Open access peer-reviewed chapter

Endoscopic Ultrasound in Pancreatic Cancer: The New Perspective

Written By

Andrada Seicean

Submitted: September 19th, 2013 Reviewed: October 1st, 2013 Published: May 14th, 2014

DOI: 10.5772/57182

Chapter metrics overview

1,797 Chapter Downloads

View Full Metrics

1. Introduction

Pancreatic cancer is one of the most deadly forms of cancer worldwide, with median survival of less than 6 months and a 5-year survival rate of 35%. Endoscopic ultrasound (EUS) was first introduced for assessment of pancreatic pathology more than 30 years ago, as transabdominal imaging yields limited information. EUS has a role in the detection, staging and sampling of pancreatic tumor. Curative-intent surgery, chemotherapy, and radiation therapy of pancreatic cancer are all performed more frequently in patients with EUS evaluation [1]. Palliative EUS-guided treatments are also possible. However, a recent large observational study reported no influence on survival [2].


2. Detection

The detection rate for pancreatic tumors by EUS is 90-100%, with good detection for tumors less than 2 cm in diameter, but EUS does not definitively rule out the presence of malignancy. In certain situations EUS may give false-negative results, especially when there is concomitant chronic pancreatitis, if the examination is performed too soon after an acute episode of acute pancreatitis, or in the presence of diffusely infiltrating carcinoma or a prominent ventral/dorsal split [3]. For patients with false-negative endoscopic ultrasound fine-needle aspiration (EUS-FNA), the risk for malignancy is higher when vascular involvement or lymph nodes are seen, with a mean of 66 days until diagnosis [4].


Two studies showed that the detection of small pancreatic tumors (diameter less than 3 cm) by EUS is better than by CT or MRI (accuracy 93% vs 53% vs 67%) [5] or than by CT or US (accuracy 100% vs 94% vs 65%) [6]. The size of tumors less than 3 cm in diameter is assessed better by EUS than the size of larger tumors (90% vs 30%) [7].

When a mass is not visible on CT, with enlargement of the pancreatic head or dilatation of the pancreatic duct, but without obstructive jaundice, EUS can reliably identify a pancreatic mass in 7-9% of cases [8-11]. If combined bilio-pancreatic dilation is present with obstructive jaundice, the prevalence of pancreatic malignancy is 85% [12]. The risk of positive findings on EUS is higher in patients with weight loss, hyperbilirubinemia, or dilation of the common bile duct [13]. If there is no dilation of the pancreatic duct in a suspected pancreatic mass, the prevalence of malignancy is 17% [14].

EUS vs MRI. Studies carried out before 2000 showed a clear superiority of EUS over MRI in tumor detection [15]. Even after advances in MRI technology, and despite excellent sensitivity of MRI (87-91%), EUS remained superior to MRI [16], albeit non-significantly so in one study [17].

EUS vs PET.EUS is more sensitive than PET in the detection of pancreatic cancer (93% vs 87%) [18]. Another study found similar sensitivities for EUS, CT, and US, with a negative predictive value of 82% on EUS [19]. Due to the high costs, however, EUS is not routinely used for detection.

EUS vs IDUS.Intraductal endoscopic ultrasound (IDUS) identifies the wall of the pancreatic duct as a hyperechoic layer and the surrounding neoplastic tissue as a hypoechoic area. IDUS yielded impressive sensitivity (100%) and specificity (91.7%) for differentiation between pancreatic cancer and chronic pancreatitis in patients with localized stenosis of the main pancreatic duct. The same study compared IDUS with EUS, CT, and ERCP, which had sensitivity of 92.9%, 64.3%, and 85.7% and specificity of 58.3%, 66.7%, and 66.7%, respectively. Another study compared IDUS, EUS, CT, and ERCP, and found higher sensitivities (75% vs 50%, 37%, and 37%, respectively) but lower specificities (67%, 67%, 33%, and 67%) [20]. However, a recent study revealed no difference between EUS and IDUS in pancreatic tumor detection, with sensitivity of 81-89% and specificity of 74-88% [19].


3. Staging

Pancreatic cancer typically has the EUS appearance of a heterogeneous hypoechoic mass with irregular margins, but based on this aspect only 55% are correctly diagnosed [21]. Lymph nodes appear as hypoechoic structures, round and well delineated, usually over 1 cm in diameter. They are found in the peri-aortic space, in peripancreatic locations, in the liver hilum, in the celiac region, or in the mediastinum (in around 10% of the cases). A positive periductal hypoechoic sign, defined as patchy hypoechoic areas adjacent to a dilated pancreatic duct, was predictive for malignancy with accuracy of 80% [22].

Figure 1.

T4 tumor of the pancreatic body. The hypoechoic lesion with invasion of the celiac trunk and gastric wall.

Figure 2.

T3 tumor of the pancreatic body. The hypoechoic lesion invades splenic vein and produces the dilation of the Wirsung duct.

The first studies used the 1987 TNM staging, which considered stage T3 as the involvement of adjacent vessels (both arteries and veins) and of neighboring organs, and found T staging accuracy of 73-94% [23-26]. Later studies used the 1997 TNM classification, which defined invasion of the portal vein, celiac trunk, and mesenteric vessels as stage T4. The results for T stage accuracy were poorer: 61- 74% for stage T3 and 78-88% for stage T4 [7,16,27,28,29]. Currently the 2002 TNM classification is being used. This includes invasion of superior mesenteric artery or celiac artery as stage T4, representing a criterion for irresectability. Using this latest classification, accuracy rises to 85% for T stage and 72% for N stage [30-31](Table 1).

Primary tumor(T)
T0No evidence of primary tumor
T1Tumor limited to the pancreas, ≤ 2 cm in greatest dimension
T2Tumor limited to the pancreas, > 2 cm in greatest dimension
T3Tumor extends beyond the pancreas but without involvement of the celiac axis or the superior mesenteric artery
T4Tumor involves the celiac axis or the superior mesenteric artery (unresectable primary tumor)
Regional lymph node(N)
N0No regional lymph node metastasis
N1Regional lymph node metastasis
Distant metastasis(M)
M0No distant metastasis
M1Distant metastasis

Table 1.

TNM Classification for Pancreatic Cancer

Vascular invasion is the main factor in resectability. Typical findings are the loss of the sonographic interface between the echogenic vessel and the parenchyma, a tumor within the vessel lumen, or the presence of collateral circulation. However, the overall sensitivity when using this criterion is modest (43%), with specificity of 91%. In a study published at the turn of the century, the positive and negative predictive values for the parameters chosen to diagnose portal venous involvement were as follows: 42% and 33% for irregular tumor-vessel relationship, 36% and 34% for visualization of tumor in the vascular lumen, 80% and 28% for complete vascular obstruction, and 88% and 18% for collateral vessels [32].

Initial comparative studies of EUS versus surgery indicated that portal vein invasion, but not encasement of the superior mesenteric artery, was reliably assessed by EUS [32-34]. A meta-analysis on pancreatic and peri-ampullary malignancies published in 2007 concluded that EUS diagnoses vascular invasion with sensitivity of 73% and specificity of 90% [35]. Recent data based on images obtained with newer digital echoendoscope, indicate good results for superior mesenteric vessel invasion or hepatic artery invasion [36]. Globally, the accuracy of vascular invasion is 83-93% [36,37].

EUS vs CT. In an early study that compared conventional CT with mechanical EUS and surgical exploration, the results were in favor of EUS, with a global accuracy of 85-98% vs 30-86% for T staging and of 72-84% vs 52-68% for N staging [5,18,24,37,38,40]. In a series of 53 surgical patients, EUS had better accuracy than multidetector CT (67% vs 46%) for T stage and similar results for N stage (44% vs 47%) [29]. A systematic review of 11 prospective studies concluded the superiority of EUS for detection [31] and this was confirmed in recent studies [30]. Newer data show better assessment of arteries, including the superior mesenteric artery, and better assessment of resectability by digital linear EUS than by CT [36,40]. Furthermore, EUS has a significant threefold advantage over CT with regard to T stage and an even higher significant advantage with regard to N stage [40].

Vascular invasion was predicted better by EUS assessment than by conventional CT evaluation (93-100% vs 45-62%) [37,38]. EUS evaluation of portal vein invasion had results superior to those of US, CT, or angiography (93% vs 67%, 74%, and 79% respectively) [41]. Also, assessment of the portal vein and of the superior mesenteric vein invasion by EUS was better than by CT [18]. However, another study showed that radial EUS predicted resectability in only 46% of cases and that T and N staging accuracy were 69% and 54% [27]. Moreover, other studies found better [15,28] or similar [42] resectability accuracies for CT. The current recommendation is to use EUS for situations where invasion is doubtful as assessed by CT. One study recommended both EUS and CT evaluation for arterial invasion [30], but this would represent a huge volume of investigations and high costs.

EUS vs MRI. The accuracy of MRI for T and N staging is 89% and 76% respectively. Arterial involvement seemed to be best evaluated by MRI in one study on 59 patients [16], but further studies are needed before MRI can be performed routinely in patients with pancreatic cancer.

EUS vs PET. Understaging using EUS and PET was comparable (25% vs 27%) in a small study of 48 surgically explored patients [43], but routine PET examination is not indicated.

EUS vs US. Although hypoechoic masses can be seen during US examination, together with dilation of the pancreatic duct or common bile duct, the accuracy of US in pancreatic cancer diagnosis is modest (sensitivity 67%, specificity 40%) [32]. US and MRI are not accurate enough for the prediction of staging and resectability; CT should be used for this purpose [44].


4. Endoscopic ultrasound fine-needle aspiration

EUS-FNA is indicated for obtaining specimens for cytology and histopathology with regard to palliative radiochemotherapy and for differential from other nodular pancreatic lesions such as chronic pancreatitis nodules, autoimmune pancreatitis, pancreatic metastasis, or neuroendocrine tumors.

The accuracy of diagnosis by FNA is 85-95% and depends on several factors: the type of needle, the number of passes, the presence of cytopathologist in the room, the technical quality of processing, and the experience of the pathologist.

Type of needle. The main advantage of EUS-FNA is the use of thin needles -- 19G, 22G, and 25 G -- to yield cytological smears or core specimens. The Tru-Cut needle and histological needles have the advantage of obtaining tissue samples which maintain the architecture of the pancreas, thus facilitating interpretation by the pathologist, especially for non-adenocarcinoma tumor types or inflammatory masses [45,46]. Cytological smears are associated with description of atypia in 1-14% of cases, similar to reports for thyroid cytology; however, the risk of malignancy in pancreatic smears is higher (25-100%) [47]. The combination of smears and core specimens revealed the diagnosis in 90-100% of cases [45,46,48] and the recommendation of the European Society of Gastrointestinal Endoscopy (ESGE) is to try to obtain material for histology routinely [49]. The overall pancreatic tissue-sampling rate for cytology using 22G needles is variable compared with histology (82-93% vs 84-87%), while the overall diagnostic accuracy of histology on each pass is only 60% for the 25G needle and 75% for the 22G needle [50].

The accuracy of diagnosis for pancreatic masses using 22G needles is up to 95% [51]. A meta-analysis compared the 22G and 25G needles for pancreatic and peripancreatic masses showed non-significant differences in sensitivity (78% vs 91%), and 100% specificity, with no difference in the number of passes or complications [52]. Repeating EUS-FNA in the case of initial negative cytology increases the diagnostic yield [53-55].

