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 19 November 2017

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View all the figures for this chapter.

Endoscopic ultrasound

Editor: Ian Penman


5. EUS: pancreatico-biliary

John Meenan

Top of page Synopsis  Next section

Endoscopic ultrasound (EUS) yields high-resolution views of the pancreatico-biliary system, superior in many cases to those given by computerized tomography (CT) or magnetic resonance imaging (MRI) and without the attendant risks of endoscopic retrograde cholangiography (ERCP).

Linear EUS allows for both diagnostic and therapeutic interventions including celiac axis neurolysis, cyst drainage, biliary stenting and brachytherapy.

Top of page Morbid anatomy  Previous section Next section

Pancreas  Previous section Next section

The pancreas lies at the juncture of the supracolic and infracolic peritoneal compartments; the transverse colon/mesentery lying anteriorly, duodenal bulb superiorly. The head is formed in the concavity of the duodenum, anterior to the inferior vena cava, aorta, and the common bile duct by which it is grooved (superolateral aspect). The uncinate process (inferomedial extension of the pancreas) reaches close to the aorta, posterior to the mesenteric vessels. The neck of the pancreas is defined by its posterior relation, the portal vein, and is grooved by the superior mesenteric vessels and the gastroduodenal artery. The body of the pancreas is triangular in cross section and extends across the left crus and left kidney, lying behind the stomach and posterior to the lesser sac. The tuber omentale is a knuckle-like protrusion on the superior aspect of the body, just inferior to the celiac axis. The pancreatic tail lies in the lienorenal ligament, reaching the hilum of the spleen.

The main pancreatic duct (Wirsung) drains the tail, body, neck, uncinate process, and posterior part of the head, emptying through the major papilla. The accessory duct (Santorini) drains the upper and lower/anterior head.

The arterial supply for the head of the pancreas is the superior pancreatico-duodenal artery, a branch of the gastroduodenal artery (celiac axis > common hepatic artery > gastroduodenal artery) which anastamoses with the inferior pancreatico-duodenal artery, a branch of the SMA. The body/tail is supplied by the splenic artery (largest branch of the celiac axis). The splenic artery supplies branches to the fundus of the stomach (short gastric arteries) and both stomach surfaces from the greater curve (left gastric epiploic artery). Local lymph nodes are pancreaticosplenic (superior border) and along the pancreatico-duodenal arteries. Innervation is from the celiac and superior mesenteric plexes.

In terms of pancreatic embryology, at just after 4 weeks, two diverticula appear. The earlier one arises in the angle between the vitellointestinal duct and the ventral wall of the foregut. This ventral pouch gives rise to the liver, gallbladder, bile ducts, and ventral pancreas. The second diverticulum arises from the dorsal wall of the duodenum and develops to give the rest of the pancreas. Pancreas divisum occurs in approximately 7% of the population.

Portal vein  Previous section Next section

The superior mesenteric vein and splenic vein (already joined with the inferior mesenteric vein) fuse behind the neck of the pancreas (level of L1) to form the portal vein. This 7 cm long vein ascends in front of the inferior vena cava, to the mouth of the lesser sac and above the duodenum enters the lesser omentum. Running behind the common bile duct and hepatic artery, it reaches the porta hepatis and bifurcates to give a short/wide right branch and a long/narrow left branch.

Common bile duct  Previous section Next section

The path of the common bile duct from porta hepatis to ampulla of Vater has three stages: (a) passes downwards between the two layers of the lesser omentum with portal vein and hepatic artery lying behind; (b) runs behind the first part of the duodenum; and (c) becomes embedded in the pancreatic head. Choledochal cysts are associated with an anomalous pancreatico-biliary junction, where there is a long common channel (usually 1 cm) between ducts.

Top of page Endosonographic anatomy  Previous section Next section

In learning to perform EUS it is important to rationalize the anatomy from what appears on the screen rather than try to impose preconceived notions of where structures 'ought to be' onto the image. It should be remembered that in performing EUS it is only possible to produce a limited number of views, hence the development of EUS stages. Learn what can be seen rather than what might be seen.

Top of page Performing EUS of the pancreas and biliary tree  Previous section Next section

Body and tail of pancreas  Previous section Next section

Radial EUS  Previous section Next section

The neck, body, and tail of the pancreas lie behind the upper body of the stomach at about 45 cm, not from the antrum, which is a relative endosonographic wilderness.

To find the upstream pancreas, withdraw the scope from the antrum with slight backward pressure on the up/down dial to keep the scope tip apposed to the gastric wall. Ensure that no liver is seen under the scope.

Keep an eye out for the golf-club head-like confluence or, more importantly, the white halo surrounding the SMA. These will be at 6–8 o'clock on the screen. Importantly, keep pulling the scope back. The initial view of the confluence will be lost but then replaced by a better one. It is this second view that is the important one (Fig. 1).

Extending from the portal confluence to the right on the screen (patient's left) is the long splenic vein. This acts as the lower border and guide to the body and tail regions. Withdrawing the scope with gentle left pressure on the left/right dial and slight clockwise scope rotation follows the gentle upward course of this vein to the splenic hilum, passing over the left kidney and lower pole of spleen (Figs 2–4).

The splenic artery lies closer to the scope and due to its tortuous course is only seen as discontinuous tubules as it weaves in and out of the EUS plane of view. The main pancreatic duct is seen as a thin black line running along the salt and pepper-like speckling of the pancreatic parenchyma.

