32 Sporadic Neoplastic Polyps of the Duodenum and Ampulla



10.1055/b-0038-149333

32 Sporadic Neoplastic Polyps of the Duodenum and Ampulla


Prashant Mudireddy and Gregory Haber



32.1 Introduction


Sporadic duodenal polyps are polyps seen in patients without a family history of genetic syndromes such as familial adenomatous polyposis (FAP). Both sporadic ampullary and nonampullary duodenal polyps are uncommon. They are usually found incidentally during upper endoscopy. With improvement in technology and devices, endoscopic resection is indicated for benign lesions. In this chapter, we discuss in detail endoscopic techniques and outcomes of endoscopic resection of both ampullary and nonampullary duodenal polyps.



32.2 Ampullary Neoplastic Polyps


The ampulla of Vater is a complex structure consisting of a papillary mound, a common pancreatobiliary channel, terminal bile duct, and terminal main pancreatic duct. 1 Ampullary neoplasms are uncommon with a reported incidence of about fewer than 1% of all gastrointestinal (GI) neoplasms and a prevalence of 0.04 to 0.12% in the general population. 2 , 3 , 4 Ampullary polyps can occur either sporadically or as a part of the genetic syndrome like FAP. 5 Endoscopic surveillance and resection remain the principal modalities for managing these patients. The surgical alternatives of a wide local excision or pancreaticoduodenal resection are reserved for those who fail or are not candidates for endotherapy.



32.2.1 Types of Ampullary Polyps


Ampullary polyps can be either benign or malignant. Adenomas are the most common benign ampullary polyps (▶Fig. 32.1). 2 Histologically, adenomas are further classified into tubular, villous, and tubulovillous. Adenomas of the ampulla follow an adenoma-to-carcinoma sequence similar to that for colon polyps. 6 The incidence of malignant transformation of ampullary adenomas to carcinomas ranges between 25 and 85%. 7 Adenomas and adenocarcinomas together constitute greater than 95% of ampullary tumors. 8 Less common benign ampullary tumors include gastric metaplasia, hyperplasia, lipomas, leiomyoma, lymphangioma, hamartoma, hemangioma, schwannoma, and neurogenic tumors. 2 Primary malignant lesions of the ampulla include adenocarcinoma, lymphoma, neuroendocrine, and signet-ring cell carcinoma. 2 Adenocarcinomas are the most common malignant lesions. Malignant lesions that can metastasize to the ampulla include melanoma, hypernephroma, breast carcinoma, and lymphoma. 2 See ▶Table 32.1.






































Table 32.1 Types of ampullary polyps

Benign


Malignant


Adenomas


Adenocarcinomas


Lipomas


Lymphomas


Fibroma


Neuroendocrine tumors


Leiomyoma


Signet-ring cell carcinoma


Lymphangioma


 


Hamartoma


 


Hemangioma


 


Carcinoids


 


Neurogenic tumors


 

Fig. 32.1 Lateral spreading ampullary adenoma.


32.2.2 Clinical Manifestations


Sporadic ampullary neoplasms are most commonly seen in patients in their 70s. They are usually asymptomatic and discovered incidentally on endoscopy or cross-sectional imaging. Patients may present with obstructive symptoms such as jaundice or pancreatitis, or bleeding which manifests as an obscure occult cause of anemia. Complaints of nausea, vomiting, or abdominal pain alone are uncommon manifestations of an ampullary lesion. 8 , 9 Jaundice is the most common symptom and seen in about 50 to 75% of patients. 8 Rarely, patients can develop cholangitis and pancreatitis. 8 In a single-center retrospective review of 157 patients with benign and malignant tumors of the ampulla, dark urine (odds ratio [OR] 14.18, 95% confidence interval [CI] 1.86–108), pruritus (OR 5.07, 95% CI 2.15–124.3), and jaundice (OR 67.24, 95% CI 15.17–297.7) were highly predictive of malignancy. Steatorrhea was moderately predictive of malignancy (OR 5.07, 95% CI 1.12–22.38). Presence of abdominal pain was more suggestive of benign tumor (OR 0.35, 95% CI 0.17–0.72). 9 See ▶Table 32.2.


























