EUS IN BENIGN PANCREATIC DISEASE

Harry Snady, M.D., Ph.D
Pancreatobiliary Treatment Group, N.Y., N.Y.

Address correspondence to:

Harry Snady, M.D., Ph.,D.
EUS Imaging
22 East 88th Street
New York, N.Y. 10128
212-876-8846

SYNOPSIS:

Diagnostic and therapeutic uses of endoscopic ultrasonography (EUS) in benign pancreatic disease are discussed. EUS criteria to diagnose chronic pancreatitis is becoming increasingly standardized. Because of its low risk and increased sensitivity, it will replace ERCP as a diagnostic test for this condition. EUS will also play an important role in determining management of pancreatic cystic lesions. EUS will have a more limited role in diagnosis and management of diseases related to lithogenic bile because of limitations of therapeutic maneuvers, which can be performed at the same time. EUS appears to be complementary to therapeutic ERCP for the aspiration/drainage of a cyst or pseudocyst. Celiac plexus nerve blocks using EUS guided injection of neurolytic agents appears to be more effective than other nerve block techniques, but still is limited in its effectiveness. .

Key words (abbreviations): Endoscopic ultrasonography (EUS), chronic pancreatitis, pancreatic cysts, pain management.

Since 1980, when endoscopic ultrasonography (EUS) was first developed, it has clearly emerged as the most accurate single test for imaging pancreatic disease (1). EUS combines and modifies the techniques of endoscopy and ultrasonography to diminish the distance between the ultrasound source and the pancreas to provide high resolution images. An ultrasound transducer is incorporated into the tip of a fiberoptic endoscope. Thus, bones, adipose tissue, and air-filled structures, which limit sound wave imaging clarity, can be avoided. In addition, the higher frequency 7.5 and 12 MHz sound waves used in EUS compared to 3.5 MHz used in standard sonography result in a greater resolution for EUS. In addition, as with all real-time sonography, the sound wave imaging plane can be oriented at any angle by turning the probe, so as to bring the area of disease into optimal focus, rather than being limited to the parallel sections that are usually 1cm apart, as is the case for computerized tomography (CT scan) and magnetic resonance imaging (MRI). By making possible the visualization of very small lesions, ductal abnormalities, and calcifications, a dramatic improvement in disease characterization and TNM tumor staging over other imaging techniques is now possible. The high accuracy of real time EUS is primarily due to both its unsurpassed resolution of the parenchyma of the pancreas and it's capability to evaluate and integrate on the same exam mucosal, vascular, ductal and parenchymal abnormalities caused by disease. To obtain information about these four types of abnormalities, four separate tests would otherwise be required: 1. Endoscopy for mucosa including the ampulla of Vater, 2. Venogram or arteriogram for veins and arteries, 3. Endoscopic retrograde cholangiopancreatography (ERCP) for the pancreatic and bile ducts, 4. CT scan or standard sonography for the parenchyma and surrounding lymph nodes. Compared to EUS, a successful ERCP will provide superior imaging of the common bile duct (CBD) and pancreatic duct.

However, when ERCP does not visualize a part of the pancreatic duct or CBD, this area is usually seen well on EUS. Pancreatography or cholangiography can even be performed with EUS guided puncture and injection of contrast into the desired duct when ERCP is unsuccessful and standard EUS does not adequately visualize the ducts.

Successful execution of EUS requires both specific equipment and special technique. The Olympus radial and linear imaging units are widely used and considered the most reliable (Olympus America, Inc., Melville, NY). The head the pancreas can be imaged by placing the echoendoscope's transducer in the duodenum. From this location the uncinate and head of the pancreas up to the neck can be imaged. From the stomach the pancreatic tail, body and neck can be imaged. Only limited imaging of the head can be accomplished from the stomach. Accurate imaging of the superior mesenteric vein and artery can only be accomplished from the descending duodenum and with a radial echoendoscope. The entire pancreas can be imaged by EUS in essentially all patients unless altered anatomy or a stenosis of the intestinal lumen is present.

