Phase I trial to evaluate the tumor and normal tissue uptake, radiation dosimetry and safety of (111)In-DTPA-human epidermal growth factor in patients with metastatic EGFR-positive breast cancer.

The safety, pharmacokinetics, biodistribution and radiation dosimetry of (111)In-DTPA-hEGF, an Auger electron-emitting radiopharmaceutical, were evaluated in a first-in-human trial. Dose escalation was performed in patients with EGFR-positive metastatic breast cancer who had received ≥2 prior courses of systemic treatment. (111)In-DTPA-hEGF (0.25 mg) was administered once intravenously (i.v.). Blood was collected for biochemistry/hematology testing and pharmacokinetic and immunogenicity analyses at selected times post injection (p.i.). Whole body planar images were acquired at 1, 4-6, 24 and 72 h p.i. and SPECT images at 24 and/or 72 h p.i. Macrodosimetry (MIRD) for the whole body and organs was estimated using OLINDA. Correlative radiological imaging was obtained at baseline, 1 and 3 months and then 6 monthly. Toxicity was scored using Common Terminology Criteria for Adverse Events (CTCAE)v2.0. Sixteen patients, median age 47 yr (range, 35-59), received (111)In-DTPA-hEGF as follows: 357-434 MBq (7), 754-805 MBq (3), 1,241-1,527 MBq (3) and 2,030-2,290 MBq (3). Fifteen were evaluable for toxicity. The commonest adverse events (AE) were flushing, chills, nausea, and vomiting occurring during or immediately p.i. One patient experienced Grade 3 thrombocytopenia (attributed to bone marrow infiltration by cancer). There were no other Grade 3 or 4 AEs. Maximum tolerated dose was not reached. Clear accumulation of radiopharmaceutical in at least one known site of disease was observed in 47% of patients. (111)In-DTPA-hEGF was cleared biexponentially from the blood with α-phase T½ of 0.16 ± 0.03 h and ß-phase T½ of 9.41 ± 1.93 h. (111)In-DTPA-hEGF was not immunogenic. The mean radiation dose estimates in mGy/MBq for whole body, liver, kidneys, spleen and thyroid were 0.08, 0.86, 0.74, 0.37 and 0.30, respectively. No objective antitumor responses were observed at the doses studied. In summary, administered amounts of up to 2,290 MBq (0.25 mg) of (111)In-DTPA-hEGF were well tolerated as a single i.v. injection.

Perifissural nodules seen at CT screening for lung cancer.

PURPOSE: To describe and characterize the potential for malignancy of noncalcified lung nodules adjacent to fissures that are often found in current or former heavy smokers who undergo computed tomography (CT) for lung cancer screening. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. Baseline and follow-up thin-section multidetector CT scans obtained in 146 consecutive subjects at high risk for lung cancer (age range, 50-75 years; > 30 pack-year smoking history) were retrospectively reviewed. Noncalcified nodules (NCNs) were categorized according to location (parenchymal, perifissural), shape, septal connection, manually measured diameter, diameter change, and lung cancer outcome at 7(1/2) years. RESULTS: Retrospective review of images from 146 baseline and 311 follow-up CT examinations revealed 837 NCNs in 128 subjects. Of those 837 nodules, 234 (28%), in 98 subjects, were adjacent to a fissure and thus classified as perifissural nodules (PFNs). Multiple (range, 2-14) PFNs were seen in 47 subjects. Most PFNs were triangular (102/234, 44%) or oval (98/234, 42%), were located inferior to the carina (196/234, 84%), and had a septal connection (171/234, 73%). The mean maximal length was 3.2 mm (range, 1-13 mm). During 2-year follow-up in 71 subjects, seven of 159 PFNs increased in size on one scan but were then stable. The authors searched a lung cancer registry 7(1/2) years after study entry and found 10 lung cancers in 139 of 146 study subjects who underwent complete follow-up; none of these cancers had originated from a PFN. CONCLUSION: PFNs are frequently seen on screening CT scans obtained in high-risk subjects. Although PFNs may show increased size at follow-up CT, the authors in this study found none that had developed into lung cancer; this suggests that the malignancy potential of PFNs is low. (c) RSNA, 2010.