Linear EUS  Previous section Next section

Starting at the celiac axis, use the axis and the SMA, which arises just below it, as fingers pointing their way to the mid-pancreatic body (Fig. 5). Advance the scope about 3–4 cm and gently pull back on the up/down dial. This will bring the coin-like cross section of the pancreas into view immediately under the transducer. The rounded splenic artery will be at 2 o'clock to the scope tip, with the larger vein lying about 2 cm deeper. The main pancreatic duct will be a black dot (Figs 6 and 7).

From this central point, clockwise rotation of the scope drives the tip across the left kidney, worm-like left adrenal, and, with full upward deflection, to the splenic hilum (Fig. 8).

Initial anticlockwise rotation would have brought the scope tip to the neck of pancreas and portal vein, but this is not the best way to find this important region. It is better, as with radial EUS, to advance the scope to the antrum and withdraw, rotating the scope tip left and right until the rounded portal vein is identified. The pancreatic duct can be seen to describe an arc around it from 9 o'clock back up towards 12 o'clock (Figs 9 and 10).

Once the portal vein has been found, it can be followed to the liver hilum by scope withdrawal. In these views, the liver lies at the bottom of the screen, not at the top as one might imagine. At the liver hilum (6 o'clock) the CBD may be seen behind and to the left of the portal vein. The anatomy of this region is best appreciated and learnt when scanning a patient with a biliary stent in situ (Figs 11 and 12).

Head and uncinate process of pancreas  Previous section Next section

Radial EUS  Previous section Next section

The head of the pancreas is seen from the duodenal bulb, the uncinate process from beyond the ampulla of Vater.

Immediately on passing the scope through the pylorus, inflate the balloon, and apply luminal suction and gentle upward pressure on the up/down dial. Usually, the gallbladder will appear at 12 o'clock, a longitudinal portal vein at 8–11 o'clock and pancreatic head, close to the scope tip at between 6 and 8 o'clock. The CBD will run downwards, to the left of the scope tip towards 6 o'clock, meeting the jet-black pancreatic duct, which describes a similar course but starts near to the portal vein and once again runs to the ampullary region at 6 o'clock. Clockwise rotation of the scope shaft moves the tip towards the ampulla, anticlockwise towards the hilum (Fig. 13).

The orientation of the structures describe is key to understanding the anatomy and performing tumor staging. Imagine the CBD, portal vein and pancreatic duct to fashion a triangle with its apex at the liver hilum (portal vein and CBD) and its lower right corner at the ampulla (CBD and pancreatic duct). This means that the patient's left (body and tail of pancreas) lie out of view to the left on the screen. (Figs 14 and 15).

Pass the scope to beyond the ampulla using EUS rather than endoscopic views and re-inflate the balloon. Then apply luminal suction and full upward deflection of the up/down dial along with anticlockwise torque on the scope shaft and slight leaning of the scope arm to the left. This light piece of acrobatics brings the aorta and IVC into view. When the spine is at 12 o'clock, the rounded, blacker aorta is towards 11 o'clock and the grey, flattened IVC towards 1 o'clock. Although this 'clockwise' orientation may be rotated from one patient to another, the mesenteric vessels (SMA and SMV) will always be at the relative 7 o'clock position (Fig. 16).

Keeping the torque on the scope, slow withdrawal allows the aorta to become longitudinal and the mesenteric vessels to unfold upwardly towards 10 o'clock (Fig. 17). The SMA is always of uniform caliber, whereas the SMV widens out to form the portal vein. When the SMA is seen to join with the aorta, the rounded left renal vein is seen in the angle formed by the arteries' origin (Fig. 18).

Further slow scope withdrawal brings the jet-black, dot-like cross section of the ampullary pancreatic duct into view. Very slight further withdrawal sees the pancreatic duct to be joined by the greyer CBD (Fig. 19).

Linear  Previous section Next section

Scanning from the bulb yields a similar orientation to that seen with radial studies: liver to the top of the screen, portal vein to the left, and pancreatic head below and immediately left of the scope tip (Fig. 20).

The portal vein is the most obvious structure, describing a gentle arc down to the mid/right part of the screen, where it merges into the SMV. The stub-like splenic vein is often seen on the left outer mid border of the portal vein. The SMV is very prominent in linear views. The SMA may be seen further out, encased in a whitish parenchyma (Fig. 21).

The CBD is a less obvious structure than when viewed with radial EUS and so takes more work to delineate. In particular, the very prominent gastroduodenal artery can easily be mistaken for the duct. Scan the region between the scope tip and the portal vein, easing off pressure on the up/down dial in order to bring out the CBD. Once found, clockwise rotation moves the scope tip down towards the ampulla, anticlockwise towards the liver and gallbladder.

The pancreatic duct is usually easy to find as it follows its horizontal course towards the right/center of the screen from the portal vein (Fig. 22).

Advancing the scope beyond the ampulla followed by withdrawal and anticlockwise torque brings views of the longitudinal aorta (7 o'clock) and uncinate process (5 o'clock) (Fig. 23). With further withdrawal, the CBD is seen to the right of the scope tip but as the transducer passes around the D1/D2 angle, the CBD flips to the left side of the screen—as would be expected from the bulb (Fig. 24).

