Endoscopic
`Oncology
`
`Gastrointestinal Endoscopy
`and Cancer Management
`
`DOUGLAS 0. FAIGEL, MD, FACG, FASGE
`
`MICHAEL L. KOCHMAN, MD, FACP, FASGE
`
`31% HUMANA PRESS
`
`NOVARTIS EXHIBIT 2007
`Roxane v. Novartis, IPR 2016-01461
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`

`
`ENDOSCOPIC ONCOLOGY
`Gastrointestinal Endoscopy
`and Cancer Management
`
`Edited by
`DOUGLAS O. FAIGEL, MD, FACG, FASGE
`Associate Professor of Medicine, Director of Endoscopy
`Oregon Health and Science University, Portland, OR
`MICHAEL L. KOCHMAN, MD, FACP, FASGE
`Professor of Medicine and Surgery, Co-Director Gastrointestinal Oncology,
`Hospital of the University of Pennsylvania, Philadelphia, PA
`
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`© 2006 Humana Press Inc.
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`accepted practices. The contributors herein have carefully checked to ensure that the drug selections and dosages set forth in this text are accurate and in accord
`with the standards accepted at the time of publication. Notwithstanding, as new research, changes in government regulations, and knowledge from clinical
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`Production Editor: Melissa Caravella
`Cover design by Patricia F. Cleary
`Cover illustration: From Fig. 5B in Chapter 3, "Image Enhancement Endoscopy," by Stephan M. Wildi and Michael B. Wallace;Fig. 2 in Chapter 13, "Diagnosis
`and Management of Gastrointestinal Lymphoma," by John G. Kuldau, Peter R. Holman, and Thomas J. Savides; and Fig. 1A in Chapter 15, "Carcinoid Tumors,"
`by Willscott E. Naugler and Gordon C. Hunt.
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`Printed in the United States of America. 10 9 8 7 6 5 4 3 2 1
`eISBN 1-59745-172-X
`Library of Congress Cataloging-in-Publication Data
`
`Endoscopic oncology : gastrointestinal endoscopy and cancer management / edited by Douglas O. Faigel, Michael L. Kochman.
` p. ; cm.
` Includes bibliographical references and index.
` ISBN 1-58829-532-X (alk. paper)
` 1. Endoscopy. 2. Gastrointestinal system--Cancer--Endoscopic surgery. 3. Gastrointestinal system--Diseases--Diagnosis.
` [DNLM: 1. Neoplasms--therapy. 2. Endoscopy, Gastrointestinal--methods. QZ 268 E556 2006] I. Faigel, Douglas O. II. Kochman, Michael L.
` RC804.E6E53 2006
` 616.99'407545--dc22
` 2005036564
`
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`25 Diagnosis and Evaluation of Pancreatic
`Ductal Adenocarcinoma
`
`KENNETHH. YU,MDANDNUZHATA. AHMAD,MD
`
`CONTENTS
`INTRODUCTION
`EPIDEMIOLOGY
`PATHOLOGY
`CLINICAL PRESENTATION
`DIAGNOSIS AND STAGING
`TISSUE ACQUISITION
`RECOMMENDATIONS
`CONCLUSION
`REFERENCES
`
`1. INTRODUCTION
`Pancreatic cancer is the fourth most common cause of cancer-
`related mortality in the United States (1). The 5-yr survival
`rate is the lowest among all cancers, with estimates ranging
`from 0.4 to 4%. The only potentially curative treatment for
`pancreatic cancer is surgical resection. However, because the
`disease is generally advanced at presentation, only 10–20% of
`patients are eligible for attempted curative resection. In these
`patients who undergo pancreaticoduodenectomy, 5-yr survival
`is somewhat better, about 20% (2). The epidemiology and clin-
`ical features of pancreatic cancer will be reviewed. A careful
`examination of current imaging technology in the staging,
`diagnosis, and evaluation of pancreatic adenocarcinoma will
`also be discussed.
`2. EPIDEMIOLOGY
`In 2003, an estimated 30,700 new cases of pancreatic can-
`cer were diagnosed, and an estimated 30,000 patients died as a
`result of their disease (3). Because of the aggressiveness of
`this cancer, the inability to diagnose it early, and the current
`lack of effective outcome altering therapies for advanced stage
`disease, mortality rates from pancreatic cancer are almost iden-
`tical to incidence rates.