TRIP: a psycho-educational programme in Hong Kong for people with schizophrenia.

'TRIP' (Transforming Relapse and Instilling Prosperity) is a ward-based illness management programme that aims to decrease treatment non-compliance and relapse rate by improving the insight and health of acute psychiatric patients with schizophrenia. Eighty-one stable male acute psychiatric patients with schizophrenia were randomized to receive the TRIP programme (n = 44) or the comparison group of traditional ward occupational therapy (WOT) programme (n = 37). Participants' insights and health were assessed by the Unawareness of Mental Disorder Scale and the Hong Kong version of the Short Form-36 (SF-36) health survey, respectively. Each group was then followed up for a 12-month period. One-way analysis of covariance (ANCOVA) showed that participants in the TRIP programme had significantly better insight and health than a comparison group during post-study measurement. Participants in the TRIP programme had significantly fewer re-admissions in the 12-month follow-up period than those who attended the WOT programme. In summary the TRIP programme, as led by an occupational therapist, was effective in improving insight, awareness of health and in having a lower re-admission rate than a traditional occupational therapy programme.

Utility and diagnostic accuracy of sonography in detecting appendicitis in a community hospital.

OBJECTIVE: The purpose of this study was to determine the utility and accuracy of sonography in diagnosing acute appendicitis in patients with suspected acute appendicitis in a general community hospital. MATERIALS AND METHODS: All reports relating to appendicitis were retrospectively obtained from archived transcription reports of nine radiologists from a geographically constrained hospital between December 1999 and December 2003 by a search on the keyword "appendicitis." These files were correlated with the histopathology reports from surgical appendectomy or findings from clinical follow-up during the same period. A survey eliciting the views of five local surgeons on the utility of sonography for the detection of acute appendicitis was also collected. RESULTS: Sonography reports for 667 patients (mean age, 34 years; range, 6-93 years) were obtained. Of these, a total of 174 had pathologically proven appendicitis and 145 had positive findings for appendicitis on sonography. The accuracy was 92%; sensitivity, 83%; and specificity, 95%. The positive predictive value was 86%, and the negative predictive value was 94%. Three of the five surveyed surgeons indicated they used sonography less than 25% of the time, with none using it more than 75%. CONCLUSION: The sensitivity, specificity, accuracy, and positive and negative predicative values of sonography performed by general radiologists in a community hospital are comparable to statistics quoted in the literature for academic institutions. The most common error was the tendency to misclassify appendixes under 6 mm. Most surgeons surveyed stated their use of sonography would increase if sonography yielded a sensitivity and specificity of 85% or greater.

Early emphysema in patients with anorexia nervosa.

Postmortem studies of patients who died in the Warsaw Ghetto during World War II suggested that death from starvation was associated with pulmonary emphysema. This study re-examines this hypothesis in patients who are chronically malnourished because of anorexia nervosa. Age, smoking history, body mass index, and pulmonary function were measured in 21 subjects with anorexia nervosa and 16 control subjects. Computed tomography (CT) scans were obtained from three regions of the lung (at the level of the aortic arch, the carina, and the posterior position of the eighth rib) using a multislice scanner. The CT measurements of lung density, emphysema, and surface area-to-volume ratio were obtained using the X-ray attenuation values. CT measurements of emphysema were greater in the group that was anorexic than in historical control subjects (p < 0.001). Furthermore, there were significant correlations between the body mass index and the CT measures of emphysema for all the patients and between diffusing capacity and the CT measurements in the patients who were anorexic. A multiple linear regression analysis showed the diffusing capacity was predicted best by the percentage of lung voxels within the large emphysematous changes category. These data demonstrate that emphysema-like changes are present in the lungs of patients who are chronically malnourished.