The role of endoscopy in ampullary and duodenal adenomas

This is one of a series of statements discussing the use of GI endoscopy in common clinical situations. The Standards of Practice Committee of the American Society for Gastrointestinal Endoscopy (ASGE) prepared this text. In preparing this guideline, a search of the medical literature was performed by using PubMed from January 1980 through December 2013 by using the keyword(s) “ampulla AND adenoma,” “ampullary adenoma,” “duodenal adenoma,” “papilla AND adenoma,” ‘‘gastrointestinal endoscopy,’’ ‘‘endoscopy,’’ ‘‘endoscopic procedures,’’ and ‘‘procedures.’’ The search was supplemented by accessing the ‘‘related articles’’ feature of PubMed, with articles identified on PubMed as the references. Pertinent studies published in English were reviewed. Additional references were obtained from the bibliographies of the identified articles and from recommendations of expert consultants. When little or no data existed from well-designed prospective trials, emphasis was given to results from large series and reports from recognized experts. Guidelines for appropriate use of endoscopy were based on a critical review of the available data and expert consensus at the time the guidelines were drafted. Further controlled clinical studies may be needed to clarify aspects of this guideline. This guideline may be revised as necessary to account for changes in technology, new data, or other aspects of clinical practice. The recommendations were based on reviewed studies and were graded on the strength of the supporting evidence by using the GRADE criteria1Guyatt G. Oxman A.D. Akl E.A. et al.GRADE guidelines: 1. Introduction—GRADE evidence profiles and summary of findings tables.J Clin Epidemiol. 2011; 64: 383-394Abstract Full Text Full Text PDF PubMed Scopus (496) Google Scholar (Table 1).Table 1GRADE system for the quality of evidence for guidelinesAdapted from Guyatt et al.1Guyatt G. Oxman A.D. Akl E.A. et al.GRADE guidelines: 1. Introduction—GRADE evidence profiles and summary of findings tables.J Clin Epidemiol. 2011; 64: 383-394Abstract Full Text Full Text PDF PubMed Scopus (496) Google ScholarQuality of evidenceDefinitionSymbolHighFurther research is very unlikely to change our confidence in the estimate of effect.⊕⊕⊕⊕ModerateFurther research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.⊕⊕⊕○LowFurther research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.⊕⊕○○Very lowAny estimate of effect is very uncertain.⊕○○○GRADE, Grading of Recommendations Assessment, Development and Evaluation. Open table in a new tab GRADE, Grading of Recommendations Assessment, Development and Evaluation. This guideline is intended to be an educational device to provide information that may assist endoscopists in providing care to patients. This guideline is not a rule and should not be construed as establishing a legal standard of care or as encouraging, advocating, requiring, or discouraging any particular treatment. Clinical decisions in any particular case involve a complex analysis of the patient’s condition and available courses of action. Therefore, clinical considerations may lead an endoscopist to take a course of action that varies from these guidelines. Adenomas of the major duodenal papilla, also known as ampullary adenomas, can occur sporadically or in the context of genetic syndromes such as familial adenomatous polyposis (FAP). These lesions have the potential to undergo malignant transformation to ampullary cancer, and their clinical significance extends beyond the need to treat any associated symptoms. Endoscopic screening and surveillance of high-risk patients, such as those with FAP, also has led to increasing recognition of ampullary adenomas.2Offerhaus G.J. Giardiello F.M. Krush A.J. et al.The risk of upper gastrointestinal cancer in familial adenomatous polyposis.Gastroenterology. 1992; 102: 1980-1982PubMed Google Scholar, 3Galandiuk S. Hermann R.E. Jagelman D.G. et al.Villous tumors of the duodenum.Ann Surg. 1988; 207: 234-239Crossref PubMed Google Scholar, 4van Stolk R. Sivak Jr., M.V. Petrini J.L. et al.Endoscopic management of upper gastrointestinal polyps and periampullary lesions in familial adenomatous polyposis and Gardner's syndrome.Endoscopy. 