`Age is clearly one risk factor for pancreatic cancer.
`Pancreatic cancer is rare before the age of 45 with the inci-
`dence rising sharply thereafter, and peaks with a 40-fold
`increased risk by the age of 80 (4). Patients with chronic pan-
`creatitis are at increased risk for developing pancreatic cancer.
`
`From: Endoscopic Oncology: Gastrointestinal Endoscopy and Cancer
`Management. Edited by: D. O. Faigel and M. L. Kochman © Humana
`Press, Totowa, NJ
`
`The most consistently attributable environmental risk factor
`for the development of pancreatic cancer is cigarette smoking.
`By one estimate, cigarette smoking is thought to account for
`25–29% of pancreatic cancer cases. It has been theorized that
`the aromatic amines present in cigarettes are responsible for
`this increased risk. With much the same chemistry, occupa-
`tional exposure to aromatic amines, for example, in chemists
`or petrochemical workers, may increase the risk of developing
`pancreatic cancer. Some plant components may inhibit the
`mutagenic effects of these amines, which could explain find-
`ings that diets high in fruits and vegetables may protect against
`development of pancreatic cancer (5).
`Genetic factors may also increase the risk of developing
`pancreatic cancer. Numerous genetic syndromes confer a
`higher relative risk of developing pancreatic cancer, including
`hereditary pancreatitis (cationic trypsinogen gene mutation),
`hereditary nonpolyposis colorectal cancer, ataxia-telangiectasia,
`Peutz-Jeghers syndrome, familial breast cancer, and familial
`atypical multiple mole melanoma (FAMMM) (6).
`
`3. PATHOLOGY
`Ductal adenocarcinomas and its variants make up more than
`90% of all malignant pancreatic exocrine tumors. The remain-
`ing 5–10% are mainly islet cell tumors. Other relatively
`uncommon tumors found in the pancreas include lymphoma,
`carcinoma metastatic from other organs, and cystic tumors.
`About 70% of ductal adenocarcinomas occur in the pancreatic
`head; the rest occur in the body or tail, or diffusely throughout
`the pancreas. Research into the molecular genetics of pancre-
`atic cancer has resulted in a better understanding of how these
`tumors occur. Pancreatic adenocarcinoma is believed to be
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`derived from pancreatic-ductular cells. One of the earliest
`genetic changes to occur is an activating mutation in the K-ras
`gene, found in virtually all pancreatic adenocarcinomas.
`Unfortunately, mutations in K-ras are not found exclusively in
`pancreatic cancers, having been discovered in the setting of
`benign pancreatic conditions and even in normal pancreas (7).
`As lesions progress, other gene mutations commonly occur.
`One frequently altered gene is the tumor-suppressor CDKN2A.
`Inactivation of this gene is seen in 80–95% of pancreatic ade-
`nocarcinomas. Notably, some kindreds with FAMMM syn-
`drome are associated with a germline mutation in CDKN2A,
`which confers a 13-fold increased risk of pancreatic cancer.
`Other important mutations commonly found in pancreatic can-
`cers include inactivation of the p53 tumor-suppressor gene and
`loss of the transcriptional regulator SMAD4. As our under-
`standing of the molecular biology of pancreatic cancer
`improves, we may be able to develop better tumor markers and
`treatments.
`
`4. CLINICAL PRESENTATION
`Patients with pancreatic cancer commonly present with
`complaints of pain, weight loss, or jaundice. Symptoms at
`presentation can vary depending on the location and stage of
`the tumor. For tumors located in the head and body of the pan-
`creas, symptoms are generally secondary to compression of
`surrounding structures; the bile duct, the pancreatic duct, duo-
`denum, and/or celiac nerves. These symptoms usually bring
`the patient to medical attention. A small tumor in the head of
`the pancreas can produce symptoms of painless jaundice,
`resulting in an early diagnosis (8). Tumors in the tail or body
`of the pancreas may cause pain and weight loss related to a
`large lesion with extension of the primary tumor. These tumors
`are usually more advanced at the time of diagnosis. Pain may
`be an indication of more advanced disease, and is seen in 80%
`of patients with locally unresectable disease, and in 85% of
`patients with advanced cancer (9).