EUS is used in three different situations for detection and diagnosis of benign pancreatic conditions, which include chronic pancreatitis, cystic lesions, and diseases, related to lithogenic bile such as stones, sludge, and chronic inflammation. The two primary therapeutic uses of EUS are for the aspiration/drainage of a cyst or pseudocyst, and for the administration of nerve blocks.

The pancreas normally has an echogenicity characterized by a homogeneous, granular pattern that is slightly finer and more hyperechoic than the liver. The outer pancreatic border is smooth. Mean anterior-posterior diameter is about 13 mm. The main pancreatic duct, which can be followed from the papilla to the tail, is usually less than 2mm (range 1 to 3mm), and has a smooth, thin, non-echogenic wall (Figure 1). Compared to the ventral pancreas, the dorsal pancreas often is slightly more echogenic. This difference must be taken into account in the evaluation of pancreatic disease. In addition, with increasing age, the echogenic pattern of primarily the dorsal pancreas becomes more course with increasing fine hyperechoic foci and a slight increase in lobularity.

Ductal anomalies have been evaluated with EUS (2,3). EUS can identify patients with anomalous connections of the pancreatic or biliary duct. Pancreas divisum has also been diagnosed with EUS using the "stack sign" (4), which has been reported to have the sensitivity of 66% and specificity of 83%.

Diagnosis of Acute Pancreatitis.

EUS has not been used to any significant extent in acute pancreatitis. Acute inflammation of the pancreas causes the following changes on EUS: enlargement, hypoechoic parenchyma, irregularity and blurring of outer margins, and compression of the pancreatic duct. In the periampullary area a focus of acute pancreatitis adjacent to the duodenal wall can cause the margin between the duodenal wall and pancreas to be poorly defined, simulating a tumor. EUS can be used to diagnose and monitor small cysts during treatment for acute, resolving pancreatitis. In patients with idiopathic acute pancreatitis EUS can be quite valuable, establishing a diagnosis in about two-thirds (5,6). The most frequent diagnosis is chronic pancreatitis. Most patients do not require subsequent ERCP.

Diagnosis of Chronic Pancreatitis.

Several studies have now shown that EUS appears to be the most sensitive method to diagnosis chronic pancreatitis. In addition, EUS can image the pancreas in patients with chronic pancreatitis to define localized areas of disease which can be resected, or dilated ducts which can be bypassed.

Initially described by Lees (7), endosonographic criteria that have been used to diagnosis chronic pancreatitis are found in both the parenchyma and pancreatic duct. Parenchymal alterations include: heterogeneous globular architecture, 5-8mm focal areas of reduced echogenicity in the periphery of the gland, increased sharp echogenic foci or bands, enlargement of the gland, accentuation of lobular architecture, and the appearance of small cysts or cavities. Pancreatic duct changes include: irregular duct pattern, increasing duct caliber, irregularity of the lumen, increased number or dilated side branches, increased echogenicity of the duct wall, intraluminal echoes (calculi and protein plugs), strictures with dilation of the main pancreatic duct, and main or branch duct disruption. Features characteristic of early pancreatitis that are usually appreciated only with EUS include: increased duct wall echogenicity, increased duct branches, and increased echogenic foci. Other changes tend to be characteristic of moderate and severe chronic pancreatitis.

The primary issue in diagnosing chronic pancreatitis with EUS is what should be the gold standard to which EUS is compared. Possible gold standards include histology, cytology, pancreatography, and pancreatic function tests. Of these, histology is clearly the most specific, with pancreatography generally being accepted as the most accurate non-pathological imaging method. Histologic confirmation of the various EUS findings has been difficult to obtain since excision or biopsy of pancreatic tissue in patients with mild pancreatitis is rarely indicated.

In studies, which evaluated histology in patients with chronic pancreatitis, disease has

been found to be focally distributed throughout the gland and included lymphocytic cell infiltrates, intralobular and periductal fibrosis, and focal dilation of the ducts with inspissated protein plugs (8). EUS features were compared to histologic findings in 34 patients having EUS followed by pancreatectomy or open surgical biopsy (9). If > 4 EUS abnormalities of chronic pancreatitis were present, sensitivity was 78% and specificity was 73% compared to histology.