1987; : 19-22Crossref PubMed Google Scholar, 5Stolte M. Pscherer C. Adenoma-carcinoma sequence in the papilla of Vater.Scan J Gastroenterol. 1996; 31: 376-382Crossref PubMed Google Scholar, 6Lindor N.M. Greene M.H. The concise handbook of family cancer syndromes. Mayo Familial Cancer Program.J Natl Cancer Institute. 1998; 15: 1039-1071Crossref Google Scholar Ampullary adenomas have historically been treated surgically. Surgical options have traditionally included pancreaticoduodenectomy (the Whipple procedure) or transduodenal ampullectomy (which can occasionally leave behind residual adenomatous tissue).7Di Giorgio A. Alfieri S. Rotondi F. et al.Pancreatoduodenectomy for tumors of Vater's ampulla: report on 94 consecutive patients.World J Surg. 2005; 29: 513-518Crossref PubMed Scopus (48) Google Scholar, 8Bohra A.K. McKie L. Diamond T. Transduodenal excision of ampullary tumours.Ulster Med J. 2002; 71: 121-127PubMed Google Scholar, 9Posner S. Colletti L. Knol J. et al.Safety and long-term efficacy of transduodenal excision for tumors of the ampulla of Vater.Surgery. 2000; 128: 694-701Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar Although surgical management often allows complete removal, it is associated with morbidity, including postoperative anastomotic dehiscence and fistulae in up to 9% and 14% of patients, respectively, and mortality rates ranging from 1% to 9%.10Cahen D.L. Fockens P. de Wit L.T. et al.Local resection or pancreaticoduodenectomy for villous adenoma of the ampulla of Vater diagnosed before operation.Brit J Surg. 1997; 84: 948-951Crossref PubMed Scopus (90) Google Scholar, 11Jordan Jr., P.H. Ayala G. Rosenberg W.R. et al.Treatment of ampullary villous adenomas that may harbor carcinoma.J Gastrointest Surg. 2002; 6: 770-775Crossref PubMed Scopus (15) Google Scholar, 12Tran T.C. Vitale G.C. Ampullary tumors: endoscopic versus operative management.Surg Innov. 2004; 11: 255-263Crossref PubMed Scopus (17) Google Scholar Endoscopic approaches to the evaluation and treatment of ampullary adenomas have developed considerably in recent years, and these techniques now represent a viable alternative to surgical therapy in select cases.13Bourke M.J. Endoscopic resection in the duodenum: current limitations and future directions.Endoscopy. 2013; 45: 127-132Crossref PubMed Scopus (11) Google Scholar, 14Ceppa E.P. Burbridge R.A. Rialon K.L. et al.Endoscopic versus surgical ampullectomy: an algorithm to treat disease of the ampulla of Vater.Ann Surg. 2013; 257: 315-322Crossref PubMed Scopus (9) Google Scholar The management of ampullary adenomas in the setting of FAP has been addressed in a previous American Society for Gastrointestinal Endoscopy (ASGE) guideline.15Hirota W.K. Zuckerman M.J. Adler D.G. et al.ASGE Standards of Practice CommitteeASGE guideline: the role of endoscopy in the surveillance of premalignant conditions of the upper GI tract.Gastrointest Endosc. 2006; 63: 570-580Abstract Full Text Full Text PDF PubMed Scopus (274) Google Scholar A side-viewing duodenoscope is generally required for optimal visualization of the papilla; however, adenomatous change of the papilla may not be apparent by visual inspection alone. Furthermore, ampullary adenomas may not be distinguishable from ampullary carcinomas or nonadenomatous polyps such as carcinoid tumors or gangliocytic paragangliomas.16Church J.M. McGannon E. Hull-Boiner S. et al.Gastroduodenal polyps in patients with familial adenomatous polyposis.Dis Colon Rectum. 1992; 35: 1170-1173Crossref PubMed Scopus (107) Google Scholar, 17Burke C.A. Beck G.J. Church J.M. et al.The natural history of untreated duodenal and ampullary adenomas in patients with familial adenomatous polyposis followed in an endoscopic surveillance program.Gastrointest Endosc. 1999; 49: 358-364Abstract Full Text Full Text PDF PubMed Scopus (118) Google Scholar Therefore, biopsy specimens from suspicious ampullary lesions are recommended and should be obtained before proceeding with attempted endoscopic resection to both confirm the diagnosis and exclude a focus of cancer. Pancreatitis has been reported after biopsies of the papilla, and, therefore, care should be taken to obtain tissue away from the pancreatic duct orifice.18Gincul R. Ciocirlan M. Dumortier J. et al.Severe acute pancreatitis following endoscopic biopsy of the minor duodenal papilla.Endoscopy. 