AUTHOR AND EDITOR INFORMATION

Section 1 of 8  

• Authors and Editors
• Papillary Tumors
• Pseudotumors
• Benign Tumors
• Neuroendocrine Tumors
• Secondary Tumors
• Sphincterotomy-associated Biliary Strictures
• References

PAPILLARY TUMORS

Section 2 of 8  

• Authors and Editors
• Papillary Tumors
• Pseudotumors
• Benign Tumors
• Neuroendocrine Tumors
• Secondary Tumors
• Sphincterotomy-associated Biliary Strictures
• References

Periampullary cancers can be broadly considered as tumors arising within 1 cm of the ampulla of Vater and include ampullary, distal bile duct, pancreatic, and duodenal cancers. However, without careful histological analysis, it is difficult, if not impossible, to differentiate the tumor type.

In the United States, the Surveillance, Epidemiology, and End Results (SEER) program has reported a decrease in the incidence of pancreatic cancer from 12.3 cases per 100,000 population in 1973 to 10.7 cases per 100,000 population in 1999. During this same period, the decline in the incidence for men was from 16.1 cases per 100,000 population to 12.1 cases per 100,000 population, and for women, the decline in the incidence was from 9.6 cases per 100,000 to 9.5 cases per 100,000 population.

The accuracy of the preoperative diagnosis of ampullary carcinoma increased from 27-73% after the introduction of fiberoptic endoscopy. Malignant papillary tumors have a more favorable course after resection when compared to pancreatic cancer. When treated with the standard Whipple procedure, the 5-year survival rates in most series are approximately 35%.

Epidemiology

Tumors of the papilla are unusual entities, compromising less than 5% of all new digestive tract neoplasms. However, cancer of the pancreas is significantly more common and is responsible for approximately 12% of digestive organ cases. The prevalence of papillary adenomas in autopsy series is 0.04-0.12%. A review of more than 1 million surgical pathology specimens only discovered 6 villous adenomas. Another report showed that only 12 of more than 400 pancreaticoduodenal tumors were papillary adenomas. The epidemiology of papillary adenomas is not significantly different from that of papillary adenocarcinomas.

Age

Papillary tumors are uncommon before the age of 45 years; 80% of papillary tumors occur between the ages of 60-80 years.

Sex

A slight male predominance exists in the incidence of papillary tumors, although this may be beginning to change.

Etiology

Although the etiology is unknown, various risk factors have been identified; of these identified risk factors, cigarette smoking may account for 25-30% of cases. Other risk factors include diet (ie, high fat, high protein, low fruit, and low vegetable intake), alcohol, coffee, occupation, the presence of other diseases (eg, chronic pancreatitis, diabetes mellitus, pernicious anemia), and prior gastric surgery. From this group, only chronic pancreatitis and adult onset diabetes mellitus of less than 2 years duration seem to be associated with an increased risk of pancreatic cancer. For example, chronic pancreatitis is associated with a 5- to 15-fold risk, whereas hereditary pancreatitis is associated with a 50- to 70-fold risk and a cumulative lifetime risk of 40% until the age of 75 years.

Pancreatic cancer may also occur in 3 other settings where there is an inherited predisposition. First, up to 10% of patients appear to have an inherited component in the absence of familial pancreatic cancer or other cancer syndrome. Second, there is an increased incidence of pancreatic cancer in individuals from families with familial pancreatic cancer in which the disease appears to be transmitted in an autosomal dominant manner with impaired penetrance. Studies have reported that 18% of these families may have BRCA2 mutations in both Jewish and non-Jewish populations. Finally, an increased risk of pancreatic cancer may occur as part of another cancer syndrome, such as familial adenomatous polyposis (FAP), hereditary nonpolyposis colorectal cancer (HNPCC), Peutz-Jeghers syndrome, familial breast-ovarian syndromes, and familial atypical multiple mole melanoma.

An adenoma-carcinoma sequence is postulated in individuals from high-risk groups, such as those with FAP. One prospective study of 18 patients with FAP or Gardner syndrome found 50% had adenomatous changes of the papillary mucosa; 2 of the 9 patients with adenomatous changes had normal-appearing papilla. 