Table 32.2 Clinical manifestations of ampullary adenomas

Jaundice


Abdominal pain


Nausea


Vomiting


Fever, chills


Pruritus


Steatorrhea


Gastrointestinal (GI) bleed


Cholangitis


Pancreatitis


In the same study, laboratory values predictive of malignancy were as follows: albumin less than 3.6 g/dL (OR 2.95, 95% CI 1.22–7.14), total bilirubin greater than 1.1 g/dL (OR 7.97, 95% CI 2.62–24.29), alkaline phosphatase greater than 126 (OR 9.73, 95% CI 3.81–24.29), alanine aminotransferase ALT greater than 47 U/L (OR 2.43, 95% CI 1.08–5.45) and aspartate aminotransferase (AST) greater than 55 U/L (OR 2.22, 95% CI 0.99–4.94). Pancreatic enzymes (amylase, lipase), white cell count, and hemoglobin were not predictive of malignancy. 9 A cholestatic liver panel with elevation of liver alkaline phosphatase or gamma-glutamyl transpeptidase (GTP) is the most specific laboratory indication of an ampullary tumor. Transaminase may be mildly elevated with a spike in values associated with acute obstruction. Bilirubin elevations herald worse obstruction usually associated with malignancy. The only exception to this is cholangitis, as a manifestation of stone disease, which is a result of the stasis associated with ampullary tumors.



32.2.3 Diagnosis


Most ampullary polyps are found incidentally on endoscopy or cross-sectional imaging. With a forward-viewing endoscope it is often difficult to distinguish a duodenal polyp from an ampullary lesion. Most often duodenoscopy with a side-viewing endoscope is necessary for optimal visualization and evaluation of an ampullary lesion. Certain features of the endoscopic appearance may help predict the benign or malignant nature of the tumor. A benign ampullary lesion is characterized by a regular margins, soft consistency, and absence of ulceration or spontaneous bleeding. 8 , 10 On the other hand, firmness, ulceration, or friability suggest possible malignancy. 5 In a study of 56 patients with ampullary lesions failure to obtain a cleavage plane with submucosal injection was the strongest predictor of malignancy (OR 28.35, 95% CI 1.9–422.75) on multivariate analysis. 11


Endoscopic biopsy of the ampulla is the mainstay of the histologic diagnosis. However, it is limited by high false-negative rates. In various studies the diagnostic yield of ampullary biopsies ranges from 45 to 80% with false-negative rates of 16 to 60%. 5 The difficulty in establishing a histologic diagnosis is attributable in part to a lack of an adequate specimen when the biopsy forceps are introduced across the right-angled elevator of a duodenoscope. A few strategies have been described to help improve the diagnostic yield of the endoscopic biopsy. These include obtaining at least six biopsy specimens and targeting the most suspicious areas such as depressed or ulcerated regions. Another maneuver to improve specimen acquisition is to grasp the tissue with the cup of the forceps but instead of pulling the forceps back into the channel of the scope, the tip of the scope is angled laterally away from the papilla to mechanically tear the tissue. 5 A definitive histologic evaluation may only be achieved after endoscopic ampullectomy (EA). 12 In a study by Sakorafas et al, about 50% of the ampullary tumors harbored foci of adenocarcinoma at the time of the diagnosis. 13 Endoscopic brush cytology is a helpful adjunctive technique especially when the tumor invades the wall of the bile or pancreatic duct manifests usually by the presence of a short stricture. 14 , 15 Diagnostic yield of brush cytology varies from 18 to 70%. 14 , 15 , 16 , 17 In a study of 74 patients with pancreatobiliary strictures, brush cytology had a sensitivity of 56%, specificity of 100%, positive predictive value of 100%, negative predictive value of 51%, and accuracy of 70%. 15


