The Applicability of Radial Endoscopic Ultrasonography in Pancreatic Diseases

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1 Radial EUS for diagnosis of pancreatic diseases CLINICAL IMAGING The Applicability of Radial Endoscopic Ultrasonography in Pancreatic Diseases Andrada Seicean, Marcel Tantau, Radu Badea, Zeno Spârchez 3 rd Medical Clinic, University of Medicine and Pharmacy, Cluj-Napoca Abstract Radial endoscopic ultrasonography (EUS) is used in pancreatic pathology for diagnosing such diseases as: chronic pancreatitis, cancer of the pancreas, neuroendocrine tumors, and the non-inflammatory cyst lesions of the pancreas. For diagnosing chronic pancreatitis, the use of more than four criteria of endoscopic diagnosis offers a high diagnostic accuracy. In the case of tumors of the pancreas, EUS detects small-size tumors, having a major diagnostic value in the preoperative staging and in assessing the tumor resectability. EUS can best identify insulinoma, while for the differential diagnosis of cystic neoplastic lesions data provided by radial EUS are not sufficient. In this respect, intracyst fluid analysis is required to identify malignant lesions or those having malignancy potential. Key words Pancreas - endoscopic ultrasonography - EUS - cystic lesions - neuroendocrine tumors - chronic pancreatitis Introduction The success of the pancreatic EUS is due to the possibility of assessing the entire pancreatic gland. This examination is not easy to perform because it requires good knowledge of the anatomy and of the relationships of the pancreas with the surrounding structures. It also requires precision for placing the endoscope into the stomach and into the duodenum. Radial EUS offers a sonographic image of 360 degrees, which is perpendicular on the plane of the echoendoscope and which is similar to the computed-tomography (CT) examination. However, this does not show the route of the J Gastrointestin Liver Dis March 2007 Vol.16 No 1, Address for correspondence: 3rd Medical Clinic 19-21, Croitorilor Str. Cluj-Napoca, Romania andradaseicean@yahoo.com puncture needle. Therefore, radial EUS is strictly a diagnostic imaging procedure. Radial EUS is used for diagnosing pancreatic diseases, such as: chronic pancreatitis, cancer of the pancreas, neuroendocrine tumors, and the non-inflammatory cystic lesions of the pancreas. Chronic pancreatitis For diagnosing chronic pancreatitis, 9 criteria are currently accepted: 4 parenchymal criteria - hyperechogenic foci, hyperechogenic strands, pseudocysts, lobularity, and 5 ductal criteria - dilated main pancreatic duct, visible side branches, hyperechogenic walls of the main pancreatic duct, irregular main pancreatic duct, stones in the main pancreatic duct (1-3) (Figs.1, 2). These changes should be seen in the dorsal pancreas, because the ventral pancreas is usually more hypoechogenic and presents hyperechogenic points and hyperechogenic strands even in healthy persons. The advisable optimal number of criteria for diagnosing chronic pancreatitis in comparison with the endoscopic retrograde cholangiopancreatography (ERCP), which is considered the gold standard if the histological examination is not available, has not been established. If the purpose of the examination is to make a diagnosis of chronic pancreatitis with a high degree of certainty, then more than 5 criteria indicate moderate or severe chronic pancreatitis on ERCP (the sensitivity is low, while the specificity is high)(4). A patient with one or two EUS criteria of chronic pancreatitis has a 90% chance of having a normal pancreatogram and it is highly probable that such a patient has no chronic pancrea-titis. In such cases, no additional tests are required and long-term follow-up is important in order to confirm the diagnosis of chronic pancreatitis (5). Using 4-5 diagnostic criteria, the EUS sensitivity ranges between 84% and 100%, while specificity ranges between 60% and 95% (4-8). The EUS can also visualize the complications induced by chronic pancreatitis: stenosing duodenitis, main bile duct compression, pseudocysts (Fig.3). When the duodenal stenosis is non-circumferencial, the differential diagnosis with duodenal tumors is a must.

