change in FVC), and the corresponding risk scoring system produced estimates of 1-year mortality risk consistent with observed data (9.9% vs. 9.7%; C statistic = 0.75; 95% confidence interval, 0.71–0.79)., Conclusions: The prognosis for patients with idiopathic pulmonary fibrosis may be accurately determined using four readily ascertainable predictors. Our simplified scoring system may be a valuable tool for determining prognosis and guiding clinical management. Additional research is needed to validate the applicability and accuracy of the scoring system.

Rationale: The 6-minute-walk test (6MWT) is a practical and clinically meaningful measure of exercise tolerance with favorable performance characteristics in various cardiac and pulmonary diseases. Performance characteristics in patients with idiopathic pulmonary fibrosis (IPF) have not been systematically evaluated., Objectives: To assess the reliability, validity, and responsiveness of the 6MWT and estimate the minimal clinically important difference (MCID) in patients with IPF., Methods: The study population included all subjects completing a 6MWT in a clinical trial evaluating interferon gamma-1b (n = 822). Six-minute walk distance (6MWD) and other parameters were measured at baseline and at 24-week intervals using a standardized protocol. Parametric and distribution-independent correlation coefficients were used to assess the strength of the relationships between 6MWD and measures of pulmonary function, dyspnea, and health-related quality of life. Both distribution-based and anchor-based methods were used to estimate the MCID., Measurements and Main Results: Comparison of two proximal measures of 6MWD (mean interval, 24 d) demonstrated good reliability (coefficient = 0.83; P < 0.001). 6MWD was weakly correlated with measures of physiologic function and health-related quality of life; however, values were consistently and significantly lower for patients with the poorest functional status, suggesting good construct validity. Importantly, change in 6MWD was highly predictive of mortality; a 24-week decline of greater than 50 m was associated with a fourfold increase in risk of death at 1 year (hazard ratio, 4.27; 95% confidence interval, 2.57- 7.10; P < 0.001). The estimated MCID was 24-45 m., Conclusions: The 6MWT is a reliable, valid, and responsive measure of disease status and a valid endpoint for clinical trials in IPF.

Aim: The aim of this study was to investigate sensitivity of 67Ga imaging and 18F-FDG PET for sarcoidosis activity and their inter observer variability., Methods: Thirty-four newly diagnosed, histologically proven sarcoidosis patients were analyzed prospectively. (67)Ga imaging and (18)F-FDG PET were performed, the presence of pulmonary and extra pulmonary lesions was evaluated and inter observer variability of both techniques was assessed., Results: Overall sensitivity to detect active sarcoidosis was 88% for (67)Ga imaging and 97% for (18)F-FDG PET. Although these results were not significantly different, 18F-FDG PET detected more lesions in the mediastinum (P<0.05), hila (P<0.05), lymph nodes (P<0.001) and extra pulmonary regions in general (P<0.001). Inter observer agreement was poor to moderate for (67)Ga imaging (kappa 0.19-0.59) and good to very good for (18)F-FDG PET (kappa 0.65-1.00)., Conclusion: (18)F-FDG PET is more sensitive than (67)Ga imaging in the assessment of sarcoidosis activity with regard to the mediastinum, hila, lymph nodes and extra pulmonary lesions in general. Furthermore, (18)F-FDG PET demonstrates a very good inter observer agreement in contrast with (67)Ga imaging and (18)F-FDG PET is therefore the nuclear imaging technique of choice in sarcoidosis assessment.

