Diagnosis and Staging of Pancreatic Cancer: Comparison of Mangafodipir Trisodium Enhanced MR Imaging and Contrast-Enhanced Helical Hydro-CT

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1 Wolfgang Schima 1 Reinhold Függer 2 Ewald Schober 1 Claudia Oettl 1 Peter Wamser 2 Florian Grabenwöger 1 J. Mark Ryan 3 Gottfried Novacek 4 Received November 2, 2001; accepted after revision February 19, Supported by the Ludwig oltzmann Institute for Clinical and Experimental Radiologic Research. 1 Department of Radiology, University of Vienna, Waehringer Guertel 18-20, Vienna, ustria. ddress correspondence to W. Schima. 2 Department of Surgery, University of Vienna, Vienna, ustria. 3 Department of Vascular/Interventional Radiology, Duke University Medical Center, DUMC 3808, Durham, NC Department of Internal Medicine 4, Division of Gastroenterology, University of Vienna, Vienna, ustria. JR 2002;179: X/02/ merican Roentgen Ray Society Diagnosis and Staging of Pancreatic Cancer: Comparison of Mangafodipir Trisodium Enhanced MR Imaging and Contrast-Enhanced Helical Hydro-CT OJECTIVE. The purpose of this study was to compare mangafodipir trisodium enhanced MR imaging performed with a phased array coil and contrast-enhanced single-detector helical CT for accuracy in the detection and local staging of pancreatic adenocarcinoma and in the differentiation between cancer and focal pancreatitis. SUJECTS ND METHODS. Forty-two patients with suspected pancreatic masses underwent contrast-enhanced helical CT and mangafodipir trisodium enhanced MR imaging at 1.5 T. The images were assessed for the presence or absence of tumors; characterization of masses; and presence of vascular invasion, lymph node metastases, or liver metastases. Imaging findings were correlated with findings at laparotomy, laparoscopy, biopsy, or follow-up. RESULTS. Focal masses were present in 36 patients (cancer, n = 26; focal pancreatitis, n = 7; other, n = 3). The sensitivity for lesion detection of MR imaging was 100% and of CT, 94%. Two small malignant lesions were missed on CT. For the diagnosis of tumor nonresectability, the sensitivity of MR imaging and CT was 90% and 80%, respectively. Liver metastases were missed on MR imaging in one of the eight patients and on CT in four. For differentiation between adenocarcinoma and nonadenocarcinoma, the sensitivity of MR imaging was 100% (positive predictive value, 90%; negative predictive value, 100%), and the sensitivity of CT was 92% (positive predictive value, 80%; negative predictive value, 67%). Receiver operating characteristic analysis revealed that the mean area under the curve for MR imaging was and for CT, (not significant). CONCLUSION. Mangafodipir trisodium enhanced MR imaging is as accurate as contrast-enhanced helical CT for the detection and staging of pancreatic cancer but offers improved detection of small pancreatic metastases and of liver metastases compared with CT. D espite the poor prognosis of patients with pancreatic cancer, surgical resection is still the only potentially curative treatment for the disease. Unfortunately, many patients present with advanced disease, so only 5 22% are considered to be candidates for resection at the time of diagnosis [1]. Patients who undergo curative surgery have 5-year survival rates that range from 17% to 36% [1], and patients with small malignancies ( 2 cm in diameter) have the best prognosis [2]. Therefore, early diagnosis and assessment of tumor resectability are the important tasks for diagnostic imaging. lthough endosonography [3] has recently been reported to offer an alternative imaging method for diagnosis, helical CT has been the standard technique for the diagnosis and staging of pancreatic carcinoma. Helical CT is a robust modality and provides excellent anatomic resolution if thin-slice techniques are used. The technical aspects of single-slice helical CT have been improved by the development of dual-phase CT and hydro-ct [4]. In dual-phase CT, the pancreas is scanned twice after a single injection of contrast material: once during the pancreatic parenchymal phase, which provides the best tumor contrast and good vessel opacification, and a second time during the portal venous phase to scan for liver metastases [4, 5]. In helical hydro-ct, the oral administration of a positive contrast agent before scanning has been replaced by the oral administration of approximately 1000 ml of water and IV administration of hyoscine-n-butyl bromide (uscopan; oehringer, Ingelheim, Germany) to reduce peristalsis. This technique distends the stomach and duodenum more and better delineates the pancreas against the water-filled duodenum [6]. JR:179, September

