Clinical Utility of Endoscopic Ultrasonography for Pancreatic Tumors

Endoscopic ultrasonography (EUS) has emerged as the most accurate single test for imaging pancreatic disease. Since the retrospective study by Yasuda et al. (1) which compared transcutaneous ultrasonography (US), computed tomography (CT), endoscopic retrograde cholangiopancreatography (ERCP) and angiography with EUS for the evaluation of pancreatic tumors, seven (2-9) other studies have appeared comparing EUS with various other pancreatic imaging techniques. The most recent articles appear in this issue. Palazzo et al. (2) prospectively show the value of EUS compared with standard techniques of US or CT. For patients with suspected pancreatic adenocarcinoma, EUS was more accurate for diagnosis and locoregional TN (tumor, lymph node) staging than US or CT, especially for lesions less than 3 cm. Yasuda et al. (3) show the accuracy of EUS in the locoregional staging of pancreatic cancer.

EUS has now been prospectively compared with US and CT (2,4), with US, CT and ERCP (5 - 10), with CT and ERCP (6), with CT and angiography (7), and with US and ERCP (8). All studies but two (4,8) excluded patients with suspected bile duct stones and evaluated only patients suspected of having pancreatic disease. These studies show that EUS is more accurate than any other test for diagnosis and staging of pancreatic tumors. EUS is also more accurate than CT for predicting resectability of a pancreatic mass (10).

However, as pointed out by Rösch and Classen (11), a critical attitude should be maintained in evaluating the real clinical utility of the small, discrete changes in pancreatic disease that are clearly and accurately imaged with EUS. Most patients with suspected pancreatic tumors will undergo at least 2 standard imaging tests during a work-up. To evaluate the clinical utility of EUS, comparing it with combined findings of conventional tests would be important. Two studies (5,6) have compared the findings of EUS with the findings of combined CT plus ERCP. In one study (6), EUS was more accurate than CT combined with ERCP; in the other study (5), results were less accurate. The difference most likely results from the different patient populations studied. Snady et al. (6) evaluated only patients with tumors less than 5 cm; 58 % were 3 cm or less. Rösch et al. (5) included patients with larger tumors ranging from 2 to 20 cm (mean 4.5 cm), and found CT combined with ERCP to be more accurate than EUS. These investigators (5) also reported that EUS was far superior to CT or ERCP for tumors less than 3 cm. Therefore, both studies indicate a clear relation between tumor size and the accuracy of the test. Examination of similar size tumors result in similar findings, with EUS being most valuable for tumors less than 3 cm. Tumors less than 3 cm are often not seen with CT; ERCP will provide excellent images of ducts, but only indirect information about parenchyma. Rösch et al. (5) further suggested EUS should be considered early in the evaluation of patients with suspected pancreatic tumors.

Of greatest interest in the data reported by Palazzo et al. (2) is the similar accuracy of US (64 %) and CT (66 %) for diagnosis of pancreatic carcinoma. If one excludes the 7 patients with tumors less than 3 cm from their data, where only 1 in 7 was seen by US or CT, the accuracy of US and CT then increases to about 80%. This finding confirms the importance of size of a pancreatic tumor in determining both its detectability by various techniques and the accuracy of those techniques in predicting resection status. For a test used to evaluate pancreatic tumors, sensitivity and specificity does not remain constant for different sizes of lesions (12). CT is quite accurate in predicting unresectable tumors, although it is not reliable in predicting resectability (12-14). When optimally performed, standard US appears to be equivalent to CT (15,16). Although CT scan can visualize the pancreas in over 90 % of cases, a tumor must be at least 2-3 cm in order to be detected (12,14). No mass may even be detected by CT scan in about 20% of pancreatic tumors thought to be resectable (14).

Therefore, an effective plan for diagnosis and treatment can be based on the size of the pancreatic lesion measured by standard US or CT without contrast (Figure 1). Studies (2,5,13,15,16) suggest that initial evaluation of suspected pancreatic tumors with US or CT without contrast will accurately stage pancreatic tumors larger than 5 cm. EUS is not likely to provide additional information for a tumor larger than 5 cm (2,5) since the EUS transducer cannot always be placed close enough to a lesion to bring its margins into optimal focus (1). For large tumors, CT scan with IV contrast can reliably confirm the extent of disease. In pancreatobiliary disease, CT scan relies primarily on distortions of fat planes in the area. Thus, given the natural history of patients with large tumors, it is quite likely that tissue planes will be altered and CT scan will be accurate. Diagnosis with fine needle biopsy or the improved method of ultrasound-guided core biopsy (17) followed by palliative bypass of biliary obstruction with an endoprosthesis or, depending on local expertise, surgical bypass, is straightforward (18,19).

