Digestive and Liver Disease
Volume 42, Issue 1 , Pages 6-15, January 2010

Endoscopic ultrasound in the evaluation of pancreaticobiliary disorders

  • A. Larghi

      Affiliations

    • Digestive Endoscopy Unit, Catholic University, Rome, Italy
    • Corresponding Author InformationCorresponding author at: Digestive Endoscopy Unit, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168, Rome, Italy. Tel.: +39 0635511515; fax: +39 0630156581.
    • ,
  • M.C. Petrone

      Affiliations

    • Division of Gastroenterology and Gastrointestinal Endoscopy, Vita-Salute San Raffaele University, Scientific Institute San Raffaele, Milan, Italy
    • ,
  • D. Galasso

      Affiliations

    • Digestive Endoscopy Unit, Catholic University, Rome, Italy
    • ,
  • P.G. Arcidiacono

      Affiliations

    • Division of Gastroenterology and Gastrointestinal Endoscopy, Vita-Salute San Raffaele University, Scientific Institute San Raffaele, Milan, Italy

Received 2 June 2009; accepted 24 June 2009. published online 10 August 2009.

Article Outline

Abstract 

The close proximity of the endoscopic ultrasound probe to the pancreas coupled with the ability to perform fine needle aspiration has made endoscopic ultrasound an extremely important technique for the evaluation of both benign and malignant pancreaticobiliary disorders. In parallel to the widespread importance of diagnostic endoscopic ultrasound, the therapeutic and interventional applications of this procedure are expanding and may become a major breakthrough in the management of pancreaticobiliary diseases. This article focuses on the utility and recent advances of endoscopic ultrasound in the diagnostic evaluation pancreaticobiliary disorders and analyses the data of well established interventional procedures such as celiac plexus neurolysis and pseudocyst drainage. Moreover, the more innovative procedures, such endoscopic ultrasound-guided biliary and pancreatic ducts access and drainage and the experimental use of direct endoscopic ultrasound-guided therapy of both solid and cystic pancreatic lesions will also be reviewed.

Keywords: Bile duct cancer, Choledocolithiasis, Chronic pancreatitis, Endoscopic ultrasound, Idiopathic acute recurrent pancreatitis, Interventional EUS, Pancreatic cancer, Pancreatic cysts, Pancreaticobiliary system

 

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1. Introduction 

The intragastric and intraduodenal position of the endoscopic ultrasound (EUS) probe in close proximity to the pancreas and the extrahepatic biliary system permits the obtainment of high-resolution images and the visualisation of local anatomic details not detected by other imaging techniques. This peculiarity, coupled with the ability to perform EUS-guided fine needle aspiration (EUS-FNA) to acquire tissue samples [1] has rapidly made EUS one of the most important and accurate tools for the evaluation of both benign and malignant pancreaticobiliary disorders [2], [3]. The precise targeting by EUS and the ease of passage of a needle into the pancreas and adjacent organs has motivated investigators to evaluate EUS not only as a method to establish a definitive tissue diagnosis, but also to gain access to the pancreaticobiliary ductal system: indications include failure of endoscopic retrograde cholangiopancreatography (ERCP), and delivering anti-neoplastic or radiosensitising agents into pancreaticobiliary lesions by direct injection for therapeutic purposes [4]. This technique, named EUS-guided fine needle injection (EUS-FNI), in association with the development of echoendoscopes with larger channels that allow the passage of stents and other accessories, has created the new field of therapeutic and interventional EUS which has found major applications in the pancreaticobiliary system.

This review article will illustrate the role of EUS in the evaluation of both benign and malignant pancreaticobiliary disorders, analyse the data of well established interventional procedures, such as celiac plexus neurolysis and pseudocyst drainage, describe innovative and experimental procedures such as EUS-guided biliary and pancreatic duct access and drainage, and the feasibility of direct EUS-guided therapy of both solid and cystic pancreatic lesions.

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2. Benign pancreaticobiliary disorders 

2.1. Choledocholithiasis 

EUS is an extremely accurate test for diagnosis of common bile duct stones (CBDS) (Fig. 1) and can be used to select patients who should undergo a therapeutic ERCP, thus avoiding the risk of complications associated with diagnostic ERCP [5]. A combination of clinical, biochemical, and morphological criteria, is used to risk stratify individuals with suspected choledocholithiasis and an intact gallbladder into three groups (Table 1). Patients with intermediate risk of choledocholithiasis benefit the most from a diagnostic test based on which a decision is made to perform a therapeutic ERCP [6]. Three recent papers have addressed this topic and found that a EUS-based approach can reduce the number of diagnostic ERCP by 60–75% in this patients’ population [7], [8], [9]. In addition, this approach is more successful in the overall evaluation of CBDS, with fewer complications than using an ERCP based approach [7], [8], [9]. Importantly, the performance of EUS for CBDS is not related to the size of the stone or to the diameter of the CBD, and it is independent on the type of echoendoscope used, with a learning curve that for this particular indication is relatively short [10]. The use of EUS instead of ERCP has been found to be cost-effective in both intermediate and high-risk patients in the context of laparoscopic cholecystectomy and in severe acute pancreatitis [11], [12].

Table 1. Risk of common bile duct stones (CBDS) in patients with suspected choledocholitiasis according to clinical, biochemical, and morphological criteria.
Risk categoryChance of CBDSClinical parametersBiochemical parametersCDB diameter
Low2–3%NoneNormal≤7mm
Intermediate20–50%Acute ascending cholangitis↑ALP ≤2X ULN8–10mm
Pancreatitis↑GGT
↑ALT or ↑AST

High50–80%Acute ascending cholangitis↑ALP ≥2X ULN≥10mm
Jaundice

Abbreviations: ALP, alkaline phosphatase; GGT, gamma-glutamyltransferase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; ULN, upper limit of normal.

A different and very important question is whether EUS or magnetic resonance cholangiopancreatography (MRCP) should be used as the first non-invasive test for suspected CBDS. MRCP has, in fact, replaced diagnostic ERCP for many indications, one being CBDS diagnosis. A recent systematic review of the literature, aimed at finding a consensus on the optimal strategy to investigate patients for CBDS after a negative transabdominal US and/or computed tomography (CT), found EUS and MRCP to have an overall high diagnostic performance, with no significant differences between the two tests [13]. The authors concluded that the use of one or the other test should be guided by local availability and expertise. It is argued that because of the complete non-invasive nature of MRCP, it should be considered the first-line investigation for CBDS [14]. However, in daily practice it can be difficult and time consuming to obtain an MRCP, while a EUS when available has the substantial advantage of being performed in an endoscopy suite where it can be followed by an ERCP if CBDS are found.

2.2. Pancreatitis 

In patients with pancreatitis, EUS should be proposed to determine the aetiology in idiopathic acute cases, especially if recurrent, to help establish the diagnosis in suspected chronic cases, and to search for choledocholithiasis when a biliary aetiology is suspected [7], [15]. In idiopathic acute recurrent pancreatitis (ARP) when no cause is identified after an initial thorough clinical, laboratory, and radiological evaluation, EUS can provide a valid alternative to and has gradually replaced the more invasive approach of bile crystal analysis and ERCP with or without sphincter of Oddi manometry [16]. Most frequent causes of ARP are occult CBD and/or gallbladder microlithiasis, while other aetiologies include unrecognised chronic pancreatitis, pancreas divisum, sphincter of Oddi dysfunction, and other less frequent etiological factors such as small pancreatic tumours or cysts. Studies that have evaluated the role of EUS in this clinical setting have reported a diagnostic yield that ranged from 32% to 88% [17]. In the largest study published to date in which the number of patients with ARP and those with an unexplained first episode of acute pancreatitis is clearly stated, the overall yield of EUS was 68% [18]. In the subgroup of patients with an in situ gallbladder, sludge (12%), stones (5%) or pancreas divisum (6%) were most commonly detected, whereas chronic pancreatitis (39%) and pancreas divisum (10%) were the most frequent diagnoses in patients who had previously undergone cholecystectomy [18]. In addition, a small subset of patients had duodenal bile sampling for microscopic analysis for crystals, which were found in about half of them. These results indicated that EUS with bile crystal analysis is of great value and substantially reduces the number of unnecessary diagnostic ERCP, as previously suggested by Tandon and Topazian [19]. In a more recent study by Mariani et al. [20], secretin administration to stimulate pancreatic secretion in order to obtain better visualisation of the bilio-pancreatic ductal system during both MRCP and EUS resulted in a better performance than ERCP evaluation. Based on these results, the authors recommended the use of secretin stimulation with both MRCP and EUS as complementary first-line examinations in the evaluation of patients with ARP [20]. The cost-effectiveness of this approach, however, remains to be established.