2009; : E195-E196Crossref PubMed Google Scholar Diagnostic (adenoma and carcinoma diagnosis) rates for ampullary biopsies of 45% to 80% have been reported, with false-negative results in 16% to 60% of patients with carcinoma.9Posner S. Colletti L. Knol J. et al.Safety and long-term efficacy of transduodenal excision for tumors of the ampulla of Vater.Surgery. 2000; 128: 694-701Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar, 19Yamaguchi K. Enjoji M. Adenoma of the ampulla of Vater: putative precancerous lesion.Gut. 1991; 32: 1558-1561Crossref PubMed Google Scholar, 20Ryan D.P. Schapiro R.H. Warshaw A.L. Villous tumors of the duodenum.Ann Surg. 1986; 203: 301-306Crossref PubMed Google Scholar, 21Yamaguchi K. Enjoji M. Carcinoma of the ampulla of Vater. A clinicopathologic study and pathologic staging of 109 cases of carcinoma and 5 cases of adenoma.Cancer. 1987; 59: 506-515Crossref PubMed Google Scholar, 22Clary B.M. Tyler D.S. Dematos P. et al.Local ampullary resection with careful intraoperative frozen section evaluation for presumed benign ampullary neoplasms.Surgery. 2000; 127: 628-633Abstract Full Text Full Text PDF PubMed Google Scholar, 23Yamaguchi K. Enjoji M. Kitamura K. Endoscopic biopsy has limited accuracy in diagnosis of ampullary tumors.Gastrointest Endosc. 1990; 36: 588-592Abstract Full Text PDF PubMed Google Scholar, 24Lee S.Y. Jang K.T. Lee K.T. et al.Can endoscopic resection be applied for early stage ampulla of Vater cancer?.Gastrointest Endosc. 2006; 63: 783-788Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar, 25Martin J.A. Haber G.B. 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Endoscopic sphincterotomy and endoscopic fulguration in the management of adenoma of the papilla of Vater.Surg Gynecol Obstet. 1989; 169: 445-448PubMed Google Scholar Biopsy of flat lesions that involve more than 1 fold can result in submucosal fibrosis, potentially impeding subsequent endoscopic resection. Orienting the forceps parallel to the folds while taking the tissue gently from between the folds may decrease the risk of subsequent fibrosis.13Bourke M.J. Endoscopic resection in the duodenum: current limitations and future directions.Endoscopy. 2013; 45: 127-132Crossref PubMed Scopus (11) Google Scholar Brush cytology may aid detection of ampullary malignancy in selected cases.30Bardales R.H. Stanley M.W. Simpson D.D. et al.Diagnostic value of brush cytology in the diagnosis of duodenal, biliary, and ampullary neoplasms.Am J Clin Pathol. 1998; 109: 540-548Crossref PubMed Google Scholar, 31Elek G. Gyokeres T. 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There is no consensus on which ampullary adenomas should undergo surveillance or resection with endoscopy or surgery. Lesions with high-grade dysplasia usually warrant therapy to prevent progression to malignancy and also to exclude malignancy missed on biopsy.44Meneghetti A.T. Safadi B. Stewart L. et al.Local resection of ampullary tumors.J Gastrointest Surg. 2005; 9: 1300-1306Crossref PubMed Scopus (32) Google Scholar, 45Zadorova Z. Dvofak M. Hajer J. Endoscopic therapy of benign tumors of the papilla of Vater.Endoscopy. 2001; 33: 345-347Crossref PubMed Scopus (82) Google Scholar Several authors have advocated that endoscopic resection should be performed only in patients without evidence of invasive cancer.46Binmoeller K.F. Boaventura S. Ramsperger K. et al.Endoscopic snare excision of benign adenomas of the papilla of Vater.Gastrointest Endosc. 1993; 39: 127-131Abstract Full Text PDF PubMed Google Scholar, 47Beger H.G. Staib L. Schoenberg M.H. Ampullectomy for adenoma of the papilla and ampulla of Vater.Langenbeck's Arch Surg/Deutsche Gesellschaft fur Chirurgie. 1998; 383: 190-193Crossref Google Scholar, 48Cheng C.L. Sherman S. Fogel E.L. et al.Endoscopic snare papillectomy for tumors of the duodenal papillae.Gastrointest Endosc. 