Gastroenterology and pancreaticadenocarcinoma: what the radiologistneeds to know

Abhik Bhattacharya,1 Namita S. Gandhi,2 Mark E. Baker,2 Prabhleen Chahal1

1Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA2Imaging Institute, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195, USA

Abstract

In this article, we review the information that radiolo-gists need to know regarding the endoscopic approach tothe diagnosis and management of pancreatic cancer. Thisincludes a review of the indications, techniques, andcomplications of endoscopic ultrasound. We also reviewinformation regarding endoscopic retrograde cholan-giopancreatography, including the various biliary drai-nage techniques and the use of endoscopic palliation forpatients with pancreatic cancer.

Key words: Pancreatic cancer—Endoscopicultrasound—ERCP—PostoperativeERCP—Postoperative EUS

Pancreatic ductal adenocarcinoma (PDAC) is the thirdleading cause of cancer-related deaths in the UnitedStates. This disease has a poor prognosis, with 5-yearsurvival rates of 31.5% for patients with localized cancer,2.7% for patients with distant disease spread, and 8.2%overall. Approximately 50% of patients with pancreaticcancer have metastatic disease at presentation; only 15%to 20% are candidates for surgery; the remaining patientshave locally advanced disease [1].The only potentialcurative option is surgical resection, which is not possiblefor most patients because of this late presentation. Manypatients undergo neoadjuvant chemotherapy if the dis-ease is borderline resectable. Treatment in most patientsis aimed at prolonging survival and improving quality oflife.

Although the staging of pancreatic cancer is primarilybased on computed tomography (CT) studies, otherexaminations performed by gastroenterologists may in-

clude endoscopic ultrasound (EUS) for tumor identifi-cation and fine-needle aspiration (FNA) cytology fordisease confirmation, as well as therapeutic endoscopicretrograde cholangiopancreatography (ERCP). Addi-tionally, several other gastroenterologist-directed endo-scopic therapeutic interventions may be used in themanagement of PDAC. The purpose of this review is tofamiliarize radiologists with these examinations and thegastroenterologists’ perspective of this disease.

Endoscopic techniques

Endoscopic ultrasound with fine-needleaspiration

EUS plays an integral role in the diagnosis of pancreaticcancer given its high sensitivity for detecting pancreaticneoplasms and its ability to provide access for FNA ofthe pancreatic mass. The sensitivity, specificity, positivepredictive value, and accuracy of EUS-FNA for thediagnosis of PDAC are 97.3%, 99.3%, 99.8%, and 97.8%,respectively [2, 3]. In fact, EUS-FNA has almost com-pletely replaced transcutaneous, image-guided biopsy fortissue diagnosis. EUS is particularly helpful in identify-ing the tumor when a mass is suspected because of biliaryand/or pancreatic ductal obstruction, but no mass hasbeen identified on either CT or magnetic resonanceimaging (MRI) (approximately 10% of cases); this isespecially common for masses smaller than 20 mm [4–6].EUS can also be used along with magnetic resonancecholangiopancreatography (MRCP) to screen high-riskpatients for pancreatic cancer [7]. Studies have alsoshown that normal EUS results have a high negativepredictive value for ruling out PDAC in lesions that wereindeterminate on cross-sectional imaging (CT/MRI) [8,9]. Factors that can lead to false negative EUS resultsinclude chronic pancreatitis, diffusely infiltrating carci-noma, a prominent ventral/dorsal split, a recent episode

Correspondence to: Namita S. Gandhi; email: gandhin@ccf.org

ª Springer Science+Business Media, LLC 2017

AbdominalRadiology

Abdom Radiol (2017)

DOI: 10.1007/s00261-017-1347-5

(< 4 weeks) of acute pancreatitis, and the presence of abiliary stent [10].

EUS technique

EUS uses a 5- to 10-MHz frequency ultrasonographyprobe with an inflatable water balloon as an acousticwindow to assess surrounding structures. There are twotypes of EUS probes: radial and linear (Fig. 1). The ra-dial echoendoscope does not have a working channel forFNA and is used mostly for luminal cancer staging.Linear echoendoscope, on the other hand, can onlyvisualize a small part of one wall of the lumen, butprovides a working channel for FNA or for a fine-needlebiopsy (FNB) needle to pass through. This type of probeis most commonly used for pancreatic mass diagnosis.

EUS-guided FNA

FNA is obtained via a transgastric (body and/or tailmass) or a transduodenal (head and/or uncinate mass)approach. Before the biopsy, the surrounding vascularstructures are identified using doppler ultrasound tominimize the risk of bleeding. On EUS, pancreatic cancerusually appears as a hypoechoic mass with irregularborders (Figs. 2, 3).