Idiopathic pulmonary fibrosis (IPF) is a devastating disease without proper treatment. Despite intensive research, the exact underlying pathogenesis remains elusive. It is regarded as a continuous injury, resulting in inflammation, infiltration, and proliferation of fibroblasts and extracellular matrix deposition, leading to an irreversible restrictive lung function deterioration and death. In this study the effect of azithromycin, a macrolide antibiotic on bleomycin-induced pulmonary fibrosis was investigated. C57BL/6 mice were intratracheally instilled with bleomycin (0.5 mg/kg) or saline. In the bleomycin group, half of the animals received azithromycin every other day from day 1 on. Bronchoalveolar lavage and histology were performed at days 7 and 35, and pulmonary function tests on day 35. At day 35, fibrotic lesions (spindle cell proliferation/collagen I deposition) were paralleled by a restrictive lung function pattern. Alterations were found in neutrophils and macrophages (innate immunity) and in T(H)2, T(H)17, and Treg cytokines (adaptive immunity). Azithromycin significantly reduced both fibrosis and the restrictive lung function pattern. This study demonstrated a beneficial effect of azithromycin on bleomycin-induced pulmonary fibrosis. A possible mechanism could be a modulation of both innate immunity and adaptive immunity. These findings might suggest a potential role for azithromycin in the treatment of IPF.

Background: Biologic predictors or biomarkers of survival in pulmonary fibrosis with a worse prognosis, more specifically in idiopathic pulmonary fibrosis would help the clinician in deciding whether or not to treat since treatment carries a potential risk for adverse events. These decisions are made easier if accurate and objective measurements of the patients' clinical status can predict the risk of progression to death., Method: A literature review is given on different biomarkers of survival in interstitial lung disease, mainly in IPF, since this disease has the worst prognosis., Conclusion: Serum biomarkers, and markers measured by medical imaging as HRCT, pertechnegas, DTPA en FDG-PET are not ready for clinical use to predict mortality in different forms of ILD. A baseline FVC, a change of FVC of more than 10%, and change in 6MWD are clinically helpful predictors of survival.

Background: Colorectal cancer (CRC) is the second most prevalent type of cancer in Europe. Early detection and removal of CRC or its precursor lesions by population screening can reduce mortality. Colonoscopy and computed tomography colonography (CT colonography) are highly accurate exams and screening options that examine the entire colon. The success of screening depends on the participation rate. We designed a randomized trial to compare the uptake, yield and costs of direct colonoscopy population screening, using either a telephone consultation or a consultation at the outpatient clinic, versus CT colonography first, with colonoscopy in CT colonography positives., Methods and Design: 7,500 persons between 50 and 75 years will be randomly selected from the electronic database of the municipal administration registration and will receive an invitation to participate in either CT colonography (2,500 persons) or colonoscopy (5,000 persons) screening. Those invited for colonoscopy screening will be randomized to a prior consultation either by telephone or a visit at the outpatient clinic. All CT colonography invitees will have a prior consultation by telephone. Invitees are instructed to consult their general practitioner and not to participate in screening if they have symptoms suggestive for CRC. After providing informed consent, participants will be scheduled for the screening procedure. The primary outcome measure of this study is the participation rate. Secondary outcomes are the diagnostic yield, the expected and perceived burden of the screening test, level of informed choice and cost-effectiveness of both screening methods., Discussion: This study will provide further evidence to enable decision making in population screening for colorectal cancer., Trial Registration: Dutch trial register: NTR1829.

Background: The randomized placebo-controlled IFIGENIA-trial demonstrated that therapy with high-dose N-acetylcysteine (NAC) given for one year, added to prednisone and azathioprine, significantly ameliorates (i.e. slows down) disease progression in terms of vital capacity (VC) (+9%) and diffusing capacity (DLco) (+24%) in idiopathic pulmonary fibrosis (IPF). To better understand the clinical implications of these findings we performed additional, explorative analyses of the IFGENIA data set., Methods: We analysed effects of NAC on VC, DLco, a composite physiologic index (CPI), and mortality in the 155 study-patients., Results: In trial completers the functional indices did not change significantly with NAC, whereas most indices deteriorated with placebo; in non-completers the majority of indices worsened but decline was generally less pronounced in most indices with NAC than with placebo. Most categorical analyses of VC, DLco and CPI also showed favourable changes with NAC. The effects of NAC on VC, DLco and CPI were significantly better if the baseline CPI was 50 points or lower., Conclusion: This descriptive analysis confirms and extends the favourable effects of NAC on lung function in IPF and emphasizes the usefulness of VC, DLco, and the CPI for the evaluation of a therapeutic effect. Most importantly, less progressed disease as indicated by a CPI of 50 points or lower at baseline was more responsive to therapy in this study.