2 78 Seicean et al Fig.1 Stone in the main pancreatic duct in a patient with chronic pancreatitis. Fig.4 Pancreatic pseudocyst in a patient with chronic pancreatitis and a recent episode of acute pancreatitis. Fig.2 Dilatation of Wirsung duct and parenchymal calcifications in chronic pancreatitis. Fig.5 Old pancreatic pseudocyst and gallbladder hydrops. Fig.3 Stenosing duodenitis, dilatation of common bile duct and dilatation of gallbladder in chronic pancreatitis. Fig.6 Pancreatic tumor of the head of the pancreas T3 without invasion of the superior mesenteric vein. Pseudocysts, which represent complications of chronic pancreatitis, can be analyzed in terms of pancreatic location, distance from the duodenal wall, their content, and the possible presence of intramural mass. Communication with the main pancreatic duct is often difficult to assess. Thus, in this respect, EUS is not so performant as ERCP. Pseudocysts do not have their own wall with epithelial lining, and they are delineated by inflammatory and fibrous tissue.

3 Radial EUS for diagnosis of pancreatic diseases 79 Fig.7 Retrograde dilatation of the main pancreatic duct in a patient with pancreatic tumor of the head of the pancreas. Fig.10 Loss of interface vessel-tumor. Fig.8 Isthmic pancreatic tumor T3 without celiac trunk invasion. Fig.11 Intravascular tumor invasion. Figu.9 Small adenocarcinoma of the head of the pancreas. Fig.12 Nonvisualization of the vessel due to tumor invasion. In early pseudocysts the wall is thin (Fig.4) and it can thicken when the pseudocysts become mature. They are usually unilocular and anechogenic. However, they can also have necrotic or infected deposits. In such a case the differential diagnosis with cystic neoplasm must be made. In other cases they present septa in the interior (Fig.5). Assessing the adjacent pancreatic parenchyma for diagnosing the possible elements of chronic or acute pancreatitis is compulsory. Using the criteria listed above for diagnosing chronic

4 80 Seicean et al 5 the positive predictive diagnostic value for the main pancreatic duct irregularity was 90% and for pseudocysts and hyperechogenic parenchymal foci was 80% (4). Acute pancreatitis. EUS reveals the pancreas enlarged in volume, hypoechogenic, with possible peripancreatic collections, but CT scan can better assess the lesions at a distance. Therefore, in diagnosing acute pancreatitis, EUS is not considered as a routine examination. It is useful only for identifying the etiology of idiopathic acute pancreatitis: lithiasis of the common bile duct, chronic pancreatitis, small tumors, pancreas divisum. Pancreatic tumors The EUS aspect of the pancreatic tumors is represented, as in the transabdominal ultrasonography (US),by a hypoechogenic mass, nonhomogeneous, with irregular borders (Figs.6-8). Diagnostic sensitivity varies between 87 and 100% (11,12). Its performances are better than those of the CT scan and multi-detector row CT (sensitivity 53-86%) (13,14). However, in comparison with MRCP they are better (94 vs 83%) (15) or worse (87 vs 96%) (12). Further studies are necessary for establishing the diagnostic value of EUS in comparison with MRI in this respect. Due to the proximity of the transducer to the duodenal wall and to the pancreatic tissue, the detection of small size tumors (diameter < 30 mm) by EUS is better than by CT or MRI (sensitivity 93%, 53% and 67 % respectively) (16). For tumors < 15 mm in diameter EUS sensitivity is definitely superior (100%) as compared with that of the dual-phase helical CT (67%) (Fig.9). There are certain limits of tumoral detection by EUS, represented by presence of chronic pancreatitis, tumoral infiltrative forms, a recent episode of acute pancreatitis (less than 4 weeks) (17). For the T stage EUS accuracy is over 60% (13,18), being exceeded in some studies by the dual-phase helical CT, but remaining better than MRI (19). EUS accuracy for N staging varies from 41% to 86% (13,16). In the presence of all four aspects suggesting malignant lymph nodes i.e. round shape, well-delimitated, size > 1 cm, hypoechogenity, the chance of malignancy is % (19). Another benefit of EUS in pancreatic tumors is the fact that it can show invasion of the great peripancreatic vessels (the superior mesenteric vessels and the portal vein) and small amounts of ascites located around the digestive duct, which constitute criteria for nonresectability (accuracy of 67-93%) (11,18,20). The vascular invasion criteria