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Comparison of Endoscopic Ultrasonography and Multidetector Computed Tomography for Detecting and Staging Pancreatic Cancer

John DeWitt, MD; Benedict Devereaux, MD; Melissa Chriswell, RN; Kathleen McGreevy, RN; Thomas Howard, MD; Thomas F. Imperiale, MD; Donato Ciaccia, MD; Kathleen A. Lane, MS; Dean Maglinte, MD; Kenyon Kopecky, MD; Julia LeBlanc, MD; Lee McHenry, MD; James Madura, MD; Alex Aisen, MD; Harvey Cramer, MD; Oscar Cummings, MD; and Stuart Sherman, MD
[+] Article and Author Information

From Indiana University Medical Center, Roudebush Veterans Affairs Medical Center, and Regenstrief Institute, Inc., Indianapolis, Indiana.


Grant Support: By 2 grants from the American Society of Gastrointestinal Endoscopy (Dr. Devereaux received an Endoscopic Outcomes and Effectiveness Award for 2001, and Dr. DeWitt received an Endoscopic Outcomes and Effectiveness Award for 2003) and 1 grant (K24 DK02756) to Dr. Imperiale from the National Institute of Diabetes and Digestive and Kidney Diseases.

Potential Financial Conflicts of Interest: Grants received: J. DeWitt (American Society of Gastrointestinal Endoscopy), B. Devereaux (American Society of Gastrointestinal Endoscopy).

Requests for Single Reprints: John M. DeWitt, MD, Department of Medicine, Division of Gastroenterology, Indiana University Medical Center, 550 North University Boulevard, UH 4100, Indianapolis, IN 46202-5121; e-mail, jodewitt@iupui.edu.

Current Author Addresses: Drs. DeWitt, Imperiale, Ciaccia, LeBlanc, McHenry, and Sherman, Ms. Chriswell, and Ms. McGreevy: Division of Gastroenterology, Department of Internal Medicine, Indiana University Medical Center, 550 North University Boulevard, UH 4100, Indianapolis, IN 46202-5121.

Dr. Devereaux, Level 1 Medical Centre, Holy Spirit Northside, 627 Rode Road, Chermside Q 4032, Australia.

Drs. Howard and Madura: Division of Surgery, Indiana University Medical Center, 550 North University Boulevard, Indianapolis, IN 46202-5121.

Ms. Lane: Indiana University School of Medicine, 1050 Wishard Boulevard, Indianapolis, IN 46202.

Drs. Maglinte and Aisen: Department of Radiology, Indiana University Medical Center, 550 North University Boulevard, Indianapolis, IN 46202-5121.

Dr. Kopecky: Irvington Radiologists, 7205 Shadeland Station, Suite 150, Indianapolis, IN 46256.

Drs. Cramer and Cummings: Division of Pathology, Indiana University Medical Center, 550 North University Boulevard, Indianapolis, IN 46202-5121.

Author Contributions: Conception and design: B. Devereaux, T.F. Imperiale, D. Ciaccia, K. Kopecky, H. Cramer, O. Cummings, S. Sherman.

Analysis and interpretation of the data: T.F. Imperiale, K.A. Lane, K. Kopecky, L. McHenry, O. Cummings, S. Sherman.

Drafting of the article: J. DeWitt.

Critical revision of the article for important intellectual content: J. DeWitt, T. Howard, T.F. Imperiale, K.A. Lane, D. Maglinte, J. LeBlanc, L. McHenry, J. Madura, A. Aisen, H. Cramer.

Final approval of the article: J. DeWitt, M. Chriswell, K. McGreevy, T. Howard, T.F. Imperiale, D. Ciaccia, K.A. Lane, D. Maglinte, K. Kopecky, J. LeBlanc, L. McHenry, J. Madura, A. Aisen, H. Cramer, O. Cummings, S. Sherman.

Provision of study materials or patients: J. DeWitt, T. Howard, D. Ciaccia, L. McHenry, J. Madura, S. Sherman.

Statistical expertise: J. DeWitt, T.F. Imperiale, K.A. Lane, J. LeBlanc.

Obtaining of funding: J. DeWitt, B. Devereaux.

Administrative, technical, or logistic support: M. Chriswell, K. McGreevy, J. LeBlanc, S. Sherman.

Collection and assembly of data: J. DeWitt, B. Devereaux, M. Chriswell, K. McGreevy, D. Ciaccia, D. Maglinte, K. Kopecky, J. LeBlanc, A. Aisen, O. Cummings.