Objective: The purpose of this study was to evaluate the effectiveness of CT colonography (CTC) as a triage technique in faecal occult blood test (FOBT)-positive screening participants., Methods: Consecutive guaiac (G-FOBT) and immunochemical (I-FOBT) FOBT-positive patients scheduled for colonoscopy underwent CTC with iodine tagging bowel preparation. Each CTC was read independently by two experienced observers. Per patient sensitivity, specificity and positive and negative predictive values (PPV and NPV) were calculated based on double reading with different CTC cut-off lesion sizes using segmental unblinded colonoscopy as the reference standard. The acceptability of the technique to patients was evaluated with questionnaires., Results: 302 FOBT-positive patients were included (54 G-FOBT and 248 I-FOBT). 22 FOBT-positive patients (7%) had a colorectal carcinoma and 211 (70%) had a lesion >or=6 mm. Participants considered colonoscopy more burdensome than CTC (p<0.05). Using a 6 mm CTC size cut-off, per patient sensitivity for CTC was 91% (95% CI 85% to 91%) and specificity was 69% (95% CI 60% to 89%) for the detection of colonoscopy lesions >or=6 mm. The PPV of CTC was 87% (95% CI 80% to 93%) and NPV 77% (95% CI 69% to 85%). Using CTC as a triage technique in 100 FOBT-positive patients would mean that colonoscopy could be prevented in 28 patients while missing >or=10 mm lesions in 2 patients., Conclusion: CTC with limited bowel preparation has reasonable predictive values in an FOBT-positive population and a higher acceptability to patients than colonoscopy. However, due to the high prevalence of clinically relevant lesions in FOBT-positive patients, CTC is unlikely to be an efficient triage technique in a first round FOBT population screening programme.

Background: Idiopathic pulmonary fibrosis is a fatal disease for which no effective treatment exists. We assessed whether treatment with interferon gamma-1b improved survival compared with placebo in patients with idiopathic pulmonary fibrosis and mild-to-moderate impairment of pulmonary function., Methods: 826 patients with idiopathic pulmonary fibrosis were enrolled from 81 centres in seven European countries, the USA, and Canada. Patients were randomly assigned (double-blind) in a 2:1 ratio to receive 200 microg interferon gamma-1b (n=551) or equivalent placebo (n=275) subcutaneously, three times per week. Eligible patients were aged 40-79 years, had been diagnosed in the past 48 months, had a forced vital capacity of 55-90% of the predicted value, and a haemoglobin-corrected carbon monoxide diffusing capacity of 35-90% of the predicted value. The primary endpoint was overall survival time from randomisation measured at the second interim analysis, when the proportion of deaths had reached 75% of those expected by the study conclusion. This study is registered with ClinicalTrials.gov, number NCT00075998., Findings: At the second interim analysis, the hazard ratio for mortality in patients on interferon gamma-1b showed absence of minimum benefit compared with placebo (1.15, 95% CI 0.77-1.71, p=0.497), and indicated that the study should be stopped. After a median duration of 64 weeks (IQR 41-84) on treatment, 80 (15%) patients on interferon gamma-1b and 35 (13%) on placebo had died. Almost all patients reported at least one adverse event, and more patients on interferon gamma-1b group had constitutional signs and symptoms (influenza-like illness, fatigue, fever, and chills) than did those on placebo. Occurrence of serious adverse events (eg, pneumonia, respiratory failure) was similar for both treatment groups. Treatment adherence was good and few patients discontinued treatment prematurely in either group., Interpretation: We cannot recommend treatment with interferon gamma-1b since the drug did not improve survival for patients with idiopathic pulmonary fibrosis, which refutes previous findings from subgroup analyses of survival in studies of patients with mild-to-moderate physiological impairment of pulmonary function., Funding: InterMune.