Other investigational techniques have included polymerase chain reaction (PCR) analysis of DNA for K-Ras gene mutations, immunohistochemical staining for p53 tumor suppressor gene, CK7, CK20, CDX2, MUC1 and MUC2, microRNA expression, and assessment of aneuploidy by flow cytometry. 5



Endoscopic Ultrasonography and Intraductal Ultrasound

Endoscopic ultrasonography (EUS) and intraductal ultrasound (IDUS) have been shown to be useful in the accurate T staging of the ampullary lesions. EUS operating at 7.5 to 10 MHz provides useful information as to the depth of the invasion of the duodenal wall and/or pancreatobiliary ducts, size and echogenicity of the tumor, and status of regional lymph nodes. 2 , 7 The reported accuracy of EUS in T staging varies between 56 and 91%, while N-stage accuracy varies between 50 and 81%. 2 EUS has been shown to be more accurate than computed tomography (CT) and magnetic resonance imaging (MRI) for T staging.


In a study of two centers comprising 50 patients, the accuracy of EUS for assessment of the T stage of ampullary neoplasms was 78% compared to 24% for CT and 46% for MRI. T-staging accuracy of EUS is decreased in the presence of a transpapillary endobiliary stent (84–72%). However, in nodal staging all three modalities were of similar efficacy (EUS 68%, CT 59%, MRI 77%, p > 0.05). 2 , 18


IDUS utilizes frequencies between 20 and 30 MHz and is performed by advancing the ultrasound probe into the common bile duct (CBD) over a guidewire. 19 In three studies evaluating the accuracy of IDUS in T staging of ampullary neoplasms, the overall accuracy ranged between 78 and 93%. 19 , 20 , 21 , 22 In a prospective study of 27 patients, it was noted that IDUS was superior to EUS and CT in tumor visualization and staging (100 vs. 59.3 vs. 29.6%, respectively). 22 In another study by Ito et al, the overall accuracy of IDUS and EUS in tumor staging were similar (78 vs. 63%, respectively, p = 0.14). 21 Based on the limited evidence available IDUS has been shown to be slightly superior to EUS in T staging. However, IDUS is not widely utilized, is more invasive, and does not evaluate regional lymph node status. 2


Is EUS needed in staging all the ampullary lesions? The consensus is divided among experts. In a survey of 79 expert biliary endoscopists (58% response rate), EUS was always utilized prior to ampullectomy by 67% responders, but only selectively by 31% of responders. 23 Some experts suggest foregoing EUS examination for lesions less than 1 cm in size and for those without obvious signs of malignancy as described earlier. 21 Suggested criteria for the performance of EUS/IDUS prior to therapy for ampullary lesions include size greater than 3 cm, malignant features observed on endoscopy, and biopsies showing high-grade dysplasia (HGD) or carcinoma in situ/T1 cancer. 24



Computed Tomography, Magnetic Resonance Imaging

MRI with cholangiopancreatography provides noninvasive assessment of the distal CBD and pancreatic ducts. It provides information about intraductal extension, ductal dilation, and anatomical variants such as pancreatic divisum. 25 CT is the most suitable for evaluation of vascular invasion and distant metastasis. 7



32.2.4 Management of Ampullary Neoplasms


Malignant ampullary lesions and benign lesions unsuitable for endoscopic therapy are treated surgically. 5 Pancreaticoduodenectomy (Whipple’s) and surgical ampullectomy (SA) are the two surgical options available. Pancreaticoduodenectomy allows complete resection of the lesions and has a very low recurrence rate but is associated with considerable morbidity and a risk of mortality. The common postoperative complications include anastomotic dehiscence (up to 9%), and fistulae (up to 14%), as well as nausea, weight loss, early satiety, and altered bowel habits. 5 The mortality rates reported in literature range between 1 and 9%, although in high-volume centers performing Whipple’s resection, the mortality rate is generally 2% or less. 5 Wide local excision is less invasive and involves removal of the entire ampulla of Vater with reimplantation of the CBD and pancreatic duct into the duodenal wall. 5 In a retrospective review comparing local excision to Whipple, SA was associated with statistically lower operative time (169 vs. 268 minutes), estimated blood loss (192 vs. 727 mL), mean length of stay (10 vs. 25 days), and overall morbidity (29 vs. 78%). 26 However, SA has been associated with recurrence rates ranging from 20 to as high as 50%. 27


