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Radiol 2332031111
Radiol 2332031111
Radiology
Willem M. L. L. G. Deserno,
MD, MSc
Mukesh G. Harisinghani, MD Preoperative Nodal Staging
Matthias Taupitz, MD, PhD
Gerrit J. Jager, MD, PhD
J. Alfred Witjes, MD, PhD
with Ferumoxtran-10 –
Peter F. Mulders, MD, PhD
Christina A. Hulsbergen van
enhanced MR Imaging1
de Kaa, MD, PhD
D. Kaufmann, MD PURPOSE: To prospectively evaluate ferumoxtran-10 – enhanced magnetic reso-
Jelle O. Barentsz, MD, PhD nance (MR) imaging for nodal staging in patients with urinary bladder cancer.
Index terms:
Bladder neoplasms, metastases, MATERIALS AND METHODS: Fifty-eight patients with proved bladder cancer
83.31, 83.33 were enrolled. Results of MR imaging performed before and after injection of
Bladder neoplasms, MR, 83.12141 ferumoxtran-10 were compared with histopathologic results in surgically removed
Iron lymph nodes. High-spatial-resolution three-dimensional T1-weighted magnetiza-
Magnetic resonance (MR), contrast
media
tion-prepared rapid acquisition gradient-echo (voxel size, 1.4 ⫻ 1.4 ⫻ 1.4 mm) and
T2*-weighted gradient-echo (voxel size, 0.8 ⫻ 0.8 ⫻ 3.0 mm) sequences were
Published online before print performed before and 24 hours after injection of ferumoxtran-10 (2.6 mg iron per
10.1148/radiol.2332031111 kilogram of body weight). On precontrast images, lymph nodes were defined as
Radiology 2004; 233:449 – 456
malignant by using size and shape criteria (round node, ⬎8 mm; oval, ⬎10 mm
axial diameter). On postcontrast images, nodes were considered benign if there was
1
From the Departments of Radiol- homogeneous decrease in signal intensity and malignant if decrease was absent or
ogy (W.M.L.L.G.D., G.J.J., J.O.B.),
Urology (J.A.W., P.F.M.), and Pathol- heterogeneous. Qualitative evaluation was performed on a node-to-node basis.
ogy (C.A.H.v.d.K.), University Medical Sensitivity, specificity, predictive values, and accuracy were evaluated with logistic
Center Sint Radboud, PO Box 9101, 6500 regression analysis.
HB Nijmegen, the Netherlands; Depart-
ments of Radiology (M.G.H.) and On-
cology (D.K.), Massachusetts General RESULTS: In 58 patients, 172 nodes imaged with use of ferumoxtran-10 were
Hospital, Boston, Mass; and Depart- matched and correlated with results of node dissection. Of these, 122 were benign
ment of Radiology, Charité Hospital Ber- and 50 were malignant. With nodal size and shape criteria, accuracy, sensitivity,
lin, Germany (M.T.). Received July 15,
2003; revision requested September 18; specificity, and positive and negative predictive values on precontrast images were
final revision received February 24, 92%, 76%, 99%, 97%, and 91%, respectively; corresponding values on postcon-
2004; accepted March 16. Address
correspondence to W.M.L.L.G.D. (e- trast images were 95%, 96%, 95%, 89%, and 98%. In the depiction of pelvic
mail: w.deserno@rad.umcn.nl). metastases, sensitivity and negative predictive value improved significantly at post-
Authors stated no financial relation- contrast compared with those at precontrast imaging, from 76% to 96% (P ⬍ .001)
ship to disclose. and from 91% to 98% (P ⬍ .01), respectively. At postcontrast imaging, metastases
Author contributions: (4 –9 mm) were prospectively found in 10 of 12 normal-sized nodes (⬍10 mm);
Guarantors of integrity of entire these metastases were not detected on precontrast images. Postcontrast images also
study, W.M.L.L.G.D., M.G.H., M.T.,
G.J.J., J.A.W., P.F.M., C.A.H.v.d.K., showed lymph nodes that were missed at pelvic node dissection in two patients.
J.O.B.; study concepts, W.M.L.L.G.D.,
M.G.H., M.T., J.O.B.; study design, CONCLUSION: Ferumoxtran-10 – enhanced MR imaging significantly improves
W.M.L.L.G.D., M.G.H., J.O.B.; litera- nodal staging in patients with bladder cancer by depicting metastases even in
ture research, W.M.L.L.G.D., M.G.H.,
G.J.J., J.A.W., J.O.B.; clinical studies, normal-sized lymph nodes.
W.M.L.L.G.D., M.G.H., M.T., J.A.W., © RSNA, 2004
P.F.M., C.A.H.v.d.K., D.K., J.O.B.; data ac-
quisition, W.M.L.L.G.D., M.G.H., M.T.,
J.A.W., P.F.M., C.A.H.v.d.K., D.K., J.O.B.;
data analysis/interpretation, all authors;
statistical analysis, W.M.L.L.G.D., G.J.J.;
manuscript preparation, W.M.L.L.G.D.,
J.O.B.; manuscript definition of intellec-
tual content, W.M.L.L.G.D., M.G.H., Cancer of the urinary bladder is one of the most common types of malignant tumor of the
M.T., G.J.J., J.A.W., P.F.M., C.A.H.v.d.K., urinary tract. Because the sequence of surgical or systemic treatment and the prognosis
J.O.B.; manuscript editing, M.G.H., G.J.J.,
J.A.W., C.A.H.v.d.K., J.O.B.; manuscript re- depend on the depth of tumor infiltration and the extent of metastatic lymph nodes (1),
vision/review, M.G.H., M.T., G.J.J., J.A.W., it is important to accurately assess the stage of the nodes prior to surgery. With current
P.F.M., C.A.H.v.d.K., J.O.B.; manuscript cross-sectional imaging modalities such as computed tomography (CT) and magnetic
final version approval, W.M.L.L.G.D.,
M.G.H., J.O.B. resonance (MR) imaging, we rely predominantly on nodal size for detecting metastases.
