Harrie C. M. van den Bosch

MRI with a lymph-node-specific contrast agent as an alternative to CT scan and lymph-node dissection in patients with prostate cancer: a prospective multicohort study

BACKGROUND In patients with prostate cancer who are deemed to be at intermediate or high risk of having nodal metastases, invasive diagnostic pelvic lymph-node dissection (PLND) is the gold standard for the detection of nodal disease. However, a new lymph-node-specific MR-contrast agent ferumoxtran-10 can detect metastases in normal-sized nodes (ie, <8 mm in size) by use of MR lymphoangiography (MRL). In this prospective, multicentre cohort study, we aimed to compare the diagnostic accuracy of MRL with up-to-date multidetector CT (MDCT), and test the hypothesis that a negative MRL finding obviates the need for a PLND. METHODS We included consecutive patients with prostate cancer who had an intermediate or high risk (risk of >5% according to routinely used nomograms) of having lymph-node metastases. All patients were assessed by MDCT and MRL, and underwent PLND or fine-needle aspiration biopsy. Imaging results were correlated with histopathology. The primary outcomes were sensitivity, specificity, accuracy, NPV, and PPV of MRL and MDCT. This study is registered with ClinicalTrials.gov, number NCT00185029. FINDINGS The study was done in 11 hospitals in the Netherlands between April 8, 2003, and April 19, 2005. 375 consecutive patients were included. 61 of 375 (16%) patients had lymph-node metastases. Sensitivity was 34% (21 of 61; 95% CI 23-48) for MDCT and 82% (50 of 61; 70-90) for MRL (McNemars test p<0.05). Specificity was 97% (303 of 314; 94-98) for MDCT and 93% (291 of 314; 89-95) for MRL. Positive predictive value (PPV) was 66% (21 of 32; 47-81) for MDCT and 69% (50 of 73; 56-79) for MRL. Negative predictive value (NPV) was 88% (303 of 343; 84-91) for MDCT and 96% (291 of 302; 93-98) for MRL (McNemars test p<0.05). Of the 61 patients with lymph-node metastases, 50 were detected by MRL, of which 40 (80%) had metastases in normal-sized lymph nodes. The high sensitivity and NPV of MRL imply that in patients with a negative MRL, the chance of positive lymph nodes is less than 11/302 (4%). INTERPRETATION MRL had significantly higher sensitivity and NPV than MDCT for patients with prostate cancer who had intermediate or high risk of having lymph-node metastases. In such patients, after a negative MRL, the post-test probability of having lymph-node metastases is low enough to omit a PLND.

Balloon angioplasty combined with primary stenting versus balloon angioplasty alone in femoropopliteal obstructions: A comparative randomized study.

AbstractPurpose: To evaluate whether balloon angioplasty combined with stenting (ST) of symptomatic femoropopliteal disease would provide better results compared with balloon angioplasty alone (BA). Methods: Fifty-one patients were randomized between ST (24 patients) and BA (27 patients). Follow-up comprised clinical and hemodynamic assessment and color-flow duplex ultrasound examinations. Results: Residual stenosis (≥ 30% diameter reduction) occurred in three BA patients, but not in the ST patients. By life-table analysis the cumulative rate of clinical and hemodynamic success after 1 year with ST was 74% (SE 9%) and for those with BA 85% (SE 7%) (p= 0.25). The primary patency at 1 year assessed by color-flow duplex ultrasound was 62% (SE 9%) for ST-treated patients and 74% (SE 8%) for BA patients (p= 0.22). Occlusion occurred in five ST patients (21%) compared with two BA patients (7%). Conclusion: ST does not improve clinical and hemodynamic outcome compared with BA. Moreover, the occlusion rate in ST-treated patients is higher.

Prostate cancer: detection of lymph node metastases outside the routine surgical area with ferumoxtran-10-enhanced MR imaging.