Top of page Benign biliary disease  Previous section Next section

Choledocholithiasis  Previous section Next section

Endoscopic retrograde cholangiography (ERCP) has long been considered the most accurate method to detect CBD calculi but several studies confirm a similar accuracy rate (> 90%) for EUS [1–4]. Direct comparison between EUS and MR cholangiography shows EUS to be the more accurate test. The sensitivity of both modalities is equally impressive at 100% but EUS had a specificity of 95% as opposed to a figure of 73% reported for MRI [3]. In particular, EUS is more accurate when choledocholithiasis occurs in the presence of an undilated bile duct (Figs 25–27).

Standard EUS is limited by the need to pass a dedicated echoendoscope. The use of a fine catheter or miniprobe, passed through the operating channel of an ERCP scope, would help to combine the strengths of these two procedures. One prospective study shows the ability of such a catheter probe used in this fashion to detect bile duct stones, with 33 of 34 stones and all papillary adenomas being identified [5].

In the clinical setting, however, to determine the presence of ductal calculi remains a significant dilemma; a balance must be struck between attendant risk (ERCP and pancreatitis) and potential inaccuracy, as well as the joker in the pack, cost effectiveness.

Clinical and biochemical criteria together with transabdominal ultrasound findings permit patient stratification into low, intermediate, and high risk for choledocholithiasis. Endosonography is the preferred investigation for low and intermediate risk groups, while ERCP remains the test of choice for patients of high risk [2,6]. But, no stone will be found in up to 34% of the latter group [2–7]. If one-third of patients undergo potentially unnecessary ERCP despite the application of rigorous selection criteria, it is reasonable to advocate the more liberal use of EUS in the evaluation of all patients with suspected choledocholithiasis as it offers both clinical and economic advantages by preventing inappropriate and more invasive imaging of the bile duct [4,8].

In the evaluation of common bile duct stones in patients with acute pancreatitis, using various imaging modalities (EUS, MRC, ERCP, and intraoperative cholangiography (IOC)), EUS was found to be most cost-effective method if the pretest probability of CBD stones was between 7% and 45% (intermediate risk). ERCP proved the most cost-effective method again in the high risk group (pretest probability of finding ductal calculi, > 45%) [9]. Sahai et al. [6] evaluated four treatment strategies (ERCP, IOC, EUS, and expectant management) in patients with suspected CBD stones prior to laparoscopic cholecystectomy and found EUS to be again the most cost-effective in the intermediate risk group (pretest probability 11–55%), expectant management best in the low risk group, and ERCP optimal in the high risk group. Moving beyond clinical application alone, a marked effect on fellow training results from switching from ERCP to EUS (and presumably MRI) [10].

Choledochal cysts  Previous section Next section

EUS is accurate in the investigation of a dilated CBD and will potentially identify neoplastic transformation, but there are no features specific to endosonography that identify a choledochal cyst [11,12]. Detail of the frequent finding of a common CBD and pancreatic duct channel (aberrant pancreatico-choledochal junction) of approximately 1 cm, however, can be seen.

Primary sclerosing cholangitis (PSC)  Previous section Next section

The diagnosis of this condition in general is problematic and is usually based on the accumulation of clinical, biochemical, and imaging parameters. Radial EUS adds useful information as those with extra-hepatic PSC show a thickening of the inner layer of the CBD wall that is not to be found with choledocholithiasis nor in those with inflammatory bowel disease and abnormal liver blood tests alone [13](Fig. 28). Endosonographic fine-needle aspiration (FNA) of a thickened CBD can be diagnostic for PSC [14].

Top of page Malignant biliary disease  Previous section Next section

Ampullary carcinoma  Previous section Next section

Endosonography is (not surprisingly) highly accurate and superior to ERCP, ultrasound, spiral CT, and MRI in detecting the presence of ampullary cancer [15–18]. The staging of ampullary lesions by EUS shows T-stage accuracy to range between 76% and 83%, with the respective accuracy for N-stage being 50–100% [15–22]. In this clinical setting, the detail yielded by EUS predicts pancreatic invasion and resectability [20,21]. But, not unexpectedly, the presence of a biliary stent had a deleterious effect on these figures [19,22]. Guided FNA of ampullary lesions is accurate (89%), sensitive (82%), and specific (100%) [23]; but there again, so is mucosal biopsy (Fig. 29).

Technically, standard probes provide very good views of this region but for small lesions or benign adenomas, high frequency miniprobes (20 MHz or greater) can be ideally suited. The use of buscopan/glucagon and water instillation provides high quality views. Perhaps the most difficult judgement to make is to determine whether there is distal CBD invasion or not, as the normal cone-shape of this area coupled with scope compression conspire against the endoscopist.

Cholangiocarcinoma  Previous section Next section

An aggressive therapeutic approach to cholangiocarcinomas, particularly those of the hilum, has been advocated [24]. Information on the accuracy of radial EUS staging is scant and although 3D intraductal imaging is now feasible, its true value is unknown as compared with other imaging modalities, including intraoperative ultrasound [25,26]. Older papers show impressive accuracy rates for radial EUS, but some question its value at the liver hilum, where views become problematic [27,28](Fig. 30).