Because the 19G aspiration needles are more rigid [56,57], they are not routinely recommended for head pancreatic biopsies [49]. However, the diagnostic accuracy for body/tail pancreatic lesions is better with 19G needles than with 22G needles [57,58], especially for the differential diagnosis of pancreatic masses.

Tru-Cut biopsy using 19G EUS-TCB needles is recommended when EUS-FNA is nondiagnostic owing to insufficient biopsy material, but cannot be used so readily in the antrum, fundus, and duodenal bulb, where the echoendoscope is angulated [59]). The tendency is to replace the 19G EUS-TCB needle with the flexible 19G needle (Flex 19, Boston Scientific, Natick, MA) or the 19G or 22G histological needle (ProCore, Wilson-Cook, Ireland). A comparison of 22G needles and histological 22G needles reported better diagnostic accuracy for 22G needles [60]. Likewise, a 25G needle showed high sensitivity of 96% when three passes were done [61].

The yield for malignancy is similar with or without use of a stylet (87% vs 83%) [62-64], but in some studies sample adequacy was significantly better when a stylet was used (75% vs 87%) [62]. Also. The amount of blood in the sample was greater when the stylet was used (75% vs 52%) [62-64]. Although no conclusion has yet been drawn, the ESGE recommendations leave it to the discretion of the endosonographer whetherto use a stylet or not [49].

The current recommendation of the ESGE is to use suction for solid masses [49]. Moreover, a prospective comparative trial showed better diagnostic accuracy when suction was applied (85% vs 75%), but more blood was present in the case of sampling with suction [65].

Most studies have used a standard back and forth technique for sampling. In a randomized trial comparing the fanning and standard techniques, the diagnostic accuracy was non-significantly different, although better in the fanning technique (76% vs 96%), with a lower number of passes to establish the diagnosis and better sensitivity after the first pass [66].

Number of passes. The current recommendation for EUS-FNA of solid pancreatic masses is at least five passes with a 22G needle [49]. In a retrospective study, a mean of two passes with combined histology and cytology provided adequate tissue for pancreatic mass diagnosis [45]. When Tru-Cut biopsy is done, more than two passes are usually necessary to improve diagnostic accuracy [67].

Presence of a cytopathologist. It is not clear whether the presence of a cytopathologist improves the diagnostic accuracy over 90%. The cytopathologic on-site rapid assessment of smear slides is reported to be better than that of monolayer prepared slides [68]. The first large prospective study (540 patients) which included cytopathologic assessment found that the agreement between cytopathology and final diagnosis was very good, but the presence of the pathologist did not significantly increase the accuracy of the diagnosis [69]. Thus, the presence of a cytopathologist does not always guarantee better results.

Features of lesion. The presence of features of chronic pancreatitis was associated with lower accuracy of EUS-FNA for the differential diagnosis of pancreatic masses (73% vs 91%) and may necessitate a higher number of passes to establish the diagnosis [70]. The presence of stents (either plastic or metallic) usually does not impede EUS-FNA [71-73], although the stent has to be placed at least one day before performing EUS-FNA [72]. There is no difference in diagnostic accuracy between lesions less or more than 3 cm in diameter [74], although one study found sensitivity as low as 40% for tumors less than 1 cm in diameter [75].


5. Differential diagnosis of pancreatic masses

A recent meta-analysis found that the sensitivity and specificity of EUS-FNA in differential diagnosis are 86% and 95%, respectively [76]. New imaging methods, such as elastography and contrast-enhanced EUS (CEUS), are considered additive to EUS-FNA in the differential diagnosis of pancreatic masses. Molecular analysis of the specimen obtained by FNA can also help in discrimination of pancreatic masses. Needle-based confocal laser endomicroscopy to provide real-time imaging at microscopic level for pancreatic cancer is still also under evaluation.


This method assesses the elasticity of tissue during the ultrasound examination. The blue aspect of pancreatic adenocarcinoma is on elastography due to hard desmoplastic tissue, while the soft normal tissue is red [77]. Based on the elastography pattern, the sensitivity and specificity for differentiation of benign and malignant pancreatic lesions were 92.3% and 80.0% respectively, compared to 92.3% and 68.9% for the conventional B-mode images [78], and the overall accuracy for diagnosis of malignancy was 94% [79]. The hue histogram analysis of elastographic images differentiated malignant from benign nodules (cut-off point: 175) with sensitivity, specificity, and accuracy of 91.4%, 87.9%, and 89.7% respectively [80,81]. Using a second-generation US machine for elastography, the strain ratio can be calculated, comparing the strain value of the mass to a strain value from a control area in the region under study. A strain ratio of 4.65 and elasticity of 0.27% were the cut-off points for differentiation of pancreatic cancer from inflammatory masses [82]. Higher strain ratios were diagnostic for malignancy with an accuracy of 98% [83,84]. Three recent meta-analyses found sensitivity of 95-99%, specificity of 69-76%, and accuracy of 89-96% [85-87]. The combination of power Doppler CEUS and elastography yielded global accuracy of 83%, with better specificity than elastography alone [88].

Contrast-enhanced EUS

The principle of the CEUS technique is based on visualization of microvessels inside the pancreatic tumor; their presence was found useful for predicting efficacy of chemotherapy [89]. The initial indication was achievement of better delineation of pancreatic nodules or better visualization of vascular involvement. However, these aspects seem not to be improved and many studies of CEUS have focused on differential diagnosis of pancreatic masses. The contrast agents are microbubbles of gas included in a hydrophilic shell. The initial studies used Levovist, which is rapidly destroyed in pulmonary capillaries. Second-generation contrast agents, such as Sonovue, Sonazoid, or Definity, have a better lifetime in the vascular flow and are able to pass the pulmonary capillaries. Hypoenhancement on CEUS is considered suggestive of adenocarcinoma, due to the presence of a high proportion of desmoplastic tissue within the tumors, with few microvessels. Using a high mechanical index and Doppler CEUS, the hypovascular aspect was suggestive of adenocarcinoma in 83-94% of patients [88,90-94]. Motion artifacts and blooming effect are frequent, however, and this method has been replaced by harmonic CEUS. This latter procedure uses frequencies resulting from non-linear oscillation of microbubbles, and the low mechanical index of the ultrasound machine allows subtraction of the tissue-derived signal from the microvessel of the tumor [95]. The qualitative interpretation of the contrast image as hypoenhanced was diagnostic for adenocarcinoma in 80-95 % of patients, presenting the prospect of successful diagnosis in the case of false-negative EUS-FNA [96-98](Figure3). Also, CEUS seemed superior to CT scan in detecting lesions under 2 cm in diameter [98].

Figure 3.

A hypoenhanced lesion of the head of the pancreas during the arterial phase of constrast uptake suggestive for pancreatic adenocarcinoma.

In total, a meta-analysis of both power Doppler and harmonic CEUS showed that hypoenhancement was associated with pooled sensitivity of 94% and specificity of 89% [99]. Qualitative interpretation can be subjective, however, and quantification of contrast uptake is expected to yield new information with improved accuracy. We used a hue histogram analysis and noted that a hypoenhanced aspect can occur even in severe chronic pancreatitis, but the level of contrast enhancement compared with surrounding tissue is much lower in adenocarcinoma than in chronic pancreatitis [100]. Using specialized software to interpret contrast data, our results were confirmed in another study where time to peak (TTP) was associated with sensitivity of 93% and specificity of 89% [101]. Using Sonazoid in 91 patients, the CEUS accuracy for detection of pancreatic cancer increased from 84% to 94% with quantitative analysis of TTP [102]. Compared with autoimmune pancreatitis, maximum intensity gain rather than TTP was confirmed as significant for pancreatic cancer contrast uptake [103]. In a comparative study of different methods in 58 patients, specificity and sensitivity were 73.7% and 61.5% for B-mode endosonography; 94.7% and 33.4% for elastography; 84.2% and 76.9% for harmonic CEUS; and 89.5% and 92.3% for power Doppler CEUS. These latter results need further evaluation due to artifacts in the power Doppler CEUS procedure [104].

Linear 3D endoscopic ultrasound, considered as a potential means of improving visualization of vessel involvement, allows the reconstruction of tumor volume, but further technical improvement of ultrasound equipment is necessary to establish the practical importance of this technique [105,106].

Digital image analysiscan obtain high diagnostic accuracy (94-97%) [107-109]. Detection of chromosomal abnormalities by fluorescence in-situ hybridization (FISH) analysis is useful when the cytology is inconclusive [110].

Molecular analysisof EUS-FNA samples is expected to improve the accuracy of diagnosis. Kras mutation occurred in 10 of 11 cases of pancreatic adenocarcinoma in which DNA amplification was successful, but in none of 16 patients with autoimmune pancreatitis. However, the fractional allelic loss did not differ between the two groups [111]. Another large study (n = 394 EUS-FNA samples) found 87% Kras mutations in pancreatic adenocarcinoma and only 3% in inflammatory masses and improved the accuracy of cancer diagnosis by 6% [112]. A recent meta-analysis showed that Kras detection in inconclusive EUS-FNA cases reduces the false-negative rate by 55.6%, with a false-positive rate of 10.7%, and the combined modality increases diagnostic accuracy from 80% to 88% [113].

In indeterminate pancreatic masses, the combination of Kras mutation detection and serum CA19-9 showed better sensitivity than serum CA19-9 alone (81% vs 54%) [11]. Identification of telomerase activity in pancreatic mass samples increased the sensitivity from 85% to 100%, maintaining 100% specificity [114].


6. Treatment

EUS can be used for direct antitumor therapy by injection, ablation, fiducial implantation to guide radiotherapy, pain treatment, and treatment of jaundice.

6.1. Antitumor therapy

Intratumoral injection for pancreatic cancer has been performed in several trials. Vaccination with dendritic cells as immunotherapy is considered a potential anti-cancer tool, and OK-432 represents a maturation stimulus for dendritic cells [115]. One early trial used concomitant immunotherapy with EUS-guided injection of OK-432, followed by intravenous infusion of lymphokine-activated killer cells stimulated with anti-CD3 monoclonal antibody. The investigators hypothesized that apoptotic cells induced by gemcitabine treatment could release tumor antigens slowly over time and that this stimulates dendritic cells to process and present tumor antigens [116]. The results were encouraging in five patients, but further studies are needed [117]. Immature dendritic cells and OK-432 were preoperatively injected intratumorally in nine patients with resectable pancreatic cancer; there were no complications, and survival was prolonged in only one patient with distant metastasis [115].

Allogeneic mixed lymphocyte cultures (cytoimplants) were injected in four patients who then survived for a mean 13.2 months, with two partial responses and one minor response. The main side effect was low-grade fever responsive to acetaminophen. No further investigation ensued [118].

Weekly injection of ONYX-015 (dl1520), an E1B-55kD gene-deleted replication-selective adenovirus that preferentially replicates in and kills malignant cells, was performed in 21 patients with irresectable pancreatic adenocarcinoma. More than half had progressive disease and developed treatment toxicity. Sepsis was noted in two patients, and duodenal perforation was seen when the injection was delivered transduodenally [119].

TNFrade is a replication-deficient adenovector containing human tumor necrosis factor (TNF)-α gene, regulated by a radiation-inducible promoter Egr-1 (early growth response). The advantage of this approach is the potential to maximize local antitumor activity and to minimize systemic toxicity. Five once-weekly intratumoral injections of TNFrade before radiotherapy and continuous infusion of 5-FU were reported as beneficial in the management of inoperable pancreatic cancer [120,121], but the phase III randomized controlled trial showed no survival advantage (6.8 months vs 7 months) [122].

