Clinical and molecular studies of the effect of imatinib on advanced aggressive fibromatosis (desmoid tumor).

PURPOSE: To determine the clinical efficacy of imatinib in patients with advanced aggressive fibromatosis (AF) and to identify the molecular basis of response/nonresponse to this agent. PATIENTS AND METHODS: Nineteen patients with AF were treated with imatinib (800 mg/d) as part of a phase II clinical study. Tumor specimens were analyzed for mutations of KIT, PDGFRA, PDGFRB, and CTNNB1 (beta-catenin). Tumor expression of total and activated KIT, PDGFRA, and PDGFRB were assessed using immunohistochemistry and immunoblotting techniques. We also measured plasma levels of PDGF-AA and PDGF-BB in patients and normal patient controls. RESULTS: Three of 19 patients (15.7%) had a partial response to treatment, with four additional patients having stable disease that lasted more than 1 year (overall 1 year tumor control rate of 36.8%). No mutations of KIT, PDGFRA, or PDGFRB were found. Sixteen of 19 patients (84%) had mutations involving the WNT pathway (APC or CTNNB1). However, there was no correlation between WNT pathway mutations and clinical response to imatinib. AF tumors expressed minimal to null levels of KIT and PDGFRA but expressed levels of PDGFRB that are comparable with normal fibroblasts. However, PDGFRB phosphorylation was not detected, suggesting that PDGFRB is only weakly activated. AF patients had elevated levels of PDGF-AA and PDGF-BB compared with normal patient controls. Notably, the plasma level of PDGF-BB was inversely correlated with time to treatment failure. CONCLUSION: Imatinib is an active agent in the treatment of advanced AF. Imatinib response in AF patients may be mediated by inhibition of PDGFRB kinase activity.

Preoperative ultrasound is worthwhile for reoperative parathyroid surgery.

OBJECTIVES/HYPOTHESIS: High-resolution ultrasound and sestamibi scanning are regarded as the first-line methods for preoperative localization of parathyroid adenomas. The utility of ultrasound in reoperative cases has been questioned because of concern that scarring will obscure normal tissue planes and vascularity that are critical to identification of an adenoma using this imaging modality. The purposes of the study were to evaluate the ability of high-resolution ultrasound to accurately localize parathyroid adenomas in the reoperative exploration and to identify any factors that influence its accuracy STUDY DESIGN: Retrospective chart review at a tertiary care academic medical center. METHODS: All patients seen in referral for parathyroid surgery between May 1994 and September 2002 underwent high-resolution ultrasound as their initial diagnostic test. Patients who subsequently underwent exploration were included in the study. Intraoperative and ultrasound findings were compared. RESULTS: One hundred forty-two patients were included, 116 without and 26 with prior exploration. The sensitivity and positive predictive value of ultrasound were 86.9% and 89.1%, respectively. These data were not significantly different in patients without (88.2% and 90%) and in patients with (80% and 84.2%) prior thyroid or parathyroid surgery. The overall accuracy was 79% with a false-negative rate of 11.3%. Thyroid nodularity was significantly more common (81.8%) in patients who had a false-positive or false-negative finding on ultrasound than in the total population (61.3%). CONCLUSION: High-resolution ultrasound is an accurate method for localizing parathyroid adenomas even in patients who have previously undergone parathyroid exploration. However, the presence of thyroid nodules can interfere with its accuracy.

Gastrointestinal imaging update: swallowing disorders and sphincter of Oddi dysfunction.

This update focuses on swallowing disorders and sphincter of Oddi dysfunction. Anatomy and physiology of swallowing are described, as are the signs, symptoms, and etiology of swallowing disorders. The imaging of these patients, particularly with videofluoroscopic swallowing study and fiberoptic endoscopic examination of swallowing, is then discussed. Sphincter of Oddi dysfunction as a cause of postcholecystectomy syndrome as well as its classification is described. This is followed by an explanation of the roles of fatty meal sonography and hepatobiliary scintigraphy in patients with sphincter of Oddi dysfunction, particularly type II and type III.

Update on gastrointestinal imaging.

The current status of three gastrointestinal imaging techniques-positron emission tomography (PET) with 18 F-fluorodeoxyglucose (FDG), computed tomographic (CT) colonography, and magnetic resonance cholangiography (MRC)--are reviewed here. FDG-PET should not be used as an initial means to identify patients with primary colorectal malignancy; for the detection of colorectal carcinoma metastases and recurrence, contrast-enhanced CT should be used to monitor patients, with the use of PET reserved for equivocal cases. CT colonography is comparable to colonoscopy for the detection of patients with colorectal polyps > or = 1 cm, and its advantages include its capability of detecting extracolonic abnormalities. MRC is a relatively new application of MR imaging, with utility in multiple clinical settings, including patients with suspected obstructive disease, choledochal cysts, primary sclerosing cholangitis or AIDS cholangiopathy, biliary-enteric anastomoses, and patients with failed or inadequate endoscopic retrograde cholangiograms.