Rationale: An efficacious medical therapy for idiopathic pulmonary fibrosis (IPF) remains elusive., Objectives: To explore the efficacy and safety of etanercept in the treatment of IPF., Methods: This was a randomized, prospective, double-blind, placebo-controlled, multicenter exploratory trial in subjects with clinically progressive IPF. Primary endpoints included changes in the percentage of predicted FVC and lung diffusing capacity for carbon monoxide corrected for hemoglobin (Dl(CO(Hb))) and change in the alveolar to arterial oxygen pressure difference P(a-a)(O(2)) at rest from baseline over 48 weeks., Measurements and Main Results: Eighty-eight subjects received subcutaneous etanercept (25 mg) or placebo twice weekly as their sole treatment for IPF. No differences in baseline demographics and disease status were detected between treatment groups; the mean time from first diagnosis was 13.6 months and mean FVC was 63.9% of predicted. At 48 weeks, no significant differences in efficacy endpoints were observed between the groups. A nonsignificant reduction in disease progression was seen in several physiologic, functional, and quality-of-life endpoints among subjects receiving etanercept. There was no difference in adverse events between treatment groups., Conclusions: In this exploratory study in patients with clinically progressive IPF, etanercept was well tolerated. Although there were no differences in the predefined endpoints, a decreased rate of disease progression was observed on several measures. Further evaluation of TNF antagonists in the treatment of IPF may be warranted. Clinical trial registered with www.clinicaltrials.gov (NCT 00063869).

The purpose of the present study was to evaluate the accuracy of the diagnosis of idiopathic pulmonary fibrosis (IPF) by respiratory physicians in six European countries, and to calculate the interobserver agreement between high-resolution computed tomography reviewers and histology reviewers in IPF diagnosis. The diagnosis of usual interstitial pneumonia (UIP) was assessed by a local investigator, following the American Thoracic Society/European Respiratory Society consensus statement, and confirmed when a minimum of two out of three expert reviewers from each expert panel agreed with the diagnosis. The level of agreement between readers within each expert panel was calculated by weighted kappa. The diagnosis of UIP was confirmed by the expert panels in 87.2% of cases. A total of 179 thoracic high-resolution computed tomography scans were independently reviewed, and an interobserver agreement of 0.40 was found. Open or thoracoscopic lung biopsy was performed in 97 patients, 82 of whom could be reviewed by the expert committee. The weighted kappa between histology readers was 0.30. It is concluded that, although the level of agreement between the readers within each panel was only fair to moderate, the overall accuracy of a clinical diagnosis of idiopathic pulmonary fibrosis in expert centres is good (87.2%).

We present the case of a patient who has a life-threatening hemoptysis caused by occlusion of the right pulmonary vein owing to external compression by excessive fibrous tissue. Because the patient's lung was essentially nonfunctional and hemoptysis persisted, we performed a pneumonectomy on her. Pathological analysis of the lung showed severe hypertensive changes in the arterial and venous microvasculature of the lung. Parenchymal-pleural to intercostal systemic venous connections had developed, facilitating venous drainage of the lung circulation. Upon review of the patient's history and the pathological and radiological evidence, we concluded that the pathological changes were caused by a variant of mediastinal fibrosis termed chronic idiopathic pulmonary hilar fibrosis, of which only a few cases have been described in the literature. A detailed case history and review of the literature are presented.