EUS-guided local injection for anaplastic carcinoma with chemosensitivity to paclitaxel was associated with complete tumor response 2 years later [123].

6.2. EUS-guided tumor ablation

EUS-guided Tumor ablation, a minimally invasive technique allowing selective ablation of tumor masses, might improve the efficacy of neoadjuvant treatments in patients not suitable for any other kind of treatment. Local ablative therapies such as radiofrequency ablation, photodynamic therapy, and brachytherapy have been applied in animal models or humans.

Tumor destruction by radiofrequency ablation (RFA) results in a scar, surrounded by normal tissue, which shrinks in the course of time. The pancreas is thermosensitive and usually responds with inflammation followed by edema, fibrotic and sometimes cystic transformation. The potential advantage of ablation under EUS control is guidance by real-time imaging into a deeply located target such as the pancreas which is extremely difficult to reach by a percutaneous approach. Moreover, the established precision of EUS in the measurement of the location and size of pancreatic masses could be used to estimate and follow up the area of ablation and then to avoid damage of surrounding structures.

The first report of EUS-guided RFA in the pancreas was in a porcine model, using a modified EUS needle and a commercial RF needle. RFA provided localized tissue ablation in a 1-cm zone from the needle catheter. One of the 13 pigs developed pancreatitis [124]. Carrara demonstrated the feasibility and efficacy of EUS-guided RFA using a Cryotherm probe in 14 pigs, with good results in spleen and liver [125]. Other investigators found the technique to be safe in the pig model, with minimal evidence of fat necrosis in intrapancreatic and/or extrapancreatic adipose tissue [126,127].

The EUS-guided RFA technique was recently successfully applied in 16 patients, but in another 6 patients either the wall or the tumor was too stiff to permit passage of the Cryotherm probe. No pancreatitis was noted in the successful group, although an increase in amylases was seen in 3 of the 16 patients [128,129]. However, the impact on survival or tumor size needs further evaluation.

Ablation with a neodymium:yttrium-aluminum-garnet laser was tried in a porcine model, following the results in hepatocellular carcinoma, and no major complications were noted [129].

EUS-guided photodynamic therapy (PDT) with the photosensitizing agent porfimer sodium was used in an animal model again and the extension of necrosis was found to be related to the light dose applied, but no human study has yet been conducted due to lack of controlling the area of necrosis, similar to laser ablation [130].

EUS-guided intraoperative interstitial brachytherapy had a moderate local tumor effect and showed some clinical benefit in one third of 15 patients, with some severe hematological complications, pancreatitis, and pseudocyst formation, but without serious clinical sequelae [131]. Another study involving EUS-guided implantation of seeds in local advanced adenocarcinoma showed improvement in pain control, but no survival benefit [132].

6.3. EUS fiducial implantation

EUS guidance can also be used for the placement of radio-opaque fiducial markers in or near the tumor. Fiducials define the tumor border and serve to guiding radiotherapy. Fiducials vary in shape -- spheres, coils, seeds, etc. -- and their EUS visibility varies [133]. They are deployed into the mass by using the 19G or the less stiff 22G needle, by means of a stylet, or by injecting sterile water into the needle. A mean number of 2-4 fiducial markers per patient have to be placed [134]. The "ideal fiducial geometry" was studied in 77 patients and the placement of fiducials judged to be better by surgery than by EUS; however, this geometry was unnecessary for successful tracking and delivery of radiation [135].There is migration of 0.8-2 mm in relation to bony landmarks [133,136], and in one study the procedure had to be repeated in 7% of the patients [137]. However, no migration-related complications have been reported to date.

6.4. Pain palliation by EUS-guided celiac plexus neurolysis

The NCCN guidelines version 2.2012 for pancreatic adenocarcinoma recommend EUS-guided celiac plexus neurolysis (EUS-CPN) for the treatment of severe tumor-associated pain. In the case of jaundice caused by an unresectable pancreatic head tumor, biliary drainage should be offered first, then EUS-CPN if pain persists. Relative contraindications to EUS-CPN include difficult access owing to anatomical distortion from previous surgery or congenital malformations. The absolute contraindications for EUS-CPN are the same as for any other invasive procedure: coagulopathy, platelets < 50 000, and patients who are unable or unwilling to cooperate [138].

The mean rate of pain alleviation is 72-80%, with a much lower rate of complete pain response [139-141]. The post-neurolytic residual pain could be related to non-visceral pain owing to invasion of the muscles or surrounding connective tissue. The bilateral technique on both sides of the celiac trunk was associated with a rate of pain alleviation of 45-88% [142-144], while the central technique, with injection above the celiac trunk, showed 68-72% alleviation [145,146]. To date, only one randomized controlled trial has compared the central and bilateral techniques of EUS-CPN; it found no difference in duration of pain relief (11 vs. 14 weeks), complete pain relief (2/29 vs. 2/21 patients), or reduction in pain medication (9/29 vs. 7/21 patients) [147,148]. The choice between central and bilateral EUS-CPN remains difficult, depending on the personal skills and experience of the individual endosonographer. We have achieved good results with the central technique, which we consider easier to perform [148].

EUS-guided direct ganglia neurolysis resulted in better pain alleviation than bilateral injection [149,150]; but no randomized study has yet compared these two techniques. No difference in pain alleviation was noted between injection of 10 or 20 ml alcohol [149].

Pain reduction was more effective and the need for increased opioids was prevented in patients without radiochemotherapy compared with patients who had radiochemotherapy [151]. The benefit of repeated EUS-CPN was studied in 24 patients and results were less encouraging. The rate of successful pain relief was much lower than for the first EUS-CPN (29% vs. 67% at 1-month follow-up), and disease progression was a factor which limited the response [152].

The predictors of pain alleviation were found to be lack of ganglia visualization [153], direct invasion of celiac ganglia, and leftward diffusion of the neurolytic agent [145]. The pain was also less severe, albeit not significantly so, for tumors located in the body or tail of the pancreas, for large tumors, and for patients with severe pain at presentation [153].

Nowadays the potential immediate complications, such as hypotension, tachycardia, pain enhancement, severe bleeding, and paraplegia, are considered rare. The late side effects include diarrhea, hypotension, fever, and paraplegia [154]. Several severe side effects have been reported, e.g., permanent lower paraplegia due to spinal cord infarction [155,156], hepatic, splenic, and renal infarction [157], and lethal perforation of aorta and stomach [158].

6.5. Palliative EUS-guided treatment of jaundice

Palliative EUS-guided treatment of jaundice should be offered as an effective alternative for percutaneous transhepatic biliary drainage when ERCP fails and surgery is not indicated. One approach is transduodenal in combination with ERCP (rendez-vous technique), with reported technical success rates of 75-100% [159,160]. EUS-guided choledochoduodenostomy with transluminal stenting is successful in 75-88% of cases [161-164], while the transgastric approach has a success rate of 65-100% [165-167]. Recently, cholecysto-antrostomy has been described as an ideal alternative if the patient has duodenal strictures with or without a duodenal metal stent and a non-dilated intrahepatic bile duct [168-169]. When duodenal stenosis is also present, double duodenal and biliary drainage by ERCP or EUS can be performed [170].

All these procedures are technically challenging and should be attempted only by very experienced endosonographers at a high-volume center for bilio-pancreatic pathology. Complications are frequent, occurring in 18-23% of cases, and are represented by pneumoperitoneum, bile peritonitis, cholangitis, bleeding, pancreatitis (in the rendez-vous approach), and stent migration (Table 2). The existing data are from single very experienced centers; further prospective multicentric results are awaited.

Author, yearNo. of patientsPC / totalTechnical success rateFunctional success ratePatency(days)Complications
Song [161]9/15 CDS13/1513/13264-CDSPneumoperitoneum-2
Stent migration -4
Shah[159]70 CDS86%(75% rendez-vous)Pancreatitis-5, hematoma-1, bile leak-1, bacteremia -1,pneumoperitoneum-1, perforation-1
Bile peritonitis-2
Kim[160]15 CDS15/1512/15Acute pancreatitis-1
Park [171]9HGS
Hara[172]18- CDS17/1817/17272Peritonitis-1
Artifon [173]3 CDS-metal
Ang [174]2 CDS-plastic
Iwamuro [175]7 CDSBile peritonitis-2
Belletruti [177]4CDS
Tang [178]
Brauer[163]12 -4 CDS
(8pancreatic mass)
Kahaleh[180]13 HGS
10 CDS
Bile leakage-1
Yamao[181]2 CDS
Puspok [182]5CDS
6/6Acute cholecystitis-1
Mallery [183]6CDS5/6

Table 2.

Studies of EUS-guided biliary drainage.

PC, pancreatic cancer; CDS, choledochoduodenostomy; HGS, hepaticogastrostomy


7. Screening of pancreatic cancer

Multislice CT detection of pancreatic cancers less than 2 cm in diameter has sensitivity of 70-80% [184,185] and that of MRI is higher [186], but EUS can detect almost twice lesions compared to other imaging methods [184,187]. For patients with elevated CA19-9, the use of EUS detected cancer in only 0.9% of patients, with the result that the cost of detecting one pancreatic adenocarcinoma was $41,133 [188]. An initial study from the National German Familial Pancreatic Cancer Registry noted potential precursors of pancreatic cancer in 4 of 182 examinations of patients from families with familial pancreatic cancer, based on EUS and MRI, and the authors concluded that screening is not justified due to the high costs and the psychological stress to the persons concerned [189].

Screening by EUS and/or MRI is important for first-degree relatives (FDRs) of patients with PC from a familial PC kindred with at least two affected FDRs; patients with Peutz-Jeghers syndrome; and carriers of p16, BRCA2, and hereditary non-polyposis colorectal cancer (HNPCC) mutations with at least one affected FDR [190]. Another study which investigated a high-risk population by means of EUS found a 6.8% rate of adenocarcinomas in the body and tail of the pancreas; two of the three patients had N1 tumors [186].


8. Conclusion

EUS is useful for the detection of pancreatic cancers less than 3 cm in diameter and for the staging of cases in which CT is inconclusive. EUS-FNA establishes the tumor type with high accuracy and a very low rate of complications, and it is useful for differential diagnosis. EUS-guided palliative treatments include neurolysis and therapy of jaundice, but intratumoral ablative therapy needs further evaluation. Screening in high-risk groups should take advantage of EUS evaluation.