Lees (7) reported that only 7 of 30 patients with pancreatitis had satisfactory confirmation of EUS findings by histology. Bhutani (10) further confirmed the correlation of EUS findings to histology by comparing 11 post-mortem pancreatic specimens with confirmed histologic evidence of chronic pancreatitis to satisfactory EUS images obtained in vitro. The finding of three or more EUS features of chronic pancreatitis correlated to the histologic diagnosis of chronic pancreatitis.

Catalano et al. (11) compared EUS images in patients with suspected chronic pancreatitis to findings on ERCP and secretin test. They evaluated only patients with non-alcoholic, acute, recurrent pancreatitis defined by 2 or more episodes of abdominal pain with elevated amylase levels. The Cambridge classification (12) was used to assess the severity of chronic pancreatitis. Visualization of the entire pancreas was achieved in all patients including the pancreatic duct. An echogenic difference between the ventral (hypoechoic) and dorsal (hyperechoic) pancreas was observed in 68%. They found good correlation of moderate and severe pancreatitis noted on EUS to findings characteristic of chronic pancreatitis on ERCP and secretin test. Patients with mild pancreatitis on EUS only somewhat correlated to ERCP because ERCP is clearly not as sensitive as EUS. Of interest, 27 of 80 patients in their series had gallbladders in situ. 23 patients underwent bile collection for microlithiasis during ERCP; microlithiasis was found in only 4 (17%). EUS did not find evidence of microlithiasis in any of the 80 patients even though EUS has been shown to be quite accurate in finding sludge in the CBD in patients with a nondiagnostic standard transabdominal sonogram (13-18).

Another study compared EUS with ERCP to diagnose chronic pancreatitis and evaluate disease severity. Sahai et al (19) concluded that the accuracy and diagnostic certainty depend on and are defined by the number of criteria present. They found that EUS had a positive predictive value of 85% for diagnosing chronic pancreatitis when more than two EUS criteria were present, and 85% for moderate to severe chronic pancreatitis if more than six EUS criteria were present. Negative predictive value was 85% for moderate to severe chronic pancreatitis if less than 3 EUS criteria were present. 34% of their patients had a history of alcohol abuse (more than 10 drinks per week). Of note, they used EUS findings only in the pancreatic body and tail since in their experience, parenchymal changes used as EUS criteria for chronic pancreatitis can be seen in the normal ventral pancreas. In my experience, the diagnosis of chronic pancreatitis can be made from findings in the head; in fact sometimes this in the only area of the pancreas with disease since chronic pancreatitis can be focal. Therefore, criteria for diagnosing chronic pancreatitis based on findings in the head are somewhat different since the hypoechoic nature of the ventral pancreas must be taken into consideration.

The focal nature of chronic pancreatitis in some patients is well known. Brand et al (20) prospectively evaluated focal pancreatic lesions. They found 13 of 34 patients with focal chronic pancreatitis simulating a tumor had no other associated diffuse parenchymal alteration usually present in chronic pancreatitis. In addition, 3 of 81 patients with a malignancy had features of chronic pancreatitis on EUS. Numerous studies have documented the presence of focal pancreatitis simulating a pancreatic cancer or pseudotumor (21,22). This appears to occur in approximately five percent of patients resected for presumed pancreatic carcinoma. In some of these patients the pancreatitis found has been called "duct destructive chronic pancreatitis" and may have an autoimmune basis based on certain histologic features (23-25). We have noted patients similar to the one reported by Kloppel et al (24) in about 1% of cases with chronic pancreatitis. Again, this type of lesion requires cytology be obtained with EUS guided fine needle aspiration (FNA).

Buscail et al. (26) prospectively evaluated 81 patients suspected of having pancreatic disease. Comparing the sensitivity for imaging studies, they found values to be 88% for EUS, 75% for CT scan, 74% for ERCP, and 58% for transcutaneous abdominal ultrasound. EUS can detect changes in the pancreas before the development of ductal lesions seen on ERCP (27, 28). In addition, patients with moderate to severe chronic pancreatitis, often diagnosed by any imaging test, have such extensive fibrosis that artifacts that can obscure an occult carcinoma often complicate even EUS images. EUS guided FNA of suspicious areas is required to improve diagnosis.