For tumors less than 5 cm, fat planes may not appear to be altered because the tumor is small and still within the pancreas, or because there is tumor-associated weight loss with accompanying loss of the required fat planes. For lesions that appear localized to the pancreas on standard US or CT and are less than 5 cm, or event too small to be imaged, EUS will provide the information required to select the most appropriate management plan, i.e. therapeutic ERCP vs. laparotomy. Performing EUS early in the evaluation of such patients, as shown in Figure 1, is likely to be clinically effective. One study (5) has noted that EUS changed clinical management in 32 % of patients studied, thus influencing clinical outcome. Reviewing the data from other studies (1-5, 7-10) confirms that EUS will markedly affect management in about 1/3 of patients when it is used in the appropriate clinical setting.

If EUS shows that the lesion appears resectable, laparoscopy conducted to rule out small liver metastases generally not seen on CT scan (21,22) may prove beneficial prior to an attempt at resection. ERCP will quite effectively provide a diagnosis of common bile duct stones or confirm the presence of a stricture. However, for small tumors, CT scan with IV contrast is unlikely to provide any additional information (14). CT with IV contrast has been found to be correct in predicting resectability in only 38 % to 45 % of patients referred for resection of a presumed small pancreatic tumor (6, 20).

Many patients would be spared a major operation if the one in ten patients who has a potentially resectable pancreatic tumor with no evidence of metastasis or involvement of portal or other major vessels could be identified. As pointed out by Warshaw et al. (12,20), operative mortality and morbidity for pancreatic surgery remain high, except in specialized centers. Improvement in the accuracy of non-operative staging of small tumors is quite likely to have a significant impact on clinical outcome.

The most important prognostic factor which correlates with resectability, survival and natural history of pancreatic tumors appears to be the size of the lesion at the time of diagnosis (22-24). For patients with a tumor size of less than 4.5 cm confined to the pancreas, surgical resection offers the only possibility of cure and has been recommended for well-nourished patients with no other medical diseases and bilirubin levels that have returned to almost normal after biliary decompression with an endoprosthesis (18). Five-year survival rate for patients with this type of resectable tumor appears to be higher than is reported for patients with all types of "resectable" tumors (17,24).

Of the present conventional methods for diagnosis of small pancreatic lesions, ERCP is the most reliable. Depending on size, ERCP will detect 60% to 90% of lesions and will differentiate benign from malignant disease in about 75% (1,5,6,25,26). However, the limited information which ERCP provides about surrounding parenchyma and blood vessels reduces its utility for staging. Compared with EUS, successful ERCP provides superior imaging of the common bile duct and pancreatic duct. However, when ERCP does not visualize a part of the pancreatic duct or common bile duct, this area is usually seen clearly with EUS. In addition, small lesions in certain parts of the pancreas may not be detected by ERCP. EUS is able to diagnose small tumors less than 2 cm not found by any other imaging techniques.

Present limitations of EUS include: 1. Optimal focal range is relatively short, only 2-4cm from the transducer. Therefore, significant portions of the right lobe of the liver may not be visualized clearly. Also, optimal focus of vessels around a tumor larger than 5 cm may not always be attained. Development of EUS instruments with the capability of scanning at lower (3.5 MHz) as well as higher (15 MHz) frequencies may help to overcome these shortcomings. 2. Even though EUS is superior to other imaging techniques, the resolution of lymph nodes, particularly those less than 1 cm, and the criteria to distinguish malignant involvement, still require improvement. 3. The echo pattern and features of EUS images of various pancreatic diseases can appear quite similar; consequently, at the present time, criteria to distinguish different diseases overlap. Some of this overlap is inherent to the ultrasound pulses. However, some of the overlap is a result of the limited experience with interpretation of EUS images. When chronic pancreatitis has been diagnosed by other methods, EUS is at present not able to reliably differentiate focal chronic pancreatitis from carcinoma. Although EUS is helpful at times, this remains a diagnostic problem that requires several imaging tests and even laparotomy.

In summary, EUS is capable of providing unsurpassed resolution of pancreatic disease. EUS can detect and stage small pancreatic tumors, even those not seen with other techniques. EUS detects vascular involvement by pancreatic tumors as accurately as angiography (1,7,27). EUS can detect chronic pancreatitis in patients where other tests have not shown diagnostic findings (28,29). The evolution of EUS image interpretation as well as equipment improvements will further improve EUS accuracy.

1. Yasuda K, Mukai H, Fujimoto S et al.: The diagnosis of pancreatic cancer by endoscopic ultrasonography. Gastrointest Endosc 1988; 34: 1-8.

2. Palazzo L, Rosseau G, Gayet B et al.: Endosonographic ultrasonography in adenocarcinoma of the pancreas. Results of a prospective study with comparison to ultrasonography and CT scan. Endoscopy 1993; 25: 143-150.