Tissue diagnosis is especially important in these pa-tients because many benign lesions such as focal autoim-mune pancreatitis, chronic pancreatitis with inflammatorypseudotumor, and severe acute pancreatitis can causejaundice and weight loss and appear similar to PDAC oncross-sectional imaging. Up to 15% of resections of sus-pected PDAC are diagnosed as benign tissue after surgery,with 40% of these cases identified as autoimmune pan-creatitis (Figs. 4, 5). EUS with FNA cytology or FNB can

Fig. 1. A, B Illustration of radial echoendoscope withoutworking channel. C, D Linear echoendoscope with workingchannel.

Fig. 2. A, B Images from a linear EUS showing hypoechoicpancreatic head mass (cursors). C Image of FNA biopsy ofthe mass under ultrasound guidance (arrow at the needle).

A. Bhattacharya et al.: Gastroenterology and pancreatic adenocarcinoma

be used to correct preoperative tissue diagnosis to mini-mize unnecessary surgeries. It can also identify othermalignant lesions such as neuroendocrine tumor, lym-phoma, or metastasis [3, 11, 12] (Fig. 6).

EUS report

The EUS report consists of descriptions of the mass it-self, the lymph nodes, and the relationship between themass and adjacent structures (especially the mesentericvessels). Masses are characterized by echogenicity, size,area of extent in the pancreas (head, body, neck, tail, or acombination), and involvement of surrounding arterialand venous structures, namely the celiac artery, superiormesenteric artery, common hepatic artery, superiormesenteric vein, portal vein, portosplenic confluence, and

splenic vein. Lymph nodes are classified as being eitherpresent or absent (N1/N0) in the peripancreatic, gastro-hepatic, and celiac region. Malignant features of nodesinclude size greater than 1 cm, hypoechoic echogenicity,sharp distinct margins, and round shape. Finally, a TNMscore is given based on these findings. Apart from pro-viding local staging information, EUS also providesinformation about metastasis to the left hepatic lobe,omental metastasis, and presence of ascites [13].

Novel EUS techniques

EUS-elastography is a new method for distinguishingbetween malignant and benign lesions based on differ-ences in the elasticity of the lesions. This techniquemakes use of a sono-elastography module in the EUSand can be used to evaluate both masses and lymphnodes [14–16]. Studies of this method have demonstratedvarying results, but the majority have found that thismethod has good sensitivity for differentiating betweenmalignant and benign lesions [14, 16–18]. Nonetheless,the use of this new technique is limited by its high cost,lack of availability, and lack of expertise among clini-cians.

Contrast-enhanced EUS is another emerging tech-nique which has the potential to differentiate amongdifferent types of pancreatic masses. Pancreatic cancer isusually hypoenhancing, whereas benign lesions such asthose seen with chronic pancreatitis and autoimmunepancreatitis are more likely to demonstrate enhancementsimilar to that seen in the rest of the pancreatic par-enchyma [19]. Studies combining elastography withcontrast-enhanced EUS have demonstrated higher sen-sitivity and specificity for differentiating between benignand malignant lesions [19, 20]. Again, however, contrast-enhanced EUS is limited by its high cost, lack of avail-ability, and lack of expertise among practitioners.

EUS vs. CT/MRI in determining resectability

Surgical resectability is one of the most importantdeterminants of disease management in patients withPDAC. EUS is equivalent to multidetector CT (MDCT)for determining the surgical resectability of PDAC;hence, it is useful to combine cross-sectional imaging (CTor MRI) with EUS to determine surgical resectabilityand to stage the tumor [4, 5, 20–22]. EUS can also beused to sample metastasis to the liver, peritoneum, ordistant lymph nodes in addition to primary tissue [23,24].

Complications of EUS and EUS-guided biopsy

Complications associated with EUS are very rare andcan be related to the procedure itself or to the sedationrequired for the procedure. Anesthesia-related compli-

Fig. 3. A 76-year-old man presented with jaundice andpancreatic and common bile duct (CBD) dilation, but no focalmass was seen on CT. A Images obtained via EUS show ahypoechoic mass with irregular borders and CBD dilation.B Image of FNA biopsy of the mass under ultrasound guid-ance (arrow at the needle).

A. Bhattacharya et al.: Gastroenterology and pancreatic adenocarcinoma

cations are similar to those seen with any other proce-dure requiring monitored anesthesia care and includeallergic reactions such as anaphylaxis and aspirationpneumonia. The most common procedure-related com-plications are pancreatitis of varying severity (0.4%) andpostprocedural pain (0.3%). Other rare complicationsinclude major bleeding (0.001%), fever (0.001%), infec-tions (0.0004%), perforation (0.0001%), and bile leakage(0.0001%) [25].