Pathophysiology

The incidence of stones in the common duct is increased in the setting of papillary cancers or adenomas. Whether this phenomenon is an indication that gallstones predispose people to papillary neoplasia or whether stones form in the bile duct as a result of stenosis is unknown. Various dietary carcinogens also have been postulated as possibly contributing to the formation of these tumors. As with other carcinogen hypothesis for papillary tumors, data are insufficient to either refute or support the propositions.

Investigators reported that disruption of the pRb-p16INK4 pathway may play a role in ampullary carcinogenesis after examining the expression status of this protein and pRb immunohistochemically in 36 ampullary cancers. Methylthioadenosine phosphorylase (MTAP) plays an important role in the salvage pathway of adenosine, and inactivation of the MTAP gene is often noted in pancreatic cancer. Hustinx et al reported that MTAP expression is lost in up to 30% of infiltrating pancreatic cancers and in a lower percentage of periampullary cancer due to homozygous deletions of both MTAP and p16INK4A/CDKN2A genes.¹ The same investigators also reported that aberrant expression of certain proteins such as 14-3-3 sigma and ERM proteins is associated with a poorer prognosis.²

Pathology

Grossly, these tumors may manifest 1 of 3 well-described appearances.

• Intramural protrusion - A bulge underneath a normal-appearing papilla
• Exposed protrusion - Neoplastic-appearing tissue extending out from an abnormal-appearing papilla
• Ulcerating

In many cases, ascertaining the true source of these neoplasms is difficult. One beneficial result is that patients frequently develop symptoms early in the course of the disease, when the tumor is relatively small. Most resection specimens contain tumors ranging 1-2 cm in size. Almost all primary papillary cancers are adenocarcinomas, though sarcomas, lymphomas, carcinoid, and islet-cell cancers also have been reported. Histologically, papillary adenocarcinomas closely resemble adenocarcinomas of the colon. As in the colon, these neoplasms range from well differentiated to moderately differentiated to poorly differentiated. One series of 34 primary papillary adenocarcinomas reported that 20% were well differentiated, 68% were moderately differentiated, and 6% were poorly differentiated. Metastatic tumors of the papilla are extremely unusual and may arise from a variety of primary lesions, including lymphomas, malignant melanomas, adenocarcinomas of the breast, and renal cell carcinomas.

Papillary adenomas, like adenocarcinomas, are histologically very similar to their colonic counterparts. One notable difference is that papillary adenomas are more likely to contain villous architecture. As in the colon, progressive dysplastic changes may occur in benign adenomas. Other pathologic categories of benign papillary tumors are important, primarily because they may be mistaken for malignancies and resected in a major operation. In one series of 118 papillary tumors in patients undergoing surgical resection, 4 patients had tumors that were nonneoplastic and classified as papillitis or pancreatitis. Benign lesions, such as lipomas and leiomyomas, rarely are observed in the papilla.

Histopathologic studies of malignant tumors of the main duodenal papilla have demonstrated that these lesions are almost exclusively adenocarcinomas. Rarely, squamous and mucinous elements may be found within these malignant tumors. In addition, these tumors may be characterized as having papillary (villous) or tubular architecture, as well as a wide range of differentiation, from highly differentiated to well differentiated.

Staging

In 1987, the staging of ampullary carcinomas was added to the tumor, node, metastases (TNM) classification of malignant tumors by the International Union against cancer, and, since then, this classification has been used widely. Of the 24 patients with carcinomas of the ampulla described by Mori et al, 5 had stage I disease (20.8%), 11 had stage II disease (45.8%), 7 had stage III disease (29.2 %), and 1 had stage IV disease (4.2 %) at diagnosis.

Endoscopic ultrasonography

In these potentially curable lesions, endoscopic ultrasonography (EUS) can have the greatest clinical impact. Endosonographically, ampullary lesions appear as hyperechoic or mixed echogenic structures that spread to the duodenal wall, common bile duct (CBD), pancreas, and/or adjacent organs and vessels. However, EUS cannot distinguish a benign papillary adenoma from a papillary carcinoma, unless infiltrative growth exists. A study evaluating preoperative staging of ampullary tumors found the overall accuracy of tumor staging to be 74% (26 out of 35) for all tumors. The accuracy for T1, T2, and T3 tumors were 67% (6 out of 9), 71% (10 out of 14), and 83% (10 out of 12), respectively. In the same study, EUS had an accuracy of 86% in helping diagnose pancreatic invasion. Because EUS is accurate for evaluating resectability of ampullary cancer, it can prevent unnecessary surgery and, thus, is critical in the management of ampullary cancers.