3. Yasuda K, Mukai H, Nakajima M et al.: Staging of Pancreatic Carcinoma by Endoscopic Ultrasonography. Endoscopy 1993; 25: 151-155

4. Amouyai P, Palazzo L Ammouyai G et al.: Endosonography: promising method for diagnosis of extrahepatic cholestasis. Lancet 1989; ii: 1195- 1198.

5. Rösch T, Lorenz R, et al.: Endoscopic ultrasound in pancreatic tumor diagnosis. Gastrointest Endosc 1991; 37: 347-352.

6. Snady H, Cooperman A, Siegel J: Clinical effectiveness of endoscopic ultrasonography compared with computed tomography and ERCP for obstructive jaundice or small peripancreatic mass. Gastrointest Endosc 1992; 38: 27-34.

7. Snady H, Cooperman A, Siegel J. Assessment of vascular involvement by pancreatic disease - a comparison of endoscopic ultrasonography to computerized tomography and angiography. Gastrointest Endoscopy 1990; 36: A197.

8. Nattermann Ch, Dancygier H: Endoscopic ultrasonography in obstructive jaundice. Gastroenterol 1991; 100:A330.

9. Buscail L, Delvaux M, Louvel D et al.: Does endoscopic ultrasonography improve the diagnosis of pancreatic disease. Gastrointest Endosc 1991; 37: A247.

10. Snady H, Cooperman A, Siegel J.: Endoscopic ultrasonography compared to computerized tomography for pre-operative staging and assessment of resectability of a pancreatic adenocarcinoma or mass. Am J Gastroenterol 1989; 84: A1210.

11. Rösch T, Classen M: Endosonography - what are the limits in gastroenterological diagnostics? Endoscopy 1991; 23: 144-146.

12. Warshaw AL, Swanson RS: Pancreatic cancer in 1988 - possibilities and probabilities. Ann Surg 1988; 208: 541-553.

13. Freeny P, Marks M, Ryan A, Traverson W: Pancreatic ductal adenocarcinoma: diagnosis and staging with dynamic CT. Radiology 1988; 166: 125-133.

14. Ross C, Sharp K, Kaufman A et al.: Efficacy of computerized tomography in the preoperative staging of pancreatic carcinoma. Am Surg 1988; 54: 221-226.

15. Lindsell, David RM: Ultrasound imaging of pancreas and biliary tract. Lancet 1990; 335: 390-393.

16. Campbell J, Wilson S: Pancreatic neoplasms: how useful is evaluation with US? Radiology 1988; 167: 341-344.

17. Jennings PR, Jennifer JD, Coral A et al.: Ultrasound-guided core biopsy. Lancet 1989; i: 1369- 1371.

18. Siegal J, Snady H: The significance of endoscopically placed prostheses in the management of biliary obstruction due to carcinoma of the pancreas: results of nonoperative decompression in 227 patients. Am J Gastroenterol 1986; 81: 634-641.

19. Anderson JR, Sorenson SN, Kruse A et al.: Randomized trial of endoscopic endoprosthesis versus operative bypass in malignant obstructive jaundice. Gut 1989; 30: 1132- 1135.

20. Warshaw A, Gu Z, Wittenberg J, Waltman A: Preoperative staging and assessment of resectability of pancreatic cancer. Arch Surg 1990; 125: 230-233.

21. Warshaw AL, Tepper JE, Shipley WU: Laparoscopy in the staging and planning of therapy for pancreatic cancer. Am J Surg 1986; 151: 76-80

22. Suzuki T Imamura M, Tamura K et al.: Correlative evaluation of angiography and pancreatoductography in relation to surgery for cancer of the pancreas. Surg 1979; 85: 644-651.

23. Nagai H, Kuroda A, Morioka Y.: Lymphatic and local spread of T1 and T2 pancreatic cancer. A study of autopsy material. Ann Surg 1986; 204: 65-71.

24. Ozaki H, Ishii K, Sato T et al.: Diagnosis of small pancreatic carcinoma. Jpn J Clin Oncol 1985; 15: 115-120.

25. Nix G, Schmitz P, Wilson J et al.: Carcinoma of the head of the pancreas: therapeutic implications of endoscopic retrograde cholangiopancreatography findings. Gastroenterology 1984; 87: 37-43.

26. Nakajima M, Yamaguchi K, Akasaka Y: Endoscopic retrograde cholangiopancreatography (ERCP) in the diagnosis of pancreatic cancer. New York: Igaku-Shoin, 1980.

27. Rösch T, Braig Ch, Gain T et al.: Staging of pancreatic and ampullary carcinoma by endoscopic ultrasonography. Gastroenterology 1992; 102: 188-199.

28. Lees WR: Endoscopic ultrasonography of chronic pancreatitis and pancreatic

pseudocysts. Scand J Gastroenterol 1986; 21: Suppl 123; 123-129.