PURPOSE To prospectively evaluate the feasibility of magnetic resonance (MR) imaging with ferumoxtran-10 in patients with prostate cancer to depict lymph node metastases outside the routine pelvic lymph node dissection (PLND) area. MATERIALS AND METHODS The study was approved by the institutional review boards at all four hospitals; patients provided written informed consent. Two hundred ninety-six consecutive men (mean age, 67 years; range, 47-83 years) with prostate cancer and an intermediate-to-high risk for nodal metastases (prostate-specific antigen level >10 ng/mL, Gleason score >6, or stage T3 disease) were enrolled. MR lymphography of the pelvis was performed 24 hours after intravenous drip infusion of ferumoxtran-10. Positive nodes at MR lymphography were indicated to be inside or outside the routine dissection area (RDA). On the basis of MR lymphography computed tomographic (CT)-guided biopsy, routine PLND, or MR imaging-guided minimal extended PLND was performed. RESULTS MR lymphography findings were positive in 58 patients. Of these, 44 had histopathologic confirmation of lymph node metastases. In 18 of 44 patients (41%), MR lymphography findings showed nodes exclusively outside the RDA, which were confirmed with MR lymphography-guided extended PLND (n = 13) and CT-guided biopsy (n = 5). In another 18 patients (41%), positive nodes were located both inside and outside the RDA at MR lymphography. In these 18 patients, routine PLND was used to confirm the nodes inside the RDA (n = 11); CT-guided biopsy was used to confirm nodes outside the RDA (n = 7). In the remaining eight patients, MR lymphography findings showed only nodes inside the RDA, which was confirmed with PLND (n = 5) and CT-guided biopsy (n = 3). In 14 of the 58 patients (24%), there was no histologic confirmation. CONCLUSION In 41% of patients with prostate cancer, nodal metastases outside the area of routine PLND were detected by using MR imaging with ferumoxtran-10.

Multicenter, Double-Blind, Randomized, Intraindividual Crossover Comparison of Gadobenate Dimeglumine and Gadopentetate Dimeglumine for Breast MR Imaging (DETECT Trial)

PURPOSE To intraindividually compare 0.1 mmol/kg doses of gadobenate dimeglumine and gadopentetate dimeglumine for contrast material-enhanced breast magnetic resonance (MR) imaging by using a prospective, multicenter double-blind, randomized protocol. MATERIALS AND METHODS Institutional review board approval and patient informed consent were obtained. One hundred sixty-two women (mean age, 52.8 years ± 12.3 [standard deviation]) enrolled at 17 sites in Europe and China between July 2007 and May 2009 underwent at least one breast MR imaging examination at 1.5 T by using three-dimensional spoiled gradient-echo sequences. Of these, 151 women received both contrast agents in randomized order in otherwise identical examinations separated by more than 2 but less than 7 days. Images, acquired at 2-minute or shorter intervals after contrast agent injection, were evaluated independently by three blinded radiologists unaffiliated with enrollment centers. Histopathologic confirmation was available for all malignant lesions (n = 144), while benign lesions were confirmed either by using histopathologic examination (n = 52) or by at least 12-month diagnostic follow-up (n = 20) with mammography and/or ultrasonography. Determinations of malignant lesion detection rates and diagnostic performance (sensitivity, specificity, accuracy, positive predictive value [PPV], and negative predictive value [NPV]) were performed and compared (McNemar and Wald tests). A full safety assessment was performed. RESULTS Significant superiority for gadobenate dimeglumine was noted by readers 1, 2, and 3 for malignant lesion detection rate (91.7%, 93.1%, 94.4% vs 79.9%, 80.6%, 83.3%, respectively; P ≤ .0003). Readers 1, 2, and 3 reported significantly superior diagnostic performance (sensitivity, specificity, and accuracy) for breast cancer detection with gadobenate dimeglumine (91.1%, 94.5%, 95.2% vs 81.2%, 82.6%, 84.6%; 99.0%, 98.2%, 96.9% vs 97.8%, 96.9%, 93.8%; 98.2%, 97.8%, 96.7% vs 96.1%, 95.4%, 92.8%, respectively; P ≤ .0094) and significantly superior PPV (91.1%, 85.2%, 77.2% vs 80.7%, 75.5%, 60.9%, respectively; P ≤ .0002) and NPV (99.0%, 99.4%, 99.4% vs 97.8%, 98.0%, 98.1%, respectively; P ≤ .0003). No safety concerns were noted with either agent. CONCLUSION Gadobenate dimeglumine is superior to gadopentetate dimeglumine for breast cancer diagnosis.