EA or more specifically papillectomy involves the resection of the mucosal layers and the superficial submucosal layers of the ampulla of Vater. 25 , 28 It is a minimally invasive technique with a high success rate and provides a safer and less invasive alternative to surgical therapy in appropriately selected cases. 5 There are no randomized trials comparing (EA to SA. However, in a retrospective study of 109 patients, EA (68 patients) was equivalent to SA (41 patients) in terms of success in the treatment for benign lesions. At the same time EA patients had a significantly reduced length of stay, lower morbidity, and readmission rates. There was no difference in the rates of mortality (0% each), margin positive excisions (20 vs. 10%, p = 0.19), or reinterventions (26 vs. 15%). These authors favored EA as an initial treatment strategy, reserving surgery as an option for those with unsuccessful endotherapy. 29



32.2.5 Endoscopic Ampullectomy


EA involves resection of the ampullary lesion to the level of the submucosa. It was first described by Suzuki et al in 1983. 30 Ten years later the first case series describing the use of EA for resection of the benign ampullary adenomas was reported by Binmoeller et al. They reported a case series of 25 patients where standard snare polypectomy technique was used to resect the lesions. 31 Since then multiple case series have been reported for benign ampullary lesions.



Indications

The 2015 American Society of Gastrointestinal Endoscopy (ASGE) guidelines on the role of endoscopy in the management of ampullary adenomas do not define precise indications for EA. 5 The general recommendations for endoscopic resection are benign histology, lack of malignant features at endoscopy, and absence of intraductal extension on EUS/IDUS. However, endoscopic techniques to manage intraductal extension have been described.


There is no consensus on the size of the ampullary adenoma that is amenable to endoscopic resection. Based on a retrospective review of 33 patients, Kim et al suggested that polyps greater than 1.5 cm or those with HGD may not be suitable for endoscopic resection due to coexistence of cancer and a high recurrence rate. In this study, polyps with low-grade dysplasia (LGD) were 1.27 +/– 0.089 cm in size, polyps with HGD were 1.81 +/– 0.99 cm in size and cancer group had a size of 1.98+/– 1.08 cm. There was a significant correlation between the size of the polyp and final pathology (p = 0.036). 32 In another retrospective study of 157 patients, benign ampullary lesions had a median size of 1.3 cm while adenocarcinomas had a size of 2 cm. 9 On the other hand some experts recommend that ampullary lesions up to 4 to 5 cm can be removed endoscopically as long as these are benign. 2 , 28 , 31 , 33 , 34 Although there is a correlation between size and the risk of malignancy, in the absence of evidence for invasive cancer, size alone is not a contraindication to endoscopic resection.


Another area of controversy in EA is the presence of intraductal extension. Some experts suggest that EA can be attempted when intraductal extension is limited to less than 10 mm. 2 , 28 , 35 , 36 In a study by Bohnacker et al, 31 patients had extension of adenomatous growth into the biliary or pancreatic ducts (two patients had extension into both the ducts) and 75 patients had no intraductal extension. The rate of curative successful endoscopic therapy in the group with intraductal extension was 43% whereas in the group without intraductal extension it was 83%. Surgery was more frequently needed in the group with intraductal extension either due to incomplete removal or recurrence (37% vs. 12%, p < 0.001). The authors concluded that in experienced endoscopist hands limited intraductal involvement is accessible to endoscopic removal and suitable for endoscopic therapy, because in about 50% surgery can be avoided. 37