A retrospective study of EUS with fine needle aspiration biopsy (EUS-FNAB) of 35 patients with suspected primary ampullary tumors reported sensitivity, specificity, positive predictive value, and negative predictive value of 82.4%, 100%, 100%, and 76.9%, respectively. The authors reported that adenocarcinomas were present in 13 patients (30%) and concluded that EUS-FNAB was an accurate test for assessing suspected primary ampullary tumors.

Clinical features

• Jaundice is observed in 80% of cases. Unlike the jaundice observed with cancer of the pancreas, jaundice produced by papillary cancers may fluctuate, especially early in the course of the obstructive process. Jaundice also draws attention to ampullary tumors at a relatively earlier stage, which may account for better cure rates for these tumors than for tumors further away from the papilla. These tumors may also bleed intermittently, resulting in occasional silver stools due to the combination of melena with acholic stools.
• Abdominal pain is present in 37-60% of cases.
• Severe and rapid weight loss is often associated with unresectability.
• Nausea and vomiting may be present.
• Pancreatitis is observed in 18% of patients.
• Migratory thrombophlebitis (Trousseau sign) is rarely the first symptom of the disease.
• Virchow node is the presence of an enlarged supraclavicular lymph node and is a sign of unresectability.
• Courvoisier sign states that in the presence of jaundice, if a gall bladder is palpable, one must exclude biliary obstruction from malignancy.

Benign tumors present less often with jaundice, reflecting the smaller tumor size and absence of the tissue invasion, though abdominal pain is common. One report of 25 patients with papillary adenomas found abdominal pain in 76% of cases, jaundice in 36% of cases, and pancreatitis in 16% of cases. The increased incidence of common duct calculi observed in both benign and malignant tumors of the papilla may account for some of the abdominal pain and jaundice observed with these lesions.

Laboratory and x-ray data

No specific laboratory studies exist for the diagnosis of pancreatic cancer.

• Increased alkaline phosphatase, gamma–glutamyl transferase (GT), and direct bilirubin
• Microcytic anemia
• Increased serum amylase and lipase

In a prospective multicenter trial that included 30 patients with ampullary carcinoma, Bakkevold et al found that the sensitivities of several diagnostic studies in making a conclusive diagnosis were as follows:

• Abdominal ultrasonography (23%)
• CT scan (58%)
• Endoscopic retrograde cholangiopancreatography (ERCP, 78%)
• ERCP and duct cytology (91%)
• Percutaneous transhepatic cholangiography (100%)

In a series of 52 patients with biopsy-proven ampullary adenomas or carcinomas, Ponchon et al noted a normal endoscopic appearance of the papilla in 37% of patients. In addition, they found that 42% of intraampullary tumors only became apparent after endoscopic sphincterotomy.

Endoscopic biopsy

The yield of endoscopic forceps biopsies has ranged from 50-90%. The use of a polypectomy snare to obtain ampullary biopsies increases the size of the specimen as compared to the use of the specimen. The risk for bleeding also is increased with the use of a polypectomy snare as compared with the use of standard forceps.

The location and the timing of endoscopic biopsies are important parameters in the diagnosis of ampullary carcinoma. Communicate the exact biopsy site to the pathologist because the morphology of the epithelium changes proximal to the papilla. Dark columnar cells that can be present (normally in the region of the papilla) could be interpreted as malignant in a specimen taken higher in the bile duct. In ulcerated tumors, biopsies should be taken at the nodular edge and not from the base because the latter consists of necrotic exudate. When biopsies are needed in a situation in which a papillotomy has been performed, they should be taken during the index procedure. Papillotomies may create histological changes, lasting at least 6 days, that mimic dysplasia.

Endoscopic sphincterotomy

Endoscopic sphincterotomy may play an important role in the diagnosis of ampullary tumors. Performing an endoscopic papillotomy is advisable only when it is considered essential for diagnostic purposes or to eliminate the possibility of a tumor simulating stone impaction.