  1. 1. Ngamruengphong S, Li F, Zhou Y, Chak A, Cooper GS, Das A. EUS and survival in patients with pancreatic cancer: a population-based study. Gastrointest Endosc. 2010 Jul;72(1):78-83, 83.e1-2.
  2. 2. Parmar AD, Sheffield KM, Han Y, Vargas GM, Guturu P, Kuo YF, Goodwin JS, Riall TS. Evaluating comparative effectiveness with observational data: Endoscopic ultrasound and survival in pancreatic cancer. Cancer. 2013; 119(21): 3861-9.
  3. 3. Bhutani MS, Gress FG, Giovannini M, Erickson RA, Catalano MF, Chak A, Deprez PH, Faigel DO, Nguyen CC; No Endosonographic Detection of Tumor (NEST) Study.The No Endosonographic Detection of Tumor (NEST) Study: a case series of pancreatic cancers missed on endoscopic ultrasonography. Endoscopy. 2004;36(5):385-9.
  4. 4. Spier BJ, Johnson EA, Gopal DV, Frick T, Einstein MM, Byrne S, Koscik RL, Liou JI, Broxmeyer T, Selvaggi SM, Pfau PR. Predictors of malignancy and recommended follow-up in patients with negative endoscopic ultrasound-guided fine-needle aspiration of suspected pancreatic lesions. Can J Gastroenterol. 2009;23(4):279-86.
  5. 5. Müller MF, Meyenberger C, Bertschinger P, Schaer R, Marincek B. Pancreatic tumors: evaluation with endoscopic US, CT, and MR imaging. Radiology. 1994;190(3):745-51.
  6. 6. Ardengh JC, de Paulo GA, Ferrari AP. Pancreatic carcinomas smaller than 3.0 cm: endosonography (EUS) in diagnosis, staging and prediction of resectability. HPB (Oxford). 2003;5(4):226-30.
  7. 7. Akahoshi K,Chijiiwa Y, Nakano I, Nawata H, Ogawa Y, Tanaka M, Nagai E, Tsuneyoshi M. Diagnosis and staging of pancreatic cancer by endoscopic ultrasound. Br J Radiol 1998; 71: 492- 496.
  8. 8. Agarwal B, Krishna NB, Labundy JL, Safdar R, Akduman EI. EUS and/or EUS-guided FNA in patients with CT and/or magnetic resonance imaging findings of enlarged pancreatic head or dilated pancreatic duct with or without a dilated common bile duct. Gastrointest Endosc. 2008;68(2):237-42.
  9. 9. Krishna NB, Mehra M, Reddy AV, Agarwal B. EUS/EUS-FNA for suspected pancreatic cancer: influence of chronic pancreatitis and clinical presentation with or without obstructive jaundice on performance characteristics. Gastrointest Endosc. 2009 ;70(1):70-9.
  10. 10. Ho S, Bonasera RJ, Pollack BJ, Grendell J, Feuerman M, Gress F. A single-center experience of endoscopic ultrasonography for enlarged pancreas on computed tomography. Clin Gastroenterol Hepatol. 2006 ;4(1):98-103
  11. 11. Wang X, Gao J, Ren Y, Gu J, Du Y, Chen J, Jin Z, Zhan X, Li Z, Huang H, Lv S, Gong Y. Detection of KRAS gene mutations in endoscopic ultrasound-guided fine-needle aspiration biopsy for improving pancreatic cancer diagnosis. Am J Gastroenterol. 2011;106(12):2104-11.
  12. 12. Krishna N, Tummala P, Reddy AV, Mehra M, Agarwal B. Dilation of both pancreatic duct and the common bile duct on computed tomography and magnetic resonance imaging scans in patients with or without obstructive jaundice. Pancreas. 2012l;41(5):767-72.
  13. 13. Singh S, Reddymasu S, Waheed S, Vail M, He J, Talapaneni J, Olyaee M. Endoscopic ultrasonography findings in patients with non-specific changes of the pancreas on computed tomography: a single-center experience. Dig Dis Sci. 2008 ;53(10):2799-804
  14. 14. Rodriguez S, Faigel D. Absence of a dilated duct predicts benign disease in suspected pancreas cancer: a simple clinical rule. Dig Dis Sci. 2010;55(4):1161-6.
  15. 15. Dufour B, Zins M, Vilgrain V, Levy P, Bernades P, Menu Y. Comparison between spiral x-ray computed tomography and endosonography in the diagnosis and staging of adenocarcinoma of the pancreas. Clinical preliminary study. Gastroenterol Clin Biol. 1997;21(2):124-30.
  16. 16. Borbath I, Van Beers BE, Lonneux M, Schoonbroodt D, Geubel A, Gigot JF, Deprez PH. Preoperative assessement of pancreatic tumors using magnetic resonance imaging, endoscopic ultrasonography, positron emission tomography and laparoscopy. Pancreatology 2005; 5(6): 553-561.
  17. 17. Ainsworth AP, Rafaelsen SR, Wamberg PA, Durup J, Pless TK, Mortensen MB. Is there a difference in diagnostic accuracy and clinical impact between endoscopic ultrasonography and magnetic resonance cholangiopancreatography? Endoscopy. 2003 ;35(12):1029-32.
  18. 18. Mertz HR, Sechopoulos P, Delbeke D, Leach SD. EUS, PET and CT scanning for evaluation of pancreatic adenocarcinoma. Gastrointest Endosc 2000; 52: 367-71..
  19. 19. Schick V, Franzius C, Beyna T, Oei ML, Schnekenburger J, Weckesser M, Domschke W, Schober O, Heindel W, Pohle T, Juergens KU. Diagnostic impact of 18F-FDG PET-CT evaluating solid pancreatic lesions versus endosonography, endoscopic retrograde cholangio-pancreatography with intraductal ultrasonography and abdominal ultrasound. Eur J Nucl Med Mol Imaging. 2008 ;35(10):1775-85.
  20. 20. Menzel J, Domschke W, Konturek JW, Gillessen A, Foerster E. Intraductal ultrasound in the pancreaticobiliary duct system. Dtsch MedWochenschr 1997;122(3): 41-49.
  21. 21. Brand B, Pfaff T, Binmoeller KF, Sriram PV, FritscherRavens A, Knöfel WT, Jäckle S, Soehendra N. Endoscopic ultrasound for differential diagnosis of focal pancreatic lesions, confirmed by surgery. Scand J Gastroenterol 2000; 35(11): 1221-1228
  22. 22. Lee SH, Ozden N, Pawa R, Hwangbo Y, Pleskow DK, Chuttani R, Sawhney MS. Periductal hypoechoic sign: an endosonographic finding associated with pancreatic malignancy. Gastrointest Endosc. 2010;71(2):249-55.
  23. 23. Rösch T, Braig C, Gain T, Feuerbach S, Siewert JR, Schusdziarra V, Classen M. Staging of pancreatic and ampullary carcinoma by endoscopic ultrasonography. Comparison with conventional sonography, computed tomography, and angiography. Gastroenterology. 1992 ;102(1):188-99.
  24. 24. Palazzo L, Roseau G, Gayet B, Vilgrain V, Belghiti J, Fékéte F, Paolaggi JA. Endoscopic ultrasonography in the diagnosis and staging of pancreatic adenocarcinoma. Results of a prospective study with comparison to ultrasonography and CT scan. Endoscopy 1993; 25(2): 143-150..
  25. 25. Tio TL, Sie LH, Kallimanis G, Luiken GJ, Kimmings AN, Huibregtse K, Tytgat GN. Staging of ampullary and pancreatic carcinoma: comparison between endosonography and surgery. Gastrointest Endosc 1996: 44(6): 706-713.
  26. 26. Buscail L, Pages P, Berthelemy P, Fourtanier G, Frexinos J, Escourrou J. Role of EUS in the management of pancreatic and ampullary carcinoma: a prospective study assessing resectability and prognosis. Gastrointest Endosc 1999; 50(1): 34-40.
  27. 27. Ahmad NA, Lewis JD, Ginsberg GG, Rosato EF, Morris JB, Kochman ML. EUS in preoperative staging of pancreatic cancer. Gastrointest Endosc 2000; 52(4): 463-468.
  28. 28. Soriano A, Castells A, Ayuso C, Ayuso JR, de Caralt MT, Ginès MA, Real MI, Gilabert R, Quintó L, Trilla A, Feu F, Montanyà X, Fernández-Cruz L, Navarro S. Preoperative staging and tumor resectability assessment of pancreatic cancer: prospective study comparing endoscopic ultrasonography, helical computed tomography, magnetic resonance imaging, and angiography. Am J Gastroenterol 2004; 99(3): 492-501.
  29. 29. Dewitt J, Devereaux B, Chriswell M, McGreevy K, Howard T, Imperiale TF, Ciaccia D, Lane KA, Maglinte D, Kopecky K, LeBlanc J, McHenry L, Madura J, Aisen A, Cramer H, Cummings O, Sherman S. Comparison of endoscopic ultrasonography and multidetector computed tomography for detecting and staging pancreatic cancer. Ann Intern Med 2004; 141(10): 753-763.
  30. 30. Tellez-Avila FI, Chavez-Tapia NC, López-Arce G, Franco-Guzmán AM, Sosa-Lozano LA, Alfaro-Lara R, Chan-Nuñez C, Giovannini M, Elizondo-Rivera J, Ramírez-Luna MA. Vascular invasion in pancreatic cancer: predictive values for endoscopic ultrasound and computed tomography imaging. Pancreas. 2012 ;41(4):636-8.
  31. 31. Dewitt J, Devereaux BM, Lehman GA, Sherman S, Imperiale TF. Comparison of endoscopic ultrasound and computed tomography for the preoperative evaluation of pancreatic cancer: a systematic review. Clin Gastroenterol Hepatol 2006; 4(6): 717-725.
  32. 32. Rösch T, Dittler HJ, Strobel K, Meining A, Schusdziarra V, Lorenz R, Allescher HD, Kassem AM, Gerhardt P, Siewert JR, Höfler H, Classen M. Endoscopic ultrasound criteria for vascular invasion in the staging of cancer of the head of the pancreas: a blind reevaluation of videotapes. Gastrointest Endosc. 2000 ;52(4):469-77.
  33. 33. Marty O, Aubertin JM, Bouillot JL, Hernigou A, Bloch F, Petite JP. Prospective comparison of ultrasound endoscopy and computed tomography in the assessment of locoregional invasiveness of malignant ampullar and pancreatic tumors verified surgically]. Gastroenterol Clin Biol. 1995;19(2):197-203.
  34. 34. Midwinter MJ, Beveridge CJ, Wilsdon JB, Bennett MK, Baudouin CJ, Charnley RM. Correlation between spiral computed tomography, endoscopic ultrasonography and findings at operation in pancreatic and ampullary tumours. Br J Surg. 1999;86(2):189-93.
  35. 35. Puli SR, Singh S, Hagedorn CH, Reddy J, Olyaee M. Diagnostic accuracy of EUS for vascular invasion in pancreatic and periampullary cancers: a meta-analysis and systematic review. Gastrointest Endosc. 2007;65(6):788-97.
  36. 36. Kala Z, Válek V, Hlavsa J, Hana K, Vánová A. The role of CT and endoscopic ultrasound in pre-operative staging of pancreatic cancer. Eur J Radiol. 2007;62(2):166-9.
  37. 37. Gress FG, Hawes RH, Savides TJ, Ikenberry SO, Cummings O, Kopecky K, Sherman S, Wiersema M, Lehman GA. Role of EUS in the preoperative staging of pancreatic cancer: a large single-center experience. Gastrointest Endosc. 1999;50(6):786-91.