2004; 60: 757-764Abstract Full Text Full Text PDF PubMed Scopus (115) Google Scholar, 49De Palma G.D. Luglio G. Maione F. et al.Endoscopic snare papillectomy: a single institutional experience of a standardized technique. A retrospective cohort study.Internat J Surg (London, England). 2014; 13C: 180-183Google Scholar, 50Boix J. Lorenzo-Zuniga V. Moreno de Vega V. et al.Endoscopic resection of ampullary tumors: 12-year review of 21 cases.Surg Endosc. 2009; 23: 45-49Crossref PubMed Scopus (33) Google Scholar, 51Kim J.H. Kim J.H. Han J.H. et al.Is endoscopic papillectomy safe for ampullary adenomas with high-grade dysplasia?.Ann Surg Oncol. 2009; 16: 2547-2554Crossref PubMed Scopus (17) Google Scholar Although endoscopic removal of ampullary adenocarcinoma has been described, this cannot be endorsed for routine management.52Jung S. Kim M.H. Seo D.W. et al.Endoscopic snare papillectomy of adenocarcinoma of the major duodenal papilla.Gastrointest Endosc. 2001; 54: 622Abstract Full Text Full Text PDF PubMed Google Scholar, 53Neves P. Leitao M. Portela F. et al.Endoscopic resection of ampullary carcinoma.Endoscopy. 2006; 38: 101Crossref PubMed Scopus (8) Google Scholar There are no definitive guidelines regarding the size or diameter above which endoscopic removal of ampullary adenomas should not be attempted. Many authors recommend that lesions ≥4 cm not be treated endoscopically, although there are reports of successful endoscopic resection of ampullary lesions of greater size.45Zadorova Z. Dvofak M. Hajer J. Endoscopic therapy of benign tumors of the papilla of Vater.Endoscopy. 2001; 33: 345-347Crossref PubMed Scopus (82) Google Scholar, 46Binmoeller K.F. Boaventura S. Ramsperger K. et al.Endoscopic snare excision of benign adenomas of the papilla of Vater.Gastrointest Endosc. 1993; 39: 127-131Abstract Full Text PDF PubMed Google Scholar, 47Beger H.G. Staib L. Schoenberg M.H. Ampullectomy for adenoma of the papilla and ampulla of Vater.Langenbeck's Arch Surg/Deutsche Gesellschaft fur Chirurgie. 1998; 383: 190-193Crossref Google Scholar, 48Cheng C.L. Sherman S. Fogel E.L. et al.Endoscopic snare papillectomy for tumors of the duodenal papillae.Gastrointest Endosc. 2004; 60: 757-764Abstract Full Text Full Text PDF PubMed Scopus (115) Google Scholar The size of the lesion, however, can affect the endoscopic approach to resection, as discussed later. Endoscopic features such as firmness, ulceration, nonlifting of the periampullary component with submucosal injection, and friability suggest possible malignancy, and such lesions should be considered for surgical excision even in the absence of malignancy on biopsy specimens.48Cheng C.L. Sherman S. Fogel E.L. et al.Endoscopic snare papillectomy for tumors of the duodenal papillae.Gastrointest Endosc. 2004; 60: 757-764Abstract Full Text Full Text PDF PubMed Scopus (115) Google Scholar Failure to obtain an adequate lift to achieve a cleavage plane for resection was the strongest predictor of malignancy in one study.54Kahaleh M. Shami V.M. Brock A. et al.Factors predictive of malignancy and endoscopic resectability in ampullary neoplasia.Am J Gastroenterol. 2004; 99: 2335-2339Crossref PubMed Scopus (42) Google Scholar ERCP, EUS, and intraductal US can provide useful information in the assessment of ampullary adenomas. They permit assessment of the degree (if any) of intraductal extension of the adenoma. EUS and intraductal US also may identify malignancy and permit evaluation of its extension beyond the muscularis propria, thus allowing triage of patients to endoscopic or surgical therapy. EUS has been shown to be superior to CT, magnetic resonance imaging, or transabdominal US for tumor staging.55Chen C.H. Yang C.C. Yeh Y.H. et al.Reappraisal of endosonography of ampullary tumors: correlation with transabdominal sonography, CT, and MRI.J Clin Ultrasound. 2009; 37: 18-25Crossref PubMed Scopus (29) Google Scholar, 56Rivadeneira D.E. Pochapin M. Grobmyer S.R. et al.Comparison of linear array endoscopic ultrasound and helical computed tomography for the staging of periampullary malignancies.Ann Surg Oncol. 2003; 10: 890-897Crossref PubMed Scopus (55) Google Scholar, 57Itoh A. Goto H. 