With some torsion of the echoendoscope, however, good views of the hilum are possible with radial instruments and even more so with linear EUS which permits two lines of view, transgastric (proximal/mid-stomach) and transbulbar. Hilar lesions can be approached for FNA either from the duodenal bulb (preferred) or the stomach. A transgastric approach can be difficult as the portal vein tends to lie between the scope and the proximal CBD; however, there can be a window of opportunity when the scope tip is slightly more distal in the stomach.

The accuracy of EUS-guided FNA of ductal lesions is impressive in expert hands, with an accuracy of 88%, with a significant impact on clinical management expected in 83% of cases [14,29]. Such impressive results must be tempered by the experiences of others who report poorer sensitivities [30–32] and suggest that tissue ought to be sampled first at ERCP followed by EUS [30].

Carcinoma of the gallbladder  Previous section Next section

Gallbladder cancer is rare in Western countries and so experience with EUS staging limited, but radial EUS does seem to have impressive accuracy in both staging these tumors and in differentiating them from benign lesions.

Broadly, gallbladder wall polyps under 5 mm are benign, those over 15 mm are of malignant potential, and those of intermediate size present a diagnostic dilemma [33]. The application of an EUS morphological scoring system provides a robust if fiddly yard-stick by which to measure risk of neoplasia, an approach whose utility is confirmed by follow-up studies [33–36]. The presence of gallstones does not seem to be a confounding factor.

Endosonographically, a tiny echogenic spot/aggregation of echogenic spots and multiple microcysts/comet tail artefact indicate cholesterol polyps and adenomyomatosis, respectively [37]. Loss of the layer pattern of the gallbladder wall is the most specific EUS finding in diagnosing gallbladder cancer [38].

Gallbladder carcinoma appears endosonographically as a hypoechoic mass, sometimes associated with focal wall calcifications. The condition of the outer hyperechoic layer of the gallbladder is central to a scoring system used for the T-staging of local cancers [39,40]. Images are classified according to the shape of the tumor and the adjacent gallbladder wall structure as follows: type A, pedunculated mass with preserved adjacent wall structures; type B, sessile and/or broad-based mass with a preserved outer hyperechoic layer of the gallbladder wall; type C, sessile and/or broad-based mass with a narrowed outer hyperechoic layer; type D, sessile and/or broad-based mass with a disrupted outer hyperechoic layer. These four categories correlate with the histologic depth of invasion and T stage, with accuracies being: type A (corresponding to pTis), 100%; type B (pT1), 76%; type C (pT2), 85%; and type D (pT3–4), 93%. Endosonography guided FNA of gallbladder masses is safe and can provide a definitive diagnosis of malignancy, though the question of needle-tract seeding rears its head [41,42].

Top of page Benign pancreatic disease  Previous section Next section

Pancreatitis  Previous section Next section

Acute pancreatitis  Previous section Next section

Patients with severe acute biliary pancreatitis, and in particular those with evidence of biliary obstruction, probably benefit from emergency ERCP and endoscopic sphincterotomy if bile duct calculi are present[43,44]. It is this final point that is the sticking point. How can we say for certain that stones are indeed present? The role of EUS in acute biliary pancreatitis has been explored and results suggest that EUS can determine which patient truly has choledocholithiasis and so would benefit from therapeutic ERCP [45–47]. There is also evidence that EUS, when used as a first line investigation in the setting of severe acute pancreatitis, is cost effective [48].

The value of EUS in the investigation of acute pancreatitis is not limited to the identification of calculi alone; EUS can determine important morphological features such as echogenicity and the presence of peripancreatic fluid collection. A prospective study by Chak et al. [45] showed a relationship between EUS findings of peripancreatic fluid and echogenicity of the pancreas and mean hospital stay.

Endosonography may define underlying etiology, such as microlithiasis, pancreas divisum, or mass lesion [49,50]. Endosonography reliably detects microlithiasis of the gallbladder with superior accuracy to that of microscopic bile examination, and will detect pancreas divisum with a sensitivity of 66% and a specificity of 83% using the presence of the 'stack sign' to indicate normal anatomy (the main pancreatic duct lies parallel to the distal bile duct and portal vein as viewed from the duodenal bulb) (Fig. 31).

The question of when to investigate an episode of apparent idiopathic acute pancreatitis is moot. Sahai's group suggest that there is no greater yield in information garnered from EUS delayed until after a further attack than if the procedure is performed immediately [51].

Chronic pancreatitis  Previous section Next section

Chronic pancreatitis is the rock on which all the capital ships of imaging flounder; they are all equally impressive when there is a barn-door example but struggle when findings are subtle. Endosonography is a sensitive tool to diagnose chronic pancreatitis, though it is not without its limitations, too. Analysis with the accumulation of nine possible criteria, five parenchymal (hyperechoic foci, hyperechoic strands, calcification, cyst formation, and ductal lobularity) and four ductal (dilation, duct irregularity, hyperechoic duct margins, and visible side branches) shows EUS to be reliable when it is either clearly normal (< 2 criteria) or clearly abnormal (> 5 criteria). By using receiver-operating curve (ROC) analysis, a threshold of three or four criteria offers the optimum compromise between sensitivity and specificity (70% each) [52]. Interobserver variation in diagnosing chronic pancreatitis with EUS is good [53](Fig 32).