are as follows: irregularity of the interface with the vessel (Fig.10), intravascular tumor growth (Fig.11), and nonvisualization of the vessel, with collateral circulation growth (Fig.12). EUS sensitivity and specificity in detecting vascular invasion is of 42-91% and %, respectively, with an accuracy similar or higher than that realized by MRI or CT scans (worse than CT scan for diagnosing invasion of superior mesenteric artery and celiac trunk, which are more deeply located, but better than angiography) (11,18,20). Neoplastic cystic lesions of the pancreas From the pancreatic cystic lesions, 80-90% are pseudocysts, 5-10% are neoplastic cystic lesions with malignant potential, while 5-10% are congenital cystic lesions. The pancreatic neoplastic cystic lesions can be assessed by EUS in terms of size, macro- or microcystic aspect, content, wall thickness, communication with pancreatic ducts, location in the pancreas, relation to vessels and surrounding organs, locoregional and distance metastases. The diagnostic accuracy in the case of noninflammatory cystic lesions of the pancreas varies largely, from 40 to 93% (21). Diagnostic accuracy in the case of malignancy, based on the EUS features, is rather low (51-82%) and is limited especially in the case of large lesions (> 5-6 cm), which escape the focus field of the transducer (22-24). Serous cystadenoma (Fig.13). This occurs predominantly in females. Its predilect location is the body and tail of the pancreas. The diagnostic criteria are as follows: microcystic aspect, < 2 cm, onion skin aspect, corresponding to the fine fibrous septa; central calcification or star-like fibrous scar. Malignancy elements such as vegetations, thickening of the walls, echogenic content or adjacent tissue mass are missing. Fine needle aspiration (FNA) is performed only in case of macrocystic lesion. Mucinous cystadenoma (Fig.14). It occurs predominantly in middle-aged females, especially in the body and tail of the pancreas. Although its typical aspect is that of a macrocyst, > 2 cm in diameter, small size mucinous cystadenomas, even milimetric ones, may exist. Peripheral calcifications, found in 15% of the patients, can also occur in other cystic lesions, as well as mural nodes or vegetations (25). The association with a tissue mass suggests malignancy (Fig.15). In the case of communication with the pancreatic duct, the differential diagnosis with side-branch IPMN (see below) must be taken into consideration. FNA is extremely useful for diagnosis confirmation. Solid - pseudopapillary tumors. In these cases EUS plays a limited role because of the large size of the lesions and of the limited examination field. The typical aspect is that of a well-delimited tumor with inner cystic formations. The pure fluid atypical forms are difficult to differentiate from the mucinous cystadenoma. Intraductal papillary mucinous tumors of the pancreas (IPMN) They are characterized by papillary proliferation of the ductal epithelium which is responsible for the mucus production, which leads to the dilation of the excretory pancreatic ducts. These lesions can develop from hyperplasia to dysplasia, to carcinoma in situ and then to invasive carcinoma. There are two anatomopathological forms with a different prognosis: - the IPMN of main pancreatic, which has a high risk of malignization (70-92 %) (Fig.16);

5 Radial EUS for diagnosis of pancreatic diseases 81 Fig.13 Serous cystadenoma. Fig.16 IPMN of main pancreatic duct. Fig.14 Mucinous degenerated cystadenoma. Fig.17 IPMN of secondary pancreatic ducts. Fig.15 Cystadenocarcinoma. Fig.18 Insulinoma. pancreatitis, the diagnosis concordance in a group of 11 observers was low (index k =0.45), and it was even lower for some individual criteria. Most of the concordant diagnoses were found for the main pancreatic duct dilation (k=0.61) and for parenchymal lobularity (k=0.51), while moderate concordances were found for calcifications (k=0.38), hyperechogenic ductal walls, and hyperechogenic strands. The lowest diagnosis concordances were found for side pancreatic ducts (5). In opposition to the findings of the previously mentioned study, other work showed that calcifications represented a criterion with absolute positive predictability for the diagnosis of chronic pancreatitis, while