The diagnosis of chronic pancreatitis (CP) can be very challenging. In particular, the real dilemma in CP is to recognize and diagnose the disease in its early stages, for which there are insufficient sensitive and specific tests available. If EUS is demonstrated to be sensitive and specific for early CP, it would really make this procedure a major breakthrough in the evaluation of this condition [21]. Of the EUS parenchymal and ductal criteria used to diagnose CP (Table 2), three of the parenchymal ones (hyperechoic foci, hyperechoic strands and parenchymal lobularity) can be visualised by EUS only, making it the most theoretical valuable test to diagnose early CP. Two major problems, however, may limit EUS in this important task: (i) some of the EUS abnormalities associated with the mild forms of CP are encountered in the elderly or in heavy alcohol drinkers [22], [23]. Therefore, it is not clear whether these abnormalities, especially when isolated, indicate physiological aging of the pancreas or mild signs of asymptomatic CP and their recognition may lead to an over-estimation in the diagnosis of CP; (ii) these subtle changes of the pancreas are uncommon and may be easily missed by inexperienced endosonographers, creating a problem of under-diagnosis. Scepticism about a possible role of EUS in early CP diagnosis comes from the observation of a high rate of EUS findings suggestive of CP in both healthy subjects and patients with abdominal pain of possible pancreaticobiliary origin [24], [25]. On the other hand, two studies have reported that about 65% of patients with early CP detected on EUS but not on other tests such as CT and secretin function tests or ERCP will eventually develop CP, which can then be detected on repeated tests that were previously negative [26], [27]. These latter results need further confirmation in prospectively followed cohorts of patients. These cohorts should contain a significant number of individuals and include both positive and negative EUS cases for early CP to assess the overall accuracy of EUS in this setting. This difficult diagnostic task might benefit from the recently published Rosemont classification for CP [28], a consensus-based system that allocated EUS features of CP into major or minor criteria with a very good inter-observer variability. Of note, the use of the EUS-guided Tru-Cut needle for the obtainment of tissue samples from patients with early CP has been attempted, but it is not recommended because of the potential complications and limited diagnostic yield [29].

Table 2. EUS criteria of chronic pancreatitis.
Parenchymal criteriaDuctal criteria
Hyperechoic fociMPD dilatation
Hyperechoic strandsIrregular MPD contour
LobularityHyperechoic MPD margins
Shadowing calcificationsVisible branch ducts
CystsIntraductal stones

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3. Pancreaticobiliary malignancies 

3.1. Pancreatic cancer 

EUS has a manifold role in the evaluation of patients with clinical suspicion of a pancreatic mass, and in those in whom a solid pancreatic lesion has already been identified. Despite recent advances in both CT and MR technologies and software, EUS is still the most accurate diagnostic test for the detection of pancreatic lesions, particularly for those smaller than 2cm [30]. Because of this characteristic, when other non-invasive cross-sectional imaging modalities have reported equivocal results, EUS should always be considered and performed when available [31], [32]. The major advantage of EUS is its high negative predictive value, close to 100%, indicating that the absence of a focal mass at EUS reliably excludes pancreatic cancer [33], [34]. However, it should be kept in mind that missed pancreatic neoplasms even in very expert hands have been reported [35]. These missed lesions occurred mainly in patients with underlying chronic pancreatitis, diffuse infiltrating carcinoma, prominent ventral/dorsal anlage, or a recent episode of acute pancreatitis; this highlights the importance of performing a follow-up EUS in cases with a strong clinical suspicion, a strategy that has been shown to have clinical value [36].

EUS can be used to assess the presence of pancreatic cancer in patients with non-specific changes on CT, such as an enlarged or a prominent pancreatic head. Three studies evaluating this clinical setting have found pancreatic cancer in 8%, 8.7%, and 22% of the patients, respectively [37], [38], [39]. In the latter study [39], the mean size of the pancreatic malignant lesions was 3.5cm, a very surprising result that may be the consequence of poor quality CT technique and interpretation in the community hospitals, where most of these exams were performed.

Another clinical scenario is a patient with a pancreatic mass detected on cross-sectional imaging studies. If the mass is clearly unresectable based on CT or MRI results, either percutaneous image-guided or EUS-FNA can be performed for tissue sampling to obtain a definitive diagnosis and offer proper treatment [40]. The choice between one or the other sampling method is highly dependent on the local expertise and the availability of EUS or interventional radiology. The percutaneous route may be indicated in patients who are at risk for sedation-related complications and in those with surgically altered upper GI anatomy. On the other hand EUS is advantageous because it provides additional staging information, i.e. the presence of lymph node metastases in the celiac, lumboaortic, retroduodenopancreatic and superior mesenteric regions and sample small pocket of previously undetected ascites. EUS offers the possibility of performing EUS-guided celiac plexus neurolysis (EUS-CPN) in patients with significant pain not controlled by narcotics during the same EUS-FNA session. When other biopsy techniques have failed, or in cases of a previous EUS-FNA not performed in a tertiary centre, the use or the repetition of EUS-FNA is strongly supported [41], [42]. Overall, EUS-FNA of pancreatic masses is safe [43], has a mean accuracy of about 85% [44], and carries a lower risk of tumour seeding than percutaneous techniques [45]. Higher accuracy rates are achieved with on-site cytopathological examination to assess specimen adequacy [46] which, however, is not available in all centres and may increase the cost of the procedure.

If after performing a CT or MRI scan the resectability of a pancreatic mass is equivocal, EUS±FNA is the next logical step to distinguish with high accuracy patients who benefit from a major surgical intervention from those with locally advanced or metastatic disease who should not undergo surgery. In terms of performance of CT and EUS for pancreatic cancer staging, a recent review has concluded that due to the heterogeneity in study design, quality and results of all the published studies it is impossible to draw definitive conclusions on the relative value of each test [47]. The best approach is to use both tests in a complementary fashion because the highest accuracy in predicting resectability is obtained by the combination of the two imaging tests [48]. If EUS demonstrates the mass to be clearly unresectable (Fig. 2A), one can proceed with FNA for tissue acquisition (Fig. 2B). In potentially resectable lesions, on the other hand, the argument for a definitive diagnosis before undergoing surgery is debated [49]. Arguments made for EUS-FNA in potentially respectable lesions include an established protocol of preoperative neoadjuvant therapy, a demand by the patient for a conclusive diagnosis of cancer before consenting to surgery, and lastly to exclude unusual histology (lymphoma, acinar cell carcinoma, solid pseudopapillary tumour and pancreatic metastases), that can be found in up to 5% of individuals with pancreatic masses and would not benefit from operation [50]. A proposed algorithm for the evaluation of solid pancreatic masses is shown in Fig. 3.