Given the inherent risks of ERCP and the difficulties of functional testing, EUS may be useful in diagnosing mild chronic pancreatitis when less sensitive tests such as CT and abdominal ultrasound are negative. Interestingly, those patients with persistent dyspepsia have a significant degree of endosonographic pancreatic abnormality (mean number 3.3) [54].

The use of EUS-guided pancreatic sampling to make the diagnosis of chronic pancreatitis does the patient no favors [55]. When applied to the differentiation between chronic pancreatitis and tumor, however, it is of value (accuracy 86% [56]) but sensitivity is low, with a sensitivity of 91% in those with a mass alone as opposed to 74% in those with a mass against a background of chronic pancreatitis [57].

Leaving aside the value of EUS in the diagnosis of chronic pancreatitis, what of its role in relieving pain? Celiac axis neurolysis is safe and effective in ameliorating such pain in those with pancreatic cancer but the benefits are of shorter duration in the setting of chronic pancreatitis, raising the question of true clinical benefit [58,59]. Such EUS-guided neurolysis, furthermore, is not without risk [60].

Autoimmune pancreatitis  Previous section Next section

The finding of an apparent symptomatic pancreatic mass in a young patient, in the absence of a family history of cancer or neuroendocrine syndrome, is suggestive of this condition.

The EUS appearances of this condition range from diffuse pancreatic enlargement to the presence of an irregular hypoechoic mass with or without sizeable local/celiac axis lymphadenopathy and so morphologically can be indistinguishable from those of cancer, but not chronic pancreatitis [61]. Corticosteroids are used for treatment.

In the diagnosis of autoimmune pancreatitis, serum IgG4 levels have been noted to be raised [62]. Tissue sampling, either FNA or trucut, will yield inflammatory cells but this alone does not exclude the presence of tumor [61,63].

Top of page Cystic lesions of the pancreas  Previous section Next section

An English nursery rhyme gives a good overview of the state-of-the-art knowledge of the diagnostic dilemma that is the pancreatic cyst. The Grand Old Duke of York had ten thousand men. He marched them up a hill and marched them down again. And when they were up, they were up, and when they were down, they were down.

This topic has been well reviewed in terms of diagnostic approach (morphology, cytology, and biochemistry [64,65]) and suggested therapeutic approach (leave alone or surgery [66–68]). The imaging and sampling strengths of EUS are belied by the twin Achilles heels of poor interobserver agreement and an inability to set definite biochemical cut off levels for carcinoembryonic antigen (CEA) [67–71].

In attempting to differentiate benign from malignant or potentially malignant cystic lesions of the pancreas, 30% of lesions are misclassified as pseudocysts [66]. Endosonography yields morphological, biochemical, and cytological information. The biochemical fluid analysis (amylase and CEA) of EUS-guided fine-needle aspiration is the most useful parameter, interobserver variation in judging cyst morphology being particularly poor. Although abnormal CEA levels (> 200 ng/l or > 800 ng/l, depending on author [64,68]) and grossly raised intracystic CA19.9 levels (> 50 000 IU/ml [64]) are indicative of a mucin-secreting cyst, no criterion other than for diagnostic cytology can reliably predict the final transition to overt cystadenocarcinoma. The presence of coexisting pathology, such as chronic lymphocytic leukemia, can further confound diagnosis [72].

The EUS-guided FNA of cystic pancreatic lesions is a safe procedure and there are no available predictors of potential complication, including intracystic bleed or infection [73,74]. But prophylactic antibiotics probably ought to be given prior to puncture (e.g. gentamicin and cefuroxime) and for 2–3 days afterwards (oral ciprofloxacin), for larger or incompletely drained lesions.

The biochemical measurement of various substances in an aspirate must be first discussed with the local laboratory as otherwise samples can be rejected. Samples for cytology must similarly be discussed on initiating an FNA service as the presence of mucosal goblet cells can sow confusion with the inexperienced cytopathologist.

Pseudocysts  Previous section Next section

Pseudocysts represent the maturation and encapsulation of a pancreas-related acute fluid collection, a process that occurs over approximately 6 weeks. If there is no 'good' history of acute pancreatitis, it is important to remain circumspect about any such cyst, particularly if it lies in the tail of the pancreas or occurs in a young female; mucinous cystadenoma and solid-cystic pseudopapillary tumors need to be excluded.

Aspiration and amylase content analysis (at least > 250 IU/ml or, preferably > 5000 IU/ml, depending on author [64,69]) will confirm the diagnosis of pseudocyst. The colour of the fluid can be quite variable, ranging from straw-colored to black when there has been a previous attempt at drainage. Cytology is generally unhelpful.

The most appropriate strategy for the non-ERCP endoscopic management of pseudocysts is not clear, the choice lying between aspiration to dryness (using a 19 G needle) or stent insertion. Such stent placement can be achieved by ballooning a tract over an 0.035-inch wire passed into the cyst via a 19 G needle or the use of either of two specialized kits from COOK: (a) cystotome, a needle-knife with an outer 10 Fr diathermy 'drilling' sheath; or (b) Giovanini needle-knife with ready-loaded 8.5 Fr straight stent. A nasocystic drain is sited in cases where the cyst contents are infected (or likely to become so).

Endosonography-guided cyst drainage is certainly feasible and results are probably favorable, even in the face of local varices, but the literature is sparse [75–77].