Endoscopic retrogradecholangiopancreatography

The role of ERCP in patients with pancreatic cancer ismainly therapeutic. This procedure is the first line forproviding biliary decompression either to facilitateneoadjuvant chemotherapy or to offer palliation andsymptom control. ERCP has lower morbidity, lowercost, and a shorter recovery period when compared tosurgery or percutaneous transhepatic biliary drainage(PTBD). It offers an 80% to 95% short-term (< 90-day)success rate in the setting of distal bile duct obstructions,with a 5% to 10% risk of complications [26].

Types of biliary stents

The two main types of stents used in ERCP are plasticstents (PS) and self-expanding metal stents (SEMS),which include covered (CSEMS), partially covered(PSEMS), and uncovered (USEMS) types. Each of thesestent types has its own utility.

Plastic stents are made of polyethylene or poly-urethane. They are the least expensive and can be easilyremoved endoscopically when necessary. The mostcommonly used plastic stent is typically 10 Fr; othertypes are either too small (7 or 8.5 Fr) or provide noadded advantage in terms of relieving obstruction or easeof deployment [27, 28]. Plastic stents are susceptible tobacterial translocation into the stent; the bacteria canform a biofilm over the stent, making the bile more vis-cous and forming sludge particles. This can lead to earlystent occlusion, which (along with the smaller diameterof these stents) limits the median patency rates to around3 months [29]. Plastic stents also have higher rates ofstent migration compared to metallic stents. Plasticstents are generally used in patients who are potential

Fig. 4. A Axial contrast-enhanced CT image shows biliarydilation (arrow). B Axial contrast-enhanced CT image showsthat the pancreatic head is ‘‘mass-like’’ (circle). C EUS imageshows a hypoechoic mass in the pancreatic head (arrows).FNA biopsy of the mass was performed. Pathology con-firmed autoimmune pancreatitis.

b

A. Bhattacharya et al.: Gastroenterology and pancreatic adenocarcinoma

candidates for surgery that is expected to occur within3 months.

SEMS are mesh-like metallic interlaced prostheseswith diameters ranging from 6 to 10 mm. These stents areeasier to deploy owing to their smaller size beforedeployment, but they expand once deployed, providingwider diameters and better biliary drainage. A Cochranereview of biliary stenting demonstrated longer patency,fewer complications, and lower re-intervention rates forSEMS when compared to plastic stents [30–32]. Hence,SEMS are becoming the preferred choice for biliarydrainage, even for preoperative cases. Although the initialcost for plastic stents is significantly lower than the costfor SEMS, the yearly cost is approximately equal becauseof the need for frequent exchanges with plastic stents [33].

USEMS are usually tethered by the biliary epithe-lium, especially where it impinges on the malignantstricture; hence, these stents are harder to remove. Tissuediagnosis is therefore critical before a USEMS is de-ployed. CSEMS have longer patency than USEMS, but

CSEMS are also more expensive [34–36]. The compli-cations associated with SEMS include stent migration,perforation, pancreatitis, cholangitis, and bleeding.Studies have shown variable results regarding the rates ofthese complications (especially stent migration), with noconclusive findings regarding which stents are moreprone to complications [34–36]. The major reasons forstent failure include tumor in-growth through USEMS(i.e., tumor extending through the meshes of the metallicstent into the lumen and occluding it), tumor overgrowth(i.e., tumor growing over the edges of the stent andblocking the lumen), and blockage from food debris(which is why patients are advised to follow a low-residuediet) [34–36].

If ERCP fails to provide adequate biliary drainage, apercutaneous transhepatic biliary drainage (PTBD)procedure is performed. This procedure has good clinicalsuccess and is efficacious in many patients, especiallywhen the catheter is positioned in the duodenum forinternal drainage. At certain centers with experiencedendosonographers, EUS-guided biliary drainage tech-

Fig. 6. A Axial T2-weighted MR image shows a T2 hyper-intense mass in the pancreatic head (arrows). B EUS imageshows a small hypoechoic pancreatic head mass (circle).FNA cytology confirmed neuroendocrine tumor.

Fig. 5. A Axial contrast-enhanced CT image shows mass-like enlargement of the pancreatic head (arrows) with calcifi-cations suggestive of chronic pancreatitis. B EUS imageshows typical features of chronic pancreatitis including calci-fications, hyperechoic strands, hyperechoic foci, and cysts.Biopsy confirmed chronic pancreatitis.