A very important clinical challenge is the differentiation of pancreatic cancer from inflammatory masses due to focal chronic pancreatitis. In this respect, EUS imaging has not proven to be reliable. New techniques such as contrast-enhanced EUS and elastography have emerged in an attempt to overcome some of the limitations of EUS [51]. Contrast-enhanced EUS to better assess the perfusion inside the pancreatic mass has been evaluated in one study using Levovist [52] and more recently using the second generation contrast agent SonoVue (Fig. 4) [53]. Both studies reported pancreatic cancer to be relatively hypoenhancing and inflammatory masses hyperenhancing compared with the surrounding pancreatic tissue, while the latter study clearly showed benefit from the use of contrast agent with an increase in the sensitivity and specificity 73.2% and 83.3% to 91.1% and 93.3% after its administration [53]. Improved results may be obtained using the contrast harmonic imaging technique as preliminary reported by Kitano et al. [54], Another new imaging technique is elastography. This technique is able to characterize the stiffness of the tissue under examination by calculating and visualizing real-time tissue elasticity. This information can be used to distinguish neoplastic pancreatic “hard” tissue from inflammatory pancreatic “soft” tissue (Fig. 5). After a preliminary experience from Giovannini et al. [55], that proved this method to be feasible, more recent studies have reported conflicting results [56], [57], [58]. Finally, DNA analysis of FNA aspirates [59] and digital imaging analysis of EUS images [60] seem promising but need further confirmation in larger patient populations.

  • View full-size image.
  • Fig. 5. 

    EUS elastographic image of a pancreatic adenocarcinoma showing mainly hard tissue (in blue) with a soft area (in green) between the lesion and the vessel below.

In parallel to the growing importance and widespread use of EUS-FNA for the evaluation of pancreatic masses, efforts have been made to develop a role for this procedure in the treatment of pancreatic cancer. The first approach involved the injection of anti-neoplastic agents under EUS guidance directly into the pancreatic tumour. Chang et al. [61] demonstrated the feasibility and safety of the injection of an allogeneic mixed lymphocyte culture (cytoimplant) in eight patients with unresectable pancreatic adenocarcinoma. Subsequently, Hecht et al. delivered an anti-tumour viral therapy, the ONYX-015 (dl1520) repeatedly into the tumour of 21 patients with advanced adenocarcinoma [62]. The ONYX-015 (dl1520) is an E1B-55kDa gene-deleted replication-selective adenovirus that preferentially replicates in and kills malignant cells, This therapy in association with intravenous administration of gemcitabine during the last 4 sessions resulted in partial disease regression in 2 patients, stabilisation in 6, minimal changes in 2 and progression in 11. Major complications were sepsis in 2 patients and duodenal perforation in 2 other patients. These complications were subsequently avoided by administration of antibiotic prophylaxis and performance of transgastric injection, respectively [62]. At the time of this review, we await the publication of the long-term results presented at DDW in 2006 of a multicentre American trial involving EUS or CT guided injection of TNFerade, a replication-deficient adenovector containing human TNFα gene, regulated by a radiation-inducible promoter Egr-1 [63]. TNFerade was injected weekly for 5 weeks in combination with continuous intravenous 5-FU (200mg/m2/d×5d/wk) and radiation (50.4Gy) in 50 patients with unresectable tumour. The preliminary results were encouraging and reported that four of the five patients whose tumours became surgically resectable had pathologically negative margins and three survived longer than 24 months [63].

More recently other EUS-guided treatment strategies have been attempted. Two series by Sun et al. [64] and Jin et al. [65] have reported EUS-guided direct instillation of radioactive seeds (brachytherapy) in 15 and 22 patients, with a modest benefit regarding reduction of pain only. On the other hand, EUS has been also used to place fiduciary markers in pancreatic tumours for image-guided radiotherapy, with a very high rate of successful placement even in patients with head or uncinate lesions [66]. Other form of therapies such as EUS-guided pancreatic photodynamic therapy and radiofrequency ablation have been evaluated in animal models [67], [68], [69], [70], but are still awaiting clinical trials.

3.2. Bile duct cancer 

Malignant bile duct tumours, i.e. cholangiocarcinomas, present as biliary strictures that need to be differentiated from strictures of benign origin, which in the proximal biliary tree corresponding to the hepatic hilum can be responsible for up to 20% of all cases [71]. In the presence of jaundice, ERCP with brush cytology and/or endobiliary forceps biopsy is usually first performed to reach a definitive diagnosis, while EUS-FNA has been used in some centres as the second diagnostic modality in case of ERCP failure [72], [73]. Studies that have investigated the role of EUS-FNA in this clinical setting have found a sensitivity ranging from 43% to 86% for all biliary strictures and from 25% to 83% for those limited to the hilum [72], [74], [75], [76], [77], [78], [79]. This wide range of sensitivity of EUS-FNA for the evaluation of hilar strictures may reflect the high skills required to sample the hilum, which can underestimate EUS-FNA performance if the sample size is small as in most of the published studies.

In a diagnostic algorithm proposed by Pavey and Gress [73], on the other hand, EUS should be considered the test of choice in patients with biliary strictures and a normal bilirubin. In these patients EUS may reveal the presence of a pancreatic mass or changes consistent with chronic pancreatitis and allows the performance of FNA for a definitive diagnosis during the same procedure. Interestingly, preliminary results from an ongoing experience have used EUS-FNA, performed with a newly developed forward viewing scope that seems to have some advantages over the conventional linear EUS scope for the visualisation of the hilar region, as a first diagnostic modality even in jaundice patients (Fig. 6) [80].

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  • Fig. 6. 

    Common bile duct (CBD) mass at the hilum detected using a newly developed forward viewing therapeutic EUS scope (GF-UCT160J-AL5, Olympus Medical System Europe, Hamburg, Germany).

Another important aspect of EUS-FNA in the evaluation hilar cholangiocarcinoma is the possibility of investigating the presence of regional lymph nodes that can be sampled providing important additional staging information. This information has a tremendous clinical impact in the selection of patients with unresectable hilar tumours who are suitable for a multidisciplinary therapeutic approach recently developed at the Mayo Clinic including chemo- and radiation-therapy in association with liver transplantation [81]. Lymph nodes can be identified in all of these patients, as reported by a landmark study from the Mayo Clinic's group, with EUS-FNA performed to distinguish benign from malignant lymph nodes with a very high accuracy, thus avoiding unnecessary transplantation in about 20% of patients [82].

3.3. Ampullary cancer 

The number of studies that have evaluated the usefulness of EUS with or without FNA in the diagnosis and staging of ampullary tumours is much lower than for pancreatic cancer. In patients with ampullary neoplasms, EUS and intraductal US (IDUS) can be helpful in assessing depth of tumour invasion and the presence of periampullary lymph nodes [83]. This information can help to decide between endoscopic versus surgical therapy and to guide the type of surgical intervention. Despite some controversy [84], EUS staging is mandatory to establish T1 stage and thus to select candidates for endoscopic resection, and when available should always be considered before endoscopic or surgical resection is performed for ampullary tumours [83].

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4. Pancreatic cysts 

Pancreatic cysts represent a wide spectrum of pathology, including inflammatory pseudocysts, benign serous cystoadenoma, and premalignant or malignant lesions, such as intraductal papillary mucinous neoplasms (IPMN), mucinous cystoadenoma and cystoadenocarcinoma, and other rare forms (Table 3). Due to the increased availability and expanding use of cross-sectional abdominal imaging, pancreatic cysts are identified much more frequently, thus posing diagnostic and therapeutic challenges to clinicians [85]. The use of EUS in this setting plays a pivotal role, both diagnostic (appearance and tissue sampling) and therapeutic (aspiration, ablation). Based on the information obtained at EUS and FNA a decision can be reached to cease further work up, follow-up with repeat imaging, or to resect the cyst [85]. An important distinction is that of mucinous from nonmucinous cysts, and this mainly relies on analysis of the cystic fluid that can be safely and efficiently sampled by EUS-FNA. Moreover, EUS has an important impact on management decisions and follow-up of patients with side-branch IPMN due to its ability to image predictors of malignancy (i.e. mural nodules) and the possibility to obtain by EUS-FNA both cyst fluid and cyst wall tissue for diagnosis [86].