Treatment

Pancreaticoduodenectomy

Surgical excision remains the mainstay of treatment of adenocarcinomas of the main duodenal papilla in patients who are at good risk without metastatic disease. Bettschart justified an aggressive surgical approach to ampullary lesions based on the overall low proportion of benign lesions, absence of postoperative mortality, and improved long-term survival in 561 patients with periampullary tumors.³ Conversely, Kim et al reported that the predictors of failure after pancreaticoduodenectomy were the staging of disease and nodal status.⁴

If the tumor is deemed resectable, the procedure of choice is a pancreaticoduodenectomy, with the Whipple version being the most popular, until the more recent development of pylorus-preserving variations. Pylorus-preserving pancreaticoduodenectomy is reported to be an easier and less time-consuming operation with less blood loss, a shorter hospital stay, and better weight gain during follow-up care. Also, no differences in the recurrence rate and patient survival exist between pylorus-preserving pancreaticoduodenectomy and the standard Whipple procedure. The operative mortality rate for the Whipple procedure has declined from 26% to less than 5%, although the associated mortality rate remains in the range of 30-60%.

Beger et al reported long-term survival as between 45-65%, and factors associated with a long-term survival were absence of lymph node involvement and absence of infiltration into the pancreas.⁵ Jarufe et al reported their experience with 251 patients with pancreatic carcinoma, of which 133 were pancreatic adenocarcinomas, 88 were ampullary, and 30 were distal common bile duct.⁶ Survival was influenced by poor tumor differentiation, surgical margin, lymph node metastases, and age, with an overall mortality of 4.8% and morbidity of 29.9%.

Regional pancreatectomy, an operation developed by Fortner, involves the en bloc removal of a tumor in or immediately adjacent to the pancreas, with an adequate soft-tissue margin and regional lymphatic drainage of the tumor. This operation may allow for a significantly higher resectability (compared to the Whipple procedure) of ampullary carcinomas with vascular involvement because it involves resection of the pancreatic segment of the portal vein, resection of involved arterial structures if necessary, and a total or subtotal pancreatectomy.

Local excision

An argument in favor of local surgical excision for small ampullary adenocarcinomas only can be made for patients who are not fit to undergo a pancreaticoduodenectomy. Although formal guidelines for follow-up with patients who have undergone local excision of the ampullary tumors do not exist, duodenoscopic surveillance is logical because the recurrence rate is not insignificant. Semiannual examination for 1-2 years followed by annual examination is a suggested surveillance schedule. However, ampullectomy for early ampullary cancer is not recommended because of the high risk of recurrence. Ampullectomy should only be recommended for patients with small lesions (pTis or pT1 1cm or less with high operative risk for pancreaticoduodenectomy).

Biliary bypass

A palliative, proximal, biliary-enteric and gastrojejunal bypass procedure often can be performed in patients who are unfit for radical procedures and who have large bulky tumors that obstruct a significant portion of the duodenal lumen and the bile duct. The operative mortality rate of patients with ampullary tumors undergoing palliative surgical bypass ranges from 17-60%, with a mean of 32%. For patients with inoperable disease without significant duodenal obstruction, consider endoscopic palliation in lieu of surgical bypass because the morbidity and mortality are lower.

Reoperation

In patients who are carefully selected, a place exists for reoperation of recurrent periampullary adenocarcinomas at a referral center for pancreaticobiliary surgery.

Endoscopic treatment

The role of endoscopy in the management of tumors of the main duodenal papilla continues to evolve. Preoperative endoscopic drainage improves liver function and nutrition, with additional opportunity to obtain biopsies if the initial diagnosis is equivocal. Endoscopic therapy is associated with a much lower mortality rate than surgical bypass procedures.

Endoscopic sphincterotomy

Endoscopic spincterotomy is an effective means of palliating patients with ampullary adenocarcinomas, and it is associated with a shorter hospital stay, fever complications, and a lower 30-day mortality rate than surgical bypasses.

Stent placement

Although the issue of stent placement for palliative management of ampullary adenocarcinomas remains unsettled, patients who are discharged from the hospital with an endoprosthesis should be instructed to seek medical attention immediately if they develop any signs or symptoms of biliary obstruction or cholangitis. Consider permanent placement of an expandable metal stent in patients with inoperable ampullary adenocarcinomas or patients who are not fit for surgery. For patients who develop stent occlusion and recurrent jaundice as a result of tumor growth, insertion of a plastic prosthesis inside the occluded metal stent or thermal ablation of the tumor has been employed. Metal stents have 2 major disadvantages, they cannot be removed and they are relatively expensive. Stents should not be placed in patients who may be surgical candidates.