Cystadenomas  Previous section Next section

Serous cystadenoma  Previous section Next section

Serous cystadenomas of the pancreas occur frequently in middle-aged females, are often symptomatic (pain or non-specific discomfort), and may be found at any site in the pancreas. They may increase in size but are generally thought to be benign (Figs 33 and 34).

The classic structure of a serous cystadenoma is that of multiple small/medium-sized cysts, set in a fibrous, stellate ('scar'), pomegranite or honeycomb like, with some having calcification. Oligocystic and megacystic forms exist, all having thin septations. Aspiration yields water-like fluid with a low CEA and amylase content. Cytology is often unhelpful.

Mucinous cystadenoma  Previous section Next section

This form of adenoma once again occurs more frequently in middle-aged females and commonly, but certainly not exclusively, is found in the tail. They are of malignant potential. These cysts tend to be single-chambered or, if septate, have thick septations. Aspiration with a 22 G needle is usually dry on first impressions until the stylet is re-introduced and mucus extruded. For this reason, it is better to use a 19 G needle from the start, needle awkwardness permitting. If the volume of the aspirate is low, the measurement of CEA and amylase (expected to be high and low, respectively) takes precedent over cytology in terms of clinical usefulness, although attempts ought to be made to sample the cyst wall or thickened septations for cells (Fig. 35).

Solid-cystic pseudopapillary tumor  Previous section Next section

The occurrence of a pancreatic cyst (often large) in an otherwise healthy young female ought to flag the possible presence of this lesion with a low but potential risk of malignant transformation. They very rarely occur in males and can be solid. The aspirate is often rust coloured with low CEA and amylase levels [78,79].

Intraductal mucin-producing tumor/neoplasm (IPMT/N)  Previous section Next section

Unlike the other cysts mentioned, these lesions are of malignant potential, arise from the main pancreatic duct or its side branches, and are frequently found in men. They are the joker in the pack of pancreatic cysts in that they may even present as chronic calcific pancreatitis (a chicken and egg situation) (Fig. 36)[80]. The side-branch variant tends to carry a better prognosis. The finding of two or more cystic lesions, all be they simple in form, at two pancreatic sites ought to raise the possibility of a field-defect and the presence of an IPMT (Fig. 37).

Although classically described as being associated with the finding of mucus extruding from the ampulla, this is not seen by any means universally. Aspiration yields a mucoid sample rich in both CEA and amylase. Cytology can identify mucinous epithelium (goblet cells) floating in mucus [81]. This appearance lays a trap for the inexperienced cytopathologist who might mistake transported gut epithelium for such cells, leading to overdiagnosis. Another cause of overdiagnosis is when the normal pancreatic duct epithelium becomes concertina-like upstream of an obstruction. Cytology will provide a diagnosis in 91% of cases, though it will underestimate tumor grade in at least 60%. Cytology of aspirated pancreatic juice is of little clinical help [82].

Mucinous cyst adenocarcinoma  Previous section Next section

Unless overtly malignant features such as irregular, invasive margins, nodularity, or the presence of lymph nodes are seen at EUS, it is very difficult to differentiate between benign and malignant cystic lesions. Neither CEA nor CA19.9 levels have definitely been shown to be diagnostic of malignant change. Cytology here is the most useful test. There are no data to assess the value of brush cytology (COOK 'Cytobrush') in this setting and potential usefulness may be limited by the stiffness of the 19 G needle through which this brush must be passed.

A cystic form of pancreatic adenocarcinoma occurs but is rare.

When performing EUS-FNA of potentially malignant lesions, consideration must be given to the issue of seeding, particularly if the target is in the body or tail of the pancreas. At these sites, the needle track crosses the lesser sac.

Top of page Solid tumors of the pancreas  Previous section Next section

Adenocarcinoma  Previous section Next section

There has been some retrenchment in the initial ecstasy at the accuracy of EUS for staging pancreatic cancer. Heady accuracy rates of > 90% have given away to those approaching a more sober 50% [83–86].

King Solomon had it about right, as the reality probably lies somewhere in between: EUS T-stage and N-stage accuracy for pancreatic cancer varies from 78 to 94% and 64 to 82%, respectively [85]. The possible superiority of multislice CT in detecting mesenteric artery involvement, however, probably spells the death-knell of radial EUS staging by the average endosonographer [15,84,87,88]. The cost effectiveness of EUS in addition to CT in this setting is, like beauty, very much in the eye of the beholder [89]. Endosonographic FNA for tissue diagnosis is cost effective [90](Figs 38, 39, 40).

The true value of EUS in the setting of pancreatic cancer is twofold, namely, the identification (or exclusion) of small lesions and the opportunity for diagnostic or therapeutic intervention [91–94].

Guided tissue sampling yields a diagnostic accuracy approaching 90% [95]. Its clinical effectiveness is best demonstrated by an ability to produce positive results where both ERCP and CT-guided sampling have failed [96]. The risk of tumor seeding is low, a single case having been reported, and certainly is less when compared with percutaneous sampling [97,98]. Furthermore, an ability to perform celiac axis neurolysis for those patients with irresectable pancreatic cancer leads to a significant reduction in pain and need for narcotics [59].