Table 3. Characteristics of pancreatic cystic lesions.
LocationCytologyViscosityCyst CEA levels (ng/mL)Cyst amylase level
SerousEvenly distributedBland PAS+Low<0.5Low
MucinousTailMucinousIncreased>200Low
IPMNHeadMucinousHigh>200High
PseudocystEvenly distributedPigmented histiocytesLow<200High

Once aspirated, cystic fluid can be analysed for cytology, viscosity, a variety of tumour markers, and for amylase (Table 3). The poor cellularity of the aspirated fluid limits the value of the cytological examination in the distinction between mucinous and nonmucinous cysts. For this distinction, cystic fluid concentration of carcinoembryonic antigen (CEA) has proved to be the most accurate marker despite considerable variation and overlap in values [87]. A CEA level less than 5ng/mL has been found in a pooled analysis of published studies to be highly diagnostic for serous cystadenomas, while levels greater than 800ng/mL are highly suggestive for mucinous lesions (Fig. 7) [88]. Determination of cyst amylase level may help to further narrow the differential diagnosis, with high levels more frequently found in cysts that communicate with the MPD (pseudocyst or IPMN). In addition, a very high sensitivity and specificity of fluid analysis has been reached by using a combination of viscosity measurements, CEA and amylase levels [89]. Promising data on the use of cystic fluid DNA analysis have been recently published [90], [91]. Though there is a poor agreement between CEA levels and DNA analysis, the combination of the two tests has been found to increase the diagnostic sensitivity exponentially [92]. The use of the Tru-Cut needle and the echo brush to distinguish the type of cyst appear less promising [93], [94].

EUS is a very sensitive tool for recognition and characterisation of an IPMN, a frequently observed cystic lesion that may involve the main pancreatic duct or a side branch (Fig. 8). The ability to detect extremely small mural nodules and to obtain samples for cytological examination is particularly important for decision making in the management of side-branch IPMN, which can be followed up in the large majority of cases [95], [96]. In contrast to the other cystic lesions, cytological evaluation is the most important parameter because the degree of atypia seems to be predictive of the presence of malignancy [97], [98]. On the contrary, it is still controversial if CEA levels are valuable to discriminate between benign and malignant IPMN [99], [100].

EUS is a valuable tool to follow-up side-branch IPMN and determine which ones will eventually need to undergo surgery. Despite what is known about the natural history of these lesions it is now well established that most of them will not require surgery [101], though careful follow-up remains necessary particularly in patients with an increase in cyst size [102]. Moreover when performing follow-up examinations, attention should be paid to the entire pancreas as invasive ductal adenocarcinomas can develop at a different site from that of the IPMN [103].

Similarly to the efforts made in pancreatic solid lesions to expand EUS-guided therapy, initial attempts have been made to develop EUS-guided cysts ablative therapy with the aim of providing a minimally invasive treatment for elderly and high-risk surgical patients. Results from preliminary studies have been encouraging. Two studies have performed cyst lavage with ethanol only [104], [105], while in another study paclitaxel was also administered [106]. Complete cyst resolution was observed in 33–79% of the patients with better results obtained with combination therapy [104], [105], [106]. Future multicentre cooperative studies are needed to further explore the therapeutic role of EUS in the field of pancreatic cysts.

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5. Therapeutic and interventional EUS 

5.1. Celiac block/neurolysis 

EUS-guided celiac plexus block (EUS-CPB) for pain control in chronic pancreatitis and EUS-CPN for cancer related pain control are the most well established interventional procedures performed under EUS guidance [107]. The plexus is composed of two ganglia, usually located anterior and lateral to the aorta at the level of the celiac trunk. Using a curvilinear array echoendoscope, this region can be easily visualised from the lesser curvature of the stomach by following the aorta to the origin of the main celiac artery. With careful inspection it also possible to directly visualize the celiac ganglia as 1–5 elongated hypoechoic structures [108], [109].

The technique for EUS-CPB and EUS-CPN is identical. A mixture of triamcinolone and bivucaine is used for CPB, while an injection of bivucaine followed by a second injection of absolute alcohol is used for CPN. The procedure is usually performed using a 19-gauge needle or a dedicated 20-gauge needle with multiple side holes and injection done at the base (central) or on either side (bilateral) of the celiac axis. In addition, direct injection into the ganglia has been retrospectively evaluated in a recent study [110]. However, this technique requires a prospective confirmatory study before it can become part of routine clinical practice.

Despite the first report was published more than 10 years ago [111], no available studies have compared EUS with radiological or surgical techniques for CPN. Similarly, only two comparative studies for CPB have been performed and found EUS to be slightly better than CT or fluoroscopic guided techniques in relieving pain in chronic pancreatitis [112], [113]. The paucity in the published data that are mainly based on observational, uncontrolled studies, resulted in a recent meta-analysis in an attempt to draw a more definitive conclusion on the usefulness of EUS-guided pain control treatments [114]. Overall, this meta-analysis found EUS-CPN and EUS-CPB to be able to relieve pain in about 80% and 60% of patients with pancreatic cancer or chronic pancreatitis, respectively. Thus the authors recommended EUS-CPN as a valid treatment for pancreatic pain, but always in adjunct with opioid analgesics and adjuvant therapy [114]. On the other hand, the evidence to support the use of steroid injection in chronic pancreatitis is lacking and future studies involving different techniques or other injected compounds are warranted [114].

5.2. Pancreatic pseudocyst drainage 

Another well established interventional EUS-guided procedure is the endoscopic drainage of pancreatic pseudocyst (PP) (Fig. 9). The theoretical advantages of using EUS instead of the traditional “blind” endoscopic approach with a therapeutic gastroscope to create a fistulous tract between the PP and the gastric (cyst-gastrostomy) or the duodenal lumen (cyst-duodenostomy) are multiple: (i) the capability of identifying a cyst with a different diagnosis; (ii) the ability to perform the procedure in cases without obvious bulging; (iii) the ability to identify intervening vessels with the aid of the Doppler with a decreased risk of bleeding, (iv) a better evaluation of the PP's content that may influence the number of stents or the type of drainage placed (stent vs. naso-cystic drainage) [115]. Despite these theoretical advantages, there is still no consensus on which technique should be utilised and in most cases the use of one or the other approach for endoscopic transmural PP drainage is guided by local expertise [116], [117]. In particular, many institutions presently still lack adequate EUS equipment and expertise to perform the procedure, as can be inferred by the results of a survey conducted among both U.S. and non-U.S. members of the American Society for Gastrointestinal Endoscopy [118].

Studies have tried to answer the question whether the use of EUS is really advantageous over the “blind” endoscopic technique. A paper from Kahaleh et al. [119], prospectively compared 99 patients who underwent PP drainage according to a predetermined treatment algorithm: patients with bulging and no portal hypertension were treated with conventional transmural endoscopic drainage (CTED), all the other with EUS-guided drainage. No difference in safety and efficacy was found [119]. A more recent study with a prospective randomised comparative design by Varadarajulu et al. [120] has reported EUS to be significantly superior to CTED mainly because of the capability of draining non-bulging lesions. The lack of bulging was, in fact, the reason to switch from CTED to EUS in 9 out of the 10 patients in whom the CTED approach failed. In all of them the second attempt under EUS guidance was successful. Because of these results and their previous experience [121], the authors concluded that EUS should be considered the first-line modality for PP drainage. Despite this, these results may reflect a possible bias due the authors high expertise in EUS procedures, a therapeutic algorithm presented and tested by Barthet et al. also strongly advocated the use of EUS in the absence of bulging and in the presence of portal hypertension [122].