6 82 - the IPMN of secondary pancreatic ducts, with low risk of malignization (30%) (Fig.17). IPMN are lesions with predominant cephalic localization and extension in the rest of the pancreatic tissue. They occur in males aged years, are frequently multiple, have a diameter < 4 cm, and in case of complete exeresis their prognosis is good. EUS allows: 1) visualization of the communication between the main pancreatic duct and a dilated side pancreatic duct; 2) differential diagnosis between an intraductal mucus deposit (as filaments or hyperechogenic round structures surrounded by a hyperechogenic ring) and a hypoechogenic intraductal polypoid lesion, and 3) visualization of the thickening of the pancreatic duct wall or of the mural nodes. The diagnostic accuracy is 92%, which is higher than that offered by US (82%) or ERCP (89%). The criteria of malignancy for IPMN currently considered are: liver metastases, lymph node involvement, or vascular invasion; association with a solid mass; diameter of the main pancreatic duct > 10 mm; diameter of the side pancreatic duct > 30 mm; existence of a mural node larger than 3 mm; thickening of the ductal wall or presence of thick septa (26). Endocrine tumors (Fig.18) Because of the good visualization of the duodenum and of the gastric wall, the area known as the gastrinoma triangle, and because of the possibility of detecting small lesions (2-3 cm), EUS is the election method for endocrine tumors diagnosis (sensitivity 82-94%)(27-30). Because only some of these tumors are secreting tumors, they can reach large sizes. The EUS aspect is usually that of a hypoechogenic well-delimited lesion, with intense vascularisation. Sometimes, their aspect is cystic, with a solid component or pure fluid. Differential diagnosis is made with chronic pancreatitis nodules, pancreatic metastases, adeno-carcinoma or other benign tumors. Conclusions Among other preoperative imaging diagnostic modalities, radial EUS presents a high accuracy in detecting, staging and establishing resectability of solid pancreatic tumors. Besides the intracystic fluid examination, it allows improvement of the preoperative diagnostic accuracy in cystic pancreatic lesions with malignant potential. In chronic pancreatitis, using more than four diagnostic criteria, EUS diagnosis has a high accuracy; on the other hand, if only one or two criteria of pancreatitis are used, it has a high negative predictive value. References 1.Sahai AV, Zimmermann M, Aabakken L et al. Prospective assessment of the ability of endoscopic ultrasound to diagnose, exclude or establish the severity of chronic pancreatitis found Seicean et al by endoscopic retrograde cholangiopancreatography. Gastrointest Endosc 1998; 48: Sahai AV. EUS and chronic pancreatitis. Gastrointest Endosc 2002; 56: S International Working Group for gastrointestinal endoscopy.reproduction of minimum standard terminology in gastrointestinal endosonography. Dig Endosc 1998; 10: Wiersema MJ, Hawes RH, Lehman GA, Kochman ML, Sherman S, Kopecky KK. Prospective evaluation of endoscopic ultrasonography and endoscopic retrograde cholangiopancreatography in patients with chronic abdominal pain of suspected pancreatic origin. Endoscopy 1993; 25: Wallace BW, Hawes RH, Durkalski V et al. The reliability of EUS for the diagnosis of chronic pancreatitis: interobserver agreement among experienced endosonographers. Gastrointest Endosc 2001; 53: Buscail L, Escourrou J, Moreau J et al. Endoscopic ultrasonography in chronic pancreatitis: a comparative prospective study with conventional ultrasonography, computed tomography and ERCP. Pancreas 1995; 10: Catalano MF, Lahoti S, Geenen JE, Hogan WJ. Prospective evaluation of endoscopic ultrasonography, endoscopic retrograde pancreatography and secretin test in the diagnosis of chronic pancreatitis. Gastrointest Endosc 1998; 48: Hollerbach S, Klamann A, Topalidis T et al. Endoscopic ultrasonography (EUS) and fine-needle aspiration (FNA) cytology for diagnosis of chronic pancreatitis. Endoscopy 2001; 33: Chong A, Romagnuolo J,Lewin D. Diagnosis of chronic pancreatitis with endoscopic ultrasound : a comparison with histopathology. Gastrointest Endosc 2005: 61;AB Kahl S, Glasbrenner B, Leodolter A, Pross M, Schulz HV, Malfertheiner P. EUS in the diagnosis of early chronic pancreatitis: a prospective follow-up study. Gastrointest Endosc 2002; 55: Gress FG, Hawes RH, Savides TLJ et al. Role of EUS in the preoperative staging of pancreatic cancer: a large single- center experience. Gastrointest Endosc 1999; 50: Ainsworth AP, Rafaelsen SR, Wamberg PA, Durup J, Pless TK, Mortensen MB. Is there a difference in diagnostic