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Sokiranski R. et al.Is a preoperative multidiagnostic approach to predict surgical resectability of periampullary tumors still effective?.Am J Surg. 2001; 182: 243-249Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar, 61Chen C.H. Tseng L.J. Yang C.C. et al.The accuracy of endoscopic ultrasound, endoscopic retrograde cholangiopancreatography, computed tomography, and transabdominal ultrasound in the detection and staging of primary ampullary tumors.Hepatogastroenterology. 2001; 48: 1750-1753PubMed Google Scholar, 62Okano N. Igarashi Y. Hara S. et al.Endosonographic preoperative evaluation for tumors of the ampulla of Vater using endoscopic ultrasonography and intraductal ultrasonography.Clin Endosc. 2014; 47: 174-177Crossref PubMed Scopus (1) Google Scholar, 66Ridtitid W. Schmidt S.E. Al-Haddad M.A. et al.Performance characteristics of EUS for locoregional evaluation of ampullary lesions.Gastrointest Endosc. 2015; 81: 380-388Abstract Full Text Full Text PDF PubMed Google Scholar Magnetic resonance imaging has been found to be superior to EUS for nodal staging for these patients, whereas CT scans and positron emission tomography scans can detect small metastases not seen on EUS or intraductal US.59Cannon M.E. Carpenter S.L. Elta G.H. et al.EUS compared with CT, magnetic resonance imaging, and angiography and the influence of biliary stenting on staging accuracy of ampullary neoplasms.Gastrointest Endosc. 1999; 50: 27-33Abstract Full Text Full Text PDF PubMed Scopus (165) Google Scholar, 60Schwarz M. Pauls S. Sokiranski R. et al.Is a preoperative multidiagnostic approach to predict surgical resectability of periampullary tumors still effective?.Am J Surg. 2001; 182: 243-249Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar One prospective study comparing EUS, intraductal US, and CT scans found that tumor visualization was superior with intraductal US (100%) compared with EUS (59%) and CT (30%).63Menzel J. Hoepffner N. Sulkowski U. et al.Polypoid tumors of the major duodenal papilla: preoperative staging with intraductal US, EUS, and CT—a prospective, histopathologically controlled study.Gastrointest Endosc. 1999; 49: 349-357Abstract Full Text Full Text PDF PubMed Scopus (112) Google Scholar The overall accuracy of intraductal US for tumor diagnosis was superior to that of EUS (88.9% vs 56.3%; P = .05). However, another study found that intraductal US may overestimate tumor staging for ampullary neoplasms.64Ito K. Fujita N. Noda Y. et al.Preoperative evaluation of ampullary neoplasm with EUS and transpapillary intraductal US: a prospective and histopathologically controlled study.Gastrointest Endosc. 2007; 66: 740-747Abstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar It is uncertain whether all patients with ampullary adenomas should undergo EUS before therapy. Some experts propose that lesions <1 cm in diameter or those that do not have obvious signs of malignancy (ulceration, induration, bleeding) do not require US evaluation before endoscopic removal.65Baillie J. Endoscopic ampullectomy.Am J Gastroenterol. 2005; 100: 2379-2381Crossref PubMed Scopus (22) Google Scholar If available, EUS examination should be considered for larger lesions or those with features concerning for malignancy before endoscopic or surgical resection is performed. ERCP with both biliary and pancreatic duct evaluation should be performed at the time of endoscopic resection to assess for evidence of extension into either ductal system. Ductography is particularly important if EUS was not performed or did not evaluate for any ductal extension of the neoplasm. Both modalities perform similarly in evaluating intraductal extension of ampullary adenomas.66Ridtitid W. Schmidt S.E. Al-Haddad M.A. et al.Performance characteristics of EUS for locoregional evaluation of ampullary lesions.Gastrointest Endosc. 2015; 81: 380-388Abstract Full Text Full Text PDF PubMed Google Scholar Several authors have used evidence of intraductal extension as a criterion for surgical referral.67Norton I.D. Gostout C.J. Baron T.H. et al.Safety and outcome of endoscopic snare excision of the major duodenal papilla.Gastrointest Endosc. 