5.3. EUS-guided access and treatment of biliary and pancreatic ducts 

Since the first cases of EUS-assisted cholangiopancreatography described more than a decade ago [123], [124], EUS-guided drainage of the biliary and pancreatic ductal systems has been increasingly used as an alternative procedure to percutaneous transhepatic cholangiography (PTC) or surgery in patients who had failed prior ERCP or in whom ERCP could not be performed because of altered anatomy of the upper GI tract [125], [126], [127], [128], [129], [130], [131], [132], [133]. Both techniques involve puncture of the target duct with a EUS needle, preferably a 19-gauge needle, which is followed by passage of a guide wire. For the biliary system, access can be done from the stomach into the left intrahepatic ducts or from the duodenum directly into the CBD. The main pancreatic duct is usually accessed transgastrically. Once in place the guide wire when possible is advanced in the direction of and through the papilla into the duodenum to allow for the performance of a rendezvous ERCP or for direct EUS transpapillary stent placement in malignant conditions. Occasionally, when the guide wire cannot be pushed into the duodenum, direct transgastric or transduodenal stent placement can be performed. Biliary drainage is reported to be highly successful with a low complication rate, while MPD drainage appears a little more difficult as proven by a higher failure and complication rates [134].

Finally, transgastric drainage of biloma and the gallbladder in high-risk patients with acute cholecystitis as a definitive treatment or as a bridge to surgery have also been described [135], [136], [137].

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6. Conclusions 

EUS with or without FNA is a major advance in the evaluation of both benign and malignant conditions, and has now been incorporated into the diagnostic algorithm of pancreaticobiliary disorders worldwide. Efforts are now directed towards the exploration of the therapeutic potential of EUS that will hopefully bring EUS to the next level moving it from a purely diagnostic to a mostly therapeutic procedure.

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Conflict of interest statement 

None declared.