accuracy and clinical impact between endoscopic ultrasonography and magnetic resonance cholangiopancreatography? Endoscopy 2003; 35: DeWitt J, Devereaux B, Chriswell M et al. Comparison of endoscopic ultrasound and multidetector computed tomography for detecting and staging pancreatic cancer. Ann Intern Med 2004; 141: Mertz HR, Sechopoulos P, Delbeke D, Leach SD. EUS, PET and CT scanning for evaluation of pancreatic adenocarcinoma. Gastrointest Endosc 2000; 52: Muller MF, Meyenberger C, Bertschinger P, Schaer R, Marincek R. Pancreatic tumors: evaluation with endoscopic US, CT and MR imaging. Radiology 1994; 190: Legmann P, Vignaux O, Dousset B et al. Pancreatic tumors: comparison of dual-phase helical CT and endoscopic ultrasonography. Am J Roentgenol 1998; 170: Bhutani MS, Gress FG, Giovaninni M et al. The No Endosonographic Detection of Tumor (NEST) study: a case series of pancreatic cancers missed on endoscopic ultrasonography. Endoscopy 2004; 36: Soriano A, Castells A, Ayuso C et al. Preoperative staging and

7 Radial EUS for diagnosis of pancreatic diseases tumor resectability assessment of pancreatic cancer: prospective study comparing endoscopic ultrasonography, helical computed tomography, magnetic resonance imaging and angiography. Am J Gastroenterol 2004; 99: Bhutani MS, Hawes RH, Hoffman BJ. A comparison of the accuracy of echo features during endoscopic ultrasound (EUS) and EUS-guided fine-needle aspiration for diagnosis of malignant lymph node invasion. Gastrointest Endosc 1997; 45: Ramsay D, Marshall M, Song S et al. Identification and staging of pancreatic tumors using coputed tomography, endoscopic ultrasound and mangafodipir trisodium- enhanced magnetic resonance imaging. Australas Radiol 2004; 48: Ahmad NA, Kochman ML, Brensinger C et al. Interobserver agreement among endosonographers for the diagnosis of neoplastic versus nonneoplastic pancreatic cystic lesions. Gastrointest Endosc 2003; 58: Brugge WR, Lewandrowski K, Lee-Lewandrowski E et al. Diagnosis of pancreatic cystic neoplasms: a report of the cooperative pancreatic cyst study.gastroenterology 2004; 126: Frossard JL, Amouyal P, Amouyal G et al. Performance of endosonography guided fine needle aspiration and biopsy in the diagnosis of pancreatic cystic lesions. Am J Gastroenterol 2003; 98: Sedlack R, Affi A, Vazquez-Sequeiros E, Norton ID, Clain JE, Wiersema MJ. Utility of EUS in the evaluation of cystic pancreatic lesions. Gastrointest Endosc 2002; 56: Koito K, Namieno T, Nagakawa T, Shyonai T, Hirokawa H, Morita K. Solitary cystic tumor of the pancreas: EUSpathologic correlation. Gastrointest Endosc 1997, 45: Napoleon B, Lefort C. Tumeur kystique et kystes vrais. In : Levy P, Ruszniewski P, Sauvanet A.Traite de pancreatologie clinique. Paris, Flammarion 2005: Palazzo L, Roseau G, Chaussade S, Salneron M, Gaudric M, Paolaggi JA. Pancreatic endocrine tumors: contribution of ultrasound endoscopy in the diagnosis of localization. Ann Chir 1993; 47: Zimmer T, Stolzel U, Bader M et al. Endoscopic ultrasonography and somatostatin receptor scintigraphy in the preoperative localization of insulinomas and gastrinomas. Gut 1996; 39: De Angelis C, Carucci P, Repici A, Rizzetto H. Endosonography in decision making and management of gastrointestinal endocrine tumors. Eur J Ultrasound 1999; 10: Gouya H, Vignaux O, Augui J et al. CT, endoscopic sonography and a combined protocol for preoperative evaluation of pancreatic insulinomas. Am J Roentgenol 2003; 181: Quiz HQ 36 An exceptional cause of bleeding from stoma An 80 year old man who had previously undergone a transverse colectomy with ascending colon colostomy and mucus fistula formation as a result of iatrogenic endoscopic transverse colon perforation was seen with recurrent bleeding from the mucus fistula (Fig 1). He described the bleeding as fresh in nature and required several blood transfusions. His past medical history included Crohn s disease which was complicated by primary biliary cirrhosis. A flexible sigmoidoscopy through the mucus fistula did not reveal any abnormalities. Questions 1. What is the cause of this man s bleeding? 2. What is the pathogenesis of this abnormality? 3. What are the available treatment methods for this condition? See page 115 for answers. Fig.1 Parastomal varices from the mucus fistula. Correspondence to: IH Mallick 104 Church Lane Scunthorpe DN15 7HA docmallick@gmail.com I H Mallick, H J Pearson Colorectal Surgery Diana Princess of Wales Hospital Grimsby, UK