Since pancreatic function testing (secretin test) is generally regarded as less sensitive than ERCP, is not surprising that studies have shown that EUS is more sensitive to changes of mild chronic pancreatitis than pancreatic function testing (11).

Numerous other studies have compared EUS to pancreatography obtained with ERCP (11, 19, 26, 29-31). In general, the more severe the pancreatitis found on ERCP, the higher the correlation to EUS. In addition, the higher the threshold number of EUS criteria to diagnose chronic pancreatitis, the greater the correlation to ERCP. The primary reason for this is that ERCP is not as sensitive a test for mild chronic pancreatitis and will not be diagnostic of the disease even though EUS will find several criteria characteristic of chronic pancreatitis. Therefore, EUS appears to be a more sensitive test to diagnose mild chronic pancreatitis. Diagnosis of chronic pancreatitis by EUS has the additional advantage of avoiding complications related to imaging by ERCP.

Interobserver agreement of EUS criteria for chronic pancreatitis has been addressed recently by Wallace et al. (32). In their study selected segments of video tapes of EUS exams of the part of the pancreas from the genu to the tail in 45 patients were reviewed by 11 endosonographers and evaluated for features of chronic pancreatitis, followed by deciding whether the tape segment shown was sufficient to diagnose chronic pancreatitis. 33 patients had abdominal pain of "suspected pancreatic origin;" 12 were "control" patients with various gastrointestinal disorders. Interobserver agreement was then evaluated both for nine features (Table 1) and for a final diagnosis of chronic pancreatitis. The study supports the conclusion that EUS is a reliable method to diagnose chronic pancreatitis among experienced endosonographers. A >70% agreement was found in 73% of cases.

Since there is relatively good interobserver agreement for the diagnosis of mild pancreatitis based on EUS, further studies are now required which would correlate this EUS diagnosis to the long-term clinical course of patients treated for mild chronic pancreatitis based on EUS when all other diagnostic tests are negative. Ideally, interobserver agreement for the EUS criteria for chronic pancreatitis should be at least >90% reliable as has been shown in some studies (29).

The diagnosis of chronic pancreatitis based on EUS is most influenced by the technical skills and experience of the echoendoscopist. Sahai et al. (19) further point out that the training required to identify and assess the body and tail is significantly less than that for proper visualization of the pancreatic head and bile ducts required for tumor staging. It has been recommended that patients with nonspecific abdominal pain should have an empiric trial of medical therapy for irritable bowel syndrome. Those that do not respond should undergo a screening EUS to evaluate for curable pancreatic or biliary disorders (17), since EUS can detect chronic pancreatitis in patients where other tests have not shown diagnostic findings.

Most recently, EUS morphology has been correlated to FNA cytology (33, 34). Hollerbach et al (33) found that the presence of epithelial cells in the FNA from the pancreas appears to be the most specific cytologic finding of chronic pancreatitis. They found normal cytology in patients with various EUS features of mild pancreatitis. Thus, EUS morphology appears to overestimate the actual presence of disease and fibrosis, but by what magnitude is uncertain. To some extent, this is due to increased hyperechoic foci with increasing age and in conditions that cause fat deposition in the pancreas. In the future, obtaining pancreatic tissue with EUS guided needle aspiration that is adequate for histology may improve the accuracy of the EUS diagnosis of chronic pancreatitis with a similar low complication rate. However, current FNA techniques only provide enough material for cytologic examination, which at the present time has only been proven to be very specific for the diagnosis of a neoplasm.

EUS is extremely accurate in diagnosing CBD stones. Accuracy rate is reported to be 95%, and similar to ERCP. Diagnosis of sludge or microlithiasis can be more difficult. By obtaining bile using ERCP or nasal duodenal intubation for drainage studies, at least 66% of patients with "idiopathic" pancreatitis are found to have microlithiasis. Microlithiasis will be found in no more than 50% by standard ultrasound. EUS, however, appears to have a much higher sensitivity, at least 80%, and up to 95%, for sludge. It may be the most sensitive test to document sludge in the CBD (6, 13-15). Dill et al. (15) found that of 66 patients with nonspecific abdominal pain, EUS showed 61 had pain related to sludge not seen on standard ultrasound. Symptoms resolved with cholecystectomy.