Background: Idiopathic pulmonary fibrosis is a chronic progressive disorder with a poor prognosis., Methods: We conducted a double-blind, randomized, placebo-controlled multicenter study that assessed the effectiveness over one year of a high oral dose of acetylcysteine (600 mg three times daily) added to standard therapy with prednisone plus azathioprine. The primary end points were changes between baseline and month 12 in vital capacity and in single-breath carbon monoxide diffusing capacity (DL(CO))., Results: A total of 182 patients were randomly assigned to treatment (92 to acetylcysteine and 90 to placebo). Of these patients, 155 (80 assigned to acetylcysteine and 75 to placebo) had usual interstitial pneumonia, as confirmed by high-resolution computed tomography and histologic findings reviewed by expert committees, and did not withdraw consent before the start of treatment. Fifty-seven of the 80 patients taking acetylcysteine (71 percent) and 51 of the 75 patients taking placebo (68 percent) completed one year of treatment. Acetylcysteine slowed the deterioration of vital capacity and DL(CO): at 12 months, the absolute differences in the change from baseline between patients taking acetylcysteine and those taking placebo were 0.18 liter (95 percent confidence interval, 0.03 to 0.32), or a relative difference of 9 percent, for vital capacity (P=0.02), and 0.75 mmol per minute per kilopascal (95 percent confidence interval, 0.27 to 1.23), or 24 percent, for DL(CO) (P=0.003). Mortality during the study was 9 percent among patients taking acetylcysteine and 11 percent among those taking placebo (P=0.69). There were no significant differences in the type or severity of adverse events between patients taking acetylcysteine and those taking placebo, except for a significantly lower rate of myelotoxic effects in the group taking acetylcysteine (P=0.03)., Conclusions: Therapy with acetylcysteine at a dose of 600 mg three times daily, added to prednisone and azathioprine, preserves vital capacity and DL(CO) in patients with idiopathic pulmonary fibrosis better than does standard therapy alone., (Copyright 2005 Massachusetts Medical Society.)

Objective: To compare thin-slice multidetector computed tomography colonography (CTC) that uses stool tagging with colonoscopy., Method: One hundred fifty patients scheduled for colonoscopy underwent high-resolution CTC. An iodinated contrast agent was added to the preparation to tag the residual colonic fluid and stool. The effect of fluid tagging was assessed first. Sensitivity and specificity were calculated for two independent readers. In addition, values were recalculated separately for the first and last 75 patients., Results: Tagging was optimal in 95.3% of the cases, and reader confidence was high. Sensitivities were 64.1%-66.7% (for the 2 readers) for 5- to 9-mm polyps and 91.7% for larger polyps. The overall specificity was 94.2% and 95%. Sensitivity improved during the study for both 5- to 9-mm polyps (from 54.2%-58.3% to 80%) and polyps larger than 9 mm (from 50% to 100%). Specificity changed nonuniformly., Conclusion: The combination of fluid tagging and high-resolution scanning in CTC showed high sensitivity and specificity, especially concerning sensitivity for polyps of 10 mm and larger.

The purpose of this study was to evaluate the feasibility of a dry bowel preparation, i.e. without laxative fluids, for virtual CT colonography (VCTC), and its impact on patient acceptance compared with conventional colonoscopy (CC). A randomly chosen patient population scheduled for CC ( n=11) was first submitted to VCTC after a dry preparation, consisting of low-residue meals combined with a small amount of a iodinated water-soluble contrast medium during each meal 3 days before VCTC. In different colon segments and between different persons, the degree of tagging in VCTC was evaluated and graded. Patient acceptance and future preference were assessed for both preparations as well as for both investigations. The mixing of the contrast with the intestinal content results in contrast impregnated stool, the tagged feces. The degree of fecal tagging was good in the majority of the patients and the colonic segments, especially in the descending colon and sigmoid. Furthermore, patient acceptance and preference were clearly in favour of VCTC compared with CC merely because of the non-invasiveness of the dry preparation. Dry bowel preparation and VCTC is a promising approach towards a patient-friendly colon cancer-screening setup.