2 Schima et al. Gadolinium-enhanced MR imaging has been shown to be equivalent or even superior to CT for imaging the pancreas [7 9]. Recently, technical advances, such as high-fieldstrength MR imaging with a phased array coil [10] and ultrafast imaging [8], have provided excellent results in terms of the detection and staging of pancreatic cancer. Mangafodipir trisodium (formerly known as manganese dipyridoxal diphosphate [Mn-DPDP]; mersham Health, Oslo, Norway) is a new organ-specific contrast agent that was originally developed for MR imaging of the liver. However, Gehl et al. [11, 12] have shown that uptake of mangafodipir trisodium also occurs in the pancreatic parenchyma but not in pancreatic tumors, leading to improved conspicuity of pancreatic cancers. With its propensity to be taken up by the liver and pancreas but not metastases, mangafodipir trisodium could be an efficient contrast agent for the MR imaging detection and staging of pancreatic cancer. In a study comparing gadolinium- and mangafodipir trisodium enhanced MR images of patients with suspected pancreatic cancer, gradient-recalled echo images that were enhanced with mangafodipir trisodium were significantly better at delineating pancreatic tumors than those enhanced with gadolinium chelates [13]. The purpose of our study was to compare prospectively the diagnostic yield of mangafodipir trisodium enhanced MR imaging performed with a phased array coil and contrast-enhanced helical CT in the detection of pancreatic masses and staging of pancreatic cancer. Subjects and Methods Patients During a period of 20 months, 42 patients referred to our institution with suspected pancreatic malignancy were enrolled in the study. The study group consisted of 24 men and 18 women with a mean age of 61 years (range, years). ll patients were prospectively examined using contrast-enhanced MR imaging and contrast-enhanced helical CT of the pancreas and liver. We obtained informed written consent from all patients before inclusion in the study. Final diagnoses were cancer in 26 patients, focal pancreatitis in seven patients, a cyst in one patient, a teratoma in one patient, metastases from hypernephroma in one patient, and no tumor in six patients. The mean lesion size was 3.7 cm (range, 1 8 cm). Twelve lesions were smaller than 3 cm in diameter, and seven tumors had a diameter of 2 cm or less. The final diagnoses were based on laparotomy or laparoscopy with intraoperative sonography and biopsy in 21 patients and on CT-guided biopsy of suspected liver metastases in three patients, of the primary tumor in three patients, and of a pseudocyst in one patient. biopsy of tumor using endoscopic retrograde cholangiopancreatographic guidance and subsequent follow-up were performed in one patient. In the other 13 patients, follow-up results over months were available to corroborate the diagnosis of benignity. MR Imaging In all patients, MR imaging was performed on a 1.5-T unit (Vision [n = 30 patients], Siemens, Erlangen, Germany; or CS-NT [n = 12 patients], Philips, est, The Netherlands) using a phased array torso coil. For both MR units, almost identical imaging parameters were used in all patients. When the Vision MR unit was used, T1- weighted breath-hold fast low-angle shot (FLSH) gradient-recalled echo images with and without fat suppression were obtained before and after the administration of contrast material. Imaging parameters of the FLSH pulse sequences were as follows: TR/TE, 174.9/4.1; flip angle, 80 ; number of acquisitions, 1; matrix size, ; 1 breath-hold; and acquisition time, 22 sec. The slice thickness was 8 mm and the slice gap was 0.8 mm for evaluation of the liver and 5 and 0.5 mm, respectively, for evaluation of the pancreas. The imaging parameters for the fat-suppressed FLSH sequences were as follows: 86.5/4.1; number of acquisitions, 1; matrix size, ; 2 breath-holds; acquisition time, 2 19 sec; slice thickness, 5 mm; and slice gap, 0 mm. In all patients, mangafodipir trisodium (Teslascan, mersham Health) was administered as an IV infusion at a dosage of 10 µmol/kg of body weight over min, depending on the volume of contrast material and venous access. fter starting the infusion, we obtained T2-weighted turbo spin-echo images with and without fat suppression. To evaluate the liver, we obtained T2-weighted fat-suppressed turbo spin-echo images using the following imaging parameters: 3500/88; number of acquisitions, 1; matrix size, ; echo-train length, 33; 2 breath-holds; acquisition time, 2 