In a recent study Erickson and Chavez (35) found that in patients suspected of having CBD stones, EUS had a higher success rate and accuracy than ERCP, detecting many diagnoses that are poorly seen (if seen it all) by ERCP. These EUS diagnoses significantly affect the patient's subsequent medical, endoscopic or surgical management. EUS with stimulated biliary drainage can diagnose microlithiasis and sludge that is not evident on standard transcutaneous sonography (15-18). Endoscopic therapy of stones and sludge with papillotomy, extraction, and/or stents still must be performed with ERCP.

Several important EUS criteria have proven to be helpful in distinguishing different types of benign cystic lesions from mucin-producing tumors of the pancreas that are malignant or have the potential for malignant transformation. Evaluation of cystic lesions in the pancreas with EUS will accurately define their location, size, number, association with pancreatic duct, thickness of the cyst wall, extent of irregularity of the cyst wall, presence of internal cystic polypoid lesions, presence of internal septae, presence of internal echoes or debris, and presence of stones. Since these findings correlate well to morphology and histology of various types of cystic lesions, they can be used to make an accurate diagnosis, to assess the malignant potential, and to determine the need for resection for most cystic lesions.

Figure 2 shows six different patterns of cystic lesions that can be distinguished with EUS (36). These patterns are most easily appreciated using the radial echoendoscope rather than a linear array echoendoscope with less than a 180 degree imaging field. EUS findings that correlate to malignant or potentially malignant cystic tumors include: associated hypoechoic mass, wall thickness >3mm, highly echogenic wall, mural irregularity or nodules, internal structures or papillary projections into the cyst lumen, internal septa >2mm, multiple septae, and multiple (but usually <6) cysts which are >2cm. Criteria that correlate with benign cysts are thin wall, single cyst, and honeycomb pattern cyst.

Recently, pancreatic cystic lesions have been reclassified (Table 2) (37). Pancreatic pseudocysts, retention cysts, and congenital cysts are of course benign. They appear as simple anechoic structures with enhancement artifact, and without a thick wall or septae.

Since the risk of developing carcinoma varies for different cystic pancreatic tumors, certain criteria appear to be most useful in diagnosing lesions with a essentially no risk of malignancy, such a serrous cyst adenoma. Malignant transformation of a serrous cyst adenoma occurs rarely, if ever. These cystic tumors have a very characteristic appearance of multiple clusters of numerous, small cystic lesions arranged in a honeycomb pattern, with the cysts measuring less than 3 mm in about 90%, and <2cm in essentially all serrous cyst adenomas (36-39). Internal septae are very thin (<0.5mm), and they can have a central echodense area. In a study of benign appearing small pancreatic cysts of unknown etiology, Ikeda et al. (39) reported that 31 asymptomatic lesions which were <2cm in 87% and had a clear thin wall, smooth contour, round or oval shape, and no septum or nodule in the lesion were benign. Only one of these types of cystic lesions progressed in size on EUS; at surgery, it was found to be a retention cyst.

When evaluating cystic tumors, the most important role of EUS is to distinguish a benign serous lesion from mucinous tumors, which have varying and increasing malignant potential depending on their type. Mucin-producing cystic tumors account for fewer than 5% of all pancreatic malignancies (37). Mucinous ductal ectasia although premalignant has a very favorable prognosis. Its origin is intraductal, rather than in parenchymal cysts or extraductal cavities. Mucin producing tumors are more commonly of the branched duct type than the main duct type, but this is not of particular diagnostic importance. Solitary and papillary epithelial tumors, ductectatic type tumors which are more commonly in the uncinate, and macrocystic tumors with cysts usually > 2cm, all have significant malignant potential and therefore should be resected depending on operative risk assessment of the patient (40-50). Characteristics, including their internal architecture, of cystic lesions of the pancreas that are < 2 cm are difficult to define on standard transcutaneous ultrasound, CT scan, or MRI. Warshaw et al. (48) reported that based on standard ultrasound or CT scan, 40% of mucinous cyst adenomas and 33% of serrous cyst adenomas were misdiagnosed as a pseudocysts because of the poor spatial resolution of these imaging techniques.