Laser therapy

Laser therapy does not extend the duration of survival and does not appear to destroy these tumors completely.

Brachytherapy

In an uncontrolled clinical trial, Siegel et al treated malignant biliary obstruction with endoscopic implantation of iridium (Ir) 192 using a double-lumen endoprosthesis. Reduction of the tumor mass was observed in 2 out of 14 patients.

Prognosis

The prognosis of adenocarcinoma of the papilla is the most favorable of all the periampullary tumors. The prognosis for patients with malignant tumors of the papilla depends on the extent of local tumor invasion and the presence or absence of vascular invasion, lymph node involvement, and distant metastases. Yokoyama et al also reported that jaundice at presentation predicts an advanced stage ampullary carcinoma and portends a poor prognosis after evaluating 59 patients with ampullary carcinoma.⁷ For patients with node negative ampullary cancer, Brown et al reported pancreaticoduodenectomy was curative in 80% of patients, and once 3-year survival is reached, long-term survival can be expected.⁸

Patients with ampullary tumors predominantly producing sialomucins have a better prognosis than patients with tumors secreting sulfated mucins. In addition, expression of carbohydrate antigen 19-9 or carcinoembryogenic antigen by ampullary carcinomas is associated with a poorer prognosis than ampullary carcinomas that do not express these antigens.

Approximately 50% of ampullary lesions are deemed resectable. In 12 series reported since 1982 for patients with ampullary carcinoma who underwent resection, the overall mean 5-year survival rate is 40%, with a range of 16-61%. As the operative mortality rate continues to decrease and the selection of patients improves, the 5-year survival rate should improve accordingly.

PSEUDOTUMORS

Section 3 of 8  

• Authors and Editors
• Papillary Tumors
• Pseudotumors
• Benign Tumors
• Neuroendocrine Tumors
• Secondary Tumors
• Sphincterotomy-associated Biliary Strictures
• References

A wide variation exists in the endoscopic appearance of normal major duodenal papillae. The only characteristic appearance distinguishing between benign and malignant disease is the presence of an ulcerative tumor mass, which was observed in 21% of patients with malignancy and in no patients with benign disease.

Leese et al reported that 49 patients of 2000 who underwent ERCP had the appearance of a periampullary carcinoma on duodenoscopy. Biopsies were taken both before and after duodenoscopy, and ERCP was attempted by the insertion of a catheter through the tumor mass. Thirty-eight patients had neoplasms and 11 had inflammatory nonneoplastic lesions that were termed pseudotumors. No statistical differences between these 2 groups were present with regard to any of the clinical features recorded, except that a higher proportion of patients with pseudotumors had epigastric pain. None of the patients with pseudotumors had a palpable gallbladder, whereas this finding was present in 16 patients with ampullary tumors.

Comparison of hematological and biochemical tests revealed significantly lower values for hemoglobin, total protein, albumin, and alanine transaminase in the group with tumors. Comparison of ERCP results disclosed that even though the diameter of the pancreatic duct tended to be larger in the group with tumors, no difference existed with respect to the CBD diameter, and the cholangiograms appeared similar in many cases. Gallstones were present significantly more often in the pseudotumor group.

Two of the 11 patients with pseudotumors were subjected to surgical excision because of the histological features on endoscopic biopsies that raised the suspicion of carcinoma. Thus, although certain clinical, laboratory, and endoscopic biopsies raised the suspicion of carcinoma, significant overlap with the findings in benign disease and malignant disease exists. When endoscopic biopsies are unequivocal for carcinoma and the suspicion of a pseudotumor exists, repeating duodenoscopy with biopsies in 2-4 weeks is indicated. A significant proportion of pseudotumors, especially those relating to gallstone disease, have resolved in this time period, thus preventing unnecessary surgery.

BENIGN TUMORS

Section 4 of 8  

• Authors and Editors
• Papillary Tumors
• Pseudotumors
• Benign Tumors
• Neuroendocrine Tumors
• Secondary Tumors
• Sphincterotomy-associated Biliary Strictures
• References

Although malignant tumors of the main papilla are more common, a number of benign neoplasms also may arise in this structure, including benign neoplasms (tubular and villous), lipomas, hamartomas, fibromas, and neurogenic tumors, including neurofibromas, granular cell tumors, leiomyomas, lymphangiomas, and hemangiomas.