`Other signs associated with pancreatic cancer include new-
`onset diabetes mellitus, malabsorption, pancreatitis, or migra-
`tory thrombophlebitis (Trousseau’s syndrome). On physical
`exam, one might find an abdominal mass or ascites at presen-
`tation in a patient with pancreatic cancer. Other findings may
`include a palpable nontender gallbladder (Courvoisier’s sign),
`often seen in patients with jaundice. In patients with wide-
`spread disease,
`left supraclavicular
`lymphadenopathy
`(Virchow’s node) or a palpable rectal shelf metastasis may be
`demonstrated.
`
`5. DIAGNOSIS AND STAGING
`The two main issues in a patient with suspected pancreatic
`cancer are to establish the diagnosis and to determine whether
`the patient is a candidate for surgical resection. If the patient is
`deemed a surgical candidate, histological proof of malignancy
`is usually not required. However, in patients with unresectable
`disease (i.e., distant metastases or major vessel involvement on
`radiographic studies) or who are not operative candidates owing
`to comorbidities, a histological diagnosis is usually required
`before proceeding with any nonsurgical palliative therapy.
`
`The tumor-node-metastasis (TNM) staging criteria for pan-
`creatic cancer as defined by the American Joint Committee on
`Cancer (AJCC) was recently updated (10). In 2002, the AJCC
`modified the tumor (T) staging system for pancreatic cancer to
`classify tumors invading the portal venous (superior mesenteric
`vein or portal vein) system as T3 (these were previously staged
`as T4) and tumors invading the celiac or superior mesenteric
`artery as T4. Based on pre-operative assessment, a resectable
`pancreatic cancer cannot involve the celiac axis or superior
`mesenteric artery. Involvement of the superior mesenteric vein
`or the portal venous confluence does not necessarily preclude
`resectability. Direct invasion of contiguous structures, such as
`bowel, spleen, kidney, or spine, and distant metastatic disease
`can preclude resectability.
`A variety of studies are available for the diagnosis and stag-
`ing of pancreatic cancer. High sensitivity and specificity are not
`the only important factors when assessing tools for preopera-
`tive staging. The ideal tools would be minimally invasive, safe,
`capable of obtaining tissue samples if needed, cost-effective,
`and widely available. Advances in technology have made avail-
`able a wide range of imaging tools, such as helical computed
`tomography (hCT), magnetic resonance imaging (MRI), endo-
`scopic ultrasound (EUS), endoscopic retrograde cholangiopan-
`creatography (ERCP), and angiography. No consensus exists as
`to the best algorithm to use for staging and determining
`resectability. The strengths and weaknesses of these technique,
`and strategies for combining these techniques will be discussed.
`5.1. TUMOR MARKERS
`Several tumor markers for pancreatic cancer have been eval-
`uated, but none has been shown to be particularly sensitive or
`specific in the diagnosis of pancreatic cancer. The most widely
`used tumor marker, cancer-associated antigen 19-9 (CA 19-9),
`has been found to have a sensitivity of 70–86% and a speci-
`ficity of 87%, depending on the cutoff used (11–13). CA 19-9
`levels, however, may also be elevated in patients with biliary
`obstruction caused by lesions other than pancreatic cancer.
`One study demonstrated that serum concentrations above
`37 U/mL had a sensitivity and specificity of 77 and 87%,
`respectively, for discriminating pancreatic cancer from benign
`pancreatic disease (14). Although not useful as a diagnostic
`tool, serial CA 19-9 levels can be a useful way to monitor
`estimating response to therapy or disease progression.
`Islet amyloid polypeptide (IAPP) is a candidate biomarker
`that has been shown to be elevated in the plasma of patients
`with pancreatic cancer, particularly those with concurrent dia-
`betes (15). IAPP appears to be secreted by pancreatic β-cells,
`and is associated with reduced insulin sensitivity. Recent stud-
`ies, however, have shown IAPP to be an ineffective tumor
`marker. A recent study evaluated plasma IAPP levels in patients
`with pancreatic cancer compared with normal controls and
`patients with other pancreatic disease (16). IAPP levels were
`elevated in pancreatic cancer patients, but overall IAPP was
`less sensitive than CA 19-9 (40 vs 75%) in diagnosing pancre-
`atic cancer. In the patients enrolled in this study who had con-
`current diabetes (46%), the sensitivity of IAPP was only 50%.