When the cystic lesion is of intermediate nature, such as those with multiple cysts of different sizes, especially if any of the septae are > 0.5 mm, aspiration and analysis of the cyst contents is required. If the cyst contains mucin, and CEA is > 5 ng/ml, resection would be recommended since malignant potential is significant. Generally, a definite diagnosis of a pancreatic cystic lesion can be made by EUS morphology alone at least 50% of the time, and only confirmed by FNA in another 20%. 30% of cystic lesions will be indeterminate based on only EUS and require analysis of the fluid obtained by FNA. Deprez et al recently showed that the combination of EUS morphology and FNA made a correct diagnosis in more than 95% (51).

EUS guided FNA for fluid analysis of cysts (50-56) can be performed using specially designed needles for aspiration (Olympus America, Inc., Wilson-Cook, Winston-Salem, NC). Pancreatitis and infections were the primary complications that usually occurred infrequently (2-4%). Analysis of tumor markers, mucin and cytology can be performed. Mucinous lesions with malignant potential can be reliably identified with a combination of cytology, mucinous staining, and CEA. Mallery et al (53) reported on cyst fluid analysis in pancreatic cystic lesions. Fluid was analyzed for mucin, cytology, and various tumor markers including CEA, CA -- 125, CA-19-9, CA-72-4, tissue polypeptide (TPA), and CA-15-3. They concluded that EUS morphology cannot accurately identify mucinous pancreatic neoplasms, which required characterization by a combination of cytology, mucinous staining and CEA level, resulting in 80% accuracy, 100% sensitivity, and 100% negative predictive value. Adding to the analysis CA15-3 and TPA levels improved results to 93% accuracy, 100% sensitivity, 88% specificity, 86% positive predictive value and 100% negative predictive value. Mild pancreatitis occurred in 2 of 78 FNA. In this study EUS morphology using the linear array echoendoscope, system was insensitive and inaccurate. As discussed above, using the radial echoendoscope, EUS morphology has been used reliably in other studies to predict the type of cystic lesion.

EUS has proven to be extremely useful in increasing the success rate in performing an endoscopic cystogastrostomy (57-60). Using EUS is reported to decrease the incidence of bleeding and perforation (25, 58). Intervening vascular structures are readily identified especially with the doppler capability of the linear array echoendoscope. When performing endoscopic pseudocyst drainage, the role of EUS appears to be: to localize the optimal site for needle knife puncture with a distance between the intestinal lumen and the pseudocyst of < 1 cm, to detect submucosal vessels or varices in the gastrointestinal wall which may be present between a possible site for needle knife puncture and the pseudocyst, to define complex or multiloculated pseudocysts which may require several sites for drainage, to document significant necrotic debris which would indicate that insertion of nasocystic catheter into the cyst to irrigate and dilute the cyst contents for improved lavage is required for a better success rate of drainage, and to diagnose pseudoaneurysms or portal hypertension which could potentially complicate endoscopic drainage. Endoscopic cystgastrostomy also requires EUS to define the optimal puncture site when no endoscopically visible bulge is present (58).

Initial drainage appears to be successful most of the time. However, even with an 89% initial success rate, late complications have been reported. Stent clogging has caused infection in 48%, and 14% can have delayed or immediate bleeding (57). Optimal technique appears to require a 3 to 5 day irrigation with nasocystic catheters and placement of 10 French drainage stents.

Celiac ganglion nerve blocks for chronic pain due to chronic pancreatitis has been used for years with only limited success (25, 61). Pain relief generally lasts < 2 months when agents are administered either intraoperatively or percutaneously using CT scan or standard ultrasound for guidance. Repeated nerve blocks are not usually effective. These results have been true for a variety of agents used such as neurolytic agents (alcohol), anti-inflammatories (steroids), or anesthetics (bupivacaine). With EUS, the celiac artery can be visualized quite easily from the posterior gastric wall just below the gastroesophageal junction. The celiac ganglia are located usually only about 3 cm from the posterior gastric wall at the level of the celiac artery. Improved placement of these agents with EUS guided celiac plexus blocks (62-65) appears to be somewhat more effective for pain due to cancer. Although effectiveness of pain relief for chronic pancreatitis with current methods appears to be less, it may be the only option if endoscopic or surgical treatment is not indicated or has not been effective. About only one of 10 patients appears to have sustained relief of pain due to chronic pancreatitis after EUS guided nerve blocks. In addition, a few patients experience significant pain after the nerve block requiring admission to the hospital. Similar findings were noted by Kim et al (62) who did not find a significant difference in pain scale for patients treated with celiac block for chronic pancreatitis. However, a significant difference was found in narcotics required every two weeks and the number of hospital days per month after the block.