  38. 38. Rivadeneira DE, Pochapin M, Grobmyer SR, Lieberman MD, Christos PJ, Jacobson I, Daly JM Comparison of linear array endoscopic ultrasound and helical computed tomography for the staging of periampullary malignancies. Ann Surg Oncol. 2003;10(8):890-7.
  39. 39. Agarwal B, Abu-Hamda E, Molke KL, Correa AM, Ho L. Endoscopic ultrasound-guided fine needle aspiration and multidetector spiral CT in the diagnosis of pancreatic cancer. Am J Gastroenterol. 2004;99(5):844-50.
  40. 40. Morris-Stiff G, Escofet X, Barry JD, Lewis WG, Puntis MC, Roberts SA. Selective use of endoscopic ultrasound in the evaluation of carcinomas of the pancreatic head. Dig Surg. 2011;28(5-6):373-8.
  41. 41. Sugiyama M, Hagi H, Atomi Y, Saito M. Diagnosis of portal venous invasion by pancreatobiliary carcinoma: value of endoscopic ultrasonography. Abdom Imaging. 1997;22(4):434-8.
  42. 42. Legmann P, Vignaux O, Dousset B, Baraza AJ, Palazzo L, Dumontier I, Coste J, Louvel A, Roseau G, Couturier D, Bonnin A. Pancreatic tumors: comparison of dual-phase helical CT and endoscopic sonography. AJR Am J Roentgenol. 1998;170(5):1315-22.
  43. 43. Shami VM, Mahajan A, Loch MM, Stella AC, Northup PG, White GE, Brock AS, Srinivasan I, de Lange EE, Kahaleh M. Comparison between endoscopic ultrasound and magnetic resonance imaging for thestaging of pancreatic cancer. Pancreas. 2011;40(4):567-70.
  44. 44. Bipat S, Phoa S, vanDelden O, Bossuyt PM, Gouma DJ, Laméris JS, Stoker J. Ultrasonography, computed tomography and magnetic resonance imaging for diagnosis and determining resectability of pancreatic adenocarcinoma: a meta-analysis. J Comput Assist Tomogr 2005; 29(4):438-445.
  45. 45. Möller K, Papanikolaou IS, Toermer T, Delicha EM, Sarbia M, Schenck U, Koch M, Al-Abadi H, Meining A, Schmidt H, Schulz HJ, Wiedenmann B,Rösch T. EUS-guided FNA of solid pancreatic masses: high yield of 2 passes with combined histologic-cytologic analysis. Gastrointest Endosc 2009; 70(1): 60-9.
  46. 46. Iglesias-Garcia J, Dominguez-Munoz E, Lozano-Leon A, Abdulkader I, Larino-Noia J, Antunez J, Forteza J. Impact of endoscopic ultrasound-guided fine needle biopsy for diagnosis of pancreatic masses. World J Gastroenterol 2007; 13(2): 289-93.
  47. 47. Abdelgawwad MS, Alston E, Eltoum IA. The frequency and cancer risk associated with the atypical cytologic diagnostic category in endoscopic ultrasound-guided fine-needle aspiration specimens of solid pancreaticlesions: A meta-analysis and argument for a Bethesda system for reporting cytopathology of the pancreas. Cancer Cytopathol. 2013 Jul 23.
  48. 48. Papanikolaou IS, Adler A, Wegener K, Al-Abadi H, Dürr A, Koch M, Pohl H, Abou-Rebyeh H, Veltzke-Schlieker W, Wiedenmann B, Rösch T. Prospective pilot evaluation of a new needle prototype for endoscopic ultrasonography-guided fine-needle aspiration: comparison of cytology and histology yield. Eur J Gastroenterol Hepatol 2008; 20(4): 342-8..
  49. 49. Savides TJ. Tricks for improving EUS-FNA accuracy and maximizing cellular yield. Gastrointest Endosc 2009; 69: S130- 132.
  50. 50. Itoi T, Itokawa F, Kurihara T, Sofuni A, Tsuchiya T, Ishii K, Tsuji S, Ikeuchi N, Kawai T, Moriyasu F.Experimental endoscopy: objective evaluation of EUS needles. Gastrointest Endosc 2009; 69 (3Pt1): 509-16.
  51. 51. Eloubeidi MA, Jhala D, Chhieng DC, Chen VK, Eltoum I, Vickers S, Mel Wilcox C, Jhala N. Yield of endoscopic ultrasound-guided fine-needle aspiration biopsy in patients with suspected pancreatic carcinoma. Cancer 2003; 99(5): 285-92.
  52. 52. Affolter KE, Schmidt RL, Matynia AP, Adler DG, Factor RE. Needle Size Has Only a Limited Effect on Outcomes in EUS-Guided Fine Needle Aspiration: A Systematic Review and Meta-Analysis.Dig Dis Sci. 2013;58(4):1026-34
  53. 53. 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(4): 567-70.
  54. 54. Nicaud M, Hou W, Collins D, Wagh MS, Chauhan S, Draganov PV. The utility of repeat endoscopic ultrasound-guided fine needle aspiration for suspected pancreatic cancer. Gastroenterol Res Pract 2010; 2010: 268290.
  55. 55. Tadic M, Kujundzic M, Stoos-Veic T, Kaic G, Vukelic-Markovic M. Role of repeated endoscopic ultrasound-guided fine needle aspiration in small solid pancreatic masses with previous indeterminate and negative cytological findings. Dig Dis 2008; 26(4): 377-82.
  56. 56. Vilmann P, Săftoiu A, Hollerbach S, Skov BG, Linnemann D, Popescu CF, Wellmann A, Gorunescu F, Clementsen P, Freund U, Flemming P, Hassan H, Gheonea DI, Streba L, Ioncică AM, Streba CT. Multicenter randomized controlled trial comparing the performance of 22 gauge versus 25 gauge EUS-FNA needles in solid masses. Scand J Gastroenterol. 2013 ;48(7):877-83.
  57. 57. Song TJ, Kim JH, Lee SS, Eum JB, Moon SH, Park do H, Seo DW, Lee SK, Jang SJ, Yun SC, Kim MH. The prospective randomized, controlled trial of endoscopic ultrasound-guided fine-needle aspiration using 22G and 19G aspiration needles for solid pancreatic or peripancreatic masses. Am J Gastroenterol 2010; 105(8): 1739-1745
  58. 58. Songür N, Songür Y, Bırcan S, Kapucuoğlu N. Comparison of 19- and 22-gauge needles in EUS-guided fine needle aspiration in patients with mediastinal masses and lymph nodes. Turk J Gastroenterol 2011; 22(5): 472-8.
  59. 59. Levy MJ, Wiersema MJ. EUS-guided Trucut biopsy. Gastrointest Endosc 2005; 62: 417-26.
  60. 60. Bang JY, Hebert-Magee S, Trevino J, Ramesh J, Varadarajulu S. Randomized trial comparing the 22-gauge aspiration and 22-gauge biopsy needles for EUS-guided sampling of solid pancreatic mass lesions. Gastrointest Endosc 2012; 76(2): 321-7.
  61. 61. Iwashita T, Nakai Y, Samarasena JB, Park do H, Zhang Z, Gu M, Lee JG, Chang KJ. High single-pass diagnostic yield of a new 25-gauge core biopsy needle for EUS-guided FNA biopsy in solid pancreatic lesions. Gastrointest Endosc 2013, 77(6):909-15.
  62. 62. Wani S, Early D, Kunkel J, Leathersich A, Hovis CE, Hollander TG, Kohlmeier C, Zelenka C, Azar R, Edmundowicz S, Collins B, Liu J, Hall M, Mullady D. Diagnostic yield of malignancy during EUS-guided FNA of solid lesions with and without a stylet: a prospective, single blind, randomized, controlled trial. Gastrointest Endosc 2012; 76(2): 328-35.
  63. 63. Wani S, Gupta N, Gaddam S, Singh V, Ulusarac O, Romanas M, Bansal A, Sharma P, Olyaee MS, Rastogi A. A comparative study of endoscopic ultrasound guided fine needle aspiration with and without a stylet. Dig Dis Sci 2011; 56(8): 2409-14.
  64. 64. Lee JK, Choi JH, Lee KH, Kim KM, Shin JU, Lee JK, Lee KT, Jang KT. A prospective, comparative trial to optimize sampling techniques in EUS-guided FNA of solid pancreatic masses. Gastrointest Endosc 2013, 77(5):745-51.
  65. 65. Sahai AV, Paquin SC, Gariépy G. A prospective comparison of endoscopic ultrasound-guided fine needle aspiration results obtained in the same lesion, with and without the needle stylet. Endoscopy 2010; 42(11): 900-3.
  66. 66. Bang JY, Magee SH, Ramesh J, Trevino JM, Varadarajulu S. Randomized trial comparing fanning with standard technique for endoscopic ultrasound-guided fine-needle aspiration of solid pancreatic mass lesions. Endoscopy 2013, 45(6):445-50.
  67. 67. Thomas T, Kaye PV, Ragunath K, Aithal GP. Efficacy, safety, and predictive factors for a positive yield of EUS-guided Trucut biopsy: a large tertiary referral center experience. Am J Gastroenterol 2009; 104(3): 584-91.
  68. 68. LeBlanc JK, Emerson RE, Dewitt J, Symms M, Cramer HM, McHenry L, Wade CL, Wang X, Musto P, Eichelberger L, Al-Haddad M, Johnson C, Sherman S. A prospective study comparing rapid assessment of smears and ThinPrep for endoscopic ultrasound-guided fine-needle aspirates. Endoscopy 2010; 42(5): 389-94.
  69. 69. Eloubeidi MA, Tamhane A, Jhala N, Chhieng D, Jhala D, Crowe DR, Eltoum IA. Agreement between rapid onsite and final cytologic interpretations of EUS-guided FNA specimens: implications for the endosonographer and patient management. Am J Gastroenterol 2006; 101(12): 2841-2847.
  70. 70. Varadarajulu S, Tamhane A, Eloubeidi MA. Yield of EUS-guided FNA of pancreatic masses in the presence or the absence of chronic pancreatitis. Gastrointest Endosc. 2005; 62(5): 728-36.
  71. 71. Ranney N, Phadnis M, Trevino J, Ramesh J, Wilcox CM, Varadarajulu S. Impact of biliary stents on EUS-guided FNA of pancreatic mass lesions. Gastrointest Endosc. 2012; 76(1): 76-83.
  72. 72. Fisher JM, Gordon SR, Gardner TB. The impact of prior biliary stenting on the accuracy and complication rate of endoscopic ultrasound fine-needle aspiration for diagnosing pancreatic adenocarcinoma.Pancreas 2011 ; 40(1):21-4
  73. 73. Siddiqui AA, Fein M, Kowalski TE, Loren DE, Eloubeidi MA. Comparison of the influence of plastic and fully covered metal biliary stents on the accuracy of EUS-FNA for the diagnosis of pancreatic cancer. Dig Dis Sci 2012; 57(9): 2438-45.
  74. 74. Ardengh JC, Lopes CV, de Lim LF, de Oliveira JR, Venco F, Santo GC, Modena JL. Diagnosis of pancreatic tumors by endoscopic ultrasound-guided fine-needle aspiration. World J Gastroenterol 2007; 13(22): 3112-6.
  75. 75. Siddiqui AA, Brown LJ, Hong SK, Draganova-Tacheva RA, Korenblit J, Loren DE, Kowalski TE, Solomides C. Relationship of pancreatic mass size and diagnostic yield of endoscopic ultrasound-guided fine needle aspiration. Dig Dis Sci 2011; 56(11): 3370-5.