17 sec; and slice thickness, 8 mm/0 mm. To evaluate the pancreas, we obtained T2-weighted turbo spin-echo images using the following imaging parameters: 3300/138; number of acquisitions, 1; matrix size, ; echo-train length, 29; 2 breath-holds; acquisition time, 2 17 sec; and slice thickness, 5 mm/0 mm. Optionally, additional multidetector MR cholangiopancreatographic pulse sequences (half-fourier acquisition single-shot turbo spin echo [HSTE]) were performed if tumors were present in the head of the pancreas. Twenty minutes after the start of contrast infusion, the T1- weighted pulse sequences were repeated. When the CS-NT MR unit was used, T1- weighted turbo field-echo, spin-echo, and fat-suppressed spin-echo sequences were performed. The following parameters were used to obtain the turbo field-echo images: 15/4.8; number of acquisitions, 1; matrix size, ; acquisition time, 3 min 39 sec; slice thickness, 5 mm; and slice gap, 2.5 mm over contiguous slices. For the spin-echo imaging, the following parameters were used: 600/14; number of acquisitions, 4; matrix size, ; acquisition time, 4 min 45 sec; slice thickness, 5 mm; and slice gap, 0.5 mm. The fat-suppressed spin-echo images were obtained with the following parameters: 700/14; number of acquisitions, 4; matrix size, ; acquisition time, 5 min 31 sec; slice thickness, 8 mm; and slice gap, 0.8 mm. fter starting the infusion of mangafodipir trisodium, we obtained T2- weighted fat-suppressed turbo spin-echo images to evaluate the liver (3000/100; number of acquisitions, 4; matrix size, ; echo-train length, 21; acquisition time, 2 min 31 sec; slice thickness, 8 mm; and slice gap, 0.8 mm). Non fat-suppressed turbo spin-echo images were obtained to evaluate the pancreas (3000/100; number of acquisitions, 4; matrix size, ; echo-train length, 18; acquisition time, 3 min 12 sec; slice thickness, 5 mm; and slice gap, 0.5 mm). Optionally, a two- or three-dimensional turbo spin-echo MR cholangiopancreatographic pulse sequence was performed if masses were present in the pancreatic head. Twenty minutes after starting the infusion, we repeated the T1- weighted pulse sequences. CT CT scans were obtained using either of two helical scanners (VE1, Philips; or Somatom Plus 4, Siemens). fter unenhanced scans of the liver and pancreas were obtained, dual-phase contrast-enhanced scans of the liver and pancreas were obtained. efore scanning was performed, ml of water was administered orally as a contrast agent and 20 mg of hyoscine-n-butylbromide (uscopan) was IV administered to reduce peristaltic artifact. Two helical sequences were performed after the IV infusion of ml (300 mg/ml) of nonionic contrast material at a rate of 4 ml/sec. The first sequence was performed 40 sec after the initiation of infusion, consisted of thin-slice images (slice thickness, 3 mm; table feed, 5 mm; reconstruction interval, 3 mm), and covered the pancreas in the pancreatic phase. The second sequence (slice thickness, 5 mm; table feed, 8 mm; reconstruction interval, 4 mm) began after a minimal interscan delay (68 75 sec after the initiation of infusion) during the portal venous phase and covered the liver and pancreas. Image nalysis CT and MR images of all patients were separately analyzed in a prospective fashion. Two radiologists who were unaware of the results of other imaging studies and the findings at surgery and histopathologic examination evaluated all the images in consensus. To minimize any learning bias, we scheduled a 3-month interval between viewing the CT scans and viewing the MR images of the same patient. Pancreatic adenocarcinoma was characterized on helical CT and on mangafodipir trisodium enhanced MR imaging as a hypodense mass or on T1-weighted as a hypointense mass that showed less or no enhancement, respectively, compared with the surrounding pancreatic parenchyma [12]. 718 JR:179, September 2002

3 Diagnosis and Staging of Pancreatic Cancer Tumor Detection Tumor size was determined by measuring the hypodense or hypointense area on CT or MR images. When pancreatitis was severe and the tumor margins could not be delineated completely, the tumor was measured in the longest diameter assessable. For all MR images and CT studies, the observers classified the presence or absence of lesions in the pancreas on a 5-point confidence scale (1 = definitely present, 2 = probably present, 3 = indeterminate, 4 = probably absent, 5 = definitely absent). If a lesion was present, the observers recorded its size and location. tween benign and malignant masses was also compared using receiver operating characteristic