A. Bhattacharya et al.: Gastroenterology and pancreatic adenocarcinoma

Fig. 7. A 56-year-old patient with metastatic pancreaticcancer and gastric outlet obstruction from duodenal invasionpresented with obstructive jaundice. A Linear array echoen-doscope image shows a dilated CBD being accessed by a 19G needle. B Fluoroscopic image after contrast administration

shows a distal CBD stenosis. C Fluoroscopic image showsguidewire traversing the site of stenosis. D, E Endoscopic andfluoroscopic image of a self-expanding metal stent placed intothe dilated CBD.

A. Bhattacharya et al.: Gastroenterology and pancreatic adenocarcinoma

niques such as choledochoduodenostomy (Fig. 7), hep-aticogastrotomy, and ‘‘rendezvous procedures’’ havebeen shown to be as effective as PTBD with lower costs[37–39]. However, the use of these techniques is limitedby a lack of expertise at most centers because of the longtime period needed for training.

Endoscopic palliation in pancreaticcancer

Gastroduodenal stenting

PDAC can cause gastric outlet obstruction due to masseffect and/or invasion of the duodenum. This occurs in10% to 25% of patients with PDAC and is a cause ofsignificant morbidity [40]. Clinical signs usually includepostprandial nausea, emesis, abdominal pain, early sati-ety, and significant nutritional decline preventing patientsfrom receiving chemotherapy. These patients can undergoa traditional bypass surgery or endoscopic placement ofduodenal SEMS that can traverse the obstruction andprovide relief. Because many patients with PDAC are toodebilitated to undergo surgery, enteral SEMS placementhas emerged as the treatment of choice. Studies compar-ing SEMS placement vs. gastrojejunostomy have shownfewer short-term complications, lower cost, shorter hos-pital stay, and no difference in quality of life or mortalitywith SEMS placement [40, 41]. However, if the patient isexpected to survive for more than 2 years, gastrojejunos-tomy is the better option owing to the better long-termresults seen with this procedure [42].

Enteral SEMS failure most commonly occurs sec-ondary to obstruction by food debris. This complicationcan be minimized if patients follow a liquid and low-residue diet. SEMS can also become obstructed fromtumor overgrowth or ingrowth, which can potentially betreated with a second stent. Complications of enteralSEMS placement include bleeding, perforation, pain,and stent migration. Delayed complications include fis-tula formation and biliary obstruction [26, 40]. Whenplacing SEMS, clinicians must try to spare the papilla sothat ERCP can be performed in the future. If it is notpossible to place enteral SEMS proximal to the papilla,future ERCP becomes very difficult because of the al-tered anatomy of the papilla [37].

Recently, EUS-guided gastrojejunostomy via place-ment of a lumen-apposing metal stent has gained trac-tion, with early studies demonstrating comparablesuccess in palliating gastric outlet obstruction with fewerre-interventions needed when compared to enteral SEMSplacement [43, 44].

Celiac plexus block/neurolysis

Pancreatic cancer can cause significant pain irrespectiveof stage. This pain can be intractable and may fail torespond to all types of medical therapy. In such cases,

EUS-guided injection of a local anesthetic such as 0.25%bupivacaine or absolute (reconstituted 98% dehydrated)ethanol into the celiac plexus/ganglion can providemoderate to significant pain relief. Celiac plexus neu-rolysis involves injection of absolute alcohol into theganglion causing destruction of the ganglion(s) andassociated pain neural pathways. This provides longerlasting palliation of pain and is preferred in most patientswith PDAC. Celiac plexus block involves injection oflocal anesthetic into the ganglion, which causes a tem-porary relief of pain. This is used more commonly forbenign conditions like pain from chronic pancreatitis[45].

EUS-guided (anterior approach) block or neurolysishas the advantage of using real time sonographic guid-ance during the procedure, which can help in precisetargeting of single or multiple ganglia using small gauge(25, 22G) needles. Use of doppler imaging during theprocedure minimizes the risk of inadvertent vascularinjection of these anesthetic agents.

Postoperative endoscopyfor pancreatic cancer

Post Whipple’s procedure

The most commonly performed surgery in patients withpancreatic cancer is Whipple’s procedure (pancreatico-duodenectomy). This surgery involves removal of thepancreas head/neck, duodenum, 20 cm of proximal je-junum, gallbladder (if present), distal common bile duct,and regional lymph nodes. In pylorus-preserving pan-creaticoduodenectomy (modified Whipple’s procedure),the entire stomach is retained; this procedure is per-formed to preserve normal gastric emptying. In bothtypes of surgeries, the stomach/gastric remnant leads intotwo limbs. The afferent limb travels superiorly, endsblindly at approximately 40–60 cm, and contains pan-creaticobiliary anastomoses. The pancreas is attached inan end-to-end or end-to-side manner to the afferent limb;the bile duct is attached in an end-to-side fashionapproximately 10 cm proximal to the end of the afferentlimb. The efferent limb maintains continuity with the restof the gastrointestinal tract.