The diffuse interstitial lung diseases (ILD) are a very complex group of disorders, of which more than 200 specific disease entities are known. All ILD are characterized by a homogenous or heterogenous affection of the lung parenchyma. In recent years there was a renewed interest in the ILD because new concepts have been developed on aetiologic influences, on pathogenetic mechanisms (of inflammation versus active fibrosis) and on genetic susceptibility and consequently on the diagnostic-therapeutic management. Yet, there remain many questions still, e.g. concerning the exact incidence and prevalence of the majority of these diseases and concerning the genetic aspects. More specifically much research has been carried out on the important group of "idiopathic interstitial pneumonias" (IIP) and in particular on "idiopathic pulmonary fibrosis" (IPF). Recently several international consensus reports have been published with guidelines on the histologic and clinical definitions and on the classification and the diagnostic-therapeutic management.

The aim of this study was to evaluate the discomfort associated with CT colonography compared with colonoscopy and bowel purgation cleansing, and to evaluate patient preference between CT colonography and colonoscopy. In a total of 124 patients, scheduled for multidetector virtual CT colonography and diagnostic colonoscopy, patient acceptance and future preference were assessed during the different steps of the procedure (colon preparation, CT examination, and conventional colonoscopy). Patients who described contradictory findings between the degree of discomfort and their preference regarding follow-up examinations were retrospectively reinterviewed regarding the reason for this discrepancy. Colonoscopy was graded slightly more uncomfortable than virtual CT colonography, but the preparation was clearly the most uncomfortable part of the procedure. Concerning their preference regarding follow-up examinations, 71% of the patients preferred virtual CT colonography, 24% preferred colonoscopy, and 5% had no preference. Twenty-eight percent of the patients preferred virtual CT colonography despite that they thought it was equally or even more uncomfortable than colonoscopy. This was mainly due to the faster procedure (17 patients), the lower physical challenge (14 patients), and the lack of sedation (12 patients) of virtual CT colonography. Factors other than the discomfort related to the examinations play an important role in the patient's preference for virtual CT colonography, namely the faster procedure, the lower physical challenge, and the lack of sedation. Since the preparation plays a major decisive factor in the patient acceptance of virtual CT colonography, more attention should be given to fecal tagging.

Background: Pollution by particulates has been consistently associated with increased cardiovascular morbidity and mortality. However, the mechanisms responsible for these effects are not well-elucidated., Methods and Results: To assess to what extent and how rapidly inhaled pollutant particles pass into the systemic circulation, we measured, in 5 healthy volunteers, the distribution of radioactivity after the inhalation of "Technegas," an aerosol consisting mainly of ultrafine (99m)Technetium-labeled carbon particles (<100 nm). Radioactivity was detected in blood already at 1 minute, reached a maximum between 10 and 20 minutes, and remained at this level up to 60 minutes. Thin layer chromatography of blood showed that in addition to a species corresponding to oxidized (99m)Tc, ie, pertechnetate, there was also a species corresponding to particle-bound (99m)Tc. Gamma camera images showed substantial radioactivity over the liver and other areas of the body., Conclusions: We conclude that inhaled (99m)Tc-labeled ultrafine carbon particles pass rapidly into the systemic circulation, and this process could account for the well-established, but poorly understood, extrapulmonary effects of air pollution.

The success of CT colonography (CTC) depends on appropriate tools for quick and accurate diagnostic reading. Current advancements in computer technology have the potential to bring such tools even to personal computer level. In this paper a technique for computed-aided diagnosis (CAD) using CT colonography is described. The method uses a combination of surface normal and sphere fitting methods to label positions in the volume data, which have a strong likelihood of being polyps, and presents them in a user-friendly way. The method was tested on a study group of 18 patients and the detection rate for polyps of 10 mm or larger was 100%, comparable to that of human readers. The price paid for a high detection rate was a large number of approximately eight false-positive findings per case. Our results show that CAD is feasible, and if the number of false positives is further reduced, then this method can be useful for clinical screenings.