Broadening the use of therapeutic EUS, the occasional failure of ERCP to access the pancreatico-biliary tree (Roux-en-Y reconstructions or luminal obstruction) has led to a further extension in the use of EUS. Two small case series show EUS-guided biliary drainage to be a potential alternative to a percutaneous transhepatic approach in such patients following unsuccessful ERCP [99,100]. An area of ongoing research is brachytherapy and the injection of anticancer drugs directly into advanced pancreatic tumors using EUS techniques [101,102], although this perhaps falls into the 'try it because you can' category of research.

Pancreatic FNA is safe [103]. It is usually best achieved with either a 22 G or 25 G needle, as increasing the caliber of the needle merely results in less maneuvrability, more blood, and a more irascible cytopathologist. The optimal number of passes is debatable, but figures of seven and five have been suggested for pancreas and lymph node, respectively [104]. For those endoscopists with a life outside their hospitals, perhaps fewer passes might suffice. The presence of a cytopathologist or technician to check for cellular adequacy does have a marked impact on accuracy and should be factored into the business plan of any such service.

The 19 G trucut needle available for EUS use is very difficult to wield in the duodenum, although good samples can be obtained from the pancreatic body/tail [105]. The general use of this instrument has been reviewed [106]. The use of low dose molecular heparin or aspirin at the time of FNA does not confer any added procedure risk nor any increased contamination of the sample by blood [107]. Endosonographic FNA only obviates the risk of seeding when it is performed for lesions in the head of the pancreas.

One enduring myth of the FNA of pancreatic cancer is 'hardness.' Unless the lesion is calcified, the majority of adenocarcinomas are soft and easily allow passage of a needle; 'hardness' can be a product of poor scope position and inadvertent use of the scope's elevator.

Screening for adenocarcinoma  Previous section Next section

The screening by EUS of those with a strong family history of pancreatic cancer or melanoma has been shown to have some merit [108], but it should be taken into account that normal pancreatic parenchyma can vary widely in echo-texture and is influenced by regular alcohol intake. Selective screening of pancreatic cancer kindreds does seem to be cost effective on a on-off basis [109].

Neuroendocrine tumors  Previous section Next section

The majority of pancreatic neuroendocrine tumors (NETs) occur in the head and are non-functioning. They tend to be hypoechoic, well demarcated, and sometimes display posterior echo-enhancement owing to their vascularity. These tumors may be pedunculated. In the detection of such tumors, EUS is highly accurate and cost effective [110,111].

The main clinical association of NETs is with multiple endocrine neoplasia syndrome (Type I), with 80% of such patients developing non-functioning NETs and to a lesser degree gastrinomas or insulinomas [112].

Functional NETs occur at disparate sites in the pancreas and duodenum: gastrinoma (50% pancreas/50% duodenal wall), insulinoma (any region), and glucagonoma (body/tail) [112,113].

On FNA, NETs have a very soft texture as one might predict from being vascular in nature—for this reason suction is best avoided. The cytological assessment of aspirates from these lesions is more complex than for adenocarcinoma, yet EUS-FNA remains highly accurate and is safe [111,114,115].

Metastases  Previous section Next section

A broad range of cancers may metastasize to the pancreas, presenting with mass lesions. They include: breast, kidney, colon, esophagus, stomach, skin, ovary, neuroendocrine, lung, chondrosarcoma, and lymphoma [116–118]. The morphology of such lesions presented at EUS is not enough to be truly diagnostic but metastases tend to be hypoechoic, rounded, and display posterior enhancement [117,118]. In the case of renal cell tumor metastases at least, low negative pressure aspiration results in improved diagnostic yield [119].

Top of page Training in pancreatico-biliary EUS  Previous section Next section

A proficiency in linear EUS is required for competent pancreatico-biliary endosonography. Whereas radial EUS might yield useful morphological and staging information, the major strength of EUS over other imaging modalities, and perhaps its future, lies in an ability to at least sample tissue but also to perform therapeutic procedures.

In respect of radial studies, American Society for Gastrointestinal Endoscopy guidelines suggest 150 procedures in total, with at least 75 being pancreatico-biliary; earlier US recommendations were for 120 such cases [120]. These figures result from educated guesswork but do seem to be borne out in practice [121,122].

Linear EUS and the acquisition of the skills for FNA, etc. would appear to take between 25 and 50 supervised cases, though there is a general realization that a long learning curve stretches into the future [123,124].

A step-by-step DVD tutorial on how to perform all aspects of radial and linear EUS consisting of text supported by animation sequences and video clips with commentary is available through COOK (UK/Ireland) and Olympus (South-east Asia) [125].

Top of page Outstanding issues and future trends  Previous section Next section

Whereas improvements in cross-sectional imaging will almost certainly negate the role of diagnostic radial EUS, interventional studies using linear systems will become more mainstream. This evolution will in some ways reflect the process that ERCP has undergone over the past decade. In the initial stages we should be looking to replace percutaneous transhepatic cholangiography with an EUS-guided procedure.

The major challenges that face EUS and its application to the pancreatico-biliary system are those of capacity and instrumentation. There are significant bottlenecks in our current ability to train sufficient numbers of proficient radial endosonographers, a situation that will become exacerbated by the demand for more linear procedures. So, perhaps now we should (or must) focus our training programs towards linear work.

Instrumentation, in terms of the needles, stent delivery systems, etc. available for therapeutic EUS, is rudimentary and needs to be addressed. We also need echoendoscopes which are less bulky but yet have larger accessory channels— maybe twin-channeled—to permit more intricate work. Perhaps developments in laparoscopic surgery can serve as a template for this.