  76. 76. Puli SR, Bechtold ML, Buxbaum JL, Eloubeidi MA.How good is endoscopic ultrasound-guided fine-needle aspiration in diagnosing the correct etiology for a solid pancreatic mass?: A meta-analysis and systematic review. Pancreas. 2013;42(1): 20-6.
  77. 77. Saftoiu A, Vilman P. Endoscopic ultrasound elastography-- a new imaging technique for the visualization of tissue elasticity distribution. J Gastrointestin Liver Dis. 2006 15(2): 161-5.
  78. 78. Giovannini M, Thomas B, Erwan B, Christian P, Fabrice C, Benjamin E, Geneviève M, Paolo A, Pierre D, Robert Y, Walter S, Hanz S, Carl S, Christoph D, Pierre E, Jean-Luc VL, Jacques D, Peter V, Andrian S. Endoscopic ultrasound elastography for evaluation of lymph nodes and pancreaticmasses: a multicenter study. World J Gastroenterol. 2009;15(13):1587-93.
  79. 79. Iglesias-Garcia J, Larino-Noia J, Abdulkader I, Forteza J, Dominguez-Munoz JE. EUS elastography for the characterization of solid pancreatic masses. Gastrointest Endosc. 2009 ;70(6):1101-8.
  80. 80. Săftoiu A, Vilmann P, Gorunescu F, Gheonea DI, Gorunescu M, Ciurea T, Popescu GL, Iordache A, Hassan H, Iordache S. Neural network analysis of dynamic sequences of EUS elastography used for the differential diagnosis of chronic pancreatitis and pancreatic cancer. Gastrointest Endosc. 2008;68(6): 1086-94.
  81. 81. Săftoiu A, Vilmann P, Gorunescu F, Janssen J, Hocke M, Larsen M, Iglesias-Garcia J, Arcidiacono P, Will U, Giovannini M, Dietrich C, Havre R, Gheorghe C, McKay C, Gheonea DI, Ciurea T; European EUS Elastography Multicentric Study Group. Accuracy of endoscopic ultrasound elastography used for differential diagnosis of focalpancreatic masses: a multicenter study.Endoscopy. 2011;43(7): 596-603.
  82. 82. Dawwas MF, Taha H, Leeds JS, Nayar MK, Oppong KW. Diagnostic accuracy of quantitative EUS elastography for discriminating malignant from benign solid pancreatic masses: a prospective, single-center study. Gastrointest Endosc. 2012 76(5): 953-61.
  83. 83. Iglesias-Garcia J, Larino-Noia J, Abdulkader I, Forteza J, Dominguez-Munoz JE. Quantitative endoscopic ultrasound elastography: an accurate method for the differentiation of solid pancreatic masses. Gastroenterology. 2010 ;139(4):1172-80.
  84. 84. Itokawa F, Itoi T, Sofuni A, Kurihara T, Tsuchiya T, Ishii K, Tsuji S, Ikeuchi N, Umeda J, Tanaka R, Yokoyama N, Moriyasu F, Kasuya K, Nagao T, Kamisawa T, Tsuchida A. EUS elastography combined with the strain ratio of tissue elasticity for diagnosis of solid pancreatic masses. J Gastroenterol. 2011;46(6):843-53.
  85. 85. Hu DM, Gong TT, Zhu Q. Endoscopic ultrasound elastography for differential diagnosis of pancreatic masses: a meta-analysis.Dig Dis Sci. 2013;58(4):1125-31.
  86. 86. Xu W, Shi J, Li X, Zeng X, Lin Y. Endoscopic ultrasound elastography for differentiation of benign and malignantpancreatic masses: a systemic review and meta-analysis. Eur J Gastroenterol Hepatol. 2013;25(2):218-24.
  87. 87. Pei Q, Zou X, Zhang X, Chen M, Guo Y, Luo H. Diagnostic value of EUS elastography in differentiation of benign and malignant solidpancreatic masses: a meta-analysis. Pancreatology. 2012;12(5):402-8.
  88. 88. Săftoiu A, Iordache SA, Gheonea DI, Popescu C, Maloş A, Gorunescu F, Ciurea T, Iordache A, Popescu GL, Manea CT. Combined contrast-enhanced power Doppler and real-time sonoelastography performed during EUS, used in the differential diagnosis of focal pancreatic masses (with videos). Gastrointest Endosc. 2010;72(4):739-47.
  89. 89. Yamashita Y, Ueda K, Itonaga M, Yoshida T, Maeda H, Maekita T, Iguchi M, Tamai H, Ichinose M, Kato J. Tumor vessel depiction with contrast-enhanced endoscopic ultrasonography predicts efficacy of chemotherapy in pancreatic cancer. Pancreas. 2013;42(6):990-5.
  90. 90. 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(7):784-9.
  91. 91. Hocke M, Schmidt C, Zimmer B, Topalidis T, Dietrich CF, Stallmach A.Contrast enhanced endosonography for improving differential diagnosis between chronic pancreatitis and pancreatic cancer.Dtsch Med Wochenschr. 2008 ;133(38): 1888-92.
  92. 92. Hocke M, Schulze E, Gottschalk P, Topalidis T, Dietrich CF. Contrast-enhanced endoscopic ultrasound in discrimination between focal pancreatitis and pancreatic cancer. World J Gastroenterol. 2006;12(2):246-50.
  93. 93. Săftoiu A, Popescu C, Cazacu S, Dumitrescu D, Georgescu CV, Popescu M, Ciurea T, Gorunescu F. Power Doppler endoscopic ultrasonography for the differential diagnosis between pancreatic cancer and pseudotumoral chronic pancreatitis. J Ultrasound Med. 2006 ;25(3):363-72.
  94. 94. Sakamoto H, Kitano M, Suetomi Y, Maekawa K, Takeyama Y, Kudo M. Utility of contrast-enhanced endoscopic ultrasonography for diagnosis of small pancreatic carcinomas. Ultrasound Med Biol. 2008;34(4):525-32.
  95. 95. Seicean A, Badea R, Stan-Iuga R, Gulei I, Pop T, Pascu O. The added value of real-time harmonics contrast-enhanced endoscopic ultrasonography for the characterisation of pancreatic diseases in routine practice. J Gastrointestin Liver Dis. 2010;19(1):99-104.
  96. 96. Napoleon B, Alvarez-Sanchez MV, Gincoul R, Pujol B, Lefort C, Lepilliez V, Labadie M, Souquet JC, Queneau PE, Scoazec JY, Chayvialle JA, Ponchon T. Contrast-enhanced harmonic endoscopic ultrasound in solid lesions of the pancreas: results of a pilot study. Endoscopy. 2010 Jul;42(7):564-70.
  97. 97. Fusaroli P, Spada A, Mancino MG, Caletti G.Contrast harmonic echo-endoscopic ultrasound improves accuracy in diagnosis of solid pancreatic masses. Clin Gastroenterol Hepatol. 2010;8(7):629-34.
  98. 98. Kitano M, Kudo M, Yamao K, Takagi T, Sakamoto H, Komaki T, Kamata K, Imai H, Chiba Y, Okada M, Murakami T, Takeyama Y. Characterization of small solid tumors in the pancreas: the value of contrast-enhanced harmonic endoscopic ultrasonography. Am J Gastroenterol. 2012;107(2):303-10.
  99. 99. Gong TT, Hu DM, Zhu Q. Contrast-enhanced EUS for differential diagnosis of pancreatic mass lesions: a meta-analysis. Gastrointest Endosc. 2012;76(2):301-9.
  100. 100. Seicean A, Badea R, Stan-Iuga R, Mocan T, Gulei I, Pascu O. Quantitative contrast-enhanced harmonic endoscopic ultrasonography for the discrimination of solid pancreatic masses. Ultraschall Med. 2010;31(6):571-6.
  101. 101. Gheonea DI, Streba CT, Ciurea T, Săftoiu A. Quantitative low mechanical index contrast-enhanced endoscopic ultrasound for the differential diagnosis of chronic pseudotumoral pancreatitis and pancreatic cancer. BMC Gastroenterol. 2013;13:2.
  102. 102. Imazu H, Uchiyama Y, Matsunaga K, Ikeda K, Kakutani H, Sasaki Y, Sumiyama K, Ang TL, Omar S, Tajiri H. Contrast-enhanced harmonic EUS with novel ultrasonographic contrast (Sonazoid) in the preoperative T-staging for pancreaticobiliary malignancies. Scand J Gastroenterol. 2010;45(6):732-8.
  103. 103. Matsubara H, Itoh A, Kawashima H, Kasugai T, Ohno E, Ishikawa T, Itoh Y, Nakamura Y, Hiramatsu T, Nakamura M, Miyahara R, Ohmiya N, Ishigami M, Katano Y, Goto H, Hirooka Y. Dynamic quantitative evaluation of contrast-enhanced endoscopic ultrasonography in the diagnosis of pancreatic diseases. Pancreas. 2011;40(7):1073-9.
  104. 104. Hocke M, Ignee A, Dietrich CF. Advanced endosonographic diagnostic tools for discrimination of focal chronic pancreatitis and pancreatic carcinoma--elastography, contrast enhanced high mechanical index (CEHMI) and low mechanical index (CELMI) endosonography in direct comparison. Z Gastroenterol. 2012;50(2):199-203.
  105. 105. Fritscher-Ravens A, Knoefel WT, Krause C, Swain CP, Brandt L, Patel K. Three-dimensional linear endoscopic ultrasound-feasibility of a novel technique applied for the detection of vessel involvement of pancreatic masses. Am J Gastroenterol. 2005;100(6):1296-302.
  106. 106. Săftoiu A.State-of-the-art imaging techniques in endoscopic ultrasound. World J Gastroenterol. 2011; 17(6):691-6.
  107. 107. Zhang MM, Yang H, Jin ZD, Yu JG, Cai ZY, Li ZS. Differential diagnosis of pancreatic cancer from normal tissue with digital imaging processing and pattern recognition based on a support vector machine of EUS images. Gastrointest Endosc. 2010;72(5):978-85.
  108. 108. Zhu M, Xu C, Yu J, Wu Y, Li C, Zhang M, Jin Z, Li Z. Differentiation of pancreatic cancer and chronic pancreatitis using computer-aideddiagnosis of endoscopic ultrasound (EUS) images: a diagnostic test. PLoS One. 2013;8(5):e63820.
  109. 109. 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(6): 861-7.
  110. 110. Kubiliun N, Ribeiro A, Fan YS, Rocha-Lima CM, Sleeman D, Merchan J, Barkin J, Levi J. EUS-FNA with rescue fluorescence in situ hybridization for the diagnosis of pancreaticcarcinoma in patients with inconclusive on-site cytopathology results. Gastrointest Endosc. 2011;74(3):541-7.
  111. 111. Khalid A, Dewitt J, Ohori NP, Chen JH, Fasanella KE, Sanders M, McGrath KM, Nikiforova M. EUS-FNA mutational analysis in differentiating autoimmune pancreatitis and pancreatic cancer.Pancreatology. 2011;11(5):482-6.
  112. 112. Ogura T, Yamao K, Sawaki A, Mizuno N, Hara K, Hijioka S, Niwa Y, Tajika M, Kondo S, Shimizu Y, Bhatia V, Higuchi K, Hosoda W, Yatabe Y. Clinical impact of K-ras mutation analysis in EUS-guided FNA specimens from pancreatic masses. Gastrointest Endosc. 2012 ;75(4):769-74.
  113. 113. Fuccio L, Hassan C, Laterza L, Correale L, Pagano N, Bocus P, Fabbri C, Maimone A, Cennamo V, Repici A, Costamagna G, Bazzoli F, Larghi A. The role of K-ras gene mutation analysis in EUS-guided FNA cytology specimens for the differential diagnosis of pancreatic solid masses: a meta-analysis of prospective studies. Gastrointest Endosc. 2013;78(4):596-608.