analysis [16]. lternative free response receiver operating characteristic curves were calculated for the observers CT and the MR imaging interpretations by plotting the true-positive fraction against the likelihood of obtaining a false-positive diagnosis. The diagnostic accuracy of each modality was estimated by calculating the mean area under the receiver operating characteristic curve (i.e., the mean z index). Results Tumor Detection and Characterization Tumor Extension and Resectability To assess for vascular invasion, the observers focused their attention on six vascular structures: the main portal vein, portal venous confluence, superior mesenteric artery and vein, celiac trunk, and hepatic artery. Invasion of the splenic artery, splenic vein, and spleen was not considered critical because they can be resected in pancreatic tail tumors. CT or MR imaging evidence of vascular compromise was defined as vessel occlusion or invasion. We used the criteria established by Lu et al. [14] and O Malley et al. [15] with some modifications to define the degree of vascular invasion. Tumors with no contiguity (defined as grade 0 by Lu et al.) and tumors with less than one-quarter circumference of arteries (defined as grade 1 by Lu et al.) were deemed resectable. Limited invasion of the portal vein, venous confluence, or the superior mesenteric vein was not considered an absolute contraindication to surgery because a radical tumor resection with venous reconstruction can be performed by our pancreas surgeons. Therefore, between one quarter and one half of the circumference of the vein contiguous with tumor (defined as grade 2 by Lu et al.) was still considered resectable [15]. The short-axis diameter of enlarged lymph nodes and the presence or absence of liver metastases and of peritoneal implants were recorded. Tumors were deemed unresectable when enlarged distant (nonperipancreatic) lymph nodes, liver metastases, or peritoneal implants were present. On the basis of the morphology and signal intensity of the lesion and on the aforementioned criteria, the observers then characterized each lesion as benign or malignant using a 5-point scale. In patients with suspected malignant masses, resectability or nonresectability of the tumor was rated on a 5-point scale (1 = definitely resectable, 2 = probably resectable, 3 = indeterminate, 4 = probably nonresectable, 5 = definitely nonresectable). Statistical nalysis To evaluate the diagnostic yield of MR imaging and CT studies, we determined the sensitivity and specificity of each modality for the detection of pancreatic tumors, for the differentiation between benign and malignant masses, and for the assessment of tumor resectability, and we calculated the 95% confidence intervals (CIs). The chi-square test was used to compare sensitivities and specificities. p value of less than 0.05 was considered significant. The performance of CT and MR imaging in differentiating be- JR:179, September 2002 Of the 36 patients with pancreatic masses, mangafodipir trisodium enhanced MR imaging detected all the masses, for a sensitiv- ity of 100%, and contrast-enhanced helical CT detected 34 of the 36 lesions, for a sensitivity of 94% (95% CI, ) (Figs. 1 and 2). Cancer was found in 26 patients, and other masses were found in 10 patients. For the differentiation of pancreatic adenocarcinoma versus nonadenocarcinoma (Table 1), the sensitivity of MR imaging and CT in the detection of malignancy was 100% and 92% (95% CI, ), respectively. The positive predictive value was 90% for MR imaging and 80% for CT, and the negative predictive value was 100% for MR imaging and 67% for CT. The mean z index for the differentiation of benign lesions from malig- C Fig year-old man with unresectable tumor of pancreatic body and tail., Thin-section helical CT image obtained during pancreatic phase reveals large pancreatic tumor (arrow) with tumor surrounding celiac trunk and hepatic artery., Unenhanced T1-weighted gradient-recalled echo MR image shows large hypointense tumor that is not well delineated. C, Mangafodipir trisodium enhanced T1-weighted gradient-recalled echo MR image differentiates between hypointense tumor and enhancing normal parenchyma (solid arrow) better than. However, extent of vascular encasement (open arrow) is better depicted by CT scan () than by MR images ( and C). 719