The most common benign tumor of the ampulla is the villous adenoma. The incidence is lower than that of ampullary carcinomas, 0.04-0.12% in autopsy series.

No sexual predilection exists.

At diagnosis, the average person is aged 62 years (range of 4 mo to 79 y).

Location

In the series of Ryan et al, 16 of 19 patients with villous tumors of the duodenum had involvement of the main duodenal papilla.

Clinical presentation

Villous adenomas of the ampulla range in size from 4 mm to 7 cm in diameter. Small tumors of the main papilla can be asymptomatic, but symptoms were present in more than 75% of reported cases.

Signs and symptoms include the following:

• Nonspecific abdominal pain (75% of cases)
• Jaundice (70% of cases)
• Upper GI bleeding (50% of cases)
• Coexisting gallbladder or CBD stones (13-20% of cases)

Diagnosis

Laboratory studies are consistent with cholestatic jaundice (increased alkaline phosphatase [AP], gamma-GT, and direct bilirubin). Imaging studies occasionally reveal a filling defect in the duodenum.

Villous adenomas of the ampulla have a high incidence of coexisting malignancy. In a surgical series, the incidence of malignant change (both carcinoma in situ and invasive carcinoma) ranges from 26-63%. Any assessment of the prevalence of malignancy within ampullary villous adenomas must be based on histopathologic analysis of the entire specimen because endoscopic biopsies have an unacceptably high false-negative rate. In one series, endoscopic examination found the tumor in 9 of 10 patients, but endoscopic biopsies missed the rate of malignant change in 5 of 9 patients, or 56%.

Surgical treatment

Given the high false-negative rate for endoscopic biopsy in detecting foci of malignancy, local surgical excision and pancreaticoduodenectomy have been the mainstays of treatment of villous adenomas of the main duodenal papilla. The selection of a surgical procedure primarily depends on the results of endoscopy and intraoperative frozen-section biopsies. For tumors without evidence of malignancy, submucosal excision is the procedure of choice, and this is combined with sphincterotomy or sphincteroplasty if the tumor is growing within the ampullary orifice. More than 85% of patients with benign villous adenomas treated with local excision do well clinically and remain free of recurrence.

If intraoperative frozen sections or examination of the local excision specimen reveals carcinoma in situ, most authorities recommend radical pancreaticoduodenectomy, though others, especially in older reports, have recommended a conservative approach with local excision alone. For lesions that contain invasive carcinoma, the operation of choice is pancreaticoduodenectomy.

Laser therapy

Endoscopic therapy for benign adenomas of the papilla is assuming a larger role. Lambert et al attempted the use of a neodymium:yttrium-aluminum-garnet (Nd:YAG) laser in 7 patients with papillary adenomas and 1 patient with an adenoma that contained a malignant focus. In 3 of these 8 patients, a previous snare resection had been performed, with incomplete removal of the tumor. Complete tumor destruction was achieved in 7 of the 8 cases; follow-up ranged from 14-53 months. Recurrence of the villous adenoma was observed after 24 months in only 1 patient. No complications were noted. In this study, argon laser photoablation seemed to be much less effective in destroying adenomatous tissue residue than the Nd:YAG laser.

In the series of 52 patients with ampullary tumors performed by Ponchon et al, 11 patients underwent attempted adenoma ablation by snare resection, laser photocoagulation, or both, after sphincterotomies. Adenomatous tissue was completely ablated in 10 patients, with a mean duration follow-up of 39 months. Five other patients with comorbid illness or metastatic malignancy underwent successful palliative treatment with sphincterotomy alone (4 patients) or with a transhepatically placed stent (1 patient). Four of these patients died of cardiac disease at a mean of 45 months after the procedure, and 1 was alive at 15 months after the sphincterotomy.