`As previously discussed, activating K-ras mutations can be
`found in virtually all pancreatic cancers. Preliminary studies
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`
`have demonstrated that K-ras mutations can be detected in
`plasma (17), in pancreatic juice obtained by ERCP (18), in
`duodenal juice obtained with secretin stimulation (19) and in
`stool (20). Sensitivity is low with current techniques, and the
`implication of K-ras mutations in patients without overt pan-
`creatic cancer is unknown.
`5.2. HELICAL CT
`CT of the abdomen should typically be the first diagnostic
`procedure performed when a pancreatic tumor is suspected. CT
`is useful in detecting pancreatic tumors, in assessing resectabil-
`ity and detecting distant metastases. Historically, sensitivity of
`conventional CT for detecting small pancreatic tumors (<3 cm)
`was as low as 53% (21). With the advent of dual-phase hCT,
`this technique has proven to be far more accurate at identifying
`pancreatic masses and determining resectability.
`In a prospective trial of 76 patients with suspected pancre-
`atic cancer, in whom dual-phase hCT scan alone was used for
`evaluation and staging (22), the positive predictive value of CT
`for resectability was determined to be 73.5%, and overall accu-
`racy was determined to be 77%. Nine patients determined to be
`resectable by CT were found to actually be unresectable
`because of liver metastases, vascular encasement, or lymph
`node metastases. Liver metastases not seen by CT were found
`at time of surgery in 20.5% of the patients. CT accurately iden-
`tified lymph node metastases in only 16.7% of patients.
`In general, positive predictive values of hCT scan for surgi-
`cal unresectability have been excellent, ranging from 89 to
`95% (23–26). Among patients with tumors judged potentially
`resectable on the basis of CT criteria, however, surgical results
`demonstrate that 60–91% of the tumors are resectable. The
`nonresectable patients had locally advanced tumors, lymph
`node metastases, or small peritoneal, omental, or hepatic
`metastases not identified by the pre-operative CT (27–29). In
`particular, CT is not reliable in predicting nodal involvement
`in pancreatic cancer, and suspicious peripancreatic nodes on
`CT should not discourage resection (30).
`One of the most common causes of unresectability not
`detected by CT is vascular involvement by tumor. The sensitivi-
`ties for vascular invasion are reported to be between 60 and 89%
`for hCT (27,28). A relatively new CT technology (hCT or multi-
`detector CT [MDCT]) may improve detection of tumor infil-
`tration of vascular structures. It will be interesting to see what
`impact multidetector CT has on improving resectability of
`pancreatic cancer.
`5.3. ENDOSCOPIC ULTRASOUND
`EUS is an imaging technique that combines endoscopy and
`ultrasonography. An ultrasound transducer is mounted on the tip
`of the endoscope, allowing accurate imaging of lesions located
`within and adjacent to the gastrointestinal wall. EUS is used
`routinely in the evaluation of numerous gastrointestinal dis-
`orders, including the diagnosis and staging of gastrointestinal
`tumors. During the last 10 yr, its applications have become more
`established, mainly because of improvements in the technology
`of endoscopes (e.g., video chip rather than fiberoptic) and ultra-
`sound transducers. The applications of EUS have also expanded
`to include EUS-guided fine-needle aspiration (FNA) of lesions
`located within and outside the gastrointestinal wall.
`
`The close proximity of the stomach and duodenum to the
`pancreas allows endosonography to provide high-resolution
`images of the pancreas and associated retroperitoneal vascular
`structures. The high resolution of EUS is particularly well
`suited to identify focal pancreatic neoplasms. A number of stud-
`ies have evaluated the accuracy of EUS in the diagnosis and
`staging of pancreatic cancer. Direct comparison of these studies
`can be difficult because of differences in the inclusion criteria
`and the gold standard. EUS is very operator-dependent; the
`accuracy of EUS is clearly dependent on the experience of the
`operator. Accuracy is improved when endosonographers have
`performed at least 100 staging examinations (31). Although the
`value of EUS in diagnosis of pancreatic cancer is recognized,
`significant controversy exists as to the exact role and timing of
`EUS in algorithms for staging pancreatic cancer. The role of
`EUS in the diagnosis and staging of pancreatic cancer will be
`reviewed in the following section.