Ann Intern Med. 2004;141(10):753-763. doi:10.7326/0003-4819-141-10-200411160-00006
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In this study, endoscopic ultrasonography was superior to multidetector CT for tumor detection and tumor staging but equivalent for nodal staging and determination of resectability of preoperatively suspected locoregional pancreatic cancer. A recent summary (31) of the 4 published trials (2124) to date (with surgical exploration in 121 patients), which compared dual-phase helical CT and endoscopic ultrasonography, concluded that endoscopic ultrasonography was statistically superior to CT for the detection and determination of resectability for pancreatic cancer. However, direct comparison of these studies is problematic because of the inclusion of patients with ampullary cancer (2123) and benign disease (22), use of endoscopic ultrasonography–guided fine-needle aspiration in only 1 study (24), inclusion of patients with distant metastasis detected on helical CT (23), variable CT technique and staging classifications used, and the relatively small numbers of patients enrolled. In the current study, patients with known or suspected benign disease, nonpancreatic cancer, or cancer with suspected locally advanced vascular (excluding portal vein) involvement or metastatic disease were excluded from enrollment. While these criteria may have underestimated the effect of CT obtained before enrollment, we believe they optimized identification of patients with probable locoregional malignancy who were most likely to benefit from surgery. In addition, these criteria are consistent with current standards of practice at most referral centers. In our study, 47% of the 53 patients with pancreatic cancer who underwent laparotomy had an R0 resection; this figure is higher than figures stated in previous reports (58).

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Figure.
Trial profile.

CT = computed tomography.

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CT vs. EUS for Pancreatic Cancer Staging: A Note of Caution to Clinicians
Posted on December 17, 2004
William M. Tierney
University of Oklahoma Health Sciences Center
Conflict of Interest: None Declared

To the Editor:

We congratulate Dewitt et al. for, "Comparison of Endoscopic Ultrasonography and Multidetector Computed Tomography for Detecting and Staging Pancreatic Cancer" (1). We highlight one inaccuracy and indicate limitations that temper acceptance of their conclusions into current patient care.

The authors incorrectly refer to the University of Michigan study (2) comparing EUS with helical CT as including patients with distant metastatic disease. Mertz et al. (3) did include 9 patients with metastatic disease in their study.

Our concerns relate to the authors' primary outcome: detection of unresectability. Tumors were deemed unresectable by distant metastatic disease or invasion of mesenteric vessels. Detection of distant metastases is best accomplished with CT, while both CT and EUS are useful for defining vascular invasion. This biases the analysis in favor of CT.

The Michigan study (2) specifically focused on vascular invasion. Dewitt et al. reported sensitivity for detecting T4 disease (EUS 88% vs. CT 71%). Presumably most had vascular invasion, but it is not specifically stated. Furthermore, it seems likely that at least 9 (6 liver and 3 distant nodal metastases detected intraoperatively) did not have complete dissection. This weakens the analysis regarding the ability of the tests to detect vascular invasion.

The protocol of performing EUS with fine needle aspiration (FNA) in all patients prior to CT is atypical. It leads to the unnecessary use of EUS in patients with distant disease and may lead to inflammatory changes in the pancreas confounding CT staging accuracy.

Most important is the problem of overstaging. Dewitt et al. reported that EUS and helical CT predictions of T4 disease were incorrect in 17% and 14%. This indicates patients with resectable disease would be denied potentially curative resection. The concept of deeming a patient unresectable by two imaging modalities has been suggested as the optimal approach, but is not perfect (4, 5). The authors' conclusions that CT alone should guide decision-making cannot be generalized into current practice. Future studies should not focus upon which single imaging modality is best, but rather what combination of tests, or staging algorithm, optimizes clinical outcomes.

1. DeWitt J, Devereaux B, Chriswell M, McGreevy K, Howard T, Imperiale TF, Ciaccia D, Lane KA, Maglinte D, Kopecky K, LeBlanc J, McHenry L, Madura J, Aisen A, Cramer H, Cummings O, Sherman S. Comparison of Endoscopic Ultrasonography and Multidetector Computed Tomography for Detecting and Staging Pancreatic Cancer. Annals Int Med. 2004;141 : 753- 763

2. Tierney WM, Francis IR, Eckhauser F, Elta G, Nostrant TT, Scheiman JM. The accuracy of EUS and helical CT in the assessment of vascular invasion by peripapillary malignancy. Gastrointest Endosc. 2001;53:182-8.

3. Mertz HR, Sechopoulos P, Delbeke D, Leach SD. EUS, PET, and CT scanning for evaluation of pancreatic adenocarcinoma. Gastrointest Endosc. 2000;52:367-71.

4. Tierney WM, Fendrick AM, Hirth RA, Scheiman JM. The Clinical and economic impact of alternative staging strategies for Adenocarcinoma of the Pancreas. Am J Gastro 2000; 95(7): 1708-13.

5. Kochman ML. EUS in pancreatic cancer. Gastrointest Endosc. 2002;56(4):S6-12.

Conflict of Interest:

None declared

Response to letter from Tierney W et al.
Posted on January 20, 2005
John M DeWitt
Indiana University Medical Center
Conflict of Interest: None Declared

We thank Drs. Tierney, Kochman and Scheiman for their interest in our article. We apologize for the incorrect reference cited.