  114. 114. Mishra G, Zhao Y, Sweeney J, Pineau BC, Case D, Ho C, Blackstock AW, Geisinger K, Howerton R, Levine E, Shen P, Ibdah J. Determination of qualitative telomerase activity as an adjunct to the diagnosis of pancreatic adenocarcinoma by EUS-guided fine-needle aspiration. Gastrointest Endosc. 2006;63(4):648–65
  115. 115. Endo H, Saito T, Kenjo A, Hoshino M, Terashima M, Sato T, Anazawa T, Kimura T, Tsuchiya T, Irisawa A, Ohira H, Hikichi T, Takagi T, Gotoh M. Phase I trial of preoperative intratumoral injection of immature dendritic cells and OK-432 for resectable pancreatic cancer patients. J Hepatobiliary Pancreat Sci. 2012;19(4):465-75.
  116. 116. Seo DW. EUS-Guided Antitumor Therapy for Pancreatic Tumors. Gut Liver. 2010; 4(Suppl 1): S76–S81.
  117. 117. Hirooka Y, Itoh A, Kawashima H, Hara K, Nonogaki K, Kasugai T, Ohno E, Ishikawa T, Matsubara H, Ishigami M, Katano Y, Ohmiya N, Niwa Y,Yamamoto K, Kaneko T, Nieda M, Yokokawa K, Goto H. A combination therapy of gemcitabine with immunotherapy for patients with inoperable locally advanced pancreatic cancer. Pancreas. 2009;38(3):e69-74.
  118. 118. Chang KJ, Nguyen PT, Thompson JA, Kurosaki TT, Casey LR, Leung EC, Granger GA. 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(6):1325-35.
  119. 119. Hecht JR, Bedford R, Abbruzzese JL, Lahoti S, Reid TR, Soetikno RM, Kirn DH, Freeman SM. 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(2):555-61.
  120. 120. Chang KJ, Lee JG, Holcombe RF, Kuo J, Muthusamy R, Wu ML. Endoscopic ultrasound delivery of an antitumor agent to treat a case of pancreaticcancer. Nat Clin Pract Gastroenterol Hepatol. 2008;5(2):107-11.
  121. 121. Hecht JR, Farrell JJ, Senzer N, Nemunaitis J, Rosemurgy A, Chung T, Hanna N, Chang KJ, Javle M, Posner M, Waxman I, Reid A, Erickson R, Canto M, Chak A, Blatner G, Kovacevic M, Thornton M. EUS or percutaneously guided intratumoral TNFerade biologic with 5-fluorouracil and radiotherapy for first-line treatment of locally advanced pancreatic cancer: a phase I/II study. Gastrointest Endosc. 2012;75(2):332-8.
  122. 122. Herman JM, Wild AT, Wang H, Tran PT, Chang KJ, Taylor GE, Donehower RC, Pawlik TM, Ziegler MA, Cai H, Savage DT, Canto MI, Klapman J, Reid T, Shah RJ, Hoffe SE, Rosemurgy A, Wolfgang CL, Laheru DA.Randomized phase III multi-institutional study of TNFerade biologic with fluorouracil and radiotherapy for locally advanced pancreatic cancer: final results. J Clin Oncol. 2013;31(7):886-94.
  123. 123. Wakatsuki T, Irisawa A, Imamura H, Terashima M, Shibukawa G, Takagi T, Takahashi Y, Sato A, Sato M, Ikeda T, Suzuki R, Hikichi T, Obara K, Ohira H. Complete response of anaplastic pancreatic carcinoma to paclitaxel treatment selected by chemosensitivity testing. Int J Clin Oncol. 2010;15(3):310-3.
  124. 124. Goldberg SN, Mallery S, Gazelle GS, Brugge WR. EUSguided radiofrequency ablation in the pancreas: results in a porcine model. Gastrointest Endosc 1999; 50: 392-401
  125. 125. Carrara S, Arcidiacono PG, Albarello L, Addis A, Enderle MD, Boemo C, Neugebauer A, Campagnol M, Doglioni C, Testoni PA. Endoscopic ultrasound-guided application of a new internally gas-cooled radiofrequency ablation probe in the liver and spleen of an animal model: a preliminary study. Endoscopy 2008; 40(4): 759-763
  126. 126. Gaidhane M, Smith I, Ellen K, Gatesman J, Habib N, Foley P, Moskaluk C, Kahaleh M. Endoscopic Ultrasound-Guided Radiofrequency Ablation (EUS-RFA) of the Pancreas in a Porcine Model. Gastroenterol Res Pract. 2012;2012:431451.
  127. 127. Kim HJ, Seo DW, Hassanuddin A, Kim SH, Chae HJ, Jang JW, Park do H, Lee SS, Lee SK, Kim MH. EUS-guided radiofrequency ablation of the porcine pancreas. Gastrointest Endosc. 2012;76(5):1039-43.
  128. 128. Arcidiacono PG, Carrara S, Reni M, Petrone MC, Cappio S, Balzano G, Boemo C, Cereda S, Nicoletti R, Enderle MD, Neugebauer A, von Renteln D, Eickhoff A, Testoni A. Feasibility and safety of EUS-guided cryothermal ablation in patients with locally advanced pancreatic cancer. Gastrointest Endosc. 2012;76(6):1142-51.
  129. 129. Di Matteo F, Martino M, Rea R, Pandolfi M, Rabitti C, Masselli GM, Silvestri S, Pacella CM, Papini E, Panzera F, Valeri S, Coppola R, Costamagna G. EUS-guided Nd:YAG laser ablation of normal pancreatic tissue: a pilot study in a pig model. Gastrointest Endosc. 2010;72(2):358-63.
  130. 130. Yusuf TE, Matthes K, Brugge WR. EUS-guided photodynamic therapy with verteporfin for ablation of normal pancreatictissue: a pilot study in a porcine model (with video).Gastrointest Endosc. 2008;67(6):957-61.
  131. 131. Jin Z, Du Y, Li Z, Jiang Y, Chen J, Liu Y. 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(4):314–320.
  132. 132. Sun S, Xu H, Xin J, Liu J, Guo Q, Li S. Endoscopic ultrasound-guided interstitial brachytherapy of unresectable pancreatic cancer: results of a pilot trial. Endoscopy.2006;38(4):399–403.
  133. 133. Khashab MA, Kim KJ, Tryggestad EJ, Wild AT, Roland T, Singh VK, Lennon AM, Shin EJ, Ziegler MA, Sharaiha RZ, Canto MI, Herman JM. Comparative analysis of traditional and coiled fiducials implanted during EUS forpancreatic cancer patients receiving stereotactic body radiation therapy. Gastrointest Endosc. 2012;76(5):962-71.
  134. 134. Park WG, Yan BM, Schellenberg D, Kim J, Chang DT, Koong A, Patalano C, Van Dam J. EUS-guided gold fiducial insertion for image-guided radiation therapy of pancreatic cancer: 50 successful cases without fluoroscopy. Gastrointest Endosc. 2010;71(3):513-8.
  135. 135. Majumder S, Berzin TM, Mahadevan A, Pawa R, Ellsmere J, Sepe PS, Larosa SA, Pleskow DK, Chuttani R, Sawhney MS. Endoscopic ultrasound-guided pancreatic fiducial placement: how important is ideal fiducial geometry? Pancreas. 2013;42(4):692-5.
  136. 136. Varadarajulu S, Trevino JM, Shen S, Jacob R. The use of endoscopic ultrasound-guided gold markers in image-guided radiation therapy of pancreatic cancers: a case series. Endoscopy. 2010;42(5):423-5.
  137. 137. Sanders MK, Moser AJ, Khalid A, Fasanella KE, Zeh HJ, Burton S, McGrath K. EUS-guided fiducial placement for stereotactic body radiotherapy in locally advanced and recurrent pancreatic cancer. Gastrointest Endosc. 2010;71(7):1178-84.
  138. 138. Soweid AM, Azar C. Endoscopic ultrasound-guided celiac plexus neurolysis. World J Gastrointest Endosc 2010; 2(6):228-31.
  139. 139. Levy MJ, Chari ST, Wiersema MJ. Endoscopic ultrasound-guided celiac neurolysis. Gastrointest Endoscopy Clin N Am 2012; 22(2):231–247.
  140. 140. Puli SR, Reddy JB, Bechtold ML, Antillon MR, Brugge WR. 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; 54(11): 2330-2337.
  141. 141. Kaufman M, Singh G, Das S, Concha-Parra R, Erber J, Micames C, Gress F. Efficacy of endoscopic ultrasound-guided celiac plexus block and celiac plexus neurolysis for managing abdominal pain associated with chronic pancreatitis and pancreatic cancer. J Clin Gastroenterol 2010; 44(2):127-134.
  142. 142. Wiersema MJ, Wiersema. Endosonography-guided celiac plexus neurolysis. Gastrointest Endosc 1996; 44:656-62
  143. 143. Gunaratnam NT, Sarma AV, Norton ID, Wiersema MJ. A prospective study of EUS-guided celiac plexus neurolysis for pancreatic cancer pain. Gastrointest Endosc 2001; 54(3):316-324.
  144. 144. Sahai AV, Lemelin V, Lam E, Paquin SC. Central vs. bilateral endoscopic ultrasound-guided celiac plexus block or neurolysis: a comparative study of short-term effectiveness. Am J Gastroenterol 2009; 104(2):326-329.
  145. 145. Iwata K, Yasuda I, Enya M, Mukai T, Nakashima M, Doi S, Iwashita T, Tomita E, Moriwaki H. Predictive factors for pain relief after endoscopic ultrasound-guided celiac plexus neurolysis. Dig Endos 2011; 23(2):140-145.
  146. 146. Ramirez-Luna M, Chavez-Tapia N, Franco-Guzman A, Garcia-Saenz-de Sicilia M, Tellez-Avila F. Endoscopic ultrasound-guided celiac plexus neurolysis in patients with unresectable pancreatic cancer. Rev Gastroenterol Mex 2008; 73(2):63-67.
  147. 147. Leblanc JK, Al-Haddad M, McHenry L, Sherman S, Juan M, McGreevy K, Johnson C, Howard TJ, Lillemoe KD, DeWitt J. A prospective, randomized study of EUS-guided celiac plexus neurolysis for pancreatic cancer: one injection or two? Gastrointest Endosc 2011; 74(6):1300-1307.
  148. 148. Seicean A, Cainap C, Gulei I, Tantau M, Seicean R. Pain palliation by endoscopic ultrasound-guided celiac plexus neurolysis in patients with unresectable pancreatic cancer. J Gastrointestin Liver Dis 2013; 22(1):59-64
  149. 149. Leblanc JK, Rawl S, Juan M, Johnson C, Kroenke K, McHenry L, Sherman S, McGreevy K, Al-Haddad M, Dewitt J. Endoscopic ultrasound-guided celiac plexus neurolysis in pancreatic cancer: a prospective pilot study of safety using 10 mL versus 20 mL alcohol. Diagn Ther Endosc 2013;2013:327036.
  150. 150. Levy MJ, Topazian MD, Wiersema MJ, Clain JE, Rajan E, Wang KK, de la Mora JG, Gleeson FC, Pearson RK, Pelaez MC, Petersen BT, Vege SS, Chari ST. Initial evaluation of the efficacy and safety of endoscopic ultrasound-guided direct ganglia neurolysis and block. Am J Gastroenterol 2008; 103(1):98-103
  151. 151. Wyse JM, Carone M, Paquin SC, Usatii M, Sahai AV. Randomized, double-blind, controlled trial of early endoscopic ultrasound-guided celiac plexus neurolysis to prevent pain progression in patients with newly diagnosed, painful, inoperable pancreatic cancer. J Clin Oncol 2011;29(26):3541-3546.