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References 

  1. Vilmann P, Jacobsen GK, Henriksen FW, Hancke S. Endoscopic ultrasonography with guided fine needle aspiration biopsy in pancreatic disease. Gastrointest Endosc. 1992;38:172–173
  2. Noh KW, Pungpapong S, Raimondo M. Role of endosonography in non-malignant pancreatic diseases. World J Gastroenterol. 2007;13:165–169
  3. Varadarajulu S, Eloubeidi MA. The role of endoscopic ultrasonography in the evaluation of pancreatico-biliary cancer. Gastrointest Endosc Clin N Am. 2005;15:497–511
  4. Chang KJ. EUS-guided fine needle injection (FNI) and anti-tumor therapy. Endoscopy. 2006;38(Suppl. 1):S88–93
  5. Tse F, Liu L, Barkun AN, Armstrong D, Moayyedi P. Nonoperative imaging techniques in suspected biliary tract obstruction. Gastrointest Endosc. 2008;67:235–244
  6. Williams EJ, Green J, Beckingham I, et al. British Society of Gastroenterology. Guidelines on the management of common bile duct stones (CBDS). Gut. 2008;57:1004–1021
  7. Liu CL, Fan ST, Lo CM, et al. Comparison of early endoscopic ultrasonography and endoscopic retrograde cholangiopancreatography in the management of acute biliary pancreatitis: a prospective randomized study. Clin Gastroenterol Hepatol. 2005;3:1238–1244
  8. Polkowski M, Regula J, Tilszer A, Butruk E. Endoscopic ultrasound versus endoscopic retrograde cholangiography for patients with intermediate probability of bile duct stones: a randomized trial comparing two management strategies. Endoscopy. 2007;39:296–303
  9. Lee YT, Chan FK, Leung WK, et al. Comparison of EUS and ERCP in the investigation with suspected biliary obstruction caused by choledocholithiasis: a randomized study. Gastrointest Endosc. 2008;67:660–668
  10. O’Toole D, Palazzo L. Choledocholithiasis—a practical approach from the endosonographer. Endoscopy. 2006;38(Suppl. 1):S23–S29
  11. Buscarini E, Tansini P, Vallisa D, et al. EUS for suspected choledocholithiasis: do benefits outweigh costs? A prospective, controlled study. Gastrointest Endosc. 2003;57:510–518
  12. Romagnuolo J, Currie G Calgary Advanced Therapeutic Endoscopy Center study group. Noninvasive vs. selective invasive biliary imaging for acute biliary pancreatitis: an economic evaluation by using decision tree analysis. Gastrointest Endosc. 2005;61:86–97
  13. Verma D, Kapadia A, Eisen GM, Adler DG. EUS vs MRCP for detection of choledocholithiasis. Gastrointest Endosc. 2006;64:248–254
  14. McMahon CJ. The relative roles of magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasound in diagnosis of common bile duct calculi: a critically appraised topic. Abdom Imaging. 2008;33:6–9
  15. Rizk MK, Gerke H. Utility of endoscopic ultrasound in pancreatitis: a review. World J Gastroenterol. 2007;13:6321–6326
  16. Al-Haddad M, Wallace MB. Diagnostic approach to patients with acute idiopathic and recurrent pancreatitis, what should be done. World J Gastroenterol. 2008;14:1007–1010
  17. Wilcox CM, Varadarajulu S, Eloubeidi M. Role of endoscopic evaluation in idiopathic pancreatitis: a systematic review. Gastrointest Endosc. 2006;63:1037–1045
  18. Yusoff IF, Raymond G, Sahai AV. A prospective comparison of the yield of EUS in primary vs. recurrent idiopathic acute pancreatitis. Gastrointest Endosc. 2004;60:673–678
  19. Tandon M, Topazian M. Endoscopic ultrasound in idiopathic acute pancreatitis. Am J Gastroenterol. 2001;96:705–709
  20. Mariani A, Arcidiacono PG, Curioni S, et al. Diagnostic yield of ERCP and secretin-enhanced MRCP and EUS in patients with acute recurrent pancreatitis of unknown aetiology. Dig Liver Dis. 2009;41:753–758
  21. ASGE Standards of Practice Committee, Gan SI, Rajan E, Adler DG, et al. Role of EUS. Gastrointest Endosc 2007;66:425–34.
  22. Bhutani MS. Endoscopic ultrasonography: changes of chronic pancreatitis in asymptomatic and symptomatic alcoholic patients. J Ultrasound Med. 1999;18:455–462
  23. Rajan E, Clain JE, Levy MJ, et al. Age-related changes in the pancreas identified by EUS: a prospective evaluation. Gastrointest Endosc. 2005;61:401–406
  24. Sahai AV, Mishra G, Penman I, et al. EUS to detect evidence of pancreatic disease in patients with persistent or nonspecific dyspepsia. Gastrointest Endosc. 2000;52:153–159
  25. Sahai AV. EUS and chronic pancreatitis. Gastrointest Endosc. 2002;56(4 Suppl.):S76–81
  26. Kahl S, Glassbrenner B, Leodolter A, et al. EUS in the diagnosis of early chronic pancreatitis: a prospective follow-up study. Gastrointest Endosc. 2002;55:507–511
  27. Catalano MF, Kaul V, Pezanoski J, et al. Long-term outcome of endosonographically detected minimum criteria for chronic pancreatitis (MCCP) when conventional imaging and functional testing are normal. Gastrointest Endosc. 2007;65:AB120
  28. Catalano MF, Sahai A, Levy M, et al. EUS-based criteria for the diagnosis of chronic pancreatitis: the Rosemont classification. Gastrointest Endosc. 2009;69:1251–1261
  29. DeWitt J, McGreevy K, LeBlanc J, et al. EUS-guided Trucut biopsy of suspected nonfocal chronic pancreatitis. Gastrointest Endosc. 2005;62:76–84
  30. DeWitt J, Devereaux B, Chriswell M, et al. Comparison of endoscopic ultrasonography and multidetector computed tomography for detecting and staging pancreatic cancer. Ann Intern Med. 2004;141:753–763
  31. Kochman ML. EUS in pancreatic cancer. Gastrointest Endosc. 2002;56(4 Suppl.):S6–S12
  32. Katz MH, Savides TJ, Moossa AR, Bouvet M. An evidence-based approach to the diagnosis and staging of pancreatic cancer. Pancreatology. 2005;5:576–590
  33. Catanzaro A, Richardson S, Veloso H, et al. Long-term follow-up of patients with clinically indeterminate suspicion of pancreatic cancer and normal EUS. Gastrointest Endosc. 2003;58:836–840
  34. Klapman JB, Chang KJ, Lee JG, Nguyen P. Negative predictive value of endoscopic ultrasound in a large series of patients with a clinical suspicion of pancreatic cancer. Am J Gastroenterol. 2005;100:2658–2661
  35. Bhutani MS, Gress FG, Giovannini M, et al. The No Endosonographic Detection of Tumor (NEST) Study: a case series of pancreatic cancers missed on endoscopic ultrasonography. Endoscopy. 2004;36:385–389
  36. Eloubeidi MA, Varadarajulu S, Desai S, Wilcox CM. Value of repeat endoscopic ultrasound-guided fine needle aspiration for suspected pancreatic cancer. J Gastroenterol Hepatol. 2008;23:567–570
  37. Ho S, Bonasera RJ, Pollack BJ, et al. A single-center experience of endoscopic ultrasonography for enlarged pancreas on computed tomography. Clin Gastroenterol Hepatol. 2006;4:98–103
  38. Horwhat JD, Gerke H, Acosta RD, et al. Focal or diffuse “fullness” of the pancreas on CT. Usually benign, but EUS plus/minus FNA is warranted to identify malignancy. JOP. 2009;10:37–42
  39. Singh S, Reddymasu S, Waheed S, et al. Endoscopic ultrasonography findings in patients with non-specific changes of the pancreas on computed tomography: a single-center experience. Dig Dis Sci. 2008;53:2799–2804
  40. Boujaoude J. Role of endoscopic ultrasound in diagnosis and therapy of pancreatic Adenocarcinoma. World J Gastroenterol. 2007;13:3662–3666
  41. Harewood GC, Wiersema MJ. Endosonography-guided fine needle aspiration biopsy in the evaluation of pancreatic masses. Am J Gastroenterol. 2002;97:1386–1391
  42. DeWitt J, McGreevy K, Sherman S, LeBlanc J. Utility of a repeated EUS at a tertiary-referral center. Gastrointest Endosc. 2008;67:610–619
  43. Eloubeidi MA, Tamhane A, Varadarajulu S, Wilcox CM. Frequency of major complications after EUS-guided FNA of solid pancreatic masses: a prospective evaluation. Gastrointest Endosc. 2006;63:622–629
  44. Chang KJ. State of the art lecture: endoscopic ultrasound (EUS) and FNA in pancreatico-biliary tumors. Endoscopy. 2006;38(Suppl. 1):S56–60
  45. Binmoeller KF, Rathod VD. Difficult pancreatic mass FNA: tips for success. Gastrointest Endosc. 2002;56(Suppl.):S86–91
  46. Klapman JB, Logrono R, Dye CE, Waxman I. Clinical impact of on-site cytopathology interpretation on endoscopic ultrasound-guided fine needle aspiration. Am J Gastroenterol. 2003;98:1289–1294
  47. Dewitt J, Devereaux BM, Lehman GA, et al. Comparison of endoscopic ultrasound and computed tomography for the preoperative evaluation of pancreatic cancer: a systematic review. Clin Gastroenterol Hepatol. 2006;4:717–725