Celiac plexus block with an FNA needle to administer steroids and bupivacaine in 80 patients was recently reported on (63). Only 25% of patients showed benefit beyond 2 weeks and only 10 percent at 24 weeks. Transient diarrhea, orthostatic hypertension, a peripancreatic abscess, and a retroperitoneal bleed due to a pseudoaneurysm occurred. In another study, (64) CT scan guided celiac plexus block was compared with EUS guided celiac plexus block. Persistent pain relief 24 weeks after celiac plexus block was found in 30% with EUS compared with only 12% with CT scan. Harada et al. (65) noted that pain control with EUS guided celiac plexus neurolysis had median duration of two weeks for patients with chronic pancreatitis, but 20 weeks for patients with malignant disease. He recommended that its use be limited to patients with pain from a pancreatic malignancy.

The main pancreatic duct and bile duct can be used to image the pancreas from the duct lumen using specially designed 20 MHz catheter transducers (66-68). Except for evaluating for intraductal stones, the use of these catheters in benign disease has not been investigated to any great extent. In general, other than evaluating bile duct tumors, the use of these catheters appears to be limited because clarity of the image beyond 1 cm from the probe is poor because of limited depth of penetration of the high frequency sound waves. Tamada et al. (67) recently showed IDUS to be significantly more accurate than ERCP in the assessment of longitudinal extension of extrahepatic bile duct carcinoma. Accuracy of determining surgical margins for IDUS compared with ERCP on the hepatic side was 86% and 50%, respectively. On the duodenal side, accuracy was 80% and 50%, respectively. The increased accuracy of preoperative IDUS in determining tumor margins appears to improve surgical planning and decrease the number of intraoperative frozen sections of margins.

It appears that EUS will most likely become the gold standard to diagnose chronic pancreatitis that is not diagnosed on plain x-ray, standard transcutaneous ultrasound, or CT scan. Because of its low risk and increased sensitivity, it will replace ERCP as a diagnostic test for this condition.

Confirmation with cytology may be beneficial for indeterminate cases.

EUS will also play an important role in determining management of cystic lesions in the pancreas. EUS appears to be very effective in determining which cystic lesions have malignant potential. If the cyst appears to be malignant or producing symptoms, they will require resection and therefore do not need FNA. Prediction of the clinical course of cyst of indeterminate nature will require EUS guided FNA and analysis of fluid.

EUS, although quite accurate in diagnosing CBD stones, will have a more limited role in diagnosis and management of diseases related to lithogenic bile because of current limitations of therapeutic maneuvers, which can be performed at the same time. In general, patients with a high suspicion of CBD stones or sludge will require therapeutic ERCP. Therefore, these patients should proceed directly to diagnostic ERCP so that required endoscopic biliary therapy can be performed simultaneously. Patients with a low suspicion for CBD stones or patients with relative contraindications to ERCP (i.e. pregnancy, bleeding disorders) can be first evaluated with EUS to determine if further invasive treatment is required.

EUS appears to be complementary to therapeutic ERCP for the aspiration/drainage of a cyst or pseudocyst.

Although celiac plexus nerve blocks using EUS guided injection of neurolytic agents appears to be more effective than other nerve block techniques, surgical bypass or resection is likely to continue as the primary method of treatment for patients with pain from chronic pancreatitis that have focal disease or do not respond to endoscopic stenting when there is a dominant stricture that can be bypassed.

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TABLE 1

EUS CRITERIA FOR DIAGNOSIS OF CHRONIC PANCREATITIS

 TABLE 2

CLASSIFICATION OF PANCREATIC CYSTIC TUMORS

 TABLE 2

CLASSIFICATION OF PANCREATIC CYSTIC TUMORS