  152. 152. McGreevy K, Hurley RW, Erdek MA, Aner MM, Li S, Cohen SP. The effectiveness of repeat celiac plexus neurolysis for pancreatic cancer: a pilot study. Pain Pract 2012; 13(2):89-95
  153. 153. Ascunce G, Ribeiro A, Reis I, Sleeman D, Merchan J, Levi J. EUS visualization and direct celiac ganglia neurolysis predicts better pain relief in patients with pancreatic malignancy (with video). Gastrointest Endosc 2011; 73(2):267-274.
  154. 154. Sakamoto H, Kitano M, Komaki T, Kudo M. Endoscopic ultrasound-guided neurolysis in pancreatic cancer. Pancreatology 2011; 11 Suppl 2:52-8
  155. 155. Fujii L, Clain JE, Morris JM, Levy MJ. Anterior spinal cord infarction with permanent paralysis following endoscopic ultrasound celiac plexus neurolysis. Endoscopy 2012; 44 Suppl 2 UCTN:E265-6.
  156. 156. Mittal MK, Rabinstein AA, Wijdicks EF. Pearls & oy-sters: Acute spinal cord infarction following endoscopic ultrasound-guided celiac plexus neurolysis. Neurology 2012; 78:e57-9.
  157. 157. Ahmed HM, Friedman SE, Henriques HF, Berk BS. End-organ ischemia as an unforeseen complication of endoscopic-ultrasound-guided celiac plexus neurolysis. Endoscopy 2009; 41 Suppl 2:E218-9
  158. 158. Loeve US, Mortensen MB. Lethal necrosis and perforation of the stomach and the aorta after multiple EUS-guided celiac plexus neurolysis procedures in a patient with chronic pancreatitis.Gastrointest Endosc 2012; 77(1):151-2.
  159. 159. Shah JN, Marson F, Weilert F, Bhat YM, Nguyen-Tang T, Shaw RE, Binmoeller KF. Single-operator, single-session EUS-guided anterograde cholangiopancreatography in failed ERCP or inaccessible papilla. Gastrointest Endosc. 2012 75(1):56-64.
  160. 160. Kim YS, Gupta K, Mallery S, Li R, Kinney T, Freeman ML Endoscopic ultrasound rendezvous for bile duct access using a transduodenal approach: cumulative experience at a single center. A case series. Endoscopy. 2010;42(6):496-502.
  161. 161. Song TJ, Hyun YS, Lee SS, Park do H, Seo DW, Lee SK, Kim MH. Endoscopic ultrasound-guided choledochoduodenostomies with fully covered self-expandable metallic stents. World J Gastroenterol. 2012; 28;18(32):4435-40.
  162. 162. Kahaleh M, Hernandez AJ, Tokar J, Adams RB, Shami VM, Yeaton P. Interventional EUS-guided cholangiography: evaluation of a technique in evolution. Gastrointest Endosc 2006; 64(1): 52-59
  163. 163. Brauer BC, Chen YK, Fukami N, Shah RJ. Single-operator EUS-guided cholangiopancreatography for difficult pancreaticobiliary access (with video). Gastrointest Endosc 2009; 70(3): 471-479
  164. 164. Burmester E, Niehaus J, Leineweber T, Huetteroth T. EUS-cholangio-drainage of the bile duct: report of 4 cases. Gastrointest Endosc. 2003;57(2):246-51.
  165. 165. Kim TH, Kim SH, Oh HJ, Sohn YW, Lee SO.Endoscopic ultrasound-guided biliary drainage with placement of a fully covered metal stent for malignant biliary obstruction. World J Gastroenterol. 2012; 18(20):2526-32
  166. 166. Park do H, Jang JW, Lee SS, Seo DW, Lee SK, Kim MH.EUS-guided biliary drainage with transluminal stenting after failed ERCP: predictors of adverse events and long-term results. Gastrointest Endosc. 2011; 74(6):1276-84.
  167. 167. Bories E, Pesenti C, Caillol F, Lopes C, Giovannini M. Transgastric endoscopic ultrasonography-guided biliary drainage: results of a pilot study. Endoscopy. 2007;39(4):287-91.
  168. 168. Itoi T, Binmoeller K, Itokawa F, Umeda J, Tanaka R. Endoscopic ultrasonography-guided cholecystogastrostomy using a lumen-apposing metal stent as an alternative to extrahepatic bile duct drainage in pancreatic cancer with duodenal invasion.Dig Endosc. 2013;25 Suppl 2:137-41
  169. 169. Itoi T, Itokawa F, Tsuchiya T, Tsuji S, Tonozuka R. Endoscopic ultrasound-guided choledochoantrostomy as an alternative extrahepatic bile duct drainage method in pancreatic cancer with duodenal invasion. Dig Endosc. 2013;25 Suppl 2:142-5.
  170. 170. Tonozuka R, Itoi T, Sofuni A, Itokawa F, Moriyasu F. Endoscopic double stenting for the treatment of malignant biliary and duodenal obstruction due to pancreatic cancer. Dig Endosc. 2013;25 Suppl 2:100-8.
  171. 171. Park do H, Koo JE, Oh J, Lee YH, Moon SH, Lee SS, Seo DW, Lee SK, Kim MH. EUS-guided biliary drainage with one-step placement of a fully covered metal stent for malignant biliary obstruction: a prospective feasibility study. Am J Gastroenterol. 2009;104(9):2168-74.
  172. 172. Hara K, Yamao K, Niwa Y, Sawaki A, Mizuno N, Hijioka S, Tajika M, Kawai H, Kondo S, Kobayashi Y, Matumoto K, Bhatia V, Shimizu Y, Ito A, Hirooka Y,Goto H. Prospective clinical study of EUS-guided choledochoduodenostomy for malignant lower biliary tract obstruction. Am J Gastroenterol. 2011;106(7):1239-45.
  173. 173. Artifon EL, Takada J, Okawa L, Moura EG, Sakai P. EUS-guided choledochoduodenostomy for biliary drainage in unresectable pancreatic cancer: a case series. JOP. 2010;11(6):597-600.
  174. 174. Ang TL, Teo EK, Fock KM. EUS-guided transduodenal biliary drainage in unresectable pancreatic cancer with obstructive jaundice. JOP. 2007 ;8(4):438-43
  175. 175. Iwamuro M, Kawamoto H, Harada R, Kato H, Hirao K, Mizuno O, Ishida E, Ogawa T, Okada H, Yamamoto K. Combined duodenal stent placement and endoscopic ultrasonography-guided biliary drainage for malignant duodenal obstruction with biliary stricture. Dig Endosc. 2010;22(3):236-40.
  176. 176. Siddiqui AA, Sreenarasimhaiah J, Lara LF, Harford W, Lee C, Eloubeidi MA. Endoscopic ultrasound-guided transduodenal placement of a fully covered metal stent for palliative biliary drainage in patients with malignant biliary obstruction. Surg Endosc. 2011;25(2):549-55.
  177. 177. Belletrutti PJ, DiMaio CJ, Gerdes H, Schattner MA. Endoscopic ultrasound guided biliary drainage in patients with unapproachable ampullae due to malignant duodenal obstruction. J Gastrointest Cancer. 2011;42(3):137-42.
  178. 178. Nguyen-Tang T, Binmoeller KF, Sanchez-Yague A, Shah JN. Endoscopic ultrasound (EUS)-guided transhepatic anterograde self-expandable metal stent (SEMS) placement across malignant biliary obstruction. Endoscopy. 2010 ;42(3):232-6.
  179. 179. Hanada K, Iiboshi T, Ishii Y. Endoscopic ultrasound-guided choledochoduodenostomy for palliative biliary drainage in cases with inoperable pancreas head carcinoma. Dig Endosc. 2009;21 Suppl 1:S75-8.
  180. 180. Kahaleh M, Hernandez AJ, Tokar J, Adams RB, Shami VM, Yeaton P. Interventional EUS-guided cholangiography: evaluation of a technique in evolution. Gastrointest Endosc 2006; 64: 52-59
  181. 181. Yamao K, Sawaki A, Takahashi K, Imaoka H, Ashida R, Mizuno N. EUS-guided choledochoduodenostomy for palliative biliary drainage in case of papillary obstruction: report of 2 cases. Gastrointest Endosc. 2006;64(4):663-7.
  182. 182. Püspök A, Lomoschitz F, Dejaco C, Hejna M, Sautner T, Gangl A. Endoscopic ultrasound guided therapy of benign and malignant biliary obstruction: a case series. Am J Gastroenterol. 2005;100(8):1743-7
  183. 183. Mallery S, Matlock J, Freeman ML EUS-guided rendezvous drainage of obstructed biliary and pancreatic ducts: Report of 6 cases. Gastrointest Endosc. 2004; 59(1):100-7
  184. 184. Steinberg WM, Barkin JS, Bradley EL 3rd, DiMagno E, Layer P, Canto MI, Levy MJ. Should patients with a strong family history of pancreatic cancer be screened on a periodic basis for cancer of the pancreas? Pancreas. 2009; 38(5):e137-50
  185. 185. Vasen HF, Wasser M, van Mil A, Tollenaar RA, Konstantinovski M, Gruis NA, Bergman W, Hes FJ, Hommes DW, Offerhaus GJ, Morreau H, Bonsing BA, de Vos tot Nederveen Cappel WH. Magnetic resonance imaging surveillance detects early-stage pancreatic cancer in carriers of a p16-Leiden mutation. Gastroenterology. 2011;140(3):850–6.
  186. 186. Poley JW, Kluijt I, Gouma DJ, Harinck F, Wagner A, Aalfs C, van Eijck CH, Cats A, Kuipers EJ, Nio Y, Fockens P, Bruno MJ. The yield of first-time endoscopic ultrasonography in screening individuals at a high risk of developing pancreatic cancer.Am J Gastroenterol. 2009; 104(9):2175-81.
  187. 187. Canto MI, Hruban RH, Fishman EK, Kamel IR, Schulick R, Zhang Z, Topazian M, Takahashi N, Fletcher J, Petersen G, Klein AP, Axilbund J, Griffin C, Syngal S, Saltzman JR, Mortele KJ, Lee J, Tamm E, Vikram R, Bhosale P, Margolis D, Farrell J, Goggins M; American Cancer of the Pancreas Screening (CAPS) Consortium. Frequent detection of pancreatic lesions in asymptomatic high-risk individuals. Gastroenterology. 2012 ;142(4):796-804; quiz e14-5.
  188. 188. Zubarik R, Gordon SR, Lidofsky SD, Anderson SR, Pipas JM, Badger G, Ganguly E, Vecchio J. Screening for pancreatic cancer in a high-risk population with serum CA 19-9 and targeted EUS: a feasibility study. Gastrointest Endosc. 2011;74(1):87-95.
  189. 189. Langer P, Kann PH, Fendrich V, Habbe N, Schneider M, Sina M, Slater EP, Heverhagen JT, Gress TM, Rothmund M, Bartsch DK. Five years of prospective screening of high-risk individuals from families with familial pancreatic cancer. Gut. 2009;58(10):1410-8.
  190. 190. Canto MI, Harinck F, Hruban RH, Offerhaus GJ, Poley JW, Kamel I, Nio Y, Schulick RS, Bassi C, Kluijt I, Levy MJ, Chak A, Fockens P, Goggins M, Bruno M; International Cancerof Pancreas Screening (CAPS) Consortium. International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer. Gut. 2013;62(3):339-47.

Written By

Andrada Seicean

Submitted: September 19th, 2013 Reviewed: October 1st, 2013 Published: May 14th, 2014