One of the new forays into the field of medical imaging is the 3-D computer imaging. Thanks to new and more performant computer processing and 3-D rendering methods it is nowadays possible to generate high resolution images of the inner surface of the colon based on CT and MR images. This article reviews the current status and research directions of virtual colonoscopy and its possible eligibility of becoming a new tool for colorectal screening.

We report the results of a prospective registration of the prevalence of interstitial lung diseases by 20 centres of respiratory medicine in Flanders from January 1992 till July 1996. The 20 centres registered a total of 362 cases. Sarcoidosis (31% with inclusion of stage I, or 22% without stage I), idiopathic pulmonary fibrosis (20%), hypersensitivity pneumonitis (13%) and unclassified forms of interstitial lung diseases (9%) were the most often diagnosed diseases. The mean age of the patients was 52 +/- 17 (SD) years, but ranged from 32 +/- 10 years in histiocytosis X to 70 +/- 13 years in drug induced interstitial lung diseases. The male to female ratio was 1.3 but ranged from 2.3 in interstitial lung diseases due to inhalation of inorganic materials to 0.8 in interstitial lung diseases due to connective tissue disease. The diagnosis was considered certain in 60%, probable in 30% and possible in 10%. In 50% of the cases the diagnosis was proven by biopsy and the most often used biopsy technique was transbronchiolo-alveolar biopsy (40% of biopsies) followed by open lung biopsy (32%). At diagnosis vital capacity was 82 +/- 22% pred. (ranging from 92 +/- 19% in sarcoidosis to 71 +/- 24% in idiopathic pulmonary fibrosis) and CO-diffusing capacity was 77 +/- 19% pred. (ranging from 77 +/- 19% in sarcoidosis to 41 +/- 13% in drug induced pneumonitis). The regional frequency of interstitial lung diseases in Flanders varied widely and was not proportional to the regional distribution of the 20 contributing centres. In conclusion this registration provides interesting information on the occurrence and presentation of the different forms of interstitial lung diseases, although it may still underestimate the real prevalence and incidence of interstitial lung diseases.

This article presents a case of appendicitis 7 years after open appendectomy. Together with the apparent CT findings we discuss the current literature of this issue.

The aim of this study was to analyse the quality and diagnostic value of lung biopsies for the diagnosis of interstitial lung disease (ILD), taken with diathermy coagulation cup forceps during medical thoracoscopy. Patients with ILD, not specified after thorough clinical assessment, high-resolution CT (HRCT), bronchoalveolar lavage and transbronchial biopsy, were studied. Medical thoracoscopy was performed in an endoscopy suite under neuroleptic anaesthesia with spontaneous ventilation. Biopsy specimens were analysed prospectively by one lung pathologist blinded to the clinical findings. Over 2 yrs, 118 samples were analysed from 24 consecutive patients. A good quality biopsy was obtained in 23 patients, and 78% of the samples were of good quality. Biopsy findings plus clinical and HRCT data revealed a relevant diagnosis in 18 patients and some diagnostic clues in four patients, for whom further examinations were needed. No major complications occurred. Chest tube drainage averaged 5.3+/-4.7 days, and was related to the total lung capacity (p=0.008), which mirrors the severity of ILD. Separate sampling of biopsies from different lobes proved to be useful in one third of the cases. In conclusion, lung biopsy sampling can be performed safely by interventional pulmonary endoscopists and has a good diagnostic yield in interstitial lung disease of unknown origin.

A 24-yr-old male, known since the age of 11 to have a nonerosive arthritis and later diagnosed as having systemic lupus erythematosus (SLE), developed subacute heart failure with diffuse lung infiltrates and died suddenly after having presented a moderate hypereosinophilia for 6 months for which no other causes besides the SLE were found. A post mortem examination revealed Löffler's endocarditis (endocarditis parietalis fibroplastica) with acute pulmonary capillaritis. This represents Löffler's endocarditis in the setting of SLE. To the best of the authors' knowledge, this association has not been reported before.