4 Schima et al. nant tumors was for CT and for MR imaging. However, the difference between the mean z index values was not statistically significant because of the sample size (two-tailed t test, p = 0.41) (Fig. 3). Three false-positive diagnoses of cancer (final diagnosis: focal pancreatitis, n = 2; cyst in a patient with liver metastases from rectal cancer, n = 1) were based on MR imaging findings (Fig. 4). Six false-positive diagnoses of cancer (final diagnosis: focal pancreatitis, n = 4; simple cyst in a patient with liver metastases from rectal cancer, n = 1; no tumor seen during follow-up, n = 1) resulted from interpretations of contrast-enhanced helical CT scans (Fig. 5). Tumor Resectability Of the 26 patients with proven pancreatic cancer, one was not evaluated further because of his poor general medical condition. In the 25 re- Fig year-old woman with small pancreatic tumor that was not revealed on CT., ERCP image shows slight narrowing of pancreatic duct (arrow) and ductal dilatation. Sphincterotomy was performed, and pancreatic stent was placed. iopsy results were negative for tumor., Contrast-enhanced CT scan fails to depict tumor (arrow) around stent in dilated common bile duct. C, Unenhanced T1-weighted gradient-recalled echo MR image shows inhomogeneity of pancreatic head, but does not show tumor. D, Mangafodipir trisodium enhanced T1-weighted gradient-recalled echo MR image shows slight dilatation of common bile duct (long arrow) and pancreatic duct (short arrow). E, Mangafodipir trisodium enhanced MR image obtained at lower level than C and D reveals small irregular hypointense tumor (arrows) at pancreatobiliary junction. Mass was proven to be adenocarcinoma at surgery. ( 2) D 720 C E JR:179, September 2002

5 Diagnosis and Staging of Pancreatic Cancer maining patients, 10 pancreatic tumors were found to be resectable and 15, nonresectable. Mangafodipir trisodium enhanced MR imaging enabled the correct diagnosis of resectability in nine patients and of nonresectability in 14 patients; one false-negative diagnosis (missed liver metastases) and one false-positive diagnosis (invasion of the portal vein, which could be treated by radical resection with venous interposition) were recorded. The sensitivity for diagnosing nonresectability was 90% (95% CI, ) and the specificity, 93% (95% CI, ). Contrast-enhanced helical CT enabled the correct diagnosis of resectability in nine patients and of nonresectability in 12 patients; three false-negative diagnoses (missed liver metastases) (Fig. 4) and one false-positive diagnosis (invasion of the portal vein, which could be treated by radical resection with venous interposition) were recorded. The sensitivity was 80% (95% CI, ) and specificity, 60% (95% CI, ). Overall, liver metastases were present in eight patients. In four patients (multiple metastases, n = 3; solitary, n = 1), liver metastases were shown on both CT and MR imaging. The observers missed small liver metastases (0.5 1 cm in diameter) on MR imaging in one patient and on CT in four patients (Fig. 6). However, in one of these patients, unresectability was correctly diagnosed at CT because vascular encasement was present. Discussion Surgical resection remains the treatment of choice for patients with pancreatic cancer. It is currently the only potentially curative therapy [1]. Unfortunately, most patients present with advanced disease at the time of diagnosis. surgeon s ability to successfully treat a patient with pancreatic cancer depends on the ability and diagnostic accuracy of imaging techniques to detect small tumors that do not disrupt the contour of the organ and reliably characterize tumor resectability. Contrast-enhanced helical CT has been the standard technique for detection and staging of pancreatic cancer [4, 17]. The purpose of our study was to compare the diagnostic accuracy of contrast-enhanced single-detector helical CT and MR imaging in the detection of focal pancreatic lesions and the staging of pancreatic cancer. Some studies have been performed to compare MR imaging and CT for the detection of pancreatic cancer [7, 9, 18]. The results of the study conducted by the Radiology Diagnostic Oncology Group TLE 1 Differentiation etween denocarcinoma and Nonadenocarcinoma by MR Imaging and by CT MR Imaging Diagnosis CT Diagnosis Final Diagnosis denocarcinoma Nonadenocarcinoma denocarcinoma Nonadenocarcinoma denocarcinoma Nonadenocarcinoma indicated that dynamic CT is superior to unenhanced non breath-hold MR imaging for the assessment of resectability [7]. Gadoliniumenhanced dynamic MR imaging performed during breath-holding proved to be equal to or slightly better than single-slice helical CT in lesion detection [9, 18]. However, these studies have shown mixed results for the determination of local tumor extension and vascular involvement on CT and