We agree that CT and MRI are superior to EUS for detection of hepatic metastases from pancreatic cancer, since most of the right lobe of the liver cannot be seen by EUS. Therefore, EUS clearly cannot replace, but may supplement, other modalities for staging of the liver. However, EUS and EUS-FNA may detect and accurately sample small metastatic liver lesions missed by other imaging modalities (1). It also may be superior to CT for detection of celiac node metastases (2) and small quantities of peritoneal fluid (3). Therefore, the overall superiority of CT to detect distant metastases may bias the spectrum of disease for the study but does not bias the analysis. We do not believe that improved MDCT imaging of the right lobe of the liver, compared to EUS, creates a significant bias in favor of CT. Furthermore, limiting analysis of enrolled patients to only those patients with confirmed locoregional disease diminishes clinical application of our results.

Only four patients with pancreatic cancer in our study who underwent surgery did not have complete assessment of vascular invasion. Although not stated in our paper, all patients with T4 malignancy had invasion into vessels other than the splenic artery or splenic vein. Information concerning vascular invasion was omitted from our study principally due to the space limitation and to focus on the issues of detection, staging and resectability. We agree with Tierney et al. that this information is critical to determine preoperative staging and intend to publish this information separately.

All patients had either CT or MRI performed outside our institution prior to enrollment in the study. Furthermore, those with obvious metastatic disease were excluded. EUS-FNA was performed prior to MDCT used in our study. We believe that this practice is more the rule rather than the exception among tertiary care centers such as our institution. Although the risk of acute pancreatitis following EUS-FNA is 1-2%, there are no data to support the contention that this potential inflammation may alter accuracy of tumor staging by CT or MRI. In our study, most CT scans were performed the same day as the EUS potentially limiting this problem.

We agree that preoperative overstaging of pancreatic tumors would potentially preclude resectable tumors from proceeding to surgery. However, the protocol we employed generally utilized surgical resection only when one or both tests showed resectability. The more relevant question, however, is whether the use of two tests permits a clinically meaningful increase in resectability as compared to one study alone. Our study did not demonstrate this but may have been underpowered to demonstrate any difference. Despite a slightly increased positive predictive value of resectability when CT or MRI are used in combination EUS (4,5), this strategy remains debatable despite possible cost reductions (4). The use of EUS for pancreatic tumors, however, will likely remain dependent on availability, referral patterns and local expertise.

References

1. DeWitt J, LeBlanc J, McHenry L, Ciaccia D, Imperiale T, Chappo J, Cramer H, McGreevy K, Chriswell M, Sherman S. Endoscopic ultrasound- guided fine needle aspiration cytology of solid liver lesions: a large single-center experience. Am J Gastroenterol. 2003;98:1976-81.

2. Romagnuolo J, Scott J, Hawes RH, Hoffman BJ, Reed CE, Aithal GP, Breslin NP, Chen RY, Gumustop B, Hennessey W, Van Velse A, Wallace MB. Helical CT versus EUS with fine needle aspiration for celiac nodal assessment in patients with esophageal cancer. Gastrointest Endosc. 2002; 55:648-54.

3. Chang KJ, Albers CG, Nguyen P. Endoscopic ultrasound-guided fine needle aspiration of pleural and ascitic fluid. Am J Gastroenterol. 1995; 90:148-50.

4. Soriano A, Castells A, Ayuso C, Ayuso JR, de Caralt MT, Gines MA, Real MI, Gilabert R, Quinto L, Trilla A, Feu F, Montanya X, Fernandez-Cruz L, Navarro S. Preoperative staging and tumor resectability assessment of pancreatic cancer: prospective study comparing endoscopic ultrasonography, helical computed tomography, magnetic resonance imaging, and angiography. Am J Gastroenterol. 2004; 99:492-501.

5. Ahmad NA, Lewis JD, Siegelman ES, Rosato EF, Ginsberg GG, Kochman ML.Role of endoscopic ultrasound and magnetic resonance imaging in the preoperative staging of pancreatic adenocarcinoma. Am J Gastroenterol. 2000; 95:1926-31.

Conflict of Interest:

None declared

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Summary for Patients

Detecting Pancreatic Cancer and Its Spread

The summary below is from the full report titled “Comparison of Endoscopic Ultrasonography and Multidetector Computed Tomography for Detecting and Staging Pancreatic Cancer.” It is in the 16 November 2004 issue of Annals of Internal Medicine (volume 141, pages 753-763). The authors are J. DeWitt, B. Devereaux, M. Chriswell, K. McGreevy, T. Howard, T.F. Imperiale, D. Ciaccia, K.A. Lane, D. Maglinte, K. Kopecky, J. LeBlanc, L. McHenry, J. Madura, A. Aisen, H. Cramer, O. Cummings, and S. Sherman.

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