In summary, size alone is not a contraindication to endoscopic resection provided there is no optical or sonographic evidence for submucosal invasion, the endoscopic features of ulceration, woody hard tissue, or submucosal extension are worrisome features for invasion. Further evaluation by EUS should then be considered. As noted in the study by Kim et al, lesions with HGD may harbor foci of cancer and the pathology of the resected tumor will determine the need for subsequent surgery. 32



EA Technique

EA is an advanced endoscopic procedure which needs considerable expertise and experience. 25 The basic technique of EA is similar to the principle used for colonoscopic polypectomy. Complete en bloc resection is preferred because it allows more accurate histologic assessment and negligible recurrence. 25 Complete en bloc resection also ensures complete removal of adenomatous tissue abutting the biliary and pancreatic orifices. For lesions with extrapapillary extension to adjacent duodenal mucosa, the papilla should be resected as a single piece and the remainder resected in as few pieces as possible (▶Fig. 32.2). 25 Use of chromoendoscopy (using methylene blue or indigo carmine) and narrow-band imaging (NBI) has been described to define the lateral margins of the ampullary polyps. 38 , 39 , 40 , 41 Itoi et al noted that NBI had a statistically significant advantage over chromoendoscopy with indigo carmine in defining the lateral margins (p < 0.05). 41

Fig. 32.2 Post endoscopic ampullectomy.


Equipment

There is no evidence to suggest that one type of snare is superior to others. The snare size is chosen according to the size of the adenoma to ensure en bloc resection. A comparison of “braided” polypectomy snares and fine wire snares has been reported. 5 Use of thin wire snares is advocated by some experts because they maximize current density for swift resection of the adenoma and limit dispersion of energy. 25 We prefer soft wire oval or hexagonal snare, which facilitates positioning of the snare over the ampulla when advanced across the elevation of the duodenoscope. We also groom the snare by manually creating a gentle curve at the tip of the closed snare prior to insertion into the accessory channel to allow smooth passage of the snare across the right angle turn over the elevator of the duodenoscope.


There are no standardized electrocautery settings for EP. The goal of the thermal energy is to achieve cutting with enough coagulation to seal vessels, but avoiding thermal injury to the pancreas. We typically use an ERBE generator with a setting of Endocut Q, effect 3, duration 2, and interval 3 (ERBE USA Inc., Marietta, Georgia, United States; Olympus ESG-100, Tokyo, Japan). 25



Technique

First step is to perform endoscopic retrograde cholangiopancreatography (ERCP) with deep cannulation and contrast injection to obtain a cholangiogram and a pancreatogram. This will identify strictures or intraductal extension of the tumor (▶Fig. 32.3; Video 32.1, Video 32.2). It also helps recannulation postresection as a roadmap of the ductal anatomy is shown. In some cases cannulation is not possible prior to resection due to distortion of the anatomy and friability and bleeding in more advanced lesions may be present. In such cases postresection cannulation is often easier once the tumor bulk has been removed. 25 Some experts suggest injecting methylene blue along with contrast into the pancreatic duct to help identify the pancreatic duct orifice postpapillectomy as the flow of blue contrast marks the orifice. 42 Sphincterotomy should generally be performed postpapillectomy. Pre-EA sphincterotomy can hinder en bloc resection and complete histologic evaluation of the resected specimen due to thermal injury. It may increase the risk of bleeding, perforation, and tumor seeding. 8 Use of submucosal fluid injection prior to resection is controversial. Fluid injection may increase technical success and decrease complications. 31 , 43 Epinephrine helps to decrease bleeding and methylene blue or indigo carmine enhances endoscopic visualization of the margins of the adenoma. However, submucosal injection may cause difficulty in the resection of small lesions. The center of the ampullary lesion is tethered down by the biliary and pancreatic ducts and may not lift. Fluid injection results in elevation of the mucosa at the margins of the papilla with a resultant “donut” effect in which the adenoma is partially buried by the elevated surrounding mucosa. This may prevent good snare entrapment and compromise complete excision. 43

Fig. 32.3 Intraductal extension of ampullary tumor.