Diathermic fulguration

Shemesh et al reported 5 patients with adenomas of the papilla who presented with obstructive jaundice and underwent successful drainage via endoscopic sphincterotomy. Four of these patients underwent local surgical excision with subsequent adenoma recurrence in all 4 within 6-18 months after the operation. The recurrent adenomas were eradicated by endoscopic diathermic fulguration using the tip of a polypectomy snare or a hot biopsy forceps; no recurrences were noted during follow-up that ranged from 12-24 months. One patient with a sessile adenoma of the papilla refused surgery and, therefore, underwent incomplete piecemeal resection of the adenoma by snare polypectomy; an adenocarcinoma at the head of the pancreas developed 40 months later.

Snare papillectomy

Binmoeller et al described 25 patients with adenomatous tumors of the main papilla who underwent radical endoscopic resection by snare papillectomy. The 3 criteria for inclusion in this study were tumor size less than 4 cm, benign endoscopic appearance, and benign histological results on at least 6 forceps biopsies. Twenty-three patients had de novo tumors, and 2 had recurrent adenomas after local surgical excision.

Endoscopic excision was performed with a pure-cutting current to the level of the muscularis propria. Residual tissue was fulgurated using a monopolar current. ERCP was performed after the papillectomies; then biliary or pancreatic duct papillotomies, or both, were performed, as well as endoprosthesis placement in some patients as satisfactory drainage was needed. Surveillance duodenoscopy was performed at 1, 6, and 12 months after the papillectomies and yearly thereafter. Immediate complications included postpapillectomy bleeding in 2 patients, necessitating local injection of epinephrine (1:20,000), and self-limited pancreatitis in 3 patients. No procedure-related deaths occurred.

Two patients had evidence of intraductal tumor extension by ERCP and were referred for surgery. The remaining 23 patients were observed for a median of 37 months. Six patients had benign recurrences (26%), usually within the first year of follow-up. Of the 6 patients with recurrences, 1 patient had tumor extension into the distal CBD and later succumbed to complications of a Whipple procedure. The remaining 5 patients with recurrence of adenomas were treated endoscopically with snare resection (1 patient), diathermic fulguration (2 patients), or combined treatment (2 patients). Three of these 5 patients were free of disease at 13, 52, and 53 months. One patient was lost to follow-up, and 1 patient underwent a pancreaticoduodenectomy after repeated fulgurations failed to completely ablate adenomatous tissue.

Silvis correctly urged caution and careful consideration of several points before embarking on endoscopic papillectomy of benign ampullary tumors. First, the patients in the study of Binmoeller et al are unusual in that no patient had cancer within the adenoma, whereas the incidence in other reports ranges from 26-63%. Second, papillectomy is associated with a significant recurrence rate and, therefore, only should be considered for patients who are likely to be compliant with an extended schedule of follow-up endoscopic surveillance procedures. Third, a papillectomy only should be performed by an endoscopist who is an expert in ERCP. Lastly, this procedure should be restricted to either patients who refuse surgery or patients who are at high risk for extensive surgical procedures.

Prognosis

Based on a review of available follow-up data, Schulten et al calculated a 5-year survival rate of 21% for patients with villous adenoma of the duodenum harboring malignant change. Celik et al also concluded that radical excision of malignant, ampullary, villous adenomas in patients at good risk provides long-term survival in one third of these patients.

NEUROENDOCRINE TUMORS

Section 5 of 8  

• Authors and Editors
• Papillary Tumors
• Pseudotumors
• Benign Tumors
• Neuroendocrine Tumors
• Secondary Tumors
• Sphincterotomy-associated Biliary Strictures
• References

Background

In a number of cases, neuroendocrine tumors have both neurogenic and endocrine elements. Lesions of endocrine origin have been termed carcinoid tumors. Duodenal carcinoids have both morphologic and functional similarities to pancreatic islet-cell tumors.

Neuroendocrine tumors are rare. Duodenal carcinoids only account for 1-5% of the total. Fewer than 40 cases of ampullary carcinoids exist in the world literature.

No sexual or age-related predilection exists.

Clinical

Although most carcinoid tumors are asymptomatic and are found incidentally, those arising at the ampulla tend to cause symptoms related to intermittent biliary obstruction.

• Abdominal pain
• Melena
• Jaundice
• Recurrent pancreatitis
• Carcinoid syndrome has not been reported in association with an ampullary carcinoid tumor. This observation probably reflects the smaller size of these tumors when detected at the ampulla, a key factor in predicting the incidence of metastases.

Differential diagnosis

The association between ampullary carcinoid islet-cell tumors and Von Recklinghausen disease was first recognized by Lee and Garber in 1970; a number of subsequent reports exist. Both cutaneous and viscerocutaneous neurofibromatoses have been associated with ampullary carcinoid islet-cell tumors.

Diagnosis

Endoscopy: No distinctive endoscopic features exist.

CT scan, MRI, and EUS: The tumor may spread locally to the duodenal wall, pancreas, or bile duct, or it may spread by metastases to local and regional lymph nodes. Lymph node metastases are observed in 25-50% of cases.

Management

In surgical management, local excision and pancreaticoduodenectomy are the 2 operations most commonly employed. Although available data are limited, pancreaticoduodenectomies may be assumed to be associated with a higher perioperative morbidity and mortality.

Prognosis

The 5-year survival rate for patients with carcinoid tumors without apparent metastasis who undergo resection was 68% and 95% in 2 different studies. Of note, the 5-year survival rates in patients with regional lymph node or distant metastasis are 83% and 38%, respectively.

SECONDARY TUMORS

Section 6 of 8  

• Authors and Editors
• Papillary Tumors
• Pseudotumors
• Benign Tumors
• Neuroendocrine Tumors
• Secondary Tumors
• Sphincterotomy-associated Biliary Strictures
• References

Secondary tumors are rare.

Causes of secondary tumors include the following:

• Renal cell carcinoma
• Melanoma
• Lymphoma
• Lymphangioma
• Endometrial adenocarcinoma

Patients present with GI bleeding, obstruction, and perforation. The treatment of secondary tumors is palliative.

SPHINCTEROTOMY-ASSOCIATED BILIARY STRICTURES

Section 7 of 8  

• Authors and Editors
• Papillary Tumors
• Pseudotumors
• Benign Tumors
• Neuroendocrine Tumors
• Secondary Tumors
• Sphincterotomy-associated Biliary Strictures
• References

Narrowing of the biliary orifice after previous endoscopic biliary sphincterotomy (EBS) has been referred to as sphincterotomy stenosis. Sphincterotomy stenosis is recognized late and is an uncommon complication of this procedure.

Background

Since its introduction in 1974, EBS has become widely accepted as the preferred treatment of choledocholithiasis, particularly in patients who have had cholecystectomies, elderly patients, or patients who are infirm. The advent of laparoscopic cholecystectomy and the resultant emphasis on minimally invasive therapy for gallstone disease has further broadened the application of this technique.

The pathogenesis of sphincterotomy-associated biliary strictures remains unclear.

Incidence

The true incidence of procedure-related Oddi stenosis (OS) is not known, in part because of variations in definitions and the manner of assessing orifice width. The recurrence of the biliary pain is reported in approximately 15% of patients after having an EBS for choledocholithiasis. OS was noted in a mean of 50% (range 30-100%) of these patients who were symptomatic, with a mean age of 4.5 years. Papillary stenosis was found 363 times (2.7%) in 13,300 diagnostic ERCP examinations at 5 gastroenterology centers in Germany.

Clinical symptoms include cholangitis, recurrent biliary pain, and intermittent jaundice.

Differential diagnosis

Malignancy

Sphincter of Oddi (SO) dysfunction

Laboratory study results include increased AP, bilirubin, gamma-GT, and 5'-nucleotidase (5'-NT).

Diagnostic studies

Right upper quadrant ultrasound - Dilated CBD

ERCP - Retraction of papilla and dilated CBD

Endoscopic treatment

These recalcitrant lesions are not amenable to repeat sphincterotomy; however, studies suggest that they may be managed successfully by serial placement of stents of incrementally increasing diameter. Hydrostatic balloon dilatation could have been considered as an alternative therapy; however, these strictures, though short, were high grade and recalcitrant to treatment, necessitating prolonged periods of stent placement (median of 12.5 mo) to achieve resolution. Serial placement of stents of incrementally increasing diameter offers sustained radial expansion of the stricture over time, contrasting the short duration of the effect of the balloon.

Surgery

Consider surgery in cases resistant to endoscopic therapy.

REFERENCES

Section 8 of 8

• Authors and Editors
• Papillary Tumors
• Pseudotumors
• Benign Tumors
• Neuroendocrine Tumors
• Secondary Tumors
• Sphincterotomy-associated Biliary Strictures
• References

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Article Last Updated: May 23, 2008