MR imaging [9, 18]. In both studies, the question about the presence of liver metastases was not addressed. Recently, mangafodipir trisodium enhanced MR imaging using a whole-body coil has been shown to be effective in the detection and staging of pancreatic cancer [19, 20]. In the study of Rieber et al. [19], helical CT enabled detection of eight of eight pancreatic tumors and MR imaging, seven of eight; however, mangafodipir trisodium enhanced MR imaging improved tumor delineation and diagnostic confidence compared with helical CT. In the study performed by Romijn et al. [20], the detection rate for cancer was slightly improved using mangafodipir trisodium enhanced MR imaging than using single-detector helical CT. However, the accuracy for tumor Fig. 3. Graph shows differentiation between benign lesions and pancreatic adenocarcinoma by receiver operating characteristic analysis. Mean area under curve is for CT (solid line) and for MR imaging (dotted line) (not significant). True-Positive Fraction staging was not improved [20]. MR imaging was equal to CT for the assessment of vascular invasion, and both modalities missed omental metastases [20]. One of the most difficult issues in imaging patients with pancreatic cancer is the assessment of vascular invasion [14, 15]. Our findings confirm the results of Romijn et al. [20]: Mangafodipir trisodium enhanced MR imaging does not improve the staging of pancreatic cancer by revealing vascular encasement. The presence of duodenal invasion is displayed even better on helical CT because the duodenum can be distended after peroral administration of a negative contrast agent, water. Unless a costly negative oral contrast agent is used at MR imaging, delineation of the duodenal wall is difficult. Extensive vascular invasion is also better displayed by helical CT because it may show dilatation of the peripancreatic veins, a finding that is suggestive of peripancreatic tumor invasion [21]. Even gadolinium-enhanced MR imaging is limited in its ability to exactly delineate vascular involvement, especially of the portal vein as a result of its oblique orientation [10, 18]. Helical CT may take another big step forward with the use of multidetector CT False-Positive Fraction JR:179, September

6 Schima et al. Fig year-old man with focal pancreatitis misdiagnosed as pancreatic adenocarcinoma on MR imaging and CT., Helical CT scan shows hypoattenuating mass (straight arrow) in pancreatic head adjacent to venous confluence. Half (180 of circumference) of superior mesenteric artery is surrounded by mass (curved arrows). djacent CT slices (not shown) revealed no abnormalities to suggest chronic pancreatitis., Mangafodipir trisodium enhanced T1-weighted gradient-recalled echo MR image reveals unenhancing mass (curved arrow) in pancreatic head around superior mesenteric artery. Remainder of pancreatic head (straight arrow) shows normal enhancement of parenchyma. Fig year-old woman with focal fatty infiltration that was misdiagnosed as tumor on CT., Thin-section CT scan obtained during pancreatic phase shows small hypodense lesion (arrow) in pancreatic head adjacent to superior mesenteric vein., Unenhanced T1-weighted gradient-recalled echo MR image shows that pancreatic head is homogenous. C, Mangafodipir trisodium enhanced MR image reveals homogenous uptake of mangafodipir trisodium (arrows); this finding ruled out tumor. Findings on contiguous slices (not shown) were similar. Diagnosis of focal fatty infiltration is most likely. Presence of tumor was ruled out by follow-up of patient over 2 years. 722 Preliminary experience with multidetector array CT has shown promising results regarding the three-dimensional display of vascular encasement [22]. Mangafodipir trisodium is an organ-specific MR contrast agent administered slowly by infusion. This agent does not lead to a T1-shortening of the blood sufficient to be exploited for MR angiography. However, the problem of black blood imaging can be overcome by new breath-hold gradient-recalled echo pulse sequences (e.g., fast imaging with steady-state free precession [Siemens], balanced fast field echo [Philips]), which render the vasculature bright even without a contrast agent. These pulse sequences may be used to supplement contrast-enhanced MR images obtained during the pancreatic phase [23]. We found that MR imaging was superior to CT for the detection of liver metastases, although the difference did not reach statistical significance because too few patients presented with metastases. This finding is of no clinical relevance because if contrast-enhanced MR imaging reveals more liver metastases than CT, nonresectability is indicated by the presence of at least one metastasis [24]. In three of the eight patients with liver metastases in our study, CT findings were negative, but MR imaging revealed small metastases. lthough one may speculate that mangafodipir trisodium enhanced MR imaging may be superior to helical CT for the depiction of liver metastases, the number of C JR:179, September 2002