Patterns of recurrent disease after recanalization of femoropopliteal artery occlusions

PurposeIn this prospective study we investigated the site, occurrence, and development of stenoses and occlusions following recanalization of superficial femoral artery occlusions.MethodsRecanalization of an occluded femoropopliteal artery was attempted in 62 patients. Follow-up examinations included clinical examination and color-flow duplex scanning at regular intervals. Arteriography was used to determine the localization of the recurrent disease relative to the initially occluded segment.ResultsDuring a mean follow-up of 23 months (range 0–69 months) 14 high-grade restenoses, indicated by a peak systolic velocity ratio ≧3.0, were detected by color-flow duplex scanning. Occlusion of the treated segment occurred in 11 patients. The cumulative 3-year primary patency rate for high-grade restenoses and occlusions combined was 44% (SE 9%). By arteriographic examination the site of restenosis was localized in the distal half of the treated vessel segment in 16 of 21 cases.ConclusionMost restenoses and occlusions occurred during the first year and most disease developed at the previous intervention site. The site of restenosis is more frequently in the distal part of the initially treated segment, a finding that may have therapeutic implications.

Free-Breathing MRI for the Assessment of Myocardial Infarction: Clinical Validation

OBJECTIVE The objective of our study was to validate free-breathing 2D inversion recovery delayed-enhancement MRI for the assessment of myocardial infarction compared with a breath-hold 3D technique. SUBJECTS AND METHODS Institutional review board approval and written informed consent were obtained. Thirty-two patients (25 men, seven women; mean age, 68 years; age range, 39-84 years) underwent breath-hold gradient-echo 3D inversion-recovery delayed-enhancement MRI and free-breathing respiratory-triggered 2D inversion-recovery delayed-enhancement MRI of the heart (scanning time, 50-80 seconds). Infarct size was quantitatively analyzed as a percentage of the left ventricle. The location and transmural extent of myocardial infarction were assessed by visual scoring. Intraclass correlation and Bland-Altman analysis were used to evaluate the agreement between the techniques for infarct quantification. Kappa statistics were used to analyze the visual score. RESULTS Excellent agreement between the two techniques was observed for infarct quantification (intraclass correlation = 0.99 [p < 0.01]; mean difference +/- SD = 0.32% +/- 2.4%). The agreement in assessing transmural extent of infarction was good to excellent between the free-breathing technique and the 3D breath-hold technique (kappa varied between 0.70 and 0.96 for all segments). No regions of infarction were missed using the free-breathing approach. CONCLUSION The free-breathing 2D delayed-enhancement MRI sequence is a fast and reliable tool for detecting myocardial infarction.

Peripheral arterial occlusive disease: 3.0-T versus 1.5-T MR angiography compared with digital subtraction angiography.

PURPOSE To prospectively evaluate the diagnostic accuracy of 3-T versus 1.5-T contrast material-enhanced (CE) magnetic resonance (MR) angiography with high spatial resolution in patients who have peripheral arterial occlusive disease, with conventional digital subtraction angiography (DSA) serving as the reference standard. MATERIALS AND METHODS Institutional review board approval and written informed consent were obtained. DSA and standardized single-injection, three-station, moving-table CE MR angiography, with similar acquisition protocols and contrast agent doses at 3 T and 1.5 T, were consecutively performed in 19 patients (13 men and six women; mean age ± standard deviation, 67 years ± 9). Stenosis was scored visually in 500 arterial segments (97.5% of all available) in consensus by two radiologists in a blinded manner (the radiologists were unaware of the field strength and prior DSA and MR angiographic results and used randomized analysis order). Contrast-to-noise ratio was determined in the vascular tree of both legs. Statistical significance in stenosis scoring was evaluated by using generalized estimating equations. Contrast-to-noise differences were evaluated with paired t tests. Agreement between MR angiography and DSA was evaluated by using Fleiss-Cohen κ statistics. RESULTS Both 3-T and 1.5-T CE MR angiography showed similar excellent agreement with DSA regarding stenosis classification (κ = 0.96 and 0.93, respectively). All sensitivity and specificity values exceeded 90%. Mean contrast-to-noise ratio was 3.0-4.2 times higher at 3 T than at 1.5 T. CONCLUSION Standardized single-injection, three-station, moving-table 3-T CE MR angiography is reliable for classification of stenosis in patients suspected of having peripheral arterial occlusive disease, and diagnostic performance was similar to that seen with 1.5-T MR angiography. There was a significantly increased contrast-to-noise ratio for identical contrast agent dose at 3-T MR angiography.

MRI for Local Staging of Colon Cancer : Can MRI Become the Optimal Staging Modality for Patients With Colon Cancer?