© RSNA, 2004 However, there is considerable overlap in size between benign and malignant nodes. By
using nodal size and morphology criteria, Jager et al (2) found that oval nodes with a
449
diameter larger than 10 mm and round
nodes with a diameter larger than 8 mm
could be characterized as malignant with
a sensitivity of 83% and specificity of
98%. With these criteria, however, the au-
Radiology
Volume 233 䡠 Number 2 Preoperative Nodal Staging of Urinary Bladder Cancer 䡠 451
RESULTS
TABLE 2
Results at Precontrast MR Imaging and Node-to-Node Comparison with
In two patients, minor side effects were Histologic Findings
seen after the start of ferumoxtran-10 in-
fusion, in the form of minor back pain Histologic Findings
Precontrast Imaging
Radiology
that disappeared after the infusion was Results Positive Negative All Nodes
stopped. After the infusion was reiniti- Positive 38 1 39
ated a few minutes later, the symptoms Negative 12 121 133
did not reappear. No medical treatment Total 50 122 172
was needed.
At pelvic lymph node dissection, an Note.—Positive results indicate metastatic nodes, and negative results indicate nonmetastatic
nodes. For precontrast MR imaging, accuracy was 92%; sensitivity, 76%; specificity, 99%; negative
average of nine nodes per patient (range, predictive value, 91%; and positive predictive value, 97%.
two to 21 nodes per patient) were re-
moved.
In 172 (43%) of 404 dissected nodes,
an accurate match could be made be- TABLE 3
tween histologic evaluation and MR im- Results at Postcontrast MR Imaging and Node-to-Node Comparison with
ages (Tables 2, 3). The remaining 232 Histologic Findings
nodes that could not be matched were
Histologic Findings
benign at histologic evaluation. Of the Postcontrast Imaging
172 matching nodes, 116 of the nodes Results Positive Negative All Nodes
that were nonmetastatic at histologic Positive 48 6 54
evaluation showed a signal intensity de- Negative 2 116 118
crease on the ferumoxtran-10 – enhanced Total 50 122 172
MR images (Fig 3). These were true-nega-
Note.—Positive results indicate metastatic nodes, and negative results indicate nonmetastatic
tive nodes on ferumoxtran-10 – enhanced nodes. For postcontrast MR imaging, accuracy was 95%; sensitivity, 96%; specificity, 95%; neg-
MR images. Of the 50 nodes that were ative predictive value, 98%; and positive predictive value, 89%.
metastatic at histologic evaluation, 48
showed no signal intensity decrease after
ferumoxtran-10 administration (true-
positive), and the other two showed a
decrease in signal intensity (false-nega-
tive).
The accuracy, sensitivity, specificity,
negative predictive value, and positive
predictive value of precontrast MR imag-
ing were 92%, 76%, 97%, 91%, and 97%,
respectively (Table 2); corresponding val-
ues for postcontrast MR imaging were
95%, 96%, 95%, 98%, and 89% (Table 3).
The sensitivity and negative predictive
value of the postcotrast imaging were sig-
nificantly better compared with those of
the precontrast imaging (P ⬍ .001 for
sensitivity, P ⬍ .01 for negative predictive
value); however, the change in specificity
Figure 3. T2*-weighted MR images (800/25.4, 30° flip angle, 3.0-mm section thickness) ob-
was not significant (P ⬎ .01).
tained in a plane parallel to psoas muscle. Precontrast image (left) shows normal-sized (7 ⫻ 3 mm)
Of the 50 metastatic lymph nodes, 38 node (ellipse). On postcontrast image (right), this node (circle) shows homogeneous signal
were enlarged (mean size, 15.3 mm; intensity decrease, and another normal-sized (7 ⫻ 4 mm) node with low signal intensity is visible
range, 10 –28 mm) on precontrast MR im- (ellipse). White area is a lymphocele. Histopathologic evaluation confirmed nonmetastatic nodes.
ages and 12 were normal in size (mean,
7.2 mm; range, 6 –9 mm). Ten of these 12
normal-sized nodes showed a lack of
ferumoxtran-10 uptake and signal inten- images (Fig 6). Six (5%) normal-sized these nodes were proved to be metastatic
sity decrease in focal areas on postcon- nodes were false-positive on these post- at histologic evaluation.
trast images, which suggested metastasis contrast MR images. Finally, extracapsular-spread disease was
(Figs 4, 5). Of the 122 benign nodes, one In nine patients, ferumoxtran-10 – en- correctly diagnosed at ferumoxtran-10–
node was false-positive on precontrast hanced MR imaging allowed metastatic enhanced MR imaging in another patient
MR images. This node was enlarged ac- nodes to be found outside of the surgical (Fig 8). Although the node was slightly ir-
cording to size criteria but was correctly field (Fig 7). In two of these nine patients, regular on precontrast images, a clearly reg-
classified as negative on the basis its low the metastatic nodes were normal-sized ular surface was seen at the low signal in-
signal intensity on the postcontrast MR benign nodes on precontrast images; tensity (normal) part and an irregular area
Volume 233 䡠 Number 2 Preoperative Nodal Staging of Urinary Bladder Cancer 䡠 453
niques and reduced respiratory and mo-
tion artifacts (13). Also, the higher
specificity in our study can be explained
by our use of a higher dose of contrast
agent (2.6 vs 1.7 mg Fe per kilogram of
Radiology
Volume 233 䡠 Number 2 Preoperative Nodal Staging of Urinary Bladder Cancer 䡠 455
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Radiology