7 Diagnosis and Staging of Pancreatic Cancer patients with liver metastases in this series was too small to prove this hypothesis. In these patients, the surgical strategy may be changed. efore laparotomy is performed, laparoscopy, which is associated with only minimal morbidity, can be used for the detection and biopsy of small metastases [24]. In a study of patients with small pancreatic metastases ( 2 cm) by Irie et al. [25], gadolinium-enhanced MR imaging revealed seven of eight and helical CT only five of eight small pancreatic metastases. In our study, mangafodipir trisodium enhanced MR imaging depicted seven of seven small pancreatic metastases, whereas CT failed to show two. lthough the number of small malignancies in each of the two series was too small to reach statistical significance, these findings suggest that contrast-enhanced MR imaging is superior to CT in delineating small malignancies. Differentiation between pancreatic adenocarcinoma and focal chronic pancreatitis remains a challenge. The lack of mangafodipir Fig year-old woman with cancer of pancreatic head and solitary liver metastasis that was missed on CT., Thin-section helical CT scan obtained during pancreatic phase shows contiguity of tumor (arrow) to lateral wall of venous confluence., CT image obtained during portal venous phase fails to show focal liver lesion. Contiguous slices (not shown) also failed to reveal lesion. C, Mangafodipir trisodium enhanced T1-weighted fat-suppressed gradient-recalled echo MR image reveals hypointense mass (arrow) in pancreatic head. Ductal dilatation and atrophy of pancreatic body and tail are visible. Enhancement of atrophic parenchyma is minimal. D, Mangafodipir trisodium enhanced gradient-recalled echo MR image reveals small subcapsular focal liver lesion (arrow). Lesion was not seen on T2-weighted MR images (not shown), which ruled out presence of cyst. ll other more centrally located hypointense structures seen could be identified as portal or hepatic venous branches by reviewing contiguous slices (not shown). trisodium uptake into the pancreatic parenchyma is not 100% specific for the presence of cancer. Neither masses associated with focal chronic pancreatitis nor atrophic parenchyma distal to an obstructed duct takes up a large amount of mangafodipir trisodium. In these areas, the presence of extensive fibrosis precludes considerable enhancement. ecause pancreatic tumors with equivocal findings on CT or MR imaging are potentially resectable, an important clinical concern is that these patients not be denied surgery. Therefore, the observers in our study were more likely to err on the side of making the diagnosis of cancer in the patients with focal pancreatitis. This tendency resulted in false-positive diagnoses of cancer on both CT and MR imaging. One patient with a presumed diagnosis of cancer on CT and MR imaging underwent Whipple s procedure. Histologic evaluation of the resected specimen revealed only focal pancreatitis. limitation of this study lies in the small number of patients with resectable tumors. C JR:179, September 2002 However, in general, the percentage of patients presenting with resectable pancreatic cancers is low. Moreover, almost all patients with cancer underwent either laparoscopy with intraoperative sonography or laparotomy to confirm the imaging findings. second limitation is the fact that all the images were assessed by viewing conventional hard-copy films. Managing large numbers of images generated by MR imaging, helical CT, and, even more so, by multidetector CT is easier using cine display. lthough cine display of the pancreas is preferred over film-based viewing for delineation of vascular structures, it is not superior in terms of lesion detection [26]. Even if cine viewing were advantageous, the results of this study would not have been biased because all CT and MR imaging examinations were reviewed on films. In conclusion, our study results show that mangafodipir trisodium enhanced MR imaging and helical CT are equivocal for local staging of pancreatic cancer but that mangafodipir D 723

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