`5.3.1. Diagnosis of Pancreatic Cancer
`There is ample evidence in the literature that EUS is the
`most sensitive method for detection of pancreatic tumors, with
`larger series demonstrating sensitivities in the range of 90%
`(21,32–37) (Fig. 1). When compared with CT scan, MRI,
`ERCP, and transabdominal ultrasound exam, EUS is more sen-
`sitive for detection of pancreatic carcinoma (21,36). This supe-
`riority is particularly evident with respect to lesions smaller
`than 3 cm in diameter (21,35,37–39). More recently, EUS has
`compared favorably with spiral CT for the detection of pancre-
`atic tumors. Legmann and colleagues compared dual-phase
`spiral CT with endosonography in patients with suspected pan-
`creatic tumors and found the two modalities equivalent in yield
`with a diagnostic sensitivity of 100% for EUS and 92% for
`spiral CT (34).
`5.3.2. Staging of Pancreatic Cancer
`Staging of pancreatic cancer is considered one of the most
`difficult aspects of EUS. However, once a mass is identified in
`the pancreas, EUS, by virtue of its ability to determine local
`extension of the tumor and to predict vascular invasion and
`thereby potential resectability, provides useful staging infor-
`mation. In a recent review of EUS in pancreatic cancer (40),
`an analysis of many of the largest series to date demonstrates a
`wide range in accuracy for TNM staging. Accuracy for T stag-
`ing ranged from 78 to 94%, and nodal (N) staging ranged from
`64 to 82%. However, more recent studies have described lower
`accuracy rates. In one series of 89 patients in whom EUS was
`compared with surgical and histopathological TNM staging
`using the 1997 TNM criteria, the overall accuracy of EUS for
`T and N staging was only 69 and 54%, respectively.
`Furthermore, only 46% of tumors that were believed to be
`resectable by EUS were actually found to be resectable during
`laparotomy. Similarly, in another recent retrospective study,
`sensitivity, specificity and accuracy of EUS for determining
`resectability of pancreatic cancer (41) were 66, 100, and 78%,
`respectively. The accuracy of vascular invasion and lymph
`node status were determined to be 85 and 71%, respectively.
`In 5 of the 10 false-negative cases, incorrectly determined by
`EUS to be resectable, the reason was understaged vascular
`invasion.
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`itself for determining resectability (83%), as well as for deter-
`mining surgical stage. An analysis was then performed to deter-
`mine which combination of tests provided the greatest accuracy.
`The analysis determined that combining CT with EUS, in any
`sequence, resulted in the highest accuracy (87%) in predicting
`resectability. A selective strategy was also tested, where CT was
`performed in all patients, and in those patients who were deemed
`resectable, EUS was performed. Accuracy was preserved in this
`study. In a cost minimization analysis, this strategy also proved
`to be favorable, when the cost savings of avoiding unnecessary
`laparotomy were taken into account.
`With the advances in cross-sectional imaging, the role of
`EUS can be more narrowly defined. EUS should be used in
`patients with suspected pancreatic cancer not well defined
`on dual-scan hCT. In patients with tumors felt to be resectable
`by CT, EUS can also be used to confirm this assessment and to
`search for distant lymph node metastases. In patients with
`unresectable tumors, EUS can be used for confirmation, and
`for tissue acquisition via FNA.
`5.4. MAGNETIC RESONANCE IMAGING
`MRI and magnetic resonance cholangiopancreatography
`(MRCP) are imaging technologies that can accurately assess
`pancreatic masses as well as both pancreatic and biliary ductal
`pathology. For routine staging, however, MRI has not been
`shown to be superior to dual-scan hCT. In a prospective trial of
`62 patients who had CT and MRI performed to assess
`resectability of pancreatic cancer (45), MRI was found to be
`inferior to CT regarding all parameters measured. The sensi-
`tivity, specificity, and accuracy of MRI were 57, 90, and 75%,
`respectively, as compared with 67, 97, and 83% for CT.