  48. Michl P, Pauls S, Gress TM. Evidence-based diagnosis and staging of pancreatic cancer. Best Pract Res Clin Gastroenterol. 2006;20:227–251
  49. Hartwig W, Schneider L, Diener MK, et al. Preoperative tissue diagnosis for tumours of the pancreas. Br J Surg. 2009;96:5–20
  50. Mortenson MM, Katz MH, Tamm EP, et al. Current diagnosis and management of unusual pancreatic tumors. Am J Surg. 2008;196:100–113
  51. Săftoiu A, Vilmann P. Role of endoscopic ultrasound in the diagnosis and staging of pancreatic cancer. J Clin Ultrasound. 2009;37:1–17
  52. Becker D, Strobel D, Bernatik T, Hahn EG. Echo-enhanced color- and power-Doppler EUS for the discrimination between focal pancreatitis and pancreatic carcinoma. Gastrointest Endosc. 2001;53:784–789
  53. Hocke M, Schulze E, Gottschalk P, et al. Contrast-enhanced endoscopic ultrasound in discrimination between focal pancreatitis and pancreatic cancer. World J Gastroenterol. 2006;12:246–250
  54. Kitano M, Sakamoto H, Matsui U, et al. A novel perfusion imaging technique of the pancreas: contrast-enhanced harmonic EUS (with video). Gastrointest Endosc. 2008;67:141–150
  55. Giovannini M, Hookey LC, Bories E, et al. Endoscopic ultrasound elastography: the first step towards virtual biopsy? Preliminary results in 49 patients. Endoscopy. 2006;38:344–348
  56. Janssen J, Schlörer E, Greiner L. EUS elastography of the pancreas: feasibility and pattern description of the normal pancreas, chronic pancreatitis, and focal pancreatic lesions. Gastrointest Endosc. 2007;65:971–978
  57. Hirche TO, Ignee A, Barreiros AP, et al. Indications and limitations of endoscopic ultrasound elastography for evaluation of focal pancreatic lesions. Endoscopy. 2008;40:910–917
  58. Săftoiu A, Vilmann P, Gorunescu F, et al. Neural network analysis of dynamic sequences of EUS elastography used for the differential diagnosis of chronic pancreatitis and pancreatic cancer. Gastrointest Endosc. 2008;68:1086–1094
  59. Khalid A, Nodit L, Zahid M, et al. Endoscopic ultrasound fine needle aspirate DNA analysis to differentiate malignant and benign pancreatic masses. Am J Gastroenterol. 2006;101:2493–2500
  60. Das A, Nguyen CC, Li F, Li B. Digital image analysis of EUS images accurately differentiates pancreatic cancer from chronic pancreatitis and normal tissue. Gastrointest Endosc. 2008;67:861–867
  61. Chang KJ, Nguyen PT, Thompson JA, et al. Phase I clinical trial of allogeneic mixed lymphocyte culture (cytoimplant) delivered by endoscopic ultrasound-guided fine-needle injection in patients with advanced pancreatic carcinoma. Cancer. 2000;88:1325–1335
  62. Hecht JR, Bedford R, Abbruzzese JL, et al. A phase I/II trial of intratumoral endoscopic ultrasound injection of ONYX-015 with intravenous gemcitabine in unresectable pancreatic carcinoma. Clin Cancer Res. 2003;9:555–561
  63. Farrell JJ, Senzer N, Hecht JR, et al. Long-term data for endoscopic ultrasound (EUS) and percutanous (PTA) guided intratumoral TNFerade gene delivery combined with chemoradiation in the treatment of locally advanced pancreatic cancer (LAPC). Gastrointest Endosc. 2006;63:AB93
  64. Sun S, Xu H, Xin J, et al. Endoscopic ultrasound-guided interstitial brachytherapy of unresectable pancreatic cancer: results of a pilot trial. Endoscopy. 2006;38:399–403
  65. Jin Z, Du Y, Li Z, et al. Endoscopic ultrasonography-guided interstitial implantation of iodine 125-seeds combined with chemotherapy in the treatment of unresectable pancreatic carcinoma: a prospective pilot study. Endoscopy. 2008;40:314–320
  66. Van Dam J, Varadarajulu S, Jin Z, EUS 2008 Working Group. EUS 2008 Working Group document: evaluation of EUS-guided implantation therapy (with video). Gastrointest Endosc 2009;69(2 Suppl.):S49–53.
  67. Chan HH, Nishioka NS, Mino M, et al. EUS-guided photodynamic therapy of the pancreas: a pilot study. Gastrointest Endosc. 2004;59:95–99
  68. Yusuf TE, Matthes K, Brugge WR. EUS-guided photodynamic therapy with verteporfin for ablation of normal pancreatic tissue: a pilot study in a porcine model (with video). Gastrointest Endosc. 2008;67:957–961
  69. Goldberg SN, Mallery S, Gazelle GS, Brugge WR. EUS-guided radiofrequency ablation in the pancreas: results in a porcine model. Gastrointest Endosc. 1999;50:392–401
  70. Carrara S, Arcidiacono PG, Albarello L, et al. Endoscopic ultrasound-guided application of a new hybrid cryotherm probe in porcine pancreas: a preliminary study. Endoscopy. 2008;40:321–326
  71. Larghi A, Tringali A, Lecca PG, et al. Management of hilar biliary strictures. Am J Gastroenterol. 2008;103:458–473
  72. Fritscher-Ravens A, Broering DC, Sriram PV, et al. EUS-guided fine-needle aspiration cytodiagnosis of hilar cholangiocarcinoma: a case series. Gastrointest Endosc. 2000;52:534–540
  73. Pavey DA, Gress FG. The role of EUS-guided FNA for the evaluation of biliary strictures. Gastrointest Endosc. 2006;64:334–337
  74. Rosch T, Hofrichter K, Frimberger E, et al. ERCP or EUS for tissue diagnosis of biliary strictures? A prospective comparative study. Gastrointest Endosc. 2004;60:390–396
  75. Lee JH, Salem R, Aslanian H, et al. Endoscopic ultrasound and fine-needle aspiration of unexplained bile duct strictures. Am J Gastroenterol. 2004;99:1069–1073
  76. Eloubeidi MA, Chen VK, Jhala NC, et al. Endoscopic ultrasound-guided fine needle aspiration biopsy of suspected cholangiocarcinoma. Clin Gastroenterol Hepatol. 2004;2:209–213
  77. Fritscher-Ravens A, Broering DC, Knoefel WT, et al. EUS-guided fine-needle aspiration of suspected hilar cholangiocarcinoma in potentially operable patients with negative brush cytology. Am J Gastroenterol. 2004;99:45–51
  78. Byrne MF, Gerke H, Mitchell RM, et al. Yield of endoscopic ultrasound-guided fine-needle aspiration of bile duct lesions. Endoscopy. 2004;36:715–719
  79. DeWitt J, Misra VL, Leblanc JK, et al. EUS-guided FNA of proximal biliary strictures after negative ERCP brush cytology results. Gastrointest Endosc. 2006;64:325–333
  80. Larghi A, Lecca PG, Ardito F, et al. Evaluation of hilar biliary strictures by using a newly developed forward-viewing therapeutic echoendoscope: preliminary results of an ongoing experience. Gastrointest Endosc. 2009;69:356–360
  81. Rea DJ, Heimbach JK, Rosen CB, et al. Liver transplantation with neoadjuvant chemoradiation is more effective than resection for hilar cholangiocarcinoma. Ann Surg. 2005;242:451–458
  82. Gleeson FC, Rajan E, Levy , et al. EUS-guided FNA of regional lymph nodes in patients with unresectable hilar cholangiocarcinoma. Gastrointest Endosc. 2008;67:438–443
  83. Standards of Practice Committee, Adler DG, Qureshi W, Davila R, et al. The role of endoscopy in ampullary and duodenal adenomas. Gastrointest Endosc 2006;64:849–54.
  84. Baillie J. Endoscopic ampullectomy. Am J Gastroenterol. 2005;100:2379–2381
  85. Brugge WR, Lauwers GY, Sahani D, et al. Cystic neoplasms of the pancreas. N Engl J Med. 2004;351:1218–1226
  86. Levy MJ. Pancreatic cysts. Gastrointest Endosc. 2009;69(2 Suppl.):S110–S116
  87. Brugge WR, Lewandrowski K, Lee-Lewandrowski E, et al. Diagnosis of pancreatic cystic neoplasms: a report of the cooperative pancreatic cyst study. Gastroenterology. 2004;126:1330–1336
  88. van der Waaij LA, van Dullemen HM, Porte RJ. Cyst fluid analysis in the differential diagnosis of pancreatic cystic lesions: a pooled analysis. Gastrointest Endosc. 2005;62:383–389
  89. Linder JD, Geenen JE, Catalano MF. Cyst fluid analysis obtained by EUS-guided FNA in the evaluation of discrete cystic neoplasms of the pancreas: a prospective single-center experience. Gastrointest Endosc. 2006;64:697–702
  90. Shen J, Brugge WR, Dimaio CJ, Pitman MB. Molecular analysis of pancreatic cyst fluid: a comparative analysis with current practice of diagnosis. Cancer Cytopathol. 2009;117:217–227
  91. Khalid A, Zahid M, Finkelstein SD, et al. Pancreatic cyst fluid DNA analysis in evaluating pancreatic cysts: a report of the PANDA study. Gastrointest Endosc. 2009;69:1095–1102
  92. Sawhney MS, Devarajan S, O’Farrel P, et al. Comparison of carcinoembryonic antigen and molecular analysis in pancreatic cyst fluid. Gastrointest Endosc. 2009;69:1106–1110
  93. Levy MJ, Smyrk TC, Reddy RP, et al. Endoscopic ultrasound-guided trucut biopsy of the cyst wall for diagnosing cystic pancreatic tumors. Clin Gastroenterol Hepatol. 2005;3:974–979