Endoscopy is most commonly used in these patientsto manage postoperative stricture or stones. CT orMRCP is performed first to assess the anatomy and todetermine whether endoscopy is necessary. Radiologistsshould be familiar with the imaging appearance of thesepostoperative cases and should provide a report regard-ing this postoperative anatomic information to help withendoscopy procedures. In patients who have undergone aconventional Whipple’s procedure, it is usually easier toreach the afferent limb where the choledochojejunostomyis located. The pancreatico-enteric anastomosis is moredifficult to cannulate because of the difficulty in locatingit within the afferent limb, especially when a side viewing

A. Bhattacharya et al.: Gastroenterology and pancreatic adenocarcinoma

scope is used [46]. A pylorus-preserving Whipple’s pro-cedure presents a more challenging anatomy for endo-scopy because of the longer distance that the scope musttravel and the sharp angulations of the afferent limbtakeoff.

When the opening of the bile duct cannot be assessedwith endoscopy, a combined interventional radiologyand ERCP procedure can sometimes be performed; thisis known as a ‘‘rendezvous’’ procedure. In this proce-dure, a percutaneous approach is used to access the bileduct with a guidewire. The guidewire is then identified bythe endoscope visually in the lumen and used for place-ment of a stent into the bile duct. Certain centers havealso used this combined approach for pancreatico-entericstrictures [47]. Detailed CT/MRI studies assessing thepostoperative anatomy are needed before a combinedprocedure is performed [48].

Alternatively, a combined EUS/ERCP procedure canbe used when the pancreatic-enteric anastomosis is dif-ficult to visualize. In this procedure, an FNA needle isplaced (using ultrasound guidance) into the pancreaticduct through the stomach wall; a guidewire is then ad-vanced through the FNA needle into the duct. Finally, a‘‘rendezvous’’ ERCP is carried out for pancreatic inter-vention. Complications of the procedures describedabove include pancreatitis, bleeding, stent dislocation,perforation, pseudocyst formation, and transient fever[49].

During Whipple’s surgery, a plastic stent is usuallyleft inside the pancreas remnant duct to prevent pan-creatic leak or stricture formation. Such stents usuallydislodge by themselves, but they can remain in the pan-creatic duct for long periods and cause abdominal pain,steatorrhea, and even chronic pancreatitis [50]. Alterna-tively, they may migrate into the biliary tree and causeobstruction. Endoscopy is useful in these scenarios forremoval of such retained/migrated stents [51].

Post distal or central pancreatectomy

In these surgeries, the anatomy of the gastrointestinaltract is not usually significantly altered, and so endo-scopy can be carried out in a standard fashion. Centralpancreatectomy involving removal of the neck and bodyleaves a pancreatic tail remnant, which is usually anas-tomosed to the posterior gastric wall or a short Rouxlimb.

Adverse events with these surgeries most commonlyinclude pancreatic leak that can develop into fistulas,pancreatic fluid collections, and pseudocyst. The Inter-national Study Group on Pancreatic Fistula [52] cate-gorizes postoperative fistulas into grades A, B, and C.Grade A fistulas resolve spontaneously, but Grade B andC fistulas can become clinically significant and requirefurther management. Symptoms include abdominal pain,fever, abscess formation, delayed gastric emptying,

bleeding, sepsis, and wound dehiscence [53]. In thesecases, ERCP-guided transpapillary stent placement canlead to resolution of fistulas [54–56]. Pancreatic fluidcollections resulting from such leaks can be drainedendoscopically via a transgastric approach and place-ment of a transpapillary stent [57, 58].

Conclusion

Gastroenterologists play an essential role in obtaining adiagnosis and performing therapeutic interventions inpatients with PDAC. EUS is very accurate in detectingPDAC and has become the standard of care forobtaining tissue diagnosis to differentiate betweenPDAC and other benign or malignant lesions. Multipleendoscopy-guided therapeutic interventions can be usedfor minimally invasive treatment and palliation in thispatient population.

Compliance with ethical standards

Funding This article was not part of any funded grant.

Conflict of interest None of the authors have any conflict of interestrelated to this article.

Ethical approval This article does not contain any studies with humanparticipants or animals performed by any of the authors.

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