BACKGROUND: Colon cancer is currently staged with CT. However, MRI is superior in the detection of colorectal liver metastasis, and MRI is standard in local staging of rectal cancer. Optimal (local) staging of colon cancer could become crucial in selecting patients for neoadjuvant treatment in the near future (Fluoropyrimidine Oxaliplatin and Targeted Receptor Preoperative Therapy trial). OBJECTIVE: The purpose of this study was to evaluate the diagnostic performance of MRI for local staging of colon cancer. DESIGN: This was a retrospective study. SETTINGS: The study was conducted at the Maastricht University Medical Centre. PATIENTS: In total, 55 patients with biopsy-proven colon carcinoma were included. MAIN OUTCOME MEASURES: All of the patients underwent an MRI (1.5-tesla; T2 and diffusion-weighted imaging) of the abdomen and were retrospectively analyzed by 2 blinded, independent readers. Histopathology after resection was the reference standard. Both readers evaluated tumor characteristics, including invasion through bowel wall (T3/T4 tumors), invasion beyond bowel wall of ≥5 mm and/or invasion of surrounding organs (T3cd/T4), serosal involvement, extramural vascular invasion, and malignant lymph nodes (N+). Interobserver agreement was compared using &kgr; statistics. RESULTS: MRI had a high sensitivity (72%–91%) and specificity (84%–89%) in detecting T3/T4 tumors (35/55) and a low sensitivity (43%–67%) and high specificity (75%–88%) in detecting T3cd/T4 tumors (15/55). For detecting serosal involvement and extramural vascular invasion, MRI had a high sensitivity and moderate specificity, as well as a moderate sensitivity and specificity in the detection of nodal involvement. Interobserver agreements were predominantly good; the more experienced reader achieved better results in the majority of these categories. LIMITATIONS: The study was limited by its retrospective nature and moderate number of inclusions. CONCLUSIONS: MRI has a good sensitivity for tumor invasion through the bowel wall, extramural vascular invasion, and serosal involvement. In addition, together with its superior liver imaging, MRI might become the optimal staging modality for colon cancer. However, more research is needed to confirm this. See Video Abstract at http://links.lww.com/DCR/A309.

Application-oriented extensions of profile flags

A glaucoma treating composition and method of treating glaucoma by administering the glaucoma treating composition to a patient are provided. The glaucoma treating composition comprises a carbostyril derivative, or acid addition salt thereof, having an intraocular pressure reducing activity in combination with an ophthalmically acceptable carrier, the barbostyril derivative being represented by the formula: wherein R1 and R2 are each lower alkyl, and the carbon-to-carbon bond between the 3-position and the 4-position of the carbostyril skeleton is a single bond or double bond.

Prognostic value of cardiovascular MR imaging biomarkers on outcome in peripheral arterial disease: a 6-year follow-up pilot study

The objective of this pilot study was to explore the prognostic value of outcome of cardiovascular magnetic resonance (MR) imaging biomarkers in patients with symptomatic peripheral arterial disease (PAD) in comparison with traditional risk factors. Forty-two consecutive patients (mean age 64 ± 11 years, 22 men) referred for contrast-enhanced MR angiography (CE-MRA) were included. At baseline a comprehensive cardiovascular MRI examination was performed: CE-MRA of the infra-renal aorta and run-off vessels, carotid vessel wall imaging, cardiac cine imaging and aortic pulse wave velocity (PWV) assessment. Patients were categorized for outcome at 72 ± 5 months follow-up. One patient was lost to follow-up. Over 6 years, six patients had died (mortality rate 14.6 %), six patients (14.6 %) had experienced a cardiac event and three patients (7.3 %) a cerebral event. The mean MRA stenosis class (i.e., average stenosis severity visually scored over 27 standardized segments) was a significant independent predictor for all-cause mortality (beta 3.0 ± standard error 1.3, p = 0.02). Descending aorta PWV, age and diabetes mellitus were interrelated with stenosis severity but none of these were significant independent predictors. For cardiac morbidity, left ventricular ejection fraction (LVEF) and mean MRA stenosis class were associated, but only LVEF was a significant independent predictor (beta −0.14 ± 0.05, p = 0.005). Diabetes mellitus was a significant independent predictor for cerebral morbidity (beta 2.8 ± 1.3, p = 0.03). Significant independent predictors for outcome in PAD are mean MRA stenosis class for all-cause mortality, LVEF for cardiac morbidity and diabetes mellitus for cerebral morbidity.