`Studies have also compared MRI with EUS. In one study,
`63 patients with pancreatic cancer who underwent both EUS
`and MRI were studied retrospectively (46). Results were
`comparable. The sensitivity and positive predictive value of
`EUS for resectability were 61 and 69%, compared with 73 and
`77% for MRI. Both imaging modalities predicted resectability
`in 18 patients, 16 (89%) of whom were found to be resectable
`on surgical exploration. Both imaging modalities predicted
`unresectability in 17 patients, of whom 4 (24%) were found to
`be resectable on surgical exploration. When both imaging
`modalities agreed on the likelihood of resectability or unre-
`sectability, the positive predictive value for resectability was
`89%, and 76% for unresectability. The authors concluded that
`neither modality alone predicted resectability with great accuracy.
`The two studies could be used in combination, as tumors deter-
`mined to be resectable by both modalities almost always were
`resectable on surgical exploration.
`Another study compared the accuracy of EUS, MRI, and CT
`in 49 patients with lesions suspicious for pancreatic cancer (21).
`MRI, compared with EUS, had a lower sensitivity (83 vs 94%),
`equivalent specificity (100% for both), and lower overall accu-
`racy (84 vs 96%). As one would expect, EUS had a high sensi-
`tivity (93%) for detecting tumors less than 3 cm in size. MRI
`had a sensitivity of only 67% for detecting these lesions.
`MRCP can be used to visualize biliary and pancreatic ducts,
`and may be useful in patients where ERCP is unsuccessful or
`nondiagnostic. MRCP was studied in 58 patients with failed or
`
`Fig. 1. Endosonographic image demonstrating a large hypoechoic
`mass in the head of the pancreas in a patient with obstructive jaundice.
`
`These studies (32,42,43) suggest that EUS may be less
`accurate than previously thought at determining local stage
`and resectability. The changes in the new TNM staging system
`are expected to increase T staging accuracy. Several factors
`have been identified that could account for the decreased accu-
`racy of EUS when compared to results from earlier studies
`(41). Selection bias is one important factor. Most patients with
`pancreatic cancer are initially diagnosed by cross-sectional
`imaging. As these imaging techniques, particularly hCT, have
`become increasingly sensitive, patients with clearly resectable
`disease are often taken straight to surgery, and are not referred
`to EUS. Similarly, patients with obvious metastases or clearly
`unresectable disease often are not referred to EUS for further
`work-up. Thus, EUS is often used to image patients who have
`tumors that are difficult to stage accurately by any modality.
`Other possible factors include the small size of earlier studies,
`which included generally fewer than 40 patients, and the
`inconsistent use of surgical staging as a gold standard to judge
`the accuracy of EUS (43,44). In addition, EUS can better
`detect vascular invasion in tumors that are smaller than 3 cm,
`which may be a factor in two studies that found EUS to be
`highly accurate in staging pancreatic cancer (31,44); More than
`half of the patients had early T1 or T2 tumors. In contrast, two
`studies where tumors were predominantly T3 or T4 (41,42), a
`more accurate reflection of clinical practice, EUS results were
`less impressive.
`A recent study investigated the most effective way of combin-
`ing imaging studies in the staging of pancreatic cancer (45). A
`total of 62 patients with suspected pancreatic cancer were evalu-
`ated by EUS, CT, MRI, and angiography. All patients were taken
`to surgery. hCT was the most accurate modality when used by
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`
`inadequate ERCP for the evaluation of suspected pancreatico-
`biliary disease (47). MRCP was technically successful in 57
`patients and resulted in a sensitivity, specificity, and diagnostic
`accuracy of 97, 100, and 98%, respectively. In a second study
`of 124 patients with suspected pancreatic cancer, MRCP had a
`sensitivity of 84% and a specificity of 97% with respect to
`diagnosing pancreatic cancer (48). These values compared
`favorably to those of ERCP with a sensitivity and specificity
`of 70 and 94%, respectively. As MRI and MRCP technologies
`mature with the development of additional techniques, such as
`ultrarapid echoplanar imaging, these modalities may find a
`better-defined role in the evaluation of pancreatic cancers.