The snare is advanced through the accessory channel of the duodenoscope. The snare is opened in a line corresponding to the long axis of the mound. The snare tip is fixed above the top of the papilla and snare is carefully opened and drawn over the papilla with the heel of the snare laid down below the inferior margin of the lesion while maintaining the position of the tip of the snare. Then snare is closed slowly entrapping the papilla and resection completed using electrocautery. 25 After the resection, the specimen should be retrieved as soon as possible before it migrates distally into the small bowel. Antiperistaltic agents such as hyoscine butylbromide 10 to 20 mg or glucagon 0.5 to 1 mg may be given intravenously prior to starting resection to decrease peristalsis. 25 Expeditious retrieval of the specimen can be achieved simply using the same snare used for resection. The specimen can be pulled up to the stomach and if it is 2 cm or greater, it is easier to drop the specimen and retrap it with a retrieval net before pulling it up through the esophagus. Alternatively, the retrieval net may be used from the outset provided the specimen is not falling down the duodenal sweep. Aspiration of the specimen through the accessory channel should be avoided to prevent fragmentation of the lesion. 5



Pancreatic Stenting

The first priority after EP should be placement of a pancreatic duct stent. 25 EP is associated with increased risk of post-procedural pancreatitis. 5 A meta-analysis of five studies (481 patients) showed that prophylactic pancreatic duct stenting prevents post-ERCP pancreatitis. Patients in no stent group had threefold higher odds of developing pancreatitis compared to the stent group (15.5 vs. 5.8%, OR = 3.2, 95% CI 1.6–6.4). 44 In general, the PD stent is placed postampullectomy but the option of preampullectomy stent placement has been evaluated. Placing the pancreatic duct stent prior to EP might be technically easier as there is no edema or cautery-related changes. A preresection pancreatic stent may also protect the pancreatic orifice from thermal injury. 2 The problem is that a preresection stent may interfere with en bloc resection. Recently Hwang et al described use of an insulated pancreatic stent in 11 patients. They placed a 5 F polytetrafluoroethylene-insulated pancreatic stent prior to EA. Then the stent and tumor were simultaneously grasped with snare. Tumor was resected with stent in place and then specimen retrieved by perpendicular needle knife incision of the snared ampullary tumor along the edge of the stent. There was no stent migration or stent-related complications. No episodes of acute pancreatitis or perforation occurred. There were four episodes of mild bleeding and one episode of late papillary stenosis. 45 Although this approach is well crafted and a way to ensure a pancreatic stent is left in situ, it is unlikely that postampullectomy stent placement in the same patients would be a problem. The same patients in whom pancreatic stent placement is difficult postprocedure are the ones in whom preampullectomy stent placement would be difficult.


The size of the pancreatic stent is not standardized. In most reported case series 5-F stents have been used, followed by 3 F and 7 F. Placing a 5-F stent might be easier and faster. 2 The principle for pancreatic stenting is to minimize damage to the duct while maintaining adequate drainage in the immediate postampullectomy period. The stent size which best approximates the duct diameter with no internal flange is most suitable. If there is tortuosity at the genu, a shorter stent which is limited to the duct in the head of the pancreas is preferable. Duration of the pancreatic stent varies widely from 24 hours to 3 months. 2 Some experts recommend stent removal after 1 to 3 days to minimize stent-induced ductal changes, while others suggest leaving the stents for 1 to 2 months to prevent stenosis. 2 As the majority of stents will migrate out spontaneously, especially postampullectomy in which the sphincter is often removed or reduced in function, we wait 2 weeks to assess migration and if the stent is still in place, it is removed endoscopically. At the same time we will inspect the resection site and remove any residual polyp tissue. 43 In spite of the general recommendation for prophylactic pancreatic stents this is not mandatory. In patients in whom the pancreatic orifice is widely patulous postampullectomy, there is no utility in placing a pancreatic stent.

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May 22, 2020 | Posted by in GASTROENTEROLOGY | Comments Off on 32 Sporadic Neoplastic Polyps of the Duodenum and Ampulla
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