Top of page References  Previous section

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Copyright © Blackwell Publishing, 2005

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Introduction
History
Current applications
Therapeutic EUS
Teaching and training EUS
Synopsis
Introduction
Radial and linear endosonographic probes
Contrast-enhanced ultrasonography
Catheter-based EUS probes (miniprobes)
  Miniprobe technique
  Miniprobes in cancer
  Other uses of miniprobes
  Miniprobe limitations
Needles and accessories for EUS
  Fine-needle aspiration
   Different types of needles
   FNA technique
   Accuracy and safety
  Core tissue biopsies
   Technique
   Accuracy and safety
Outstanding issues and future trends
References
Synopsis
EUS for cancer staging
Esophageal cancer staging with EUS
  Esophageal cancer TNM staging
  Technique for performing EUS staging of esophageal cancer
  EUS of stenotic esophageal tumors
  EUS evaluation of superficial tumors
  EUS evaluation of lymph nodes
  EUS-FNA of peri-esophageal lymph nodes
  Accuracy and limitations of EUS staging of esophageal cancer
  EUS re-staging of esophageal cancer after chemoradiation
  Impact of EUS staging on esophageal cancer management
Gastric cancer staging with EUS
  Gastric cancer TNM staging
  EUS staging of advanced gastric adenocarcinoma
  EUS staging of early gastric adenocarcinoma
  EUS staging of gastric MALT lymphoma
Rectal cancer staging with EUS
  Rectal cancer TNM staging
  Pathologic staging of rectal cancer
  Surgical management of rectal cancer
  Management algorithm for rectal cancer (Fig. 17)
  Technique for performing EUS rectal cancer staging
  EUS staging of rectal cancer
  Accuracy of EUS in staging rectal cancer
  EUS vs. CT and MRI for rectal cancer staging
  EUS/FNA for rectal cancer lymph node staging
  Stenotic rectal tumors
  Rectal EUS staging after radiation therapy
  Colon cancer staging with EUS
Anal cancer staging with EUS
Pancreatic cancer
  Staging of pancreatic cancer
  EUS staging of pancreatic cancer (Figs 12,13)
  Combination of EUS and CT/MRI for pancreatic cancer staging and determining resectability
  EUS-FNA for staging pancreatic cancer
  Recommendations for EUS staging of pancreatic cancer
Ampullary cancer
Extrahepatic bile duct cancer
Future trends and outstanding issues
References
Synopsis
Introduction
Endoscopic and EUS examination
GISTs
  Origin and development of GISTs
  Molecular biology of GIST: c-kit
  CD34 and other immunohistochemistry
  Clinical features
  Pathology
  Predicting malignant behavior: role of molecular markers
  Predicting malignant behavior: role of EUS
  Tissue sampling of GISTs
  EUS-guided fine-needle aspiration
  Therapy: surgery
  Therapy: imatinib
Leiomyomas
  Clinical features and diagnosis
  EUS features
Lipomas
  Clinical features and diagnosis
  EUS features
Granular cell tumors
  Clinical features
  Pathology
  Endoscopic and EUS features
  Treatment of granular cell tumors
Duplication cysts
  Clinical features
  EUS features
  Treatment of duplication cysts
Carcinoid tumors
  Clinical features and pathology
  Biochemistry
  Endoscopic and EUS features
  Appendiceal carcinoids
  Ileal carcinoids
  Rectal carcinoids
  Gastric and duodenal carcinoids
Ectopic pancreas ('pancreatic rest')
  Clinical features
  EUS features
Extrinsic compressions
Varices
Future trends and outstanding issues
References
Synopsis
Morbid anatomy
  Pancreas
  Portal vein
  Common bile duct
Endosonographic anatomy
Performing EUS of the pancreas and biliary tree
  Body and tail of pancreas
   Radial EUS
   Linear EUS
  Head and uncinate process of pancreas
   Radial EUS
   Linear
Benign biliary disease
  Choledocholithiasis
  Choledochal cysts
  Primary sclerosing cholangitis (PSC)
Malignant biliary disease
  Ampullary carcinoma
  Cholangiocarcinoma
  Carcinoma of the gallbladder
Benign pancreatic disease
  Pancreatitis
   Acute pancreatitis
   Chronic pancreatitis
   Autoimmune pancreatitis
Cystic lesions of the pancreas
  Pseudocysts
  Cystadenomas
   Serous cystadenoma
   Mucinous cystadenoma
   Solid-cystic pseudopapillary tumor
   Intraductal mucin-producing tumor/neoplasm (IPMT/N)
   Mucinous cyst adenocarcinoma
Solid tumors of the pancreas
  Adenocarcinoma
   Screening for adenocarcinoma
  Neuroendocrine tumors
  Metastases
Training in pancreatico-biliary EUS
Outstanding issues and future trends
References
Synopsis
Non-invasive imaging modalities
  Chest CT
  Positron emission tomography
Invasive staging
Endoscopic ultrasound-guided fine-needle aspiration
  Accuracy for diagnosing malignancy
  EUS and identification of metastatic disease
  EUS technique
  Limitations of EUS-FNA
Combined minimally invasive staging with endoscopic ultrasound and endobronchial ultrasound
Outstanding issues and future trends
  EUS-FNA and molecular markers in lung cancer
References

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