  94. Al-Haddad M, Raimondo M, Woodward T, et al. Safety and efficacy of cytology brushings versus standard FNA in evaluating cystic lesions of the pancreas: a pilot study. Gastrointest Endosc. 2007;65:894–898
  95. Tanaka M, Chari S, Adsay V, et al. International consensus guidelines for management of intraductal papillary mucinous neoplasms and mucinous cystic neoplasms of the pancreas. Pancreatology. 2006;6:17–32
  96. Schmidt CM, White PB, Waters JA, et al. Intraductal papillary mucinous neoplasms: predictors of malignant and invasive pathology. Ann Surg. 2007;246:644–651
  97. Michaels PJ, Brachtel EF, Bounds BC, et al. Intraductal papillary mucinous neoplasm of the pancreas: cytologic features predict histologic grade. Cancer. 2006;108:163–173
  98. Maire F, Voitot H, Aubert A, et al. Intraductal papillary mucinous neoplasms of the pancreas: performance of pancreatic fluid analysis for positive diagnosis and the prediction of malignancy. Am J Gastroenterol. 2008;103:2871–2877
  99. Pais SA, Attasaranya S, Leblanc JK, et al. Role of endoscopic ultrasound in the diagnosis of intraductal papillary mucinous neoplasms: correlation with surgical histopathology. Clin Gastroenterol Hepatol. 2007;5:489–495
  100. Pitman MB, Michaels PJ, Deshpande V, et al. Cytological and cyst fluid analysis of small (< or =3cm) branch duct intraductal papillary mucinous neoplasms adds value to patient management decisions. Pancreatology. 2008;8:277–284
  101. Bassi C, Crippa S, Salvia R. Intraductal papillary mucinous neoplasms (IPMNs): is it time to (sometimes) spare the knife?. Gut. 2008;57:287–289
  102. Rautou PE, Lévy P, Vullierme MP, et al. Morphologic changes in branch duct intraductal papillary mucinous neoplasms of the pancreas: a midterm follow-up study. Clin Gastroenterol Hepatol. 2008;6:807–814
  103. Kobayashi G, Fujita N, Noda Y, et al. Mode of progression of intraductal papillary-mucinous tumor of the pancreas: analysis of patients with follow-up by EUS. J Gastroenterol. 2005;40:744–751
  104. Gan SI, Thompson CC, Lauwers GY, Bounds BC, Brugge WR. Ethanol lavage of pancreatic cystic lesions: initial pilot study. Gastrointest Endosc. 2005;61:746–752
  105. Dewitt JM, Mcgreevy K, Collier K, Brugge WR. Ethanol pancreatic injection of cysts (EPIC): Preliminary results of a prospective multicenter, randomized double blinded study. Gastrointestinal Endosc. 2007;65:AB106
  106. Oh HC, Seo DW, Lee TY, et al. New treatment for cystic tumors of the pancreas: EUS-guided ethanol lavage with paclitaxel injection. Gastrointest Endosc. 2008;67:636–642
  107. Hawes RH, Van Dam J, Varadarajulu S . EUS 2008 Working Group document: interventional EUS—a road map for the future. Gastrointest Endosc. 2009;69(2 Suppl.):S1–S2
  108. Gerke H, Silva RG, Shamoun D, et al. EUS characteristics of celiac ganglia with cytologic and histologic confirmation. Gastrointest Endosc. 2006;64:35–39
  109. Levy M, Rajan E, Keeney G, et al. Neural ganglia visualized by endoscopic ultrasound. Am J Gastroenterol. 2006;101:1787–1791
  110. Levy MJ, Topazian MD, Wiersema MJ, et al. Initial evaluation of the efficacy and safety of endoscopic ultrasound-guided direct Ganglia neurolysis and block. Am J Gastroenterol. 2008;103:98–103
  111. Wiersema MJ, Wiersema LM. Endosonography-guided celiac plexus neurolysis. Gastrointest Endosc. 1996;44:656–662
  112. Gress F, Schmitt C, Sherman S, et al. A prospective randomized comparison of endoscopic ultrasound- and computed tomography-guided celiac plexus block for managing chronic pancreatitis pain. Am J Gastroenterol. 1999;94:900–905
  113. Darisetty S, Lakhtakia S, Gupta R, et al. Clinical trial: A randomized trial comparing fluoroscopy guided percutaneous technique versus endoscopic ultrasound guided technique of celiac plexus block for treatment of pain in chronic pancreatitis. Aliment Pharmacol Ther. 2009;29:979–984
  114. Puli SR, Reddy JB, Bechtold ML, et al. EUS-guided celiac plexus neurolysis for pain due to chronic pancreatitis or pancreatic cancer pain: a meta-analysis and systematic review. Dig Dis Sci. 2009;[epub ahead of print]
  115. Fockens P. EUS in drainage of pancreatic pseudocysts. Gastrointest Endosc. 2002;56(4 Suppl.):S93–S97
  116. Vazquez-Sequeiros E. Drainage of pancreatic fluid collections: is EUS really necessary?. Gastrointest Endosc. 2007;66:1120–1122
  117. Baron TH. Drainage of pancreatic fluid collections: is EUS really necessary?. Gastrointest Endosc. 2007;66:1123–1125
  118. Yusuf TE, Baron TH. Endoscopic transmural drainage of pancreatic pseudocysts: results of a national and an international survey of ASGE members. Gastrointest Endosc. 2006;63:223–227
  119. Kahaleh M, Shami VM, Conaway MR, et al. Endoscopic ultrasound drainage of pancreatic pseudocyst: a prospective comparison with conventional endoscopic drainage. Endoscopy. 2006;38:355–359
  120. Varadarajulu S, Christein JD, Tamhane A, et al. Prospective randomized trial comparing EUS and EGD for transmural drainage of pancreatic pseudocysts (with videos). Gastrointest Endosc. 2008;68:1102–1111
  121. Varadarajulu S, Wilcox CM, Tamhane A, et al. Role of EUS in drainage of peripancreatic fluid collections not amenable for endoscopic transmural drainage. Gastrointest Endosc. 2007;66:1107–1119
  122. Barthet M, Lamblin G, Gasmi M, et al. Clinical usefulness of a treatment algorithm for pancreatic pseudocysts. Gastrointest Endosc. 2008;67:245–252
  123. Harada N, Kouzu T, Arima M, et al. Endoscopic ultrasound-guided pancreatography: a case report. Endoscopy. 1995;27:612–615
  124. Wiersema MJ, Sandusky D, Carr R, et al. Endosonography-guided cholangiopancreatography. Gastrointest Endosc. 1996;43:102–106
  125. Bataille L, Deprez P. A new application for therapeutic EUS: main pancreatic duct drainage with a “pancreatic rendezvous technique”. Gastrointest Endosc. 2002;55:740–743
  126. François E, Kahaleh M, Giovannini M, et al. EUS-guided pancreaticogastrostomy. Gastrointest Endosc. 2002;56:128–133
  127. Mallery S, Matlock J, Freeman ML. EUS-guided rendezvous drainage of obstructed biliary and pancreatic ducts: Report of 6 cases. Gastrointest Endosc. 2004;59:100–107Kahaleh M, Hernandez AJ, Tokar J, et al. Interventional EUS-guided cholangiography: evaluation of a technique in evolution. Gastrointest Endosc. 2006;64:52–59
  128. Will U, Thieme A, Fueldner F, et al. Treatment of biliary obstruction in selected patients by endoscopic ultrasonography (EUS)-guided transluminal biliary drainage. Endoscopy. 2007;39:292–295
  129. Bories E, Pesenti C, Caillol F, et al. Transgastric endoscopic ultrasonography-guided biliary drainage: results of a pilot study. Endoscopy. 2007;39:287–291
  130. Yamao K, Bhatia V, Mizuno N, et al. EUS-guided choledochoduodenostomy for palliative biliary drainage in patients with malignant biliary obstruction: results of long-term follow-up. Endoscopy. 2008;40:340–342
  131. Tarantino I, Barresi L, Repici A, et al. EUS-guided biliary drainage: a case series. Endoscopy. 2008;40:336–339
  132. Kahaleh M, Hernandez AJ, Tokar J, et al. EUS-guided pancreaticogastrostomy: analysis of its efficacy to drain inaccessible pancreatic ducts. Gastrointest Endosc. 2007;65:224–230
  133. Tessier G, Bories E, Arvanitakis M, et al. EUS-guided pancreatogastrostomy and pancreatobulbostomy for the treatment of pain in patients with pancreatic ductal dilatation inaccessible for transpapillary endoscopic therapy. Gastrointest Endosc. 2007;65:233–241
  134. Shami VM, Kahaleh M. Endoscopic ultrasonography (EUS)-guided access and therapy of pancreatico-biliary disorders: EUS-guided cholangio and pancreatic drainage. Gastrointest Endosc Clin N Am. 2007;17:581–593
  135. Shami VM, Talreja JP, Mahajan A, et al. EUS-guided drainage of bilomas: a new alternative?. Gastrointest Endosc. 2008;67:136–140
  136. Kwan V, Eisendrath P, Antaki F, et al. EUS-guided cholecystenterostomy: a new technique (with videos). Gastrointest Endosc. 2007;66:582–586
  137. Lee SS, Park do H, Hwang CY, et al. EUS-guided transmural cholecystostomy as rescue management for acute cholecystitis in elderly or high-risk patients: a prospective feasibility study. Gastrointest Endosc. 2007;66:1008–1012

PII: S1590-8658(09)00292-8

doi:10.1016/j.dld.2009.06.021

Digestive and Liver Disease
Volume 42, Issue 1 , Pages 6-15, January 2010

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