2002; 56: 239-243Abstract Full Text Full Text PDF PubMed Google Scholar, 68Catalano M.F. Linder J.D. Chak A. et al.Endoscopic management of adenoma of the major duodenal papilla.Gastrointest Endosc. 2004; 59: 225-232Abstract Full Text Full Text PDF PubMed Scopus (194) Google Scholar, 69Norton I.D. Geller A. Petersen B.T. et al.Endoscopic surveillance and ablative therapy for periampullary adenomas.Am J Gastroenterol. 2001; 96: 101-106Crossref PubMed Google Scholar Other investigators have shown that <1 cm of extension into the common bile duct or pancreatic duct does not preclude endoscopic therapy because tissue invading to this level may be endoscopically exposed and ablated.54Kahaleh M. Shami V.M. Brock A. et al.Factors predictive of malignancy and endoscopic resectability in ampullary neoplasia.Am J Gastroenterol. 2004; 99: 2335-2339Crossref PubMed Scopus (42) Google Scholar, 70Bohnacker S. Seitz U. Nguyen D. et al.Endoscopic resection of benign tumors of the duodenal papilla without and with intraductal growth.Gastrointest Endosc. 2005; 62: 551-560Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar Balloon dilation or balloon catheters may facilitate endoscopic resection of intraductal extension of ampullary adenomas by exposing or inverting involved tissue.71Dzeletovic I. Topazian M.D. Baron T.H. Endoscopic balloon dilation to facilitate treatment of intraductal extension of ampullary adenomas (with video).Gastrointest Endosc. 2012; 76: 1266-1269Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar, 72Kim J.H. Moon J.H. Choi H.J. et al.Endoscopic snare papillectomy by using a balloon catheter for an unexposed ampullary adenoma with intraductal extension (with videos).Gastrointest Endosc. 2009; 69: 1404-1406Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar Addition of chromoendoscopy agents may aid in enhancing endoscopic visualization of adenoma margins. Chromoendoscopy with nonabsorptive dye such as indigo carmine also can be used to avoid incomplete resection, especially when the margins of a flat lesion are difficult to discern.13Bourke M.J. Endoscopic resection in the duodenum: current limitations and future directions.Endoscopy. 2013; 45: 127-132Crossref PubMed Scopus (11) Google Scholar, 73Dekker E. Boparai K.S. Poley J.W. et al.High resolution endoscopy and the additional value of chromoendoscopy in the evaluation of duodenal adenomatosis in patients with familial adenomatous polyposis.Endoscopy. 2009; 41: 666-669Crossref PubMed Scopus (16) Google Scholar Techniques of endoscopic removal of ampullary adenomas remain nonstandardized likely because of the small number of formal investigations of this practice. The term ampullectomy refers to removal of the entire ampulla of Vater and is a surgical term for procedures that require surgical reimplantation of the distal common bile duct and pancreatic duct within the duodenal wall. Technically, when endoscopic resection of lesions at the major papilla are performed, only tissue from the papilla can be removed endoscopically, and thus the term papillectomy is more appropriate than the term ampullectomy, although the 2 often are used interchangeably in the literature.74Han J. Kim M.H. Endoscopic papillectomy for adenomas of the major duodenal papilla (with video).Gastrointest Endosc. 2006; 63: 292-301Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar Several authors have used submucosal injection immediately before endoscopic papillectomy in a manner similar to that used before performing EMR. The failure of a lesion to manifest a lift sign is associated with malignancy and is considered a contraindication to attempted complete endoscopic resection (although further endoscopic therapy could be performed as a form of palliation in a poor operative candidate).54Kahaleh M. Shami V.M. Brock A. et al.Factors predictive of malignancy and endoscopic resectability in ampullary neoplasia.Am J Gastroenterol. 2004; 99: 2335-2339Crossref PubMed Scopus (42) Google Scholar Fluids injected into the submucosa have included saline solution, epinephrine, and viscous materials such as hydroxypropyl methylcellulose.48Cheng C.L. Sherman S. Fogel E.L. et al.Endoscopic snare papillectomy fo