`5.5. ENDOSCOPIC RETROGRADE
`CHOLANGIOPANCREATOGRAPHY
`ERCP has no role in evaluating the resectability of pancre-
`atic tumors. ERCP cannot evaluate vascular invasion, lymph
`node status, or metastatic disease. ERCP may be useful, how-
`ever, in patients with suspected pancreatic cancer where cross-
`sectional imaging is unable to identify a mass. ERCP can more
`closely examine common bile and pancreatic ducts for evi-
`dence of malignant stricture or obstruction. Findings sugges-
`tive of a malignant tumor include the “double-duct sign” (Fig. 2),
`which signifies obstruction of the common bile and pancreatic
`ducts. Tissue for diagnosis can also be obtained by biopsy,
`sampling of pancreatic juice, or brushings. Palliation of pruri-
`tus and jaundice by placing an endoprosthetic in an obstructed
`duct may be performed. In patients where ERCP and stent
`placement are being considered, it has been suggested that
`cross-sectional imaging for staging be performed first.
`Inflammation caused by manipulation of the biliary tree or
`imaging artifacts induced by the presence of a stent could
`obscure visualization of small tumors and impede staging (8).
`In addition, air artifact from a biliary stent can also alter accu-
`racy of endosonographic staging of pancreatic cancer.
`5.6. POSITRON EMISSION TOMOGRAPHY
`18F fluorodeoxyglucose positron emission tomography
`(PET) works on the principle that malignant cells selectively
`take up and retain the positron emitting radiotracer 18F fluoro-
`deoxyglucose, a glucose analog. Pancreatic adenocarcinomas,
`similar to other cancers, have increased glucose consumption
`when compared with normal pancreatic tissue. Several studies
`have found PET to be more accurate than other imaging
`modalities in the detection of pancreatic cancer. In small
`lesions, less than 2 cm in diameter, PET has been found to be
`more sensitive than CT (49). In a range of studies, PET has a
`high level of accuracy in detecting pancreatic cancers, 85–91%
`(50–54). Sensitivity (85–100%) and specificity (67–88%)
`are also relatively high and comparable to some competing
`technologies.
`Despite excellent sensitivity for detecting pancreatic cancer,
`PET is unable to provide the accurate anatomical information
`needed to stage tumors. PET cannot accurately assess vascular
`invasion or invasion of adjacent visceral structures, and is
`therefore a poor tool for determining resectability. False-posi-
`tive results can occur in the setting of active pancreatitis,
`autoimmune pancreatitis, or any other conditions that cause
`pancreatic inflammation (49,55). False-positive results for
`
`Fig. 2. ERCP image depicting stricture in the pancreatic and common
`bile duct, the so-called “double-duct sign,” in a patient with a pancre-
`atic head adenocarcinoma.
`
`liver metastases have been reported in the setting of intrahep-
`atic cholestasis (56). False-negative results can occur in the
`setting of hyperglycemia. Of concern, some studies have also
`shown that false-negative results may occur in early-stage pan-
`creatic cancers (55,57).
`One area where PET may be useful is in the detection of
`distant metastases not seen by CT. In one study, 17%of patients
`deemed resectable by CT and angiography were found to have
`distant metastases by PET (58). The superiority of PET com-
`pared to CT and MRI in detecting distant metastases is con-
`firmed in a recent study (59). Given the current state of the
`technology, PET does not have a routine role in the staging of
`pancreatic cancer. With the development of new scanners, such
`as the hybrid PET–CT scanners, which combine the physio-
`logical information provided by PET and the morphological
`information provided by CT, a more useful role in the staging
`of pancreatic cancer might evolve.
`
`6. TISSUE ACQUISITION
`In patients with unresectable pancreatic cancer, it is neces-
`sary to have a histological diagnosis before a course of treat-
`ment can be initiated. Some surgeons and patients desire to
`have a pathological diagnosis, even if the tumor appears
`resectable. Historically, tissue from pancreatic lesions has been
`obtained percutaneously by CT-guided FNA, ultrasound-
`guided FNA, or laparoscopic-guided biopsy (Fig. 3). Evolution
`of techniques using EUS-FNA of targeted tissue provides sev-
`eral advantages over the older techniques. EUS-FNA can
`obtain tissue from lesions too small to